E-value, while the chlorophytes showed either a different conserved motif or no conserved motif at all. These results suggest that these same genes are expressed coordinately in non-vascular plants; this coordinate expression may have been one of the prerequisites for the development of conducting tissues in plants. We have also analyzed the phylogeny of conserved proteins that may be involved in phloem function and development. The presence of CmPP16, APL, FT, and YDA in chlorophytes suggests the recruitment of ancient regulatory networks for the development of the vascular tissue during evolution while OPS is a novel protein specific to vascular plants.The phloem is the conduit through which photoassimilates are distributed from autotrophic to heterotrophic tissues and is involved in the distribution of signaling molecules that coordinate plant growth and responses to the environment. Phloem function depends on the coordinate expression of a large array of genes. We have previously identified conserved motifs in upstream regions of the Arabidopsis genes, encoding the homologs of pumpkin phloem sap mRNAs, displaying expression in vascular tissues. This tissue-specific expression in Arabidopsis is predicted by the overrepresentation of GA/CT-rich motifs in gene promoters. In this work we have searched for common motifs in upstream regions of the homologous genes from plants considered to possess a “primitive” vascular tissue (a lycophyte), as well as from others that lack a true vascular tissue (a bryophyte), and finally from chlorophytes. Both lycophyte and bryophyte display motifs similar to those found in Arabidopsis with a significantly low  The vascular tissue played an essential role in the adaptation of plants to land, allowing the great diversification of tracheophytes, plants harboring conducting tissues. While non-vascular land plants are also quite diverse and include species that have successfully colonized a variety of niches, the sheer number of tracheophyte species as well as its diversity in geographical distribution, shape and size is overwhelming. This in no small part has resulted from this evolutionary innovation.The evolution of specialized cell types that gave rise to conducting tissues allowed the distribution of nutrients to all plant organs, which evidently also led to cell and tissue specialization, or, as is also termed, a division of labor. The vascular tissue gave rise more recently to two well-defined transport systems within plants, the xylem and the phloem. While the first one has a direct role in the delivery of water and mineral nutrients from roots to aerial tissues, the phloem is involved in the transport of fixed carbon as well as other nutrients from photosynthetic to heterotrophic tissues. In addition, a wealth of evidence indicates that the vasculature functions in signaling between distant tissues  and bryophytes. Although obviously the extant representatives of chlorophytes and non-vascular bryophytes cannot by any means be considered primitive or less evolved than vascular plants, it can be argued that they share some primitive features common to all plants ancestors, such as unicellularity or less modified cell types. These can also illustrate the likely steps  that gave rise to modern vascular plants, evidently starting with the evolution of multicellularity. Next, specialization occurred in such manner that originated heterotrophic cells, including those that were able to absorb mineral nutrients and water from soil as well as those that gave rise to reproductive tissue  harbor an overrepresented common motif, directing gene expression in the vasculature in mature leaves . First, the protein sequences from Arabidopsis were obtained through the Arabidopsis Information Resource . Afterwards, a BLAST search was carried out using the corresponding Arabidopsis protein sequence as query into the proteome database of interest; afterwards the upstream 1 kb sequences were obtained for each protein homolog from the data set (see Tables Upstream sequences from extant plant taxa were retrieved from phytozome (www.genevestigator.com/).The Functional categorization was obtained from TAIR. The tissue specific gene expression was obtained form GENEVESTIGATOR . BLAST analysis was done in the Phytozome database (www.phytozome.net) and the most representative proteins in each taxa were selected. Aminoacid sequences were aligned using CLUSTAL X2  encoded kinases, 20 (35%) for nucleotide binding proteins and 14 (25%) for transcription factors; also, in most of them phloem from different organs is the tissue in which tgese genes are generally expressed at higher levels (data not shown), according to the Genevestigator database Table . There iPhyscomitrella patens as the sole representative of bryophytes; a tracheophyte with a less developed conducting tissue, Selaginella moellendorffii; and several dicot and monocot species. Also included are five species of chlorophytes showing colonial organization (Volvox carteri) as well as unicellular algae. The results of this analysis suggest that most dicots harbor a GA/CT rich motif similar to the Arabidopsis SETPs  those that did show such high values were present in few promoters and were quite degenerate. For example, in Coccomyxa subellipsoidea no motif with an E-value smaller than 1 was found, indeed, it was the only SETPH set in which no common motifs were found  supports the notion that these genes are expressed in a coordinated manner, and may be expressed also in its conducting tissues. On the other hand, C/G rich motifs with a low A/T content were detected in the P. patens SETPHs, which may be related to the GA/CT rich motif observed in tracheophyte SETPHs , these were present in a smaller subset of SETPHs, but at a high frequency in such promoters. Thus a more precise measurement of specific motif abundance was required in order to compare the frequency of such motifs in chlorophyte SETPHs as well as the GA/CT motif in embryophyte SETPHs.The same analysis was applied to the chlorophytes SETPHs in order to search for common motifs and determine whether these SETPHs may be expressed coordinately. Quite different motifs were found in this case; and, as mentioned before, one SETPH did not harbor common motifs, except for three shared by few promoters and of a degenerate nature Figure . It mustE-values per promoter was determined. Of mention, aside from the GA/CT and A/T rich motifs found in embryophytes, as well as the CGT and A/T rich motifs in chlorophytes, additional ones were found in other SETPHs. For example, a G-Box was found overrepresented in the Citrus clementina SETPH  with novel features that may arose via gene or genome duplication, may had an important role in the evolution of multicellularity and in the development of new adaptation mechanisms . The vascular tissue of plants is such an adaptation, while not necessarily a prerequisite for colonization of terrestrial ecosystems. Considering the diversity of non-vascular plants, it is evident that the vascular system represented an advantage that allowed the diversification and occupation of a large array of niches by tracheophytes, as well as a large increase in size. In particular, although the information regarding the factors involved in phloem differentiation and function is still fragmentary, recent work has discovered the role of some genes in phloem development  ALTERED PHLOEM DEVELOPMENT (APL). This protein is member of the MYB coiled-coil transcription factor family required for the proper formation of sieve elements and companion cells, and additionally inhibits xylem differentiation as demonstrated by analysis of www.phytozome.net). Figure E-value ranging from 10−14 to 10−16, but showing in all cases similarity restricted to the N-terminus, which corresponds to the MYB DNA-binding domain . Additionally, the chlorophyte sequences are much larger (300–350 amino acids in length in chlorophytes vs. 130–150 amino acids in tracheophytes), and it is possible that the tracheophyte CmPP16 was derived from the aforementioned segment of an ancestral chlorophyte C2-domain containing protein. It must be mentioned that the Neighbor-Joining method failed to produce a meaningful dendrogram; the topology of this tree is essentially a large polytomy  ecosystems, such as embryo, stomata, and vascular tissue , a GA/CT-rich motif overrepresented in these upstream regions , At1g34260 from Arabidopsis, was likewise capable of directing vascular expression when adjacent to the CaMV minimal promoter, although only consistently in T0 plants  was important for the evolution of the plant vascular system. Our results involving the phylogenetic analysis of selected proteins required for phloem differentiation and/or function  support such notion Figure .S. moellendorfii forms a monophyletic group with P. patens as a sister taxon , which was used as outgroup. Two bursts of evolutionary change occurred in the lineages giving rise to P. patens and S. moellendorffii. One important burst is also observed within the angiosperms in the monocot clade, which is in agreement with the number of potential protein homologs clustered within this subgroup; no other important changes in the evolutionary rate are evident within angiosperms. One explanation for this could be that no important duplication events occurred during the evolution of FT genes in flowering plants outside the monocots. Three major clades are observed in the unrooted tree for flowering plants .Studies of viral movement proteins in plant systems have highlighted important mechanisms used for plant virus to utilize the host machinery operating in long distance communication system in plants and hence establish viral infection , In addition to YDA, the stomatal and embryo developmental programs share other elements of the MAPK pathway. These tissues predate the origin of the vascular tissue; therefore it can be hypothesized that YDA as well as other factors could have been recruited during the appearance of the vascular tissue Figure .The plant vascular system allowed the great diversification of extant plants, in geographical distribution, structural diversity and size. The fossil record has shed light on the morphological steps likely to have occurred during the evolution of this tissue. The analysis of the genes involved in vascular tissue cell differentiation in different species with varying degree of vascular specialization, or lack thereof may help reconstruct which molecular factors were initially required for the appearance of the vasculature. On the other hand, the analysis of the expression pattern of this set of genes in both vascular and non-vascular plants will be important to reconstruct the genetic networks involved in its evolution. Given the importance of phloem and xylem in plant productivity , this knowledge will have important applications. A more complete knowledge of such networks will benefit from the deciphering of gymnosperm genomes, as well as from streptophytes, the closest algal relatives of land plants. In all, our results suggest that the coordinate expression of a set of genes, as well as the appearance of novel genes, and the recruitment of existing ones with a role in other signaling and developmental networks, were important for the evolution of the plant vascular system.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The disproportionate effects of the 2009 H1N1 pandemic on many Canadian Aboriginal communities have drawn attention to the vulnerability of these communities in terms of health outcomes in the face of emerging and reemerging infectious diseases. Exploring the particular challenges facing these communities is essential to improving public health planning. In alignment with the objectives of the Pandemic Influenza Outbreak Research Modelling (Pan-InfORM) team, a Canadian public health workshop was held at the Centre for Disease Modelling (CDM) to: (i) evaluate post-pandemic research findings; (ii) identify existing gaps in knowledge that have yet to be addressed through ongoing research and collaborative activities; and (iii) build upon existing partnerships within the research community to forge new collaborative links with Aboriginal health organizations. The workshop achieved its objectives in identifying main research findings and emerging information post pandemic, and highlighting key challenges that pose significant impediments to the health protection and promotion of Canadian Aboriginal populations. The health challenges faced by Canadian indigenous populations are unique and complex, and can only be addressed through active engagement with affected communities. The academic research community will need to develop a new interdisciplinary framework, building upon concepts from ‘Communities of Practice’, to ensure that the research priorities are identified and targeted, and the outcomes are translated into the context of community health to improve policy and practice. The mandate of Pan-InfORM is to develop knowledge translation methodologies with the aim of bridging the gaps between theory, policy, and practice. In a poThe presence of indigenous stakeholders was crucial in meeting the workshop objectives and providing a national forum to establish new partnerships, and foster research collaborations with Aboriginal health organizations. Modellers presented important research findings with relevance to indigenous health, and highlighted the importance of community-specific planning for vulnerable populations. From the standpoint of public health, the workshop uncovered some critical issues facing underserved communities in terms of access to healthcare services and program delivery. Representatives from health departments shared their knowledge and experiences with addressing the disparities in healthcare access for many Aboriginal communities across Canada. Through in-depth and collegial discussions, important inputs that must be encapsulated in modelling frameworks were identified, and the challenges that are involved in developing health policies were presented.Aboriginal populations face different challenges during emerging infectious diseases. Some of these challenges result from limited access to and the delivery of health services, particularly when some of Canada’s constitutionally identified Aboriginal peoples have different levels of government responsible for the provision of healthcare. The federal government generally provides for First Nations and Inuit populations, whereas Métis citizens generally fall under provincial health jurisdictions. What compounds this, however, is that First Nations and Métis citizens might live quite geographically close, but experience differential access to healthcare and non-insured health coverage. These differences can begin to be eliminated through collaborative multi-jurisdictional efforts designed to address the health needs of affected individuals, particularly those living in remote areas.Aboriginal communities in the province of Manitoba, especially in the northern region, were severely affected by the 2009 pandemic,6. Data During outbreaks of the H1N1 virus in Manitoba, a Tripartite table was established, which included representatives from the provincial and federal governments as well as representatives from First Nations and Métis self-governing organizations. The provincial minister of health liaised and dialogued regularly with the Tripartite table to develop communication strategies for access to primary healthcare in northern Manitoba. In addition, a table for ‘Equity and Ethics’ was established to collect feedback from communities and ensure that their respective citizens would receive equitable access to vaccine and other health resources. To facilitate responses, planning measures included the establishment of teams that were deployed to remote areas for the delivery of patient-care. Patients with severe outcomes requiring hospitalization were transported to the southern part of the province for access to critical care. However, indigenous leaders stressed the importance of developing self-care systems. In response to this concern, Manitoba Health aided with the distribution of H1N1 flu kits to communities where pharmacies and nursing stations were absent or not readily accessible. The provincial government also supported the use of traditional medicines and communicated the relevant information as to where such resources could be located.Lessons learned from Manitoba’s experience during the H1N1 pandemic included understanding that organizations and communities have developed their own plans for responding to emerging crises, and this underscores the necessity for effective communications at all levels of the healthcare system and community for the development of a coherent strategy. This waTo enhance the perspectives of northern communities, several impediments to adequate healthcare delivery during the H1N1 pandemic in the territory of Nunavut were discussed. Cross-cultural barriers remain a key challenge in Nunavut, as many of the healthcare professionals practicing in the territory are often considered outsiders. There is a general lack of orientation to the territory for outside staff, especially with regards to language training. The learning of Nunavut’s two languages is not mandatory and classes are limited to basic training. Concerns regarding the potential to recruit and retain public health staff in Nunavut remain unaddressed. Nunavut still stores public health records in paper-based forms as opposed to electronic systems implemented in Canada at large, which causes problems in maintaining accurate records and surveillance systems. Although the need to generate and update these systems is known, vocalizing this concern has been limited. Furthermore, regulations that have been put in place to protect public health are often rendered obsolete as few people are trained in policing these regulations. The lack of adherence to, or inadequate level of compliance with some regulations has resulted in an increased health burden in the Inuit communities.The social determinants of health can be categorized as: distal , intermediate , and proximal . Colonization is a particularly important historical consideration, as are neo-colonial policies because they perpetuate discrimination and social exclusion, even into the twenty-first century. These processes hinder the development of healthy identities and self-esteem, and are ultimately responsible for poor mental and physical health. Chronic mental diseases affecting indigenous communities include schizophrenia, bipolar disorder and major depressive disorder, as well as post-traumatic stress disorder and addiction. Most astounding is the suicide rate among First Nations youth (aged 15–24), which is eight times the national average for females and five times the national average for males in Canada,10.Other important social determinants of health include poverty, poor education, and overcrowded housing, which have a strong correlation to chronic and infectious diseases. The United Nations’ Human Development Index has been applied to Canada to understand the differences in quality of life and wellbeing between indigenous and non-indigenous populations. OverallGeographic locale is a key factor in determining the level of access to healthcare, with the most underserved communities being those that are the most isolated and remote in the country. Often these communities belong to indigenous groups living in the northern regions of the provinces and across the territories. Approximately 78% of the Inuit population lives in Nunavut where resources pertaining to health practitioners and medical equipment are limited. GeograpRecognizing that limited access to healthcare acts as one of the perpetuating factors to increased rates of respiratory illness in Aboriginal populations, a team of researchers has been conducting research to provide contrasting results if this limitation were removed,14. The Although the link between social factors and health outcomes is strong, Canada’s approach to protecting vulnerable populations has focused on emergency services rather than prevention. A study conducted at York University’s Canadian Homelessness Research Network analyzed how emergency response to homelessness impacts the vulnerability of homeless populations in the event of a pandemic, and how it presents impediments to effective pandemic planning. This stThe first wave of the 2009 H1N1 pandemic exposed the vulnerability of Aboriginal populations to poor outcomes, demonstrating the inefficacy of the polysaccharide vaccine that was in use at the time. This alerted Health Canada to fund a study that assessed the safety and immunogenicity of a new adjuvanted vaccine (Arepanrix) in a sample of Aboriginal adults. A leadiHeamophilus Infuenzae type A (Hia), which has emerged during the past decade in Canadian Aboriginal communities[Heamophilus Infuenzae[In the vaccine research domain, a study is currently being conducted for the development of a new vaccine candidate against munities-22. The munities-20. In aInfuenzae. The emeHelicobacter pylori (H. pylori), is yet another prevalent infection in Canadian Aboriginal populations. H. pyloA major obstacle to developing appropriate health policies and responsive healthcare delivery is a lack of specific data. Although data may be available for particular regions, there is a general lack of streamlining in data sets across multiple jurisdictions, as well as between hospital databases and public health surveillance systems in Canada. As a result, public health professionals are often faced with a deficiency of information to make informed policy decisions. Thus, incomplete data may be adapted or used out of the context in efforts to inform the development of programs and strategies.During the workshop, disease modellers discussed some key areas in which detailed population level data play a critical role in understanding the risk of infection and outcomes in different vulnerable groups. For example, the results of a study on comparative analysis of age distribution of infection and hospitalization during the H1N1 outbreak, presented a marked difference in the risk of infection between First Nations and non-First Nations populations in Manitoba. The stuinsilico using computer simulation experiments.The need for detailed data is also important for the assessment of effectiveness and cost-effectiveness of intervention measures in the face of competing strategies. Presented results of an ongoing research study highlighted the potential utility of an agent-based modelling approach to determine the most effective antiviral treatment and prophylaxis strategies for influenza infection control, and to evaluate the effect of limiting intervention duration. In summWorkshop participants stressed the importance of developing relationships with Aboriginal stakeholders to ensure that their voices are heard in policy-making, and their needs are addressed in strategy development and program delivery. Yet, it can be difficult for researchers to honour all aspects of diversity in their work and use holistic and inclusive approaches, which equally weigh different systems of knowledge. To navigate these pertinent challenges, the use of a “Communities of Practice” (CoP) model was presented. The CoP model, defined as a group of people who have common concerns, a set of problems, and a passion about solving the problems,29, consWithin the context of CoP, the Director of the Institute of Aboriginal Peoples’ Health (IAPH) of the Canadian Institutes of Health Research (CIHR) outlined the institute’s two primary goals. First, the IAHP aims to increase awareness, understanding, and appreciation of Aboriginal beliefs, in addition to traditional knowledge among researchers, peer reviewers, and the Canadian population by extension. Second, the IAPH places a high priority on recognizing, promoting, and incorporating the excellence and rigour of methodologies derived from indigenous norms. The objective is to have these methodologies incorporated into the way the IAPH conducts its research, rather than remaining a mere side note. The IAPH aims to increase the number of First Nations, Inuit, and Métis researchers conducting Aboriginal-related health research, as well as the number and quality of their research activities. The IAPH also takes a grassroots approach in its support of community-based organizations that are eligible to receive and manage funds on behalf of the CIHR, thereby increasing the communities’ abilities to address their own health issues.The workshop highlighted three general areas of research that are neither discrete nor inclusive but can be labeled as instrumental, symbolic, or conceptual. Instrumental research measures impact, symbolic research argues a position, and conceptual research evaluates whether the right questions are being formulated. Each form of research has its own relevancy and can be more commonly associated with certain academic disciplines. For example, with respect to the topic of health risks among homeless populations, instrumental research may ask how shelters can be made more hygienic, while conceptual research would question whether it makes more sense to provide housing to homeless individuals rather than warehouse them in shelters. Both types of research are important for public health and through interdisciplinary knowledge translation activities, the pertinent questions can be debated, re-framed and re-formulated so that they are meaningful and address public health concerns. The underlying process is complex and there will always be political challenges involved; however it is important that resources be marshaled to address these public health issues to produce maximum benefits to the communities at risk.With unique population characteristics that place some Aboriginal communities at increased risk for adverse health consequences, it is imperative for public health authorities to identify vulnerable segments of the population, and in cooperation with local officials within the community, determine effective and feasible health responses. These responses must also take into account factors such as jurisdictional issues and the variability of Aboriginal public health infrastructures. While effectiveness is a necessary criterion for the identification of optimal health responses, these factors must also be considered for assessing the feasibility of such responses in different community settings. Taking into consideration these underappreciated aspects and realities of vulnerable populations, the workshop highlighted that modelling and simulations are invaluable tools that permit the rapid testing of hypotheses for the subsequent design and implementation of response strategies to address the needs of these populations. By permitting simultaneous observations of disease-related outcomes at multiple levels of communities and the healthcare system, models can inform the development of community-wide and specific contingency plans that incorporate the full spectrum of harms related to disease spread and benefits associated with response activities.st century was a public health success in the modern era[The workshop was successful in bringing together key stakeholders, policy decision makers, and researchers from a wide array of disciplines, each with their own perspective but all with the common goal of improving the health status of Canada’s indigenous populations. During the preceding decade, Canada has experienced the emergence of novel diseases that have caused tremendous public concern and economic consequences, including the 2003 SARS epidemic and the 2009 influenza pandemic. The rapid containment of SARS as the first major infectious disease threat of the 21dern era, but alsdern era-34.The objectives of this networking event, and the spectrum of participants, attested to the fact that in the relatively short period of time since the inception of Pan-Inform, significant progress has been achieved through the hosting of bi-annual workshops of this scale. These networking activities have encouraged more intricate disciplinary dialogues, which challenge participants to re-evaluate their assumptions so that they are eventually resolved or dissolved. As a result of such interdisciplinary approaches, new and stronger links between theory, policy and practice have been forged. A strength of the workshop was the presentation of how appropriate use of data can lead to novel scientific findings that influence policy and practice. This is realized by involving the research community, affected populations, and policy makers in the interpretation and contextual use of data, which is becoming increasingly important as modellers aim to introduce ever more complex structures into the models such as social network patterns. Public health challenges and research methods discussed during the workshop led to key recommendations outlined in TablePresentations given during the workshop were evidence for the opening of a new chapter in Canadian public health research and practice involving indigenous populations. Ongoing studies for the development of vaccines for diseases to which Aboriginal populations are prone, as well as projects that are population specific and function on community engagement are examples of movements towards addressing indigenous populations health protection. In moving forward, research should be integrated with planning, building capacity, and harmonizing response activities at all levels and across the healthcare system to help develop holistic policies that are context-specific and incorporate indigenous perspectives.The authors declare that they have no competing interests.KR and SM wrote the first Draft of this paper. MD, NP and JW contributed to the final version. All authors have read the paper and approved it.Data represented in FigureThe pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/12/1098/prepub


Citation analysis has become an important tool for research performance assessment in the medical sciences. However, different areas of medical research may have considerably different citation practices, even within the same medical field. Because of this, it is unclear to what extent citation-based bibliometric indicators allow for valid comparisons between research units active in different areas of medical research.A visualization methodology is introduced that reveals differences in citation practices between medical research areas. The methodology extracts terms from the titles and abstracts of a large collection of publications and uses these terms to visualize the structure of a medical field and to indicate how research areas within this field differ from each other in their average citation impact.Cardiac & cardiovascular systems, Clinical neurology, and Surgery. In each of these fields, there turn out to be large differences in citation practices between research areas. Low-impact research areas tend to focus on clinical intervention research, while high-impact research areas are often more oriented on basic and diagnostic research.Visualizations are provided for 32 medical fields, defined based on journal subject categories in the Web of Science database. The analysis focuses on three fields: h-index and the impact factor, do not correct for differences in citation practices between medical fields. These indicators therefore cannot be used to make accurate between-field comparisons. More sophisticated bibliometric indicators do correct for field differences but still fail to take into account within-field heterogeneity in citation practices. As a consequence, the citation impact of clinical intervention research may be substantially underestimated in comparison with basic and diagnostic research.Popular bibliometric indicators, such as the  An advanced visualization methodology is used to show how citation practices differ between research areas within a medical field. In particular, substantial differences are revealed between basic and diagnostic research areas on the one hand and clinical intervention research areas on the other hand. Implications of the analysis for the use of bibliometric indicators in the medical sciences are discussed.The analysis reported in this paper starts from the idea that drawing explicit boundaries between research areas, for instance between basic and clinical areas, is difficult and would require many arbitrary decisions, for instance regarding the treatment of multidisciplinary topics that are in between multiple areas. To avoid the difficulty of drawing explicit boundaries between research areas, the methodology adopted in this paper relies strongly on the use of visualization. The methodology uses so-called term maps article or review and that were published between 2006 and 2010. For each publication, citations are counted until the end of 2011.The first methodological step is the definition of scientific fields. This study uses data from the Web of Science (WoS) bibliographic database. This database has a good coverage of the medical literature result, study, patient, and clinical evidence. Filtering out these noun phrases is crucial. Due to their general meaning, these noun phrases do not relate specifically to one topic, and they therefore tend to distort the structure of a term map. Apart from excluding general noun phrases, noun phrases that occur only in a small number of publications are excluded as well. This is done in order to obtain sufficiently robust results. The minimum number of publications in which a noun phrase must occur depends on the total number of publications in a field. For the three fields discussed in the next section, thresholds between 70 and 135 publications were used.Using natural language processing techniques, the titles and abstracts of the publications in a field are parsed. This yields a list of all noun phrases  that occur in these publications. An additional algorithm Alzheimer and short-term memory may be expected to co-occur a lot, indicating a strong relation between these two terms. The matrix of term co-occurrence frequencies serves as input for the VOS mapping technique Given a selection of 2000 terms that together characterize a field, the next step is to determine the number of publications in which each pair of terms co-occurs. Two terms are said to co-occur in a publication if they both occur at least once in the title or abstract of the publication. The larger the number of publications in which two terms co-occur, the stronger the terms are considered to be related to each other. In neuroscience, for instance, www.vosviewer.com) is used to visualize the term maps resulting from the above steps.In the final step, the color of each term is determined. First, in order to correct for the age of a publication, each publication’s number of citations is divided by the average number of citations of all publications that appeared in the same year. This yields a publication’s normalized citation score. A score of 1 means that the number of citations of a publication equals the average of all publications that appeared in the same field and in the same year. Next, for each of the 2000 terms, the normalized citation scores of all publications in which the term occurs (in the title or abstract) are averaged. The color of a term is determined based on the resulting average score. Colors range from blue (average score of 0) to green (average score of 1) to red (average score of 2 or higher). Hence, a blue term indicates that the publications in which a term occurs have a low average citation impact, while a red term indicates that the underlying publications have a high average citation impact. The VOSviewer software Cardiac & cardiovascular systems, Clinical neurology, and Surgery. These fields were selected because they match well with our areas of expertise. The maps are based on, respectively, 75,314, 105,405, and 141,155 publications from the period 2006–2010. Only a limited level of detail is offered in www.neesjanvaneck.nl/basic_vs_clinical/. The webpage also provides maps of 29 other medical fields as well as of all 32 medical fields taken together.Cardiac & cardiovascular systems and Clinical neurology maps . In this case, the difference with the outcomes of the analysis reported in the present paper seems to indicate that the selected journal differs from the cardiovascular field as a whole in terms of the characteristics of its basic and clinical publications.) In another relatively small study, reported in Ref. Although differences in citation impact between basic and clinical research have been mentioned in earlier studies A number of limitations of the methodology of the present study need to be mentioned. First of all, because the visualization methodology does not draw explicit boundaries between research areas, no exact figures can be provided on citation impact differences between, for instance, basic and clinical research. On the other hand, by not drawing explicit boundaries, many arbitrary choices are avoided and more fine-grained analyses can be performed. Another methodological limitation is the ambiguity in the meaning and use of terms. Some terms may for instance be used both in basic and in clinical research. Although a term selection algorithm was employed to filter out the most ambiguous terms, some degree of ambiguity cannot be avoided when working with terms. Other limitations relate to the bibliographic database that was used. The WoS database has a good coverage of the medical literature, but to some extent the analysis might have been affected by gaps in the coverage of the literature. Also, the analysis depends strongly on the field definitions offered by the WoS database.h-index and the impact factor or more sophisticated field-normalized indicators, may therefore lead to an underestimation of the impact of certain types of research compared with others. In particular, the impact of clinical intervention research may be underestimated, while the impact of basic and diagnostic research may be overestimated.The results reported in this paper lead to the conclusion that one should be rather careful with citation-based comparisons between medical research areas, even if in a bibliographic database such as WoS the areas are considered to be part of the same field. Field-normalized bibliometric indicators, which are typically used by professional bibliometric centers, correct for differences in citation practices between fields, but at present they fail to correct for within-field differences. The use of bibliometric indicators, either the There is an urgent need for more accurately normalized bibliometric indicators. These indicators should correct not only for differences in citation practices between fields of science, but also for differences between research areas within the same field. Research areas could for instance be defined algorithmically based on citation patterns


The effect of the recent world recession on population health has featured heavily in recent international meetings. Maternal health is a particular concern given that many countries were already falling short of their MDG targets for 2015.th century time series data from 14 high and middle income countries to investigate associations between previous economic recession and boom periods on maternal and infant outcomes (1936 to 2005). A first difference logarithmic model is used to investigate the association between short run fluctuations in GDP per capita  and changes in health outcomes. Separate models are estimated for four separate time periods.We utilise 20The results suggest a modest but significant association between maternal and infant mortality and economic growth for early periods (1936 to 1965) but not more recent periods. Individual country data display markedly different patterns of response to economic changes. Japan and Canada were vulnerable to economic shocks in the post war period. In contrast, mortality rates in countries such as the UK and Italy and particularly the US appear little affected by economic fluctuations.The data presented suggest that recessions do have a negative association with maternal and infant outcomes particularly in earlier stages of a country's development although the effects vary widely across different systems. Almost all of the 20 least wealthy countries have suffered a reduction of 10% or more in GDP per capita in at least one of the last five decades. The challenge for today's policy makers is the design and implementation of mechanisms that protect vulnerable populations from the effects of fluctuating national income. What effect is the current worldwide recession likely to have on the health of populations, particularly those in the least wealthy countries? This key question has featured strongly in international meetings such as the G8, and as a focus of several initiatives, including the High Level Taskforce for Innovative Financing . Prior tThe study used GDP per capita as a general descriptor for the state of the economy. Recession is generally defined as two quarters of negative economic growth. The impacts are clearly felt beyond a change in income in particular on levels of employment, poverty and unequal effects on different socio-economic groups. GDP per capita does not fully account for all these influences but provides a useful summary variable for the general health of the economy that is available universally and consistently available for most countries unlike, for example, unemployment and poverty rates where local definitions and conventions vary widely.The link between individual income and health outcomes is well established at an individual level. At a national level, whilst it is self evidently true that poorer countries generally have inferior health status, the link between changes in income and health outcomes is less clear cut. There are a number of routes through which recession may impact on health outcomes Figure . HousehoIn addition, spending on health care services is determined by the State's ability to raise funds through taxation, social insurance or other means. This in turn affects the ability of a national government to properly finance basic services (2). A recent study of progress towards the Millennium Development Goals (MDGS) found that the direct influence of GDP on health was positive but relatively modest . At the Recession also impacts on the State's ability to fully finance transfer payments such as pension and unemployment benefits, which in turn affect health improving expenditures (3). A sharp decline in the real value of state pensions in Russia during the late 1990 s, for example, was associated with a reduction in the use of health services, protein consumption and life expectancy amongst pensioners .The negative effect on spending may be offset somewhat if a government chooses to protect basic health services at the expense of other commitments. It is thought, for example, that in Cuba preferential access given to services for women and children may have helped to protect basic health outcomes from the worst effects of the US embargo . AssistaA Russian study suggests that health is also affected positively or negatively by consumption of other goods and behaviours (4). In the United States, data suggest that recessions tend to lead to reductions in fertility . This stThe relationship between health and income is thus not uni-directional nor consistent across time or settings. Better health can drive improvements in livelihoods and contribute to increased national wealth . There ith century in order to examine the effect of income on infant and maternal mortality.One of the problems with assessing the effect of recession is assembling a sufficient time series of data on health outcomes. A recent study took advantage of the substantial dataset provided by the Demographic and Health Surveys, a standard survey methodology examining reproductive and child health and now applied in more than 75 countries, to examine the association between economic growth and infant mortality across 59 countries. The study found a substantial negative effect of per capita income on infant mortality . In thisThe analysis focuses on 14 high and middle income countries: high income countries were United Kingdom, United States, Japan, Italy, Canada, France, and Germany; low/middle income countries were Argentina, Brazil, Malaysia, Mexico, Nicaragua, Russia and Thailand. The time series for each country was assembled from a variety of historical sources. For high income countries data were obtained from as early as 1915, but records from this time until the mid-1930 s are patchy and inconsistent, resulting in implausible estimates  is GDP per capita in real (2000) US dollars, CBR is the crude birth rate and u is the lag. A lag of five years is used for all models. The reason is that mortality data are mostly available at five year intervals. Whilst it is possible to impute values between these years, there is no possibility of picking up genuine fluctuations in mortality on a more regular basis. The use of a fixed lag is less restrictive than it seems: in the context of this model, a lag means that the cumulative five year change in GDP is expected to have a cumulative five year association with health outcomes.Where We investigate the dataset in two stages. First, both fixed and random effects panel regression were used to explore the effect of changing per capita income on maternal, infant and neonatal mortality. A Hausman test, used to test the consistency of random versus fixed effects, was statistically significant (P < 0.01), implying that random effects are inconsistent and a fixed model should be used for both the upper and middle/low income country groups. Separate estimation was carried out for the (now) upper income countries and low/middle income countries. The dataset for the upper income countries was divided into fifteen year time periods: 1936 to 1950, 1951 to 1965, 1966 to 1980 and 1981 to 2005. The data for low/middle income countries is not divided by periods because of the small number of observations available for the earlier time periods. One of the potential problems with this specification is simultaneity bias if gdp per capita both determines maternal and infant outcomes and is affected by them. The use of change variables should minimise this risk. An instrumental variable (xtivreg in Stata) method that mitigates simultaneity leading to inconsistent estimates was also estimated. A time trend and total fertility rate were used to instrument the change in GDP variable. A Hausman test was also used to compare specifications and test for inconsistency. The tested was rejected (p > 0.5) for both low/middle and upper income groups suggesting no evidence of simultaneity.A second stage of modelling was to focus on each country individually and the differences in association between per capita income and health during the four post-war time periods. Statistical tests - Durbin Watson (DW) and Breusch-Pagan - indicated that ordinary least squares regression is inefficient as a result of heteroscedastic and autocorrelated (lag 1) errors. Durbin Watson statistics all indicated positive serial correlation with the statistic below the lower bound of significance . A generalised least squares model with robust standard errors was therefore used . Post-estimated DW statistics suggested that the correction had successfully eliminated serial correlation from the estimation for Canada, Italy and Japan and reduced for United States and UK (the statistic was in the zone of indeterminacy).A negative association (significant at 5% level) between changes in income and outcomes was found for both maternal and infant mortality Table . EstimatLack of data precludes a separation of results by period for the low/middle income country group. Pooled estimations for maternal and infant outcomes suggest a significant negative effect of income Table . A 10% rWhilst the associations explored in this pooled analysis are statistically significant, the magnitude of the effects is relatively modest. The data series Figure  suggest There is evidence to suggest that income is becoming less important as a determinant of mortality outcomes today than it was in the past . TechnolFurthermore, there seem to be differences in the experiences of the countries in the group. Since the Second World War, economic cycles appear to have a substantially greater association with maternal mortality in Japan, Italy and Canada than in the United States or the United Kingdom. The reasons for these differences are not entirely clear. In the United Kingdom, for example, it could be conjectured that the introduction of the National Health Service ensured financial access in good times and bad, and for all types of health problems. Yet similar risk pooling was not and still is not available in the United States for all conditions, despite the introduction of Medicaid and Medicare in the 1960 s. The US system does, however, provide free Emergency Room  care which will include emergency complications during acute pregnancy and childbirth. There is also some evidence that families in the United States and in other developed economies make adjustments to their expectations about family size in response to economic cycles. This 'feedback' may, in turn, help to minimise adverse effect on health outcomes, particularly amongst the poorest groups. There is good historical and contemporary evidence that the burden of maternal mortality within developed and developing countries is borne disproportionately by the poor -19. The Substantial reductions in GDP per capita in richer countries are rare. Recession is generally defined as negative growth for two or more consecutive quarters, and negative growth of more than 5% is unusual . Yet in th century which exhibit inconsistencies and implausible fluctuations. Finally, the processes and factors that affect maternal and infant health are likely to be different from those affecting other measures of health status. The results may not, therefore, be general to the health of other population sub-groups.The limitations of the analysis presented here inevitably arise from the data, both in scope and quality. Interpretation of long time series of mortality and birth data -over 70 years for some countries - must acknowledge the risk of artefact effects owing to changing definitions and completeness and quality of data capture, problems which are further compounded by cross-country and pooled analyses. We have endeavoured to limit some of these risks by excluding data for the early years of the 20th century are repeated for countries at similar stages of development today, particularly as many of these countries have considerably larger populations and much higher levels of mortality. The challenge for today's policy makers is the design and implementation of mechanisms that protect vulnerable populations from the effects of fluctuating national income [The historical evidence presented in this paper yields conclusions that are necessarily speculative, but nevertheless suggest that health gains, particularly in countries at an early stage of development, are vulnerable to fluctuating GDP. Substantial additional maternal and infant deaths can be expected if the associations noted here for richer countries during the 20l income . Financil income . These il income . SecondlThe current global challenge brought about by financial collapse comes at a time when progress towards achieving the MDGs requires speeding-up and scaling-up. The key question is whether the challenge can catalyse the invariably difficult decision of rationing scarce resources - here to protect mothers and infants.The authors declare that they have no competing interests.Paper conception: WJG, TE. Acquisition of data: SC, LD, AEF. Analysis and interpretation of data: WJG, TE, AEF. Drafting of manuscript: TE, WJG. Critical revision: TE, WJG, SC, LD, AEF. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/10/727/prepub


We examine the temporal evolution of digital communication activity relating to the American anti-capitalist movement Occupy Wall Street. Using a high-volume sample from the microblogging site Twitter, we investigate changes in Occupy participant engagement, interests, and social connectivity over a fifteen month period starting three months prior to the movement's first protest action. The results of this analysis indicate that, on Twitter, the Occupy movement tended to elicit participation from a set of highly interconnected users with pre-existing interests in domestic politics and foreign social movements. These users, while highly vocal in the months immediately following the birth of the movement, appear to have lost interest in Occupy related communication over the remainder of the study period. Information communications technologies play a crucial role in the development and persistence of many modern social movements The Twitter platform, like other information communication technologies, has the potential to confer a number of benefits to burgeoning social movements In related work To establish the extent of Occupy participant engagement with Twitter over time, here we study the total amount of Occupy-related traffic on the platform from September 2011 through September 2012. With respect to this measure of activity, we find that Occupy traffic has diminished by orders of magnitude relative to peak activity volumes in late 2011. This effect is evident even in concerted attempts to revive the movement's flagging levels of engagement, with activity returning to baseline within a week of May 1st, 2012 reoccupation efforts.Finding little evidence of sustained activity, we turn our attention to Occupy participants themselves, in hopes of understanding how these users were changed as a result of engaging with the movement online. Using a random sample of 25,000 Occupy users, we study changes in behavior at the individual level with respect to attention allocation and social connectivity. From this analysis we are left to conclude that, on Twitter, Occupy evoked interest from a highly-interconnected community of users with pre-existing interest in domestic politics and foreign social movements. Though we find statistically significant changes in political interests and social connectivity over the study period, the magnitude of these changes pales in comparison to the amount of attention these individuals allocated to the Occupy Wall Street cause.tweetshashtags. By following one or more accounts, a user creates a personalized feed that aggregates into a single, private stream the content produced by the followed accounts. Hashtags, short tokens prepended with a pound sign , allow the content produced by many individuals to be aggregated into a public, topic-specific stream including all the tweets containing a given token.Twitter is a social networking platform that allows individuals to consume content from and contribute content to streams comprised of 140-character messages known as Although by default each user's tweets are publicly visible, the audience for an individual's content is largely limited to his or her network of immediate followers, attaining greater levels of visibility only when it is rebroadcast by large numbers of other users. By including a hashtag in a tweet, however, an individual can contribute content to a high-profile stream, and thereby engage with users who might never otherwise see the content. It is this kind of communication, which represents engagement with a topically cohesive community of users unconstrained by social network structure, that is the primary focus of this study.retweet content produced by another individual, rebroadcasting it to his or her audience of followers, or mention another user in a tweet, which functions as a publicly-visible message targeting that individual.In addition to engaging with different content streams, users can interact with one another in two primary ways. A user can https://dev.twitter.com/docs/streaming-apis/streams/public). In addition to information about the content and users associated with a tweet, the Twitter streaming API provides timestamp metadata that allow for the historical reconstruction of the time series presented in this study.We rely on two primary datasets extracted over a 15-month period from an approximately 5–10% sample of the entire public Twitter stream , a second set relating to foreign social movements, and a third relating to domestic political communication. As we are interested exclusively in the attention allocation habits of Occupy users, we identified the set of hashtags relating to domestic political communication and foreign social movements by manually inspecting the 300 hashtags most frequently used by individuals in the random sample. All of the analyses in this article rely on time series describing changes to measured quantities over the course of the study period. Each time series is produced by computing a single statistic on disjoint sets of tweets partitioned into adjacent, temporally non-overlapping bins of At various times over the course of the study period, our system experienced service outages that affected our ability to collect data from the Twitter API. Amounting to 15 days in total, these periods are: September 29 to October 4, 2011; October 11–12, 2011; December 28–30, 2011; February 11–13, 2012; February 16–17, 2012; and May 28–31, 2012. Owing to the fact that the measures we employ reflect relative composition of the stream rather than its absolute volume, these outages do not unduly influence the statistical character of our results.Let us first focus to the total number of tweets in the Occupy corpus over the course of the year. In light of this finding, we wish to gain insights into the character of the individuals from which Occupy drew its support. We begin by studying how Occupy user interests changed in time, examining the frequency with which 25,000 random individuals produced content relating to one of three topics: Occupy Wall Street, foreign social movements, and domestic politics. Based on the random sample described in engaged user ratioAs we are interested in the behavior of individuals who were active on Twitter at a given time, we identify the set of users engaged user attention ratio. Among the set of users engaged with a topic, we next examine the extent to which that topic tends to dominate their content production activity. To accomplish this, let us consider, for each user As expected, a large fraction of users produced Occupy related content during the period of peak activity, with more than 40% of sampled users allocating on average 64% of their attention to the topic during the third week following the initial protests. However, this intense focus on the subject is not sustained over the course of the following year, with the engaged user ratio decaying to less than 5% in the last three months of the study period. Moreover, comparing the engaged user attention ratios from the first half of the period following the initial Occupy protests (With respect to foreign social movements and domestic political communication, we observe that users who would go on to engage with the Occupy movement online tended to exhibit interest in these topics before the initial protest activity in September, 2011. Comparing the engaged user ratios in the first 12 weeks of the study period with those observed during the last 12 weeks of the study period, we find a significant but small increase in domestic political communication activity. This conclusion is based on a two location t-test for a difference in sample means, in which we reject the null hypothesis (Finally, let us examine the extent to which Occupy users tended to interact with one another over the course of the study period. To this end we focus on the proportion of retweets and mentions produced by active users in the random sample that involved another user who produced at least one Occupy-related tweet during the year following the movement's inception. This proportion is computed with respect to all of a user's retweets and mentions, regardless of content, rather than just those related to Occupy Wall Street. Inspecting the 95% confidence interval bands in While interest and activity relating to the Occupy movement has substantially diminished, one could envision that increased levels of engagement with the political process online might constitute a positive outcome for the movement's participants. Along these lines, however, Occupy users remain barely changed, exhibiting a slight increase in attention paid to domestic politics and a slight decrease in attention paid to foreign social movements. Relative to the dramatic behavioral changes these users exhibited in the early stages of the movement, and the magnitude of Occupy-related communication in general, these changes constitute a somewhat underwhelming long-term effect.Similarly, a supporter of the movement might take as a promising outcome increased levels of interaction among Occupy users. Such a scenario could indicate that these individuals formed a more tight-knit community over the course of the year, creating social and communication bonds that may help to facilitate the efficient spread of information, potentially even reinforcing individual propensity for offline activity Taken together, these data suggest that, on Twitter, the Occupy movement tended to elicit participation from a set of highly interconnected users with pre-existing interests in domestic politics and foreign social movements. These same users, while highly vocal in the months immediately following the movement's birth, appear to have lost interest in Occupy-related communication over the remainder of the study period, and have exhibited only marginal changes in their attention allocation habits and social connectivity as a result of their participation.These findings should not be taken to suggest that the Occupy movement itself has failed, as an argument can be made that the movement played a role in increasing the prominence of social and economic inequality in the public discourse. Though it would be unreasonable to argue that users could have maintained the frenetic pace of Occupy's earliest days, it is doubtless that supporters may have hoped for a more sustained discourse than is evident from the near-complete abandonment of these once high-profile communication channels.


Increased temperatures and changes in rainfall patterns as a result of climate change are widely recognized to entail potentially serious consequences for human health, including an increased risk of diarrheal diseases. This study integrates historical data on temperature and rainfall with the burden of disease from cholera in Tanzania and uses socioeconomic data to control for the impacts of general development on the risk of cholera. The results show a significant relationship between temperature and the incidence of cholera. For a 1 degree Celsius temperature increase the initial relative risk of cholera increases by 15 to 29 percent. Based on the modeling results, we project the number and costs of additional cases of cholera that can be attributed to climate change by 2030 in Tanzania for a 1 and 2 degree increase in temperatures, respectively. The total costs of cholera attributable to climate change are shown to be in the range of 0.32 to 1.4 percent of GDP in Tanzania 2030. The results provide useful insights into national-level estimates of the implications of climate change on the health sector and offer information which can feed into both national and international debates on financing and planning adaptation.  With continuous and increasing rates of morbidity associated with waterborne diseases, especially in Sub-Saharan Africa , this grThere is increasing emphasis on quantifying the health impacts from climate change ,5. RecenThis vulnerability to current climate variability and future climate change can be reduced by means of adaptation. Adaptation, broadly defined, would include all current and future activities or interventions that reduce or prevent additional cases of disease or deaths attributable to climate change . AdaptatThere exist several reviews and studies of the costs of health intervention programmes which address the prevention of climate-related diarrhea and cholera ,22,23,24Specifically, this article focuses on Tanzania, where several major cholera epidemics have occurred in recent decades . The anaHistorical data on deaths and cases of cholera were acquired from the Ministry of Health in Dar es Salaam. Two data sets were available. One data set covering cholera cases throughout the country on a monthly basis between January 1998 and December 2004, while a second data set for cholera cases and deaths were available on an annual basis for the whole of Tanzania (1977 to 2004), as well as for 21 of its regions (1998 to 2004). The climate variables were acquired from the Tanzania Meteorological Agency, and include rainfall  and temperatures (monthly mean of daily minimum and maximum temperatures). The variables represent the average of 19 weather stations throughout the country. In addition to climate and health variables, socioeconomic data ,31,32,33The rather limited reliability of the econometric analyses due to the reduced number of observations (7 years) in the datasets should be acknowledged in advance. The dataset containing data aggregated at the monthly level allowed the observation of any seasonal trend in cholera cases and climate variables that cannot be observed with the annual data. Looking at the data, it was observed that a seasonal pattern seems to exist between June and October when lower minimum/maximum temperatures and lower total rainfall coincide with lower cases of cholera .et al. [In order to analyze the magnitude of the burden of cholera attributable to climate change, it is useful to decide on the different scenarios that the analysis will be based on. For this purpose, climate-change predictions for the specific locality, as well as population growth and economic development, will need to be considered. The approach used in this study follows the methodological framework suggested by Chiabai et al. , who est0Scenario C, for 2030, is the baseline scenario and does not include climate change. The scenario is based on the baseline projections of Mathers and Loncar [d Loncar . These pd Loncar  take intd Loncar , taking WHO Weekly Epidemiological Reports 2000–2010 [WHO Weekly Epidemiological Reports 2000–2010. The results from the econometric analysis described in the next section suggest a CFR equal to 0.078. However, the dataset available for this estimation comprised only 15 observations, which compromises the reliability of this estimate. Therefore, the average CFR for cholera in Tanzania provided by the WHO was used, which is also a more conservative estimate (0.0318). As the projections for diarrheal diseases are not released at country levels but are only available at the regional level, the initial step was to downscale the projected number of deaths at the country level. This was done using the projections of Mathers and Loncar  of total000–2010 . Next, tLastly, to supplement the estimated deaths and cases, a measure of population health has been estimated by combining data on mortality and non-fatal health outcomes into a single figure. For this purpose, Disability-Adjusted Life-Years (DALY) was applied. Several other measures, besides DALY, have been devised in the literature, including the Quality-Adjusted Life Year (QALY), Disability-Adjusted Life Expectancy (DALE) and the Healthy Life Year (HeaLY) ,39,40,41YLL is estimated as YLL = DN × XE where DN is number of deaths, and XE is life expectancy at age of death. A life expectancy at birth of 63.8 years (both sexes combined) by 2030 based on the UN World Population Prospects [YLD is estimated as YLD = I × DW × L, where I is the total number of cases, DW is disability weight, and L is the duration of each cholera episode. YLD estimates are limited to loss of health experienced by individuals, and do not take into account other aspects of the quality of life or well-being, or the impacts of one individual’s health condition on other people. Disability weight captures valuation of time lived in a non-optimal health state viewed from societal preferences. The disability weight ranges between 0  and 1  and quantifies judgments about the overall levels of health associated with different health states, not judgments on the relative values of lives lived, persons, overall well-being, quality of life or utility. In estimating YLD a disability weight of 0.15 is used. This is equivalent to that used by the WHO [DALY measures disease burden and combines years of life lost (YLL) from premature deaths with years of life lived with disabilities (YLD). rospects  is used.rospects . Here, a the WHO , which i1Scenario C, builds on 0Scenario C and estimates the number of cholera cases, deaths and DALYs in the light of projected climate-change impacts. The estimates are produced by taking into account the relative risk of contracting cholera projected for 2030, which represents the relative change in the dependent variable given a one-unit change in the explanatory variable. The relative risk applied here is based on an econometric analysis of the relationship between climate variability and cases of cholera as described in the next section. The relative risks are applied to the projected number of cases calculated in 0Scenario C. The difference between the estimates derived in the two scenarios (with and without climate change) represents the burden of disease attributable to climate change. The calculations for 1Scenario C assume a 1 and 2 degree Celsius temperature increase respectively, based on the IPCC [The second scenario, et al. [Calculations of the burden of disease attributable to climate change are based on the Impact Fraction suggested by McMichael et al. . The Impi is defined as the impact fraction attributable to climate change for disease i; Pi is the proportion of the population exposed to the disease; and RRi is the relative risk of the disease under different climate scenarios.where IFIn order to investigate trends in the seasonal pattern, regression analyses, using Stata/SE version 10.1 for Windows, were conducted where a dummy variable, ‘drought’, equals 1 between June and October and zero at other times. A time-trend variable was also used to capture the possible socio-economic effects on cholera cases that were not available at the month level. For example, it seems reasonable to assume that the population, the percentage of the population with access to safe water and sanitation, education levels and income all grew over time between 1998 and 2004.et al. [et al. [In order to investigate the potential relationship between climate variability and cases of cholera to identify the relative risk, Poisson regression analysis was initially used . A Pois [et al. . The spewhere health endpoint is the incidence of cholera cases or deaths in period t (month or year); climate variable represents rainfall or temperature; and X is a vector of socioeconomic factors that may explain the health endpoint . For each dataset, different models have been tested with specifications combining all the available explanatory variables. The preferred models were chosen according to the level of significance of regressors in each model and the goodness-of-fit of each model . Details of the preferred models are given in Annex 1. A time-trend variable was integrated into the model to capture the effect of other socioeconomic variables that potentially influence cholera cases and that were absent from this dataset.In the context of assessing the total costs of health impacts attributable to climate change, several measures will need to be taken into account. These include preventive and reactive adaptation measures, in addition to the costs of residual damages. In the case of cholera , it is far from realistic to assume that preventive adaptation measures can reduce the risk of disease equivalent to the additional risk of disease due to climate change. Hence some costs are expected to be allocated to reactive adaptation measures in terms of cholera cases continuing to be treated after preventive adaptation measures have been put in place. Nevertheless, only a certain proportion of health impacts are assumed to be reduced with adaptation measures, and the costs of residual damages in terms of morbidity and mortality which cannot be avoided with adaptation measures need to be included in the total costs of the impacts. All costs are calculated at constant 2006 US dollar rates.Preventive adaptation measures, which in the case of cholera are thought of mainly in the form of hygiene, water and sanitation programmes , are ass1Scenario C) with the unit costs per case treated.The cholera cases that remain after preventive adaptation measures have been introduced are treated with reactive measures. First, information on cost estimates and the management of a cholera patient admitted to a hospital was obtained from the Tanzanian Ministry of Health in Dar es Salaam. Cholera patients are not treated as outpatients but isolated in a special cholera ward or unit during treatment. Treatment on average takes five days per case and includes infusions, oral rehydration salt, and antiseptics. In addition to treating the cholera patient, people who have had contact with cholera patients are placed under surveillance for five days and given preventive treatment or therapy as outpatients. The total unit cost per case of managing a cholera-admitted, patient including treatment, cost of bed, personnel and outpatient surveillance, is, according to the Ministry of Health, US $98. In the cost estimates in this study, it is assumed that all cases that remain after the introduction of preventive measures are treated with reactive measures. The additional costs of reactive adaptation measures are therefore calculated by multiplying the number of cases attributable to climate change . Therefore, the costs of morbidity include productivity losses that remain after the introduction of preventive adaptation measures. These losses are calculated from daily wages multiplied by days out of work as a result of being sick. For this purpose, the average weighted wage for a person aged fifteen and above is based on the employment figures given in the Tanzanian Integrated Labor Force Survey 2006 . The weidCost = deathscc2030 × VOSL, where dCost is the total cost of cholera deaths attributable to climate change, and 2030ccdeaths is the number of deaths attributable to climate change.To account for the loss of lives attributable to climate change, a GDP-adjusted Value of Statistical Life (VOSL) method has been used. Broadly VOSL measures individual willingness to pay to reduce the risk of death and it has been used widely in environmental economics to value mortality impacts . The VOSFinally, the total economic costs of cholera attributable to climate change are estimated by totaling the costs of reactive adaptation and the costs of impacts remaining after the introduction of preventive adaptation measures. The costs of impacts are estimated from cases (productivity losses) and deaths. As previously mentioned, the costs of preventive measures are not included in the calculations of total costs of cholera attributable to climate change, since these cost measures are assumed to be implemented in line with Tanzania’s national development objectives. The GDP share of total cost in Tanzania by 2030 has been calculated on the basis of GDP projections for annual GDP growth rates for Sub-Saharan Africa .The pair-wise correlation analysis showed that cholera cases are positively correlated with minimum temperature, maximum temperature and their one-month lags . The linear correlation between cholera cases and total rainfall was not significant. This result suggests that cholera cases in Tanzania might be better explained by temperatures than by rainfall. The results using the dataset gathered per month  showed aThe risk ratio was estimated to be equal to 1.29 using the monthly data set. In other words, an increase in temperature equal to 1 degree Celsius would increase the relative risk for cholera cases in Tanzania by 29 percent. Using the annual data for all Tanzania’s regions (the panel of regions), temperature also explained cholera cases better . In thisThe total number of cases is expected to increase from the baseline of 369,783 cases up to as many as 615,356 cases, with an additional 245,573 cases for the upper boundary scenario, given a 2 degree Celsius temperature increase by year 2030. For the more moderate scenario with only 1 degree Celsius increase in temperature, still with the upper boundary scenario, the additional number of cases will be 107,237. For the most moderate scenario, namely lower boundary and 1 degree Celsius increase in temperature, the additional number of cases attributed to climate change will be 55,467. With regard to deaths, the numbers will increase from the baseline of 11,759 deaths to 19,568 for the upper boundary scenario with a 2 degree Celsius temperature increase. This is equal to an additional 7,809 deaths attributable to climate change. For the most moderate scenario, the additional number of deaths is limited to 1,764. The results of the cost estimates  shows thThere are few detailed studies of adaptation costs in the health sector, and this study is the first to link cases of cholera to environmental and socioeconomic factors in predicting climate change impacts to cholera in Tanzania and assessing the related costs. Unlike earlier studies costing adaptation, this study does not keep the baseline incidence of disease fixed at current levels. Instead it incorporates a future baseline disease burden, which implies a reduction in the incidence rates that may be primarily attributed to economic growth and developments that the health sector would undergo in the future. However, accurate cost estimates require robust impact assessments and, given the lack of consistent long-term datasets, the reliability of the econometric analyses is to some extent limited. It is likely that, with more time-specific data available on health and climate variables, the results could show even stronger impacts. et al. [et al. [In addition, the impacts of climate variability on the burden of disease in the form of cholera are complex and dependent on a number of risk factors from local socio-environmental conditions. For a waterborne disease, the results presented in this paper may seem high, with a 15 to 29 percent increase in the relative risk per degree Celsius, in comparison to the 5 percent increase as predicted by WHO  for Sub-et al.  predict  [et al. . The res [et al. ,7,8,9, aThe cost estimates used for reactive adaptation are based on unpublished data from the Tanzanian Ministry of Health. These costs are considerably higher than the costs of treating diarrhea since diarrheal patients can be treated as outpatients, while treatment of cholera has to include hospitalization for an average of five days per case, as well as the cost of surveillance of other people than the patient. In Zambia, average inpatient costs for diarrhea are estimated to by USD 78 per bed day , while fIn estimating total costs, the costs of preventive measures were not included, since it was assumed that these would be implemented along with general socio-economic development and according to Tanzania’s national goals of near-universal water and sanitation coverage by 2025. Accordingly, improved sanitation and hygiene facilities are vital components of the planning and provision of water supply services . HoweverAnother problem arising from the cost estimates is the issue of valuing costs that take the form of increases in mortality . This imThe results presented in this article, despite their limitations, increase our understanding of the implications of climate change on health impacts in Tanzania, and provide indications of cost implications imposed by the additional burden of cholera.Integrating both climate variables and socioeconomic variables in one model confirms that conditions of human health are influenced by many factors and cannot be addressed in isolation. The results of these effects in relation to the impacts of climate change suggest that it would be highly beneficial to improve socioeconomic indicators, including access to water and sanitation, even more quickly than originally planned. The existing time frame for water and sanitation programmes is challenged, with considerable benefits to be gained from more rapid implementation than originally planned. This also includes health education, levels of health service systems and disease surveillance, in addition to measures for early diagnosis and prompt treatment, and the control or prevention of epidemics. Such health-based measures should be viewed in the context of broader development, where the main means to adapt is improvements in general living standards. There is unquestionably a wide array of other benefits for improving performance on these indicators, since they influence a number of other development objectives such as nutrition and education. The estimates, based on assumptions of climate-change projections, suggest that the cholera health cost of increased temperatures of 1 to 2 degree Celsius by 2030 will be in the range of 0.03 to 0.12 percent of GDP for treatment costs alone (cost of reactive adaptation), while total additional cost attributable to climate change, including productivity losses and the value of lost lives, averages out at around 0.75 percent, but may be as much as 1.4 percent of GDP by 2030 for the upper boundary. The magnitude of these cost estimates is substantial, and considerably higher than the current budgets allocated for diarrheal diseases in most developing countries. Thus budgetary increases will be needed if treatment is to be provided to deal with the additional burden of disease attributable to climate-change which cannot be avoided through preventive adaptation measures.The current study has several strengths compared to previous literature on the implications of climate change and the costs of adaptation in the health sector. Compared to most estimates, which are made on regional levels, the scope of assessment has been on the national level, offering interesting insights for policy-makers in evaluating potential adaptation measures at more local and national levels. The cost estimates provide useful information which can feed into both national and international debates on financing and planning adaptation. In addition, the estimates take into account expected future economic development in Tanzania, which includes a strengthening of the health system and hence has an impact on the projections of incidence.The implications of the results for future studies suggest that climate change will cause large additional economic burdens for both societies and households. Consequently, it is vital to quantify the burden of disease attributable to climate change at the national and local levels as opposed to the regional levels, since the vulnerability of human health to climate change in terms of exposure  and capacity to cope and adapt (socioeconomic variables) may vary considerably between time and place. Therefore more and improved projections of future risks are necessary for local  decision-making, in addition to making further efforts to refine the national costs of preventive and reactive adaptation measures in the health sector.


By the latter half of this century, countries bearing large populations such as China and India will also eventually begin to experience aging of their populations. Therefore, the development of technologies related to medical care, health, and welfare are considered extremely crucial. In addition to expectations for the development of medical technologies arising from needs of the global economy, there are also increasing expectations for the creation of new medical technologies stemming from trends in development and practical application of the life sciences. AIST’s Second Period Research Strategy of the AIST  in Japan established in April 2006 also clearly states that developments in science and technology focusing on humans will become the mainstream future trend  conducted a survey for the purpose of assessing the role that medical equipment and technology has played in clinical medicine since the 1950s. The medical equipment that contributed most to clinical medicine/medical care in the 20r period . The listh century, the so-called grand compilation of technologies such as image-guided computer-assisted surgery and robotic surgery, has begun and is being used in clinical application. In the future, extremely delicate and precise microscopic surgery that cannot be performed by a surgeon can be possible through the combination of new surgery support systems and the surgeon’s skill. Thus, progresses in medical treatment technologies simultaneously promote the development of medicine itself. Many new medical findings, such as the progress in anesthesiology required in awake surgery, are appearing in rapid succession. Progress in biomedical engineering in the 20th century has greatly transformed the concept of health care itself, by transfiguring it dramatically from a form of “classical medical care” to that of “leading edge medical care assisted by instrumentation and imaging.” Furthermore, social demands to “enhance and maintain a high quality of medical treatment, health and welfare” in this aging society are behind the anticipation for further developments in this field in the future.Development of biomedical instrumentation technology to measure the physical and chemical information and signals emitted by the living body in a minimally (or non-) invasive and continuous manner, was responsible for establishment of the concept of patient monitoring within clinical medicine. It thus contributed greatly to “enhancement of the quality of medical care.” Furthermore, the technology such as medical imaging evolved into two-dimensional from one-dimensional measurements, and was further developed into three-dimensional measurements, and made speedier as well. Now, it is not an overstatement to say that medical imaging has entered four-dimensional measurement. Meanwhile, treatment technologies have also progressed from highly invasive operative treatments to minimally invasive techniques such as endoscopic surgery. At the end of the 20st century have united in a common purpose and have been active thus. Later, in 2001, the National Institute for Bioimaging and Bioengineering (NIBIB) was founded within the National Institutes of Health (NIH), based upon the foundation of the Bioengineering Consortium (BECON). In accordance with this concept for BECON in USA, Japan also established the Medical Engineering Technology Industrial Strategy (METIS) consortium in 2001.The United States established AIMBE with the assistance of the National Science Foundation (NSF) and others, in February 1992, with the following foresights. First, the focus of medical technology will shift from diagnostic to treatment technology; progresses in molecular biology will bring genetic engineering into diagnostic technology; micro- and nano-treatment technologies will be developed as the ultimate in minimally invasive endoscopic treatment technology; and further, regenerative medicine, the ultimate treatment method, will become possible in the near future through tissue engineering. In AIMBE, many academic societies involved in research and development of new medical treatment technologies of the 21st century medical technology are based upon nanomedicine, regenerative medicine and genetic medicine.As analysis of the human genome is virtually complete, medical technology will now evolve into a technology where various interdisciplinary technologies are multiply combined, from the level of molecules and genes below 100 nm, to tissue and organs, and further to virtual human science per individual level. In addition to the technology of mass cell culture, the validation technology for assuring the quality of the cells and tissue produced is an essential element in allowing medical technology employing tissue engineering to mature into a clinical technology. Thus the development of minimally invasive measurement techniques for regenerative medicine is anticipated. Molecular imaging technology is of growing interest with relevance to the genetic treatment technology. Molecular imaging is of potential in enabling direct observation of function expression of genes in genetic treatments, while various molecular imaging techniques are also anticipated for other function-specific imaging. In clinical medicine, the structure and function of the protein produced by the gene is more often linked directly to the disease rather than the genetic information itself. The proteome is attracting post-genome attention, and it requires a method of analysis different from that of the genome. The protein chip is also being developed as a new technique.st century. The wireless capsule endoscope manufactured by Israel’s Given Imaging Ltd. was approved in Europe in May and by the U.S. FDA in August of 2001. The small intestine is a digestive tract with a total length of 7-8 m, and unlike the large intestine, it is virtually unfixed within the body cavity. It has been referred to as “the last Dark Continent” in gastroenterology. Now, however, the time has come for endoscopic technology to demonstrate the effect in finally allowing observation of the entire digestive tract. Meanwhile, endoscopic systems are used not only in the diagnosis of diseased regions, but are also demonstrating great effect in treatments, such as gastric polyp snare loop techniques, which began from biopsy under direct vision by fiberscope starting in 1965, laser hemostatic techniques which followed, as well as in resections of the gastric mucous membrane. Hence, history shows that endoscopic technology is an area in which Japan leads the world. At the same time, it has technical innovation and market creation ability, as well as competitiveness of product development against Europe and U.S., as seen in Endoscopy may be cited as a typical example of minimally invasive instrumentation technology. In 1950, the gastrocamera was developed in Japan for the first time in the world. Then the prototype of the present-day endoscope was developed in 1957, consisting of a fiberscope endoscope for extracorporeal observation and imaging. Later, the electronic endoscope consisting of an endoscope equipped with a CCD camera on its tip was developed. Furthermore, the capsule endoscope was developed in the beginning of the 21In addition, in the future of diagnostic endoscopy, this author hopes to see alleviation of the discomfort experienced upon insertion and during observation  as well as improvements in diagnostic capabilities . Meanwhile in treatment endoscopy, extended applications of new minimally invasive endoscopic surgical treatments can be expected, such as in endoscopic fetal surgery and endoscopic brain surgery, as well as further coordination with navigation technologies and surgery support systems to allow safe execution of these procedures.In addition, various developments are anticipated in endoscopic treatment techniques, from the conventional treatments centering on physical energies, to fusion with drug delivery systems as in the case of the drug-eluting stent, as well as endoscopic systems fused with cell and genetic treatments, to be discussed later.About 30 years ago, practical application of the X-ray CT made possible tomography of the human brain, thus revolutionising the diagnosis of neurological disorders. In addition, about 20 years ago, MRI was made clinically applicable, and the technological progress to follow allowed for revolutionary developments in diagnostic imaging of the total body. Although diagnostic imaging and molecular biology are examples of the technologies/disciplines that brought about significant reform to modern medicine, today, they are attracting attention in the further evolved form of molecular imaging. The morphological diagnostic methods of X-ray CT and MRI are already beneficial for functional diagnosis, while SPECT and PET are even becoming established as methods for metabolism diagnosis. As developments in functional MRI and PET have enabled for the understanding of higher brain functions and to conduct molecular function imaging and molecular imaging, they are hoped to serve as the platform technology for genetic treatment evaluation methods and new drug discoveries.The objective of molecular imaging is to make visible the activities of the living body on a molecular level over time by commanding various imaging methods, to thereby understand the significance of molecular mechanisms in life science. The information thus obtained is used not only to understand molecular mechanisms, but may be used also as the basic data for diagnosis. It may potentially provide findings to become the seeds for development of new future medicine, such as drug developments and application to drug delivery techniques. Molecular imaging is regarded as a “specific function imaging,” thus targets for realising imaging, which are currently being tried, include neurotransmission/receptor imaging, antibody/peptide imaging, and also a genetic imaging technique using antisense and reporter genes .“Molecular imaging” is evolving in two directions: (1) visualisation targeting specific molecules in the living body, and (2) visualisation on a microscale, in the range of cells. Future technical development and research needs to be promoted in each of these directions. In addition, dynamic time-course visualisation in the form of “molecular dynamic imaging” is also an important element.The first direction stated above is a field best performed by conventional nuclear medical equipment (PET in particular), thus future issues will most likely be dominated not by imaging techniques but rather by the development of drugs such as tracers. Meanwhile, the second direction above requires technical developments in the imaging technology itself. New magnetic resonance spectroscopic imaging (MRSI) and other new imaging methods are anticipated to replace the conventional MRI. In addition, molecular imaging will become extremely important as the validation technology for regenerative medicine and cell therapy, which will lead to progress of great importance to medicine in the future.Immediate issues in molecular imaging include the following:18F-labeled deoxyglucose (FDG), which is also used in humans, is becoming the gold standard in cancer diagnosis, although various other techniques are also being explored. In the future, the knowledge from cell biology needs to be extended to imaging technology of the entire body, and to develop new imaging agents as well. In the metastasis of cancer cells, the relation of in vivo inter-cell bonding is not well understood, but the mechanism of metastasis and development of cancer is expected to be elucidated through imaging.Molecular imaging is important in many aspects of cancer, its largest target. Presently, Molecular imaging is important in molecular and gene therapies, where the reporter gene must be used effectively. There are two techniques for molecular imaging using gene expression: antisense therapy and a method using the reporter gene.By uniting the research of genes and new receptors with imaging technologies, then fusing together various methods of imaging, it becomes possible to image the dynamic processes within the living body. Then, by further applying such information, it is more likely to become applicable to diagnosis and assessment of various illnesses, and is expected to allow easy viewing of the distribution of drugs used in treatment.Optical technology, and the technology for utilisation of near infrared rays in particular is recently making remarkable progress. The possibility for light from substances within the body to be imaged by tomography using this technology allows various things to be employed as reporter genes. Continuous changes can then be observed for prolonged periods using optical technology, unlike the case with PET which is not practical as it causes exposure.As described above, in molecular imaging, the knowledge of molecular biology and also interfaces with various engineering technologies are crucial. Thus, in addition to the collaboration between medicine, engineering and industry advocated nowadays, further coordination with medicine and biology is also required.st century. In addition to conventional technologies, biotechnology and nanotechnology made applicable are being fused anew into medical technology. The advanced health care that citizens benefit from every day is realised upon the latest medical knowledge and equipment/technology. Medical equipment has, in the past, shown progress every ten years. Computerisation and systemisation of measuring and monitoring equipment for biophenomena was implemented in the 1960s; various medical imaging technologies were born in the 1970s; minimally invasive endoscopic diagnosis and treatment technologies appeared in the 1980s; and robotic surgery was realised in the 1990s. An extremely interesting fact is the Japanese medical system also underwent radical transformations in sync with these stages. In the 1960s, it was “scale-up of the volume of health care” by establishing more medical facilities; in the 1970s, it was “improvement in the quality of health care”; in the 1980s, it was “the issue of medical costs”; and finally in the 1990s, it was “the balance between cost and quality of health care.” The nature of Japan’s health care has actually been affected directly by the progress in, and supply of, medical equipment and technologies. The fact constitutes a typical example of the coordination between technical development and the social system, suggesting that developments in medical technologies are not merely limited to the realm of scientific research.As illustrated above, medical technology has been experiencing significant transformations since entering the 21A stable supply of advanced health care quite simply represents the needs of the public and society. In the future, “translational research” needs to be urgently constructed and should consist of “basic medicine and engineering research” such as the combination of bio- and nanotechnologies and further augmented with new knowledge. These outcomes are then used to actually implement Product Realisation Research for supply to the clinical medicine.