A requisite for ethical human subjects research is that participation should be informed and voluntary. Participation during the informed consent process by way of asking questions is an indicator of the extent to which consent is informed.The aims of this study were to assess the extent to which parents providing consent for children's participation in an observational tuberculosis (TB) research study in India actively participated during the informed consent discussion, and to identify correlates of that participation.In an observational cohort study of tuberculosis in infants in South India, field supervisors who were responsible for obtaining informed consent noted down questions asked during the informed consent discussions for 4,382 infants who were enrolled in the study. These questions were post-coded by topic. Bivariate and multivariate analysis was conducted to examine factors associated with asking at least one question during the informed consent process.In total, 590 out of 4,382 (13.4%) parents/guardians asked any question during the informed consent process. We found that the likelihood of parents asking questions during the informed consent process was significantly associated with education level of either parent both parents being present, and location.The findings have implications for planning the informed consent process in a largely rural setting with low levels of literacy. Greater effort needs to be directed towards developing simple participatory communication materials for the informed consent process. Furthermore, including both parents in a discussion about a child's participation in a research study may increase the extent to which consent is truly informed. Finally, continuing efforts need to be made to improve the communication skills of research workers with regard to explaining research processes and putting potential research participants at ease. The aims of this study were to assess the extent to which parents providing consent for children's participation in an observational tuberculosis (TB) research study in India actively participated during the informed consent discussion, and to identify correlates of that participation.An essential requirement for ethical research is that participation in trials should be informed and voluntary. However, operationalization of the principle of informed consent in community settings with low levels of education and research literacy can pose challenges, especially since standardized consent protocols may not be applicable across different social, cultural and economic settings -3. MedicResearchers have started to work towards developing cross-cultural understandings of research ethics by examining research literacy and the informed consent process in sub-Saharan Africa, North Africa and Asia -7,9-14. Recent reviews of the research process in developing country settings have endorsed the importance of community-level participation and subsequent individual consent for research, particularly in rural areas where community level decision-making is more prevalent compared to urban areas ,5,6,21. In order to ensure ethical research across different social and cultural contexts, there is a need for more empirical evidence to understand the informed consent process. This is particularly important in developing countries, where the enforcement of codes of medical research ethics may be weaker. The analysis reported in this paper contributes to debates about how to increase researchers' engagement with research participants, by focusing on the process of consent for enrolling children in a community-based prospective study to assess the incidence of pulmonary tuberculosis (TB) in infants in rural South India. We were interested in examining the extent to which individuals giving consent actively participated in the consent process, and identifying the correlates of participation. The proxy measure for participation was whether any question was asked during the consent discussion.The study reported here analyses data collected during the informed consent discussions for an observational, cohort study that was designed to assess the incidence of TB in infants enrolled within 2 weeks of birth and followed up for a period of 2 years. The study was conducted in the Palamaner area of Chittoor district in Andhra Pradesh, and the study area included villages and towns. The area is largely rural and semi-urban, with the majority of the population being involved in agriculture or agriculture related activities. The study area was divided in to 594 population units of discrete villages and towns, with a minimum population of 200. These were classified as rural low development, rural high development, or semi-urban, on the basis of infrastructure and development indicators including electricity, road and transport, and presence of a school and health facility. Infants were included in the study if they were BCG-vaccinated and were available for follow up for 2 years after enrollment, and a parent or guardian provided informed consent. Infants were randomized to active surveillance  or passive surveillance . The study did not involve any investigational product, but included a standardized protocol of TB diagnostic procedures if infants were suspected of having TB. Of a total of 7,424 recorded births in the study area, 4,878 fulfilled inclusion criteria and 4,382 (89.8%) were enrolled as participants. The study was approved by the institutional ethical review board of the St John's National Academy of Health Sciences and the Ministry of Health Screening Committee of the Government of India, in addition to which it underwent ethical review by a contracted Ethical Review Board of the Aeras Global TB Vaccine Foundation.The field supervisors in the study team were responsible for obtaining informed consent. This team of 12 (with some replacements over the course of the study) was all male, each with a minimum of 12 years of school education. A minority of them had received a tertiary education. Study physicians and research nurses were not involved in the consent process, in case the power differential between health care providers and the study population influenced parents' decisions about whether to enrol their children in the study.Study personnel were trained on ICH-GCP  guidelines and on informed consent procedures as part of a professional development program. They were sensitized to the historical antecedents of current guidelines for the protection of human volunteers in clinical research. Specific to this research study, all personnel involved in obtaining consent were instructed to encourage questions from the parent providing consent and to note down the questions and comments at the back of the consent form if the questions went beyond simple clarifications of the contents of the informed consent form.Parental consent was taken from any parent who was available at the home of potential participants. Initially a confidential setting was sought for the consent process. In practice, however, the discussions often took place in the presence of other family members or neighbours after the parent indicated his or her comfort with their presence. In this situation, the study team members were instructed to ensure that the decision to participate should be taken independently by the parent, without pressure from the other people present. Research coordinators and study managers would observe the informed consent process on supervisory visits and provide feedback to field supervisors to strengthen participatory consent practices.The informed consent form was translated into colloquial Telugu, the local language. It was structured around questions, as the study team felt that this approach is more intuitive than a narrative consent form for both the study personnel and parents . The maiOnce recruitment for the research study was completed, the questions asked during the informed consent were coded into a range of different categories, loosely corresponding with the structure of the informed consent document. As many of the questions did not correspond exactly to the questions posed in the informed consent sheet, new codes were also created. The informed consent data were entered into the larger database for the study, which included socio-economic household characteristics.The data were analysed in Statistical Package for the Social Sciences v. 17.0 (SPSS). Frequencies for type of question asked were calculated first. Subsequently, cross-tabulations with chi squared tests were conducted to identify statistically significant associations between asking a question during the consent discussion and a range of household social, economic and demographic variables. These included level of development of settlement in which the household was situated ; mother's age; religion ; Caste ; and, mother's and father's education and occupation. Household construction material and household cooking fuel use were also assessed as indicators of socio economic status (SES); stone and brick construction was considered higher SES and all other constructions lower SES, and liquid petroleum gas was considered higher SES and all other types of cooking fuel use were considered lower SES. Other variables that were examined were household exposure to TB (we thought this might increase questions asked); both parents being present during consenting; and, which parent - mother or father - signed the consent form. Finally, the relationship between the fieldworker taking the consent and participation in the informed consent discussion was explored.In the next stage of analysis, a multivariate logistic regression model was constructed to examine the effect of socio-economic and demographic variables on participation in the informed consent discussion. The binary outcome variable was "Did either parent ask a question during the informed consent discussion?" All the variables from the bivariate analysis that had shown significant association were included, except for the identity of the fieldworker. The reason for excluding the fieldworker variable was that our focus in the multivariate analysis was to identify participant related factors affecting participation in informed consent.Out of the 4,382 children enrolled in the study, 4,095 (98.6%) of informed consent forms were signed by the child's mother. The child's father signed the consent form for 60 children (1.4%), and a guardian signed for 2 children. In only 287 cases (6%) were both parents present during the informed consent process. Out of these children, the mother signed the consent form for 271 (94.5%) children. In total, 590 out of 4,382 (13.4%) parents/guardians asked any question during the informed consent process.Table Table Other factors that were associated at the p < 0.05 level were religion (with Muslims being more likely to ask questions), caste , parental occupation, and which parent signed the consent form (more questions were asked when fathers signed). Factors that did not appear to have a statistically significant association with participation during the consent discussion were mother's age, the house construction material (another indicator of socio-economic status), and reported household exposure to TB.Table Location had an effect on participation, with residents of low development rural areas least likely to ask questions, and residents of semi-urban areas most likely to ask questions. Education level was important, with those of a higher education level more likely to ask questions than those with a lower education level. The number of parents present during the consent discussion had a large effect on participation, with questions much more likely to be asked if both parents were present (Odds ratio = 7.5). All other variables were not significantly associated with asking questions; possibly because they are collinear with education and their effect is captured in the model by the education variable, or because of the small number of observations.Institutional and government ethical review boards play an important role in ensuring that clinical and epidemiological research studies have well-defined and documented procedures for obtaining voluntary and informed consent from research participants. However, too often, little attention is paid to how the processes of obtaining consent are conducted. Important indicators of these processes are the extent to which research subjects participate in consent discussions and understand the nature of the research study. In developing countries, a further concern is that many of the principles of medical ethics have been developed within the social context of Europe and North America, and local considerations for obtaining consent may need to be better understood. The conduct of research studies in children poses further questions for how to establish procedures for obtaining parental consent that respect the autonomy of parents as well as protect the interests of the child. This study of participation in consent discussions in a community-based neonatal study contributes to the thinking about research engagement with participants, and consent for vulnerable populations.Only a small fraction (13.5%) of parents asked any questions during the informed consent process. One possible reason for low participation could have been that a significant number of doubts and concerns were clarified during the prior community information sessions (n = 196). Community sessions had been held in schools and village meeting spaces, and were attended by students, teachers and parents. However, when we analysed the focus of the 176 questions that has been recorded over the course of the community information sessions, the majority of these (61.3%) were related to doubts about signs and symptoms of TB. The relatively few questions asked about the study procedures indicate that the community information sessions are not likely to be a major explanatory factor for low participation in the informed consent process. Another possible reason for low participation is that the study was being conducted under the auspices of an organization that has provided charitable health services in the community for more than 30 years; this may have led to an implicit trust in the beneficence of any study being conducted, associated with lower likelihood of expressing doubt or seeking clarification.If participation is taken as an indicator of the extent to which consent is informed, it is a matter of some concern that so few questions were asked during the informed consent discussions, despite significant efforts being made on the part of the research team to encourage open discussion and questioning, and allow households to be involved in the consent process. This may well result in poor understanding of the nature of the research study, as found in other settings ,18,22. TThe fact that more questions were asked in our study when both parents were present may indicate a greater confidence to ask questions in a group setting. However, some of this effect may also be gender-related, with fathers more likely to ask questions to researchers than mothers . This effect may be even more pronounced in our study, since all of the study team members obtaining consent were male. These findings suggest that further research is needed to understand the extent to which participation in informed consent discussions is influenced by the gender of both the research participant and study team members.There are some limitations to this study. First, asking questions during the consent process is taken as an indicator of the extent to which consent is informed; this may not necessarily correspond with actual knowledge and understanding of the research process. Second, we made the assumption that field supervisors were equally likely to write down any questions asked during the consent process. It is possible, however, that the likelihood of recording questions asked was related to the ability/interest of fieldworkers. We believe that the periodic supervision by the project coordinator of field supervisors for the consent process and recording of questions strengthens the validity of data. Another issue is the possible relationship between fieldworker characteristics and parents' comfort asking questions. In bi-variate analysis, we found an association between the fieldworker who took the consent and whether any question was asked; however, we did not have sufficient information on fieldworker characteristics  to conduct further analysis of this important area. Given that previous research in South Africa found that the quality of informed consent was better when consenters had more experience , and othOur findings provide two important lessons for planning the process of informed consent for enrolling children in research studies in developing country settings. First, given that socio-economic status and education are significant predictors of whether any questions were asked during the informed consent process, it is critical to put more effort into considering innovative approaches for making discussions during the consent process more interactive. This may involve including pictures, stories, and some test of understanding of the study aims and procedures. A primary concern for researchers should be to make the process more accessible and meaningful for research participants of all socio-economic groups, and to raise the level of research literacy within the community. Apart from carefully considering the content of informed consent procedures, the impact of training research team members in communication skills  on research subjects' participation and comprehension should be examined in future research. The collection of data on participation can also serve as a useful monitoring indicator for quality of informed consent processes within research studies.A second issue for consideration in conducting research with children is the amount of effort that should be put into seeking two parents' participation in the consent process, where possible. Although mothers are the primary caregivers of children and are likely to be easier to reach in a household study, our analysis showed that fathers were much more likely to ask questions during the informed consent process. In order to promote consent that is truly informed, it may be desirable to create more opportunities for fathers to discuss research studies with research workers. Given that fathers are harder to reach during working hours, this could increase the costs of the consent process significantly, which can be a deterrent where research funds are constrained. If mothers are targeted as the primary consenters for children's studies, participation in consent may be increased by having female research workers conduct the consent discussion; it would be valuable to conduct further research to test this hypothesis.Finally, this research points to the importance of generating more empirical evidence on consent and understanding of informed consent in different settings, and of building quality assurance of these procedures into research protocols. With the growing volume of health research being conducted across different social, cultural and economic settings, it is critical for researchers to continue to introspect on ethical aspects of their work and increase their engagement with research participants.The authors declare that they have no competing interests.DR conducted the primary analysis and drafted the manuscript. NJ was involved in conceptualizing the study, coordinated the data collection, contributed to the interpretation of the data, and reviewed the manuscript. LG was involved in conceptualizing the study and reviewing the manuscript. SB was involved in interpreting the data and reviewing the manuscript. HG was involved in conceptualizing the study, interpreting the data, and reviewing the manuscript. MV was involved in conceptualizing the study, contributed to the analysis and interpretation of the data, and reviewed the manuscript. All authors read and approved the manuscriptThe pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6939/12/3/prepub


We examined the quality of the information on the use of surfactant and the use of and duration of nasal continuous positive airway pressure (nCPAP), oxygen supplementation, and mechanical ventilation in the Danish Neonatal Clinical Database (NeoBase).We included all neonates born with a gestational age < 32 weeks admitted to a Neonatal Intensive Care Unit (NICU) at two university hospitals in 2005. On discharge, the clinicians complete a structured form with information related to the delivery and course of stay in the NICU. These forms were entered into the NeoBase. The nurses’ daily bedside documentation was used as reference standard. Concordance was used as a measure of agreement between the NeoBase and the reference standard. For the dichotomous variables the concordance was defined as the sensitivity of the information registered in the NeoBase. For the continuous variables, it was based on the discrepancy in days between the NeoBase and the reference standard. The percentage of concordance was described as high (> 90), moderate (70–90) or low (< 70).Overall, 153 infants participated in the study. Concordance was high for all dichotomous variables. The NeoBase slightly underestimated the duration of nCPAP and mechanical ventilation. The duration of oxygen therapy was neither over- nor underestimated in the NeoBase. Concordance was low for all continuous variables if we assumed that the registered information was identical. It was 100% for duration of mechanical ventilation and moderate for nCPAP and oxygen supplementation if we allowed for a discrepancy of 1 day.The NeoBase is a valuable tool for clinical and epidemiologic research and quality assurance regarding neonatal respiratory disease. Neonatal clinical databases have been established in most developed countries. They may contain information from a single hospital, a region, a country, or several countries. The Danish neonatal database, the NeoBase, was established in 1996, and has been used in various neonatal intensive care units (NICUs) throughout the country for variable time periods. The NeoBase was originally designed with the purpose of benchmarking nationally and internationally. For this reason the variables necessary to create critical risk score for babies (CRIBI and later CRIBII)  were colRespiratory problems are the most common cause of admission to NICUs, affecting 2–3% of all newborns. Many factors, including prematurity, gender, mode of delivery, and genetic predisposition, are involved in the aetiology of these problems ,5. SeconSecondary data may constitute a valuable and cost-efficient alternative to the use of primary data in epidemiologic research -9. HowevWe sought to evaluate the quality of the following respiratory variables in the NeoBase: surfactant administration, nasal continuous positive airway pressure (nCPAP), oxygen supplementation, and mechanical ventilation. We evaluated data from the North and Central Denmark Regions, an area with a population of 1.8 million people and about 23,000 deliveries per year.To our knowledge, no studies have previously evaluated the data quality of respiratory variables in neonatal databases.The evaluation of the NeoBase included all very preterm neonates born in 2005 with a gestational age less than 32 weeks and admitted to one of the two level III NICUs in the regions: Aalborg University Hospital and Aarhus University Hospital, Skejby, Denmark.The NeoBase contains clinical and demographic information on all newborns admitted to the NICUs in the North and Central Denmark Region. Clinicians at the neonatal departments routinely register the information on a structured form that includes birth weight, gestational age, Apgar scores, cerebral complications, and treatment of respiratory distress, pneumothorax, persistent ductus arteriosus, necrotising enterocolitis, and infections. The following data on respiratory treatment and support are registered: surfactant administration (yes/no) and duration of days of nCPAP, oxygen supplement, and mechanical ventilation. These data are collected from medical records and nurses’ charts at the time of a patient’s discharge from the hospital. At discharge all patients hospitalised in Denmark receive ICD10 codes covering the diseases and procedures during their stay in the hospital. The physician who discharges the patient typically provides these codes. All ICD10 codes are recorded electronically and stored in the Danish National Patient Register (DNPR) [Very preterm and very sick infants admitted to NICUs are under close observation by the bedside nurse, and the observations are registered on structured charts for each infant. Because of their frequent, prospective bedside observations of the infants, the nurses’ charts were used as reference standard in the evaluation of the NeoBase. Treatment with nCPAP, oxygen, and mechanical ventilation is routinely registered hourly along with the patient’s vital signs during every shift. Surfactant administration and changes in nCPAP, oxygen, and mechanical ventilation are immediately registered. The information from the nurses’ charts was extracted by SA without knowledge of the value of the variables in the NeoBase for the particular patient.We estimated the data quality of the dichotomous variables (treatment versus no treatment), surfactant administration, nCPAP, oxygen supplementation, and mechanical ventilation, by calculating the sensitivity, specificity, and the positive and negative predictive values of the information registered in the NeoBase  using thMeasures of association are presented with 95% confidence intervals calculated by use of the binomial function in the STATA statistical software version 12.The continuous variables, duration of oxygen supplementation, nCPAP, and mechanical ventilation, were analysed and illustrated in accordance with Kristensen et al.  by studyPercentage of concordance was used as a measure of agreement between the NeoBase and the reference standard. For the dichotomous variables the concordance was defined as the sensitivity of the information registered in the NeoBase. For the continuous variables, the concordance was based on the discrepancy in days between the NeoBase and the reference standard. Percentage of concordance was calculated, allowing a discrepancy of 0, 1, and 2 days between the registrations. The percentage of concordance was described as high (> 90), moderate (70–90), or low (< 70) .In Denmark, approval from the Ethics Commitee and the Protection agency is not mandated for local quality assurance databases and registries based on medical records and bed side registrations.A total of 164 very preterm neonates were admitted to the two hospitals in 2005. For 11 neonates, the nurses’ charts were missing. Thus, we evaluated information from 153 (93%) patients. Demographic and clinical characteristics of the patients are shown in Table Among the 153 patients who participated in the study, information in 11 was incomplete with regard to a single variable in the reference standard. Thus, 151, 145, 152, and 153 patients were evaluated with respect to treatment with nCPAP, oxygen, surfactant, and mechanical ventilation.Evaluation of the dichotomous variables is shown in Table Following stratification by dichotomous gestational age at 28 completed weeks or less and above 28 weeks, we found no differences in the concordance of dichotomous or continuous variables. Furthermore, no differences in concordance were observed between the two hospitals (data not shown).We found that concordance was high between the information from a clinical database, the NeoBase, and the reference standard (detailed bedside registration) for all four dichotomous treatment variables: surfactant administration, nCPAP, oxygen supplementation, and mechanical ventilation in very preterm newborns. Concordance was low for the continuous variables if no discrepancy was allowed. If agreement was defined as within 1 day, the concordance improved to a moderate level for duration of oxygen supplementation and nCPAP therapy. Complete agreement was seen for duration of mechanical ventilation under the same conditions.An advantage of the study was the use of the nurses’ charts as reference standard in the evaluation of the NeoBase. Nurses chart all vital signs, such as oxygen saturation, respiratory frequency, blood pressure, heart rate, and any changes in these, along with treatment on a structured chart throughout their shifts in accordance with the chart’s time schedule or doctors’ orders. The observations are current and frequent. Thus, the evaluation of the NeoBase was based on a reference standard validated by use in the clinical setting and during the care of the newborn. This information is also used by the medical staff on rounds and whenever the infant’s condition deteriorates. Thus, errors are likely to be few and unrelated to hospital or specific newborns. Furthermore, the information from the nurses’ charts for this particular study was extracted by the same person (SA) without knowledge of the value of the variables in the NeoBase for the particular patient. Thus, there was no inter-individual variation in the extraction of data from the charts.A limitation of the study was that the evaluation was based on a relatively small study population. However, the confidence intervals for the sensitivities and the positive predictive values calculated were quite small for the dichotomous variables.The concordance may vary according to specific characteristics related to the infant or the way chart or database information is gathered, i.e. neonates of extremely low gestational age may be more closely monitored or monitored in a different way than neonates of higher gestational age. Also, the concordance may have been influenced by NICU-specific registrations. However, we found that the concordance was unrelated to gestational age and hospital.The quality of the data in the clinical databases may depend on the workload of the clinician who completed the form for the database as well as the clinician’s motivation. The motivation may depend on the degree of feedback of information from the database. In both NICUs, completion of the forms was mandatory at the time of discharge of the newborn. However, feedback to the clinicians was only carried out sporadically. We were unable to identify periods with heavy workload to rule out whether this may have influenced validity.Considering treatment and duration of oxygen and nCPAP therapy, the quality of registered data may depend on the level of the NICU, being lower from level III than from level II units due to more complicated patients. Both units included in this study were level III units. Therefore we expect validity for other units in Denmark to be as good or even better for some of the variables tested.We conclude that the registration of variables related to newborn respiratory morbidity in the clinical database of newborns in Denmark, the NeoBase, had a quality that makes the NeoBase a valuable tool for clinical and epidemiologic research and quality assurance. Thus, simple and structured registration by physicians with a high workload can be used for these purposes.nCPAP: Nasal continuous positive airway pressure; NeoBase: Danish neonatal clinical database; NICU: Neonatal intensive care unit; PPV: Positive predictive value; NPV: Negative predictive value.The publication is funded by The Danish Council for Independent Research. The funder did not have any role in the study design, analysis, interpretation or dissemination of research findings. The authors declare that they have no competing interests.JPP, TBH, and FE contributed to the conception and design of the study. SA extracted data and conducted the analysis, with support from JPP, TBH, and FE. The first draft of the manuscript was written by SA and FE. All authors contributed to data interpretation and critical revision of the manuscript. All authors have read and approved the final version submitted.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2431/14/47/prepub


The Golden Helix Pharmacogenomics Days are international scientific meetings aiming to educate healthcare professionals and biomedical scientists about pharmacogenomics and personalized medicine. In this meeting report, we provide an overview of the scientific lectures and the topics discussed during the 6th Golden Helix Pharmacogenomics Day that was held in Belgrade, Serbia last June 5, 2012. The scientific program included lectures by the local and international speakers from Europe and the United States. Pharmacogenomics is referred to as the study of variations in DNA sequence and gene expression as related to drug efficacy and toxicity. It is a base for the implementation of personalized medicine, a young but rapidly advancing field of health care. The goal of personalized medicine is to identify genomic and clinical information in order to predict individual risk of developing disease, the course of disease and response to treatment of a person.The Golden Helix Pharmacogenomics Days are international educational scientific meetings that are organized by the Golden Helix Institute of Biomedical Research ,2 jointlThe 6th Golden Helix Pharmacogenomics Day was organized in Belgrade, Serbia by the Golden Helix Institute of Biomedical Research, the Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, and the National Association for Enhancement and Development of Regenerative Medicine, Belgrade, Republic of Serbia, endorsed by the Pharmacogenomics for Every Nation Initiative (PGENI) and Ministry of Education and Science, Republic of Serbia, and supported by the Complete Genomics, Cryo-Save, Imel Group and Illumina.The meeting was attended by over 180 registered participants. In this meeting report, we provide an overview of the scientific lectures and present the highlights of this meeting.The most powerful tools of disease research and translational medicine are the next-generation sequencing methods. As a result of their development, we also entered into the golden age of pharmacogenomics. Dr Radoje Drmanac  delivered the keynote lecture and gave the inspirational overview of sequencing by hybridization, which led to the industrialization of whole genome sequencing. Drmanac first got the idea how to revolutionize sequencing method while he was working at the Genetic Engineering Center in Belgrade . While Complete Genomics currently has the capacity to sequence 1000 genomes per month, their next big goal is to sequence 100 times more genomes during the same time and with an improved quality, and most importantly, lower costs ,5. The wSnezana Pajovic  addressed the importance of pharmacogenomic polymorphisms from the medical point of view. Modern medicine recognizes inter-individual differences in the capability of persons to metabolize a given drug. Contrary to transient adverse drug effects, e.g. caused by allergies, if a person has a genetic disability to metabolize a drug, it will be persistent through lifetime. Pajovic stressed the importance of performing pharmacogenomic tests for the benefit of the patient and as a paradigm of personalized medicine. Furthermore, physicians could easily make a drug choice which is especially important when a life-long therapy is needed. At the end, she pointed out that the pharmacogenomic testing should be used to reduce the overall healthcare costs.Sonja Pavlovic  pointed out that the physicians growingly recognize the need to perform genetic tests in order to optimize the treatment dose. Giving the state of the art of pharmacogenomic testing, Pavlovic highlighted that there is an immense number of candidates for pharmacogenomic testing  and thatVita Dolzan  and Sabina Semiz  gave valuable insights into the pharmacogenomics in Slovenia and Bosnia and Herzegovina. They presented centers that perform pharmacogenomic tests and have infrastructure for pharmacogenomic research in these countries. Dolzan also presented recently organized interdisciplinary doctoral program in biomedicine as a base for education of future pharmacogenomic experts in Slovenia. Both Dolzan and Semiz are participating, on behalf of their countries, in the PGENI that is coordinated in Europe by the Golden Helix Institute of Biomedical Research ,11.George P Patrinos  outlined the steps that can be taken by countries with good health system infrastructure, but there are insufficient resources for individual patient genotyping in routine practice to improve patient treatment and reduce healthcare cost. Patrinos underlined that Serbia is one of the 18 European countries that are currently participating in the PGENI, which also endorsed this event . On thisTPMT genotype. These patients, even heterozygous TPMT carriers, had no hematological complications, no febrile neutropenias, and no therapy interruptions [Florian Graedler  gave an overview of the next generation sequencing and array technologies and their applications in pharmacogenomics. Serbian experience of pharmacogenetics in clinical practice was presented by Lidija Krivokapic-Dokmanovic . A thiopurine drug 6-mercaptopurine is used in maintenance phase of the standard therapy in childhood ALL. In the retrospective and prospective study of thiopurine toxicity in Serbian childhood ALL patients, Dokmanovic explained how the modified therapeutic protocol for treatment of the ALL children was introduced at the University Children’s Hospital in Serbia . In the ruptions . This noTPMT gene. The distribution and frequency of VNTR alleles and VNTR genotype of Serbian population were presented. The transcriptional potential of each VNTR allele detected was determined in functional CAT assays [TPMT gene transcription was presented. Zukic further discussed the latest experiments on thiopurine influence on VNTR region. Decrease of TPMT gene promoter activity under the influence of thiopurine drugs was VNTR architecture-dependent [Staying focused on the same drug, Branka Zukic  gave an overview of the current research on a novel potential pharmacogenomic marker, the variable number of tandem repeats , in the promoter region of the T assays . Also, tependent . FurtherUGT1A1) gene, (TA)7TAA, represents one of the clinically most relevant pharmacogenomic markers. Moreover, this variant is equally important as a diagnostic marker for patients with Gilbert’s syndrome. At this symposium, Stojiljkovic presented the first data about variants in the UGT1A1 gene found in Serbian Gilbert’s syndrome patients and healthy volunteers. Not only that patients with Gilbert’s syndrome were genotyped so that their hyperbilirubinemia is not confused with more severe hepatic lesions, but also the data deduced from healthy volunteers proved that (TA)7TAA pharmacogenomic marker is very important in Serbian population. Stojiljkovic also underlined the third but not least application of the UGT1A1 genetic test on (TA)7TAA. She reminded that this test should be used in clinical trials with investigational drugs to differentiate between persons not knowing to have Gilbert’s syndrome and those in whom hyperbilirubinemia is caused by liver toxicity of a tested drug.Next, Maja Stojiljkovic  pointed out that the most frequent variant of uridine diphosphate glucoronosyltransferase 1A1  focused her lecture on fine optimization of the drug dose based on pharmacogenomic tests. Giving that anticoagulant drugs have narrow therapeutic range, she highlighted that besides information about genomic variants, attention must be paid to a drug’s interaction with other drugs and the existence of other health conditions and diseases. Rakicevic presented Serbian experience with significant markers for thromboembolism prevention and treatment . These pAn added value of this symposium was its interdisciplinarity. Side by side with biomedical experts, Hajrija Mujovic  shared her view on the legal issues of pharmacogenomic testing in Serbia. She defined that the increasing development of biomedicine led to formation of a new legal discipline called medical rights. Mujovic pointed out that principal legal issues of the medical rights are based on social justification and responsibility, health improvement, equality in treatment, non-discrimination, freedom of choice, respect of individual dignity and integrity, personal security and respect of privacy. She added that informed consent is always a prerequisite for genetic testing and that a person should understand what for their sample is going to be used. Furthermore, one must not feel obligated to perform any genetic test because of the fear that otherwise he/she would not be treated properly. Mujovic concluded the talk with a reminder that research practice in general, and thus pharmacogenomic testing as well, should be conducted with respect to the Universal Declaration on Bioethics and Human Rights and International Declaration on Human Genetic Data, both issued by UNESCO ,18.The 6th Golden Helix Pharmacogenomics Day in Belgrade provided information on research and application of pharmacogenomics in Serbia and neighboring countries. The most recent data on common clinically applicable pharmacogenomic markers were presented. Also, the importance of WGS was emphasized. WGS is of particular value when it comes to rare pharmacogenomic variants, those that, due to their low frequency, are not screened with usual pharmacogenomic tests, and therefore, cause severe adverse drug effect.As with the previous meetings of this international series, the 6th Golden Helix Pharmacogenomics Day highlighted various areas of interest in pharmacogenomics, where many internationally renowned scientists gave excellent overviews of the existing applications and demonstrated the way and the rapid pace that the field is moving. The Golden Helix Institute of Biomedical Research aims to establish the Golden Helix Pharmacogenomics Days as one of the main educational and outreach activities for PGENI ,11 in EuThe authors declare that they have no competing interests.MS, AF, LDK, GN, GPP, SP and BZ participated in the design and preparation of this meeting report. All authors read and approved the final manuscript.


As care and antiretroviral treatment (ART) for people living with HIV/AIDS become widely available, the number of people accessing these resources also increases. Despite this exceptional progress, the estimated coverage in low- and middle-income countries is still less than half of all people who need treatment. In addition, treatment discontinuation and non-adherence are still concerns for ART programs. Governments and partner institutions have sought to implement a variety of interventions addressing the main reasons behind the low coverage of, discontinuation of, and non-adherence to ART. Food assistance is one of those interventions; increasing evidence suggests that this type of intervention has the potential to improve ART outcomes. However, to our knowledge, no study has estimated its costs in detail. The objective of this study was to assess the costs of a program providing food assistance to HIV/AIDS patients in Sofala province, Mozambique, in 2009.We performed a retrospective analysis of the costs of providing food assistance, based on financial and economic costs. We used the ingredients approach to estimate costs, which involved multiplying the total estimated quantities of goods and services actually employed in providing the intervention by their respective unit prices.In 2009, the cost of providing food assistance to HIV/AIDS patients was $2.27 million, with capital and recurrent costs accounting for 1% and 99% of total costs, respectively. Food made up the largest component, at 49% of total costs. At 24%, transport operating costs were the second largest item. The cost per patient served was $288 over 3 months.The food distribution program carries significant costs. To assess whether it provides value for money, the present study results should be interpreted in conjunction with the program’s impact, and in comparison with other programs that aim to improve adherence to ART. Our costing analysis revealed important management information, indicating that the program incurred relatively large overhead costs. This result raises questions regarding the efficiency of implementing this food distribution program. As care and antiretroviral treatment (ART) for people living with HIV/AIDS becomes widely available, the number of people accessing them also increases. At the end of 2010, 6.65 million people were receiving treatment in low- and middle-income countries, an increase of 27% from December 2009, since tGovernments and partner institutions such as the World Health Organization (WHO), the Joint United Nations Program on HIV/AIDS, the United Nations World Food Program (WFP), and major HIV/AIDS initiatives such as the US President’s Emergency Plan for AIDS Relief have sought to implement a variety of interventions addressing the main reasons behind the low coverage of, discontinuation of, and non-adherence to ART. Food assistance, which is aimed at improving the physical ability of patients to take ART and to render it more clinically effective, is one of those interventions-11. TherEstimating program costs is important for a number of reasons. First, costs could be used to assess allocative efficiency by determining whether a program provides value for money, for example, by comparing its costs and effects to those of other investments in health (e.g. food assistance versus tuberculosis control). Second, costs could be used to assess technical efficiency by determining whether a program provides value for money within the same domain, for instance, by comparing its costs and effects with those of alternative options for providing food assistance. Third, it could be used for management purposes, such as planning improvement by identifying larger-cost items and potentials for savings,21. In tWe evaluated the food assistance program as implemented by the United Nations WFP in collaboration with Health Alliance International (HAI) and the Ministry of Health. HAI is a non-governmental organization that initiated operations in Mozambique in 1987. Its mission is to support the development of policies that foster social and economic equity for all, with a focus on public-sector health systems and a progressive realization of the right to health. In 2003, in partnership with the government of Mozambique, HAI began to support the implementation and expansion of ART for HIV/AIDS patients. It is within this partnership that HAI also collaborates with the WFP in providing food assistance for HIV/AIDS patients in Sofala province.The WFP is responsible for the provision of food, health centers are responsible for the identification of eligible patients, and HAI is responsible for the distribution of food to patients. This intervention is provided to HIV/AIDS patients of all ages, including children. It is also provided to tuberculosis patients and to pregnant and breast-feeding women enrolled in prevention of mother-to-child transmission programs. The objective is to ensure patient nutritional recovery and treatment success.2,earning no income or less income than the monthly national minimum income, and many dependents. Patients were identified before or after they started ART. They were first identified by a social worker; patient eligibility was later confirmed by a clinician. After being identified, patients received an identification card that entitled them to collect food at the distribution site, usually a warehouse or health facility. They received food assistance once per month for a period of three months, after which they were reassessed to determine whether their nutritional status had improved. If improved, patients were discharged from the program; otherwise, the patients remained in the program for an additional 3–6 months. Food assistance consisted of 10 kg of soya, 5 kg of cowpeas, and 25 kg of maize.The criteria for inclusion in the food assistance program were body mass index below 18.5 kg/mThis study was approved by the Mozambican National Bioethics Committee.We undertook the costing analysis from a provider perspective: the costs incurred by the three organizations implementing the food assistance program . The cost calculations apply to all 13 districts in Sofala province over the implementation period of 2009.To estimate costs incurred by HAI and the health facilities, we used the ingredients approach by multiplying the total estimated quantities of goods and services actually employed in providing the intervention by their respective unit prices. This approach is useful because it makes it possible to later identify what is driving the total costs, and how to improve the use of available resources. We obtaTo estimate the costs incurred by WFP at the program level in Sofala province, we used a top-down approach based on the number of people reached by the intervention; we allocated transport and other program costs together (rather than separating transport and program) because we did not have information on the breakdown of costs at the national level by line item. We compared the total number of people served at the national level with the number of HIV/AIDS patients served in Sofala province, and used this proportion to estimate the costs at the province level. We distributed the program costs among categories according to the percentage of each category out of the total value of the national budget. For example, if staff costs corresponded to 6% of total value in the WFP budget allocated to Mozambique, we also allocated 6% of the food program costs in Sofala province for staff costs. We obtained details on costs incurred by the WFP in their budget allocated to Mozambique.To determine the costs of the intervention, we interviewed people in various job categories and visited five places where the intervention was actually implemented. These places were selected based on convenience of access. We divided the costs identified according to the activities performed in two phases of program implementation of the program: the start-up and post start-up phases. For the start-up phase (the time between the decision to implement an intervention and starting its delivery to the first beneficiary), we only included data on the costs of initial training . For the post start-up phase (the period of implementation), we included costs based on three main activities: planning and monitoring, patient identification, and food distribution.For planning and monitoring, we only included staff costs. For the health facilities, we based our estimates on expenditure data and included staff costs at the provincial level . For HAI (the organization responsible for food distribution), we included staff costs at the national and provincial levels  and at the district level (multidisciplinary team manager and administrative assistant). To assess staff time spent in these activities, we interviewed four administrative assistants, one nutritional assistant, the program manager, the program coordinator, and three multidisciplinary team managers. The nutritional assistant provided us with estimates of time spent by the health director and the chief medical doctor.Similarly, for patient identification, we only included staff costs incurred at the district level by health facilities, since these were responsible for the identification of patients eligible to receive food assistance. We included the costs of 13 health facilities, one health facility per district. To assess staff time spent at the health facilities, we interviewed five social workers, who also provided estimates of time spent by medical doctors.Regarding food distribution, we only included the costs incurred by HAI, since it was responsible for food distribution. We included the costs of transport, materials and supplies, equipment, training, and staff at the district level Table . To asseFor WFP, the organization that provided the food, we included the costs of staff, transport, and equipment. We obtained details about the price and quantities of food from an interview with the head of the program unit in Sofala province.We measured financial costs at the time the expenditure was incurred. We included staff, food, materials and supplies, and transport operational costs as recurrent costs Table . ForeignWe calculated economic costs by annuitizing capital goods on the basis of their useful life at a discount rate of 3%, as recommended by most guidelines. We inclWe calculated the cost per patient served by dividing the total costs of providing food assistance by the number of patients served . We implemented a sensitivity analysis to determine whether the results were sensitive to discount rate, staff time use, equipment prices, and the overhead costs of HAI and the health facilities.For the year 2009, the costs of providing food assistance to HIV/AIDS patients was $2,271,656 , followed by HAI (44.9%) and health facilities  to ensure the minimum acceptable consumption levels of people who are already in difficulty, (ii) to prevent people who are susceptible to adverse events and shocks from becoming more vulnerable (by stopping them from having to sell their assets), (iii) to promote people’s ability to become less vulnerable in the future (by helping them to build assets and achieve stronger livelihoods), and (iv) to promote social justice through promoting the rights and empowerment of the poor and vulnerable.Our findings reveal important information for program budgeting and for the identification of potential cost savings. Notably, the costs of food distribution were as high as the costs of the food itself, both accounting for approximately half of the total costs. If the food program were scaled up, little economies of scale should be expected, as these costs are all variable.Several of the limitations of the present study may be addressable by future investigations. First, we only included data on the costs of training for the start-up phase, which may have underestimated the true costs incurred during this phase. Second, we did not include the overhead costs of the HAI and the health facilities in our analysis, but these costs may be significant. Third, we did not include the time and travel costs that patients incur to receive food assistance. Insights into these patient costs would allow program decisions regarding the optimal location for food distribution. Fourth, we used a top-down approach to estimate costs incurred by the WFP. This allocation of program costs on the basis of the number of people reached may have contributed to the high share of the WFP in total costs. Future research could attempt to address this limitation by measuring all resource use via a more detailed approach, such as the ingredients approach, in order to improve cost estimation. Fifth, we only analyzed the costs of the food and of program implementation, and did not consider the quality of the implementation. Future research could address this issue by including an assessment of the process of beneficiary targeting. Insights into these issues would allow program managers to better understand whether the program was delivered as expected and perhaps aid in explaining why a program is or not effective.Despite calls for more economic analysis of interventions to improve treatment outcomes,28-31, tThe food distribution program carries significant costs. To assess whether it provides value for money, the present study results should be interpreted in conjunction with the program’s impact, and in comparison with other programs that aim to improve adherence to ART. Our costing analysis revealed important management information, in the sense that the program incurred relatively large overhead costs. This observation raises questions regarding the efficiency of its implementation.The authors declare that there are no competing interests.Both authors contributed to the design of the study. MP collected and analyzed data and drafted the manuscript. RB contributed advice on all aspects of study implementation and a critical revision of data analysis, interpretation of the results, and the manuscript. Both authors approved the manuscript.


Tobacco smoking is a leading cause of premature death and disability, and over 80% of the world's smokers live in low- or middle-income countries. The objective of this study is to assess demographic and socioeconomic determinants of current smoking in low- and middle-income countries.We used data, from the World Health Survey in 48 low-income and middle-income countries, to explore the impact of demographic and socioeconomic factors on the current smoking status of respondents. The data from these surveys provided information on 213,807 respondents aged 18 years or above that were divided into 4 pooled datasets according to their sex and country income group. The overall proportion of current smokers, as well as the proportion by each relevant demographic and socioeconomic determinant, was calculated within each of the pooled datasets, and multivariable logistic regression was used to assess the association between current smoking and these determinants.The odds of smoking were not equal in all demographic or socioeconomic groups. Some factors were fairly stable across the four datasets studied: for example, individuals were more likely to smoke if they had little or no education, regardless of if they were male or female, or lived in a low or a middle income country. Nevertheless, other factors, notably age and wealth, showed a differential effect on smoking by sex or country income level. While women in the low-income country group were twice as likely to smoke if they were in the lowest wealth quintile compared with the highest, the association was absent in the middle-income country group.Information on how smoking is distributed among low- or middle-income countries will allow policy makers to tailor future policies, and target the most vulnerable populations. Tobacco use is a leading cause of premature death and disability. Every year between five and six million deaths worldwide are attributed to tobacco use and exposure to second hand smoke During the twentieth century, tobacco use rose to epidemic proportions, mostly due to aggressive marketing by the tobacco industry. Tobacco consumption is still rising globally, largely because the industry is targeting young people and women in many low- and middle-income countries For many low-income countries, data collected over the past decade through the Global Tobacco Surveillance System Whilst tobacco surveillance activities provide useful information for the implementation of tobacco control efforts, the World Health Surveys provide the opportunity to examine complex patterns of tobacco use and to identify the social determinants of smoking. The objective of this study is to assess demographic and socioeconomic determinants of current smoking in low- and middle-income countries. While there are some examples of studies exploring the determinants of smoking at national level Face-to-face interviews were used in all 48 countries. Written consent was obtained in all surveys. A standard consent form approved by the ethics review committee was read to the respondent in the respondent's language. Once the respondent agreed to participate in the survey, if the respondent was literate the form was provided to the respondent to read over and sign and was countersigned by the interviewer. If the respondent was illiterate and gave consent to participate, the interviewer confirmed this consent and signed on the form that the respondent had been read the form, had understood the study and agreed to participate. This procedure was approved by the institutional review boards. The full list of collaborating partners in the 48 countries where the ethical procedure is reviewed and approved is provided in http://unstats.un.org/unsd/default.htm) and also non-response, post-stratification corrections were made to sampling weights The World Health Survey was conducted by the World Health Organization in 2002–04 to provide valid, reliable, representative and comparable population data on the health status of adults, aged 18 years and older, in 70 countries from all regions of the world There were only a couple of high-income countries where the data for smoking were gathered in the World Health Survey, hence the setting of this study was 48 low- and middle-income countries, in which data for current smoking were available, as well as the demographic and socioeconomic factors studied. Initially 234,548 respondents were eligible but 20,741 (9%) were excluded from the analyses due to missing data on one or more variables of interest. The data from 213,807 respondents aged 18 years or above were divided into 4 pooled datasets according to their sex and country income group. Country income group refers to the World Bank's development categories as of 2005 which are based on the per capita Gross National Incomes (GNI) from 2003 (the year the survey was carried out) Current smoking was defined as a binary variable indicating whether the respondent currently smoked any tobacco product such as cigarettes, cigars or pipes. Current smokers included both daily and occasional smokers. In four countries  data were also collected on the use of smokeless tobacco. For the purpose of this analysis, individuals who only used smokeless tobacco were considered non-smokers.The following demographic and socioeconomic factors were also included: age, , sex, marital status , highest attained educational level , whether the respondent was employed, whether the respondent lived in a rural or an urban area, and country of residence. Furthermore, a binary variable showing whether the respondent was the main economic provider for the household was also included. To evaluate wealth, a dichotomous hierarchical ordered probit model was used to develop an index of the long-running economic status of households based on owning selected assets and/or using certain service The overall proportion of current smokers, as well as the proportion by each relevant demographic and socioeconomic determinant, was calculated within each of the pooled datasets. Multivariable logistic regression was used to assess the association between current smoking and the potential demographic and socioeconomic determinants according to sex and country income group. All analyses were weighted accounting for the individual survey sample designs. Specifically, each respondent in the country datasets was given a post-stratification sampling weight. This weight reflected each country's population, in such a way that if the sample size for two given countries are the same (but the population sizes of the countries are different), more weight is given to the country with higher population when calculating the pooled estimates. Stata11 was used in all analyses.125,416 men and women from 27 middle-income countries, and 88,391 from 21 low-income countries were included in the analyses. The crude weighted prevalence of smoking was higher in the middle-income country group compared with the low-income country group for both men and for women. While this difference was only marginal in men (over 35% of men smoked in both country income groups), the prevalence of smoking in women in the middle-income country group was over double that of the low-income country group  we do not believe non-response will have influences the overall results.Health levels vary across different groups of the population and such differences can be determined socially, demographically, economically or geographically. When differences are preventable or reversible, they represent health inequity which is considered a social injustice Table S1Study population  by sex and country, World Health Survey, 2002–2004.(DOC)Click here for additional data file.Table S2Weighted crude prevalence of current smoking by sex and country .(DOC)Click here for additional data file.Table S3Bivariable analysis of the odds of current smoking by sex and country income group according to individual demographic and socioeconomic factors .(DOC)Click here for additional data file.List S1List of in-country collaborating partners.(XLS)Click here for additional data file.


Telepathology, which is an emerging form of telemedicine in Canada, is defined as the electronic transmission of pathological images, usually derived from microscopes, from one location to another. There are various applications of telepathology, including case referral for an expert opinion, provision of an emergency service in the absence of a resident pathologist, and education. Until now, there has been relatively little use of telepathology for core diagnostic services in the absence of a local pathologist, but this practice is likely to increase in the future. The Laval University Integrated Health Network is in the process of deploying a telepathology system, primarily to provide an intraoperative frozen section service to small hospitals in sparsely populated areas which are experiencing a severe shortage of on-site pathologists. The telepathology project involves 17 hospitals located in five regions of eastern Quebec, Canada. This paper describes the study protocol that will be used to evaluate the benefits associated with the project.A panel of experts was first assembled by Canada Health Infoway to agree on a set of benefits indicators that could be applied to all telepathology projects across Canada. Using the set of indicators as an input, we have developed a three-step study protocol. First, a survey questionnaire will be distributed to appraise the way pathologists, pathology technologists and surgeons perceive the telepathology system and its impacts. Second, a series of semi-structured interviews will be conducted with project leaders and telepathology users at sites that are representative of all the hospitals in the Laval University Integrated Health Network. The overall aim is to better understand the expected and unexpected effects of telepathology on health care professionals and patients as well as on the regional organization and delivery of care services. Finally, a pre-post design using secondary data is proposed to evaluate a wide array of tangible benefits to the patients, the health care providers, the hospitals, and the region as a whole.The Laval University Integrated Health Network's telepathology project is expected to yield positive and significant results that are relevant internationally. Our findings will provide valuable information on the nature and extent of benefits associated with telepathology systems intended to provide an intraoperative frozen section service to remote hospitals experiencing a shortage of specialists. Pathology is a scientific field concerned with the study of the nature and causes of diseases. Anatomic pathology, which is at the heart of this paper, is a medical specialty concerned with the diagnosis of diseases based on the gross, microscopic, chemical, immunologic, and molecular examination of organs, tissues, and whole bodies (autopsies). Because pathology examinations serve as the basis for a large percentage of decisions about diagnosis, treatment, hospital admission, and discharge, their annual number have increased in recent years in step with health care demand and, ultimately, with population growth and demographic aging. While an increase in the supply of pathologists would appear to be essential to maintaining patient care, the number of pathologists has declined in many developed countries over the last decade. This has been the case in Japan ,2, AustrA shortage of pathologists has several consequences. The most direct is a longer turn-around time before a diagnosis can be made on a specimen . KnowingOne way to counteract the scarcity of pathologists and help them obtain a second opinion is to adopt telepathology, which is defined as the practice of pathology at a distance. Telepathology uses telecommunications technologies to facilitate the transfer of image-rich pathology data between distant locations for the purposes of diagnosis, education, and research . TelepatMicroscopic static examinations work well when there is no ambiguity as to the images the laboratory technologist should submit to the pathologist . A microOnce installed, a telepathology system can be used for distant primary diagnoses, expert referrals, quality assurance, and education . For disWith telepathology, intraoperative frozen section analyses can be performed whenever a pathologist is available at a remote location. The procedure usually unfolds as follows: a laboratory technologist manipulates the specimen locally while it is filmed; a pathologist performs a gross examination of the specimen from another location examining the specimen and interacting with the technologist via a monitor and tells her where to cut; the technologist prepares one or more slides from the section then digitizes and stores them in a repository; and the pathologist accesses the images, performs his examination and provides his diagnosis directly to the surgeon by phone. The present study focuses specifically on this hybrid telepathology service: intraoperative frozen section examinations of virtual slides.Examinations of intraoperative frozen sections have been performed via telepathology for over 20 years. In 1989, a Norwegian hospital decided to cover another facility located 400 km away using a motorized video-microscope that could be remotely controlled. The project was then expanded to four other hospitals . In JapaWe conducted a scoping review  to identAccording to Drummond et al. , evaluatOur evaluative approach is based on DeLone and McLean's information systems success model, illustrated in Figure The province of Quebec counts 7.9 million inhabitants and its health system is public. The health system is divided into four regions, each under the responsibility of a different University Integrated Health Network (UIHN). The mandate of each UIHN is to coordinate tertiary health care services, teaching and research provided by its faculty of medicine and its associated teaching hospitals so as to improve access to health care by streamlining relationships between primary care providers - doctors and regional hospitals - and upper-level care providers for specialized procedures. Each UIHN is also responsible for coordinating technology evaluation and health intervention methods in order to improve productivity and efficiency on its territory. In 2004, the Quebec Health Ministry asked each UIHN to submit a business case for a major regional telehealth project. The Laval University Integrated Health Network  proposed a telepathology project, which is described next.2 (approximately the size of Germany). Its population density is quite low. Figure The telepathology project involves 17 hospitals located in 5 geographic regions of eastern Quebec, Canada . The areAt the beginning of 2010, six of the 17 hospitals had no pathology laboratory and seven hospitals had a laboratory but were functioning with 0, 1 or 1.25 full-time equivalent pathologists , a macroscopic imaging station , visualization and communication software , computer stations, and storage servers.In 2006, the Laval UIHN decided to invest in a large telepathology project to offer the population in peripheral, intermediary and remote regions improved access and continuity with respect to specialized services. The CAN$6.2 million project is financed by the Quebec Health Ministry and Canada Health Infoway, an independent not-for-profit corporation that works as a strategic investor of funds provided by the Canadian government. In May 2011, the status of the project was as follows: the equipment had been delivered, physically installed and configured, and biomedical technicians, laboratory technologists and pathologists had been trained at 14 of the 21 sites. The equipment had been delivered, physically installed and configured but training had not been given at five other sites, mainly the ones that had to build a pathology laboratory before receiving the equipment. Finally, at the last site, the equipment had been delivered but further steps were delayed because the building posed a security risk, according to a recent seismic study. The equipment delivered to each site comprised a slide scanner , the patients  and the UIHN as a whole . To achieve this, pre-post analyses will be performed using data from different information systems - i.e. laboratory information systems, operating room information systems, and telepathology visualization and communication systems - available at each hospital. More specifically, data from these systems will be obtained for two 6-month periods: post implementation data will be obtained for the six first months after system deployment, and pre implementation data will be gathered for the corresponding 6 months of the previous year.Given the exploratory nature of our study, it was decided to limit our sample to two specific procedures: sentinel lymph node analyses for breast cancer and surgical margin analyses for colorectal cancer. According to the Laval UIHN authorities, these procedures are among the most common ones requiring intraoperative frozen section diagnoses. In order to capture a broad range of effects, both anticipated and unanticipated, and to better understand the nature of the effects according to the context, our pre-post analysis will be conducted in three different settings. First, we will investigate a remote hospital where telepathology was deployed in order to avoid a break in services; the on-site pathologist left between the pre and post periods (thereby leaving the site with no pathologist). Our second setting is a remote hospital where pathology services were nonexistent. With the arrival of telepathology, a mini-laboratory was installed at this site, and a pathology technologist was trained so that medical interventions requiring pathology services could now be provided. Finally, we will investigate the effects of telepathology at a regional hospital where a number of pathologists left between the pre and post periods without being replaced, causing breaks in services.The psychometric properties of our survey measures will be assessed first. For one thing, the reliability and construct validity of all scales will be measured. One interpretation of the reliability criterion is the internal consistency of a test, i.e. the extent to which the items are homogeneous . In thisAs for the qualitative data, interview transcripts and observation notes will be analyzed using the NVivo software package. The constructs in our conceptual framework Figure  will be Lastly, a paired two-sample test of means (t-test) will be conducted to determine whether any differences found between pre and post measures are significant , density of population (medium to very low), physicians' remuneration mode (fee-for-service) and pathologist shortage (moderately severe). Therefore, more evaluative studies will need to be conducted in other regions or countries to enhance the generalizability of our findings.To our knowledge the ongoing telepathology project at the Laval UIHN is unique in Canada and is expected to yield significant results that are relevant both nationally and internationally. Results will provide valuable information to healthcare managers and decision makers who must find more effective and efficient ways to provide accessible care services to patients and, more specifically, patients living in rural regions. A demonstration of both perceived and actual impacts will likely contribute to the promotion of telepathology at the individual (patient and provider), organizational and regional levels. We hope that the study protocol provided here will guide other researchers interested in evaluating such projects and contribute to the overall development of a solid knowledge base regarding the range of benefits associated with telepathology in health care organizations.UHN: University health network; UIHN: University integrated health network.The authors declare that they have no competing interests.MCT, GP and CS led the design of the study. MCT and GP developed the instruments and drafted the manuscript. BT and CS participated in the critical review of the manuscript. All authors gave final approvals on the version of the manuscript submitted for publication.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/12/64/prepub


Fukushimura Brain Bank (FBB) was established under the auspices of Fukushimura Hospital, a legally incorporated medical institution. It is managed completely within the private sector."Fukushi" is a Japanese word that means welfare and "mura" is a village. We have several buildings for the aged and disabled, and about 800 elderly people reside within the complex.The Fukushimura Hospital was established in 1982 and is managed by the Sawarabi MedicalCooperative. It currently has 487 beds. Our patients mainly have dementia and cerebrovascular problems. The hospital plays a pivotal role within the village and acts as the central facility.FBB was established in 1990. We have a long history of collecting samples, not only from patients but also from residents of our care houses and nursing homes within the Fukushimura complex. This allows us as medical doctors and researchers to obtain clinical information or blood samples, sometimes even before the onset of illness. In our institute, all clinical and pathological dataare held in the office of individual data management.In collecting FBB samples, we always keep in mind future biochemical and molecular analyses and collaborations. The brains are separated into two hemispheres. One hemisphere is fixed in formalin for neuropathological analysis and the other is precisely subdivided into coronary sections and small blocks which are saved in Eppendorf tubes. After samples are photographed, they are frozen on dry ice (slices) and in liquid nitrogen (tubes). Finally, all material is stored at -80 degrees in 9 refrigerators for later use in research.Although our bank has gone unrecognized in the past, our farsighted efforts have been gaining considerable attention in recent years in Japan. We now have over 20 collaborators and supply more than 30 research institutes with our samples. In addition, our research institute was approved in 2004 by the Japanese Ministry of Education, Culture, Sports, Science and Technology, as one of the non-governmental institutes which is permitted to apply for governmental grants and we became a member of the Comprehensive Brain Science Network in 2010. FBB at the Choju Medical Institute, Fukushimura Hospitalis a unique facility and one of the most active brain banks in the world.


Particle and Fibre Toxicology has become a well recognized open access, peer-reviewed, online journal with an  impact factor of 5.5. This major achievement is due to the dedication of former Editors-in-Chief Professors Ken Donaldson and Paul Borm, and, of course also due to the high quality of manuscripts that have been submitted by authors from all over the world. Recent years have shown a significant increase in papers dealing with nanomaterials and nanotoxicology, whilst the small margin between ambient PM exposure and current standards continues to provide a constant flow of manuscripts on this topic. This however, does not imply that we can relax now.Within 5 years of its first publication in December 2004,  PFT has received over 270 manuscripts, with a sharp increase in the number of submissions in 2010 compared to the previous year. Of the 270 manuscripts submitted, approximately 50% have been accepted for publication and this percentage is likely to decrease due to a more stringent editorial policy, resulting in the publication of even higher quality papers in the future. Thirty percent of all the publications were from North-America, 63% from Europe and the remaining portion were from Asia and Australia. The number of papers that deal with engineered nanoparticles versus those that cover ambient PM remains similar. However, very few papers focus on workplace or indoor exposure. Most important is the fact that the average number of citations per paper is still increasing, which of course will strongly affect the journal's impact factor.To date, PFT will critically evaluate the soundness of exposure characterization in submitted papers. Primary particle size is often very different from what we see when particles interact with biological systems. This can be due to particle agglomeration or aggregation during the production, handling and storage of particles. Another major influence of particle size is the coating of the particle, whether or not on purpose. Protein coronas and other particle surface modifications have been described in several studies as having major impacts in the toxic properties of nanomaterials and particles . Desp. DespPFTarticles . This isin vitro systems, oral or dermal applications, intravenous injections, or as aerosols for inhalation studies. This demands closer collaboration with physicist, chemists and experts on exposure assessment and as such implies multidisciplinary studies. Inclusion of appropriate control/benchmark particles is always encouraged so that the particle effects can be contextualised. Studies that have been performed under well-defined conditions and preferably with exposure scenarios that are within range of real life exposure are particularly welcome for publication in PFT. PFT functions as a forum for scientific debate and communication between toxicology and disciplines that develop particles and fibres as well as those that assess the risk for adverse human health and environmental effects, including epidemiology, material sciences and nanomedicine. PFT will remain an open access, peer-reviewed, online journal for novel scientific data, hypotheses and reviews on the toxicological effects. Moreover, since risk assessment of particles and fibres requires information on the hazard as well as the exposure, submission of research into exposure assessment is encouraged, provided that links are being made to toxicology [PFT also welcomes studies that are explicitly done for the purpose of risk assessment, e.g. those following OECD Technical Guidelines.Research articles should always contain a good description of the particles in the formulation in which they have been studied, either in suspension for use in xicology . PFT als


Reduction in size and power consumption of consumer electronics has opened up many opportunities for low power wireless sensor networks. One of the major challenges is in supporting battery operated devices as the number of nodes in a network grows. The two main alternatives are to utilize higher energy density sources of stored energy, or to generate power at the node from local forms of energy. This paper reviews the state-of-the art technology in the field of both energy storage and energy harvesting for sensor nodes. The options discussed for energy storage include batteries, capacitors, fuel cells, heat engines and betavoltaic systems. The field of energy harvesting is discussed with reference to photovoltaics, temperature gradients, fluid flow, pressure variations and vibration harvesting. Such networks have significant potential in a variety of applications, including monitoring of animal health and behaviour, structural monitoring for mining equipment and measuring water salinity levels of oceans and rivers.With these opportunities come a number of new challenges. Sensor nodes are usually battery powered, so as sensor networks increase in number and size, replacement of depleted batteries becomes time consuming and wasteful. Additionally, a battery that is large enough to last the life, say five years, of a sensor node would dominate the overall size of the node, and thus would not be very attractive or practical. Additionally, the battery chemistries often involve toxic heavy metals, and present disposal issues, regardless of rechargeable technology.As a result, there is a clear need to explore novel alternatives to power sensor networks/nodes, as existing battery technology hinders the widespread deployment of these networks. By harvesting energy from their local environment, sensor networks can achieve much greater run-times, years not months, with potentially lower cost and weight.Power for wireless sensor nodes can be split into two main technology categories: energy storage and energy harvesting. This paper reviews the state-of-the art technology in each of these fields, outlining different powering options for sensor nodes. These include energy storage utilizing batteries, capacitors, fuel cells, heat engines and betavoltaic systems and energy harvesting methodologies including photovoltaics, temperature gradients, fluid flow, pressure variations and motion harvesting.3.Energy storage is the basis of present technology and involves powering the sensor node from energy stored at the node; a key example of this is batteries. This energy may be stored in different forms ranging from electrical charge to hydrocarbon based fuels. By itself, energy storage cannot deliver energy indefinitely, as at some stage the energy will be depleted and need replenishing. The metric used for comparison of these devices is their average energy density, Joules per unit volume; typically this is J/cm3, rather than their average energy density.Energy harvesting is a newer approach and relies on technology to gather energy from the surrounding environment using, for example, solar cells or fluid turbines. It involves converting the ambient energy inherent in the sensor node's environment into electrical energy. By doing so, a sensor node will have the opportunity to extend its life to a range determined by the failure of its own components rather than by its previously limited power supply. The metric used for comparison of energy harvesting devices differs from that used for energy storage as they don't have a fixed amount of energy intrinsic to their volume. Therefore, energy harvesting devices will be rated on their average power density or Watts per unit volume, W/cmdirect current of approximately 100 mA. Some energy harvesting techniques generate much higher voltages, produce AC power, or simply do not have sufficient power to run the node directly. The result of this is that electronics are required to condition the power for the device and, critically, secondary energy storage in the form of capacitors or rechargeable batteries will be required. Section 4 deals with issues of power conditioning.In general, energy harvesting will not directly power a sensor. This may be because the levels of power are too low, or it may be as a result of the power being in the wrong form. Typically, sensors and nodes require a voltage in the range 2 – 10 V and peak Many of the power options involve taking a technology which has been proven on large scale applications and scaling it down to dimensions suitable for the sensor node. This approach often runs into technical difficulties due to different effects which come into play at smaller scales. Some of these effects, which are detailed in this report, include thermal effects as a device's ratio of surface area to volume changes, viscosity issues involving fluid flow at smaller scale and problems related to increasing volume taken up by battery connectors, packaging and other essential hardware. However, through the persistent work of researchers, many technologies have overcome these obstacles and are nearing fruition.It should be noted that in the context of this review, the term micro-scale is used to describe nodal elements with sizes of approximately 100 mm on a side, masses of less than 100 gm (not including batteries or associated transducers) and power requirements of less than 100 mW.To give examples of the energy requirements of sensor nodes, The Fleck3 is a CSIRO product and a range of data was easily sourced, unlike the XBeeTM and MICAzTM which are both commercial products, for which full specifications were unavailable. The power consumption is very dependant on the various transmit/store duty cycle components and should not be interpreted as a measure of the efficiency of the device. Note that the nodes in 3 ..41]. Theet al. 43]. AddiDespite the net generation of electrical energy from a transducer with a passive rectifier dc-dc converter technique  and 41]41], the et al. 47]. Ulti5.This review has identified the developing problem inherent with present energy and power supply methods for wireless sensor nodes. One issue is modern battery energy densities failing to improve at the same rate as other components in a wireless sensor node. This leads to existing sensor node volumes being dominated by that of the battery volume. In addition, the power demands of sensor nodes can range up to 6 orders of magnitude. This range is caused by the varying power demands of different modes, such as transmission, data collection or reception of signals. To further complicate the issue, these modes are done varying duty cycles. Recent solutions involve catering for the largest demand leaving the power system massively over sized for large portions of the node's operating time.Reviewing the work into power technologies for sensor nodes reveals that there are many different approaches which seem to have the capability of solving the aforementioned problems. Energy harvesting delivers long life, while micro-batteries provide back-up power and micro-supercapacitors enable high power pulses. However, to date there is no ‘one size fits all’, robust system available on the marketplace to provide power for wireless sensor networks for an arbitrary application. One reason for this is due to the bulk of research focusing on one particular technology only for the solution. The problem with this is that in scenarios where one technology may thrive, others may fail, while in a different scenario the first technology may fail while others thrive. This has the effect of making these power systems very application specific. This seems to call for a power system which utilises a hybrid solution of many different technologies able to cater to any scenario. In the last few years this idea has been investigation with papers starting exploration of this scheme  to 54]..54].Research thus far into hybrid power solutions for wireless sensor nodes has been elementary, mostly outlining the potentials and benefits of such systems but failing to get into the detail of how such systems would be optimised. The problems faced in the integration of individual energy storage and harvesting technologies for varying power loads is similar to that of faced by distribute energy or micro-grids. Just as a micro-grid relies on smart software and electronics to integrate numerous sources and loads, to control and manage energy and power, and to provide system stability, so to should the sensor node's “nanogrid” rely on such smart aids to ensure its optimal operation.Short of a ‘one size fits all’ solution for powering sensor nodes, designers need to choose the right mix of energy storage and harvesting options for their particular application. Once again, drawing inspiration from micro-grids reveals the strength of the National Renewable Energy Laboratory's (NREL) HOMER™ software. HOMER™ is considered to be one of the world's most powerful and widely used micro-power design models. HOMER™ simulates and optimises stand-alone and grid-connected power systems comprising any combination of wind turbines, photovoltaic (PV) arrays, run-of-river hydro power, biomass power, internal combustion engine generators, micro-turbines, fuel cells, batteries, and hydrogen storage, serving both electrical and thermal loads . A similSome of the individual technologies themselves showed areas of achievable improvements. As mentioned in the vibration harvesting section work into dynamic resonant tuning of the oscillating harvester is lacking as well as a harvester with more than one degree of freedom. Also there seems to be some synergy between the harvesting techniques employed for vibrations and the radioactive actuated piezoelectric cantilever, perhaps a device could be made incorporating both giving the advantage of the consistent power supply of the radioisotope to balance out the intermittent, stochastic nature of the vibration source, and the advantage of high power density of vibration harvesters to balance out the low power density of the radioisotope.The use of flexible batteries and flexible solar cells seems beneficial due to their ability to double as structural components for sensor networks. This factor may allow them to be used as part of the node structure and thus cut down on volume and mass of the node. The use of temperature differentials was discussed; unfortunately however the low efficiencies that come with environmental differentials of approximately 10 K may limit the use of this source of energy except for specific applications near heat sources. Finally, two energy harvesting techniques were found for which no research could be uncovered at the micro-scale. These were wind power and pressure variations. At the micro-scale these may offer some interesting areas of study. Due to the scaling issues the utilisation of these forms of energy at this scale may require altogether different technologies.Commercial availability is a determination of whether a member of the non-scientific community can buy the product. All of the noted technologies, except those involving pressure gradients, are available at an academic level. Finally, it should be noted that most technologies have a very wide range of available performance figures. This is a reflection of the wide range of methodologies that exist even within the same general theme. As technologies mature, these levels of variance should be expected to narrow.6.The information presented in this paper is provided as a review of the present state-of-the art technology in powering wireless sensor nodes. These nodes are, by their nature, small in size and require a correspondingly small source of power.Many of the technologies presented are based on devices that work at the macro scale. However, when scaled down to nodal sizes, their efficiencies become prohibitively small. Of the systems that exist at the moment, the best source of energy for short term use (less than one year) remains the battery. Fuel cells are quickly growing in capacity and it should be expected that they will equal and surpass battery storage capability within two years. While interesting, the political and practical aspects of betavoltaics would seem to preclude their widespread use in civilian application.In terms of energy harvesting, the outstanding contender at the moment is photovoltaics. Vibration harvesting offers some opportunity where size or location disallow solar. The practical applications behind pressure and temperature change methods are presently not mature enough, though the science appears well understood.