The increase of human life span will have profound implications in Public Health in decades to come. By 2030, there will be an estimated 1.2 billion women in post-menopause. Hormone Replacement Therapy with synthetic hormones is still full of risks and according to the latest developments, should be used for the shortest time possible. Searching for alternative drugs is inevitable in this scenario and science must provide physicians with other substances that can be used to treat the same symptoms with less side effects. Systematic research carried out on this field of study is focusing now on isoflavones but the randomised controlled trials and reviews of meta-analysis concerning post-menopause therapy, that could have an important impact on human health, are very controversial. The aim of the present work was to establish a theoretical calculation suitable for use as a way to estimate the “Theoretical Efficacy (TE)” of a mixture with different bioactive compounds as a way to obtain a “Theoretical Efficacy Related to Estradiol (TERE)”. The theoretical calculation that we propose in this paper integrates different knowledge about this subject and sets methodological boundaries that can be used to analyse already published data. The outcome should set some consensus for new clinical trials using isoflavones (isolated or included in mixtures) that will be evaluated to assess their therapeutically activity. This theoretical method for evaluation of a possible efficacy could probably also be applied to other herbal drug extracts when a synergistic or contradictory bio-effect is not verified. In this way, it we may contribute to enlighten and to the development of new therapeutic approaches. Since then, many researchers, all over the world turned their attention to isoflavones and initiated studies to explore its effects. Today, one of the major concerns about isoflavones lays in the definition of a suitable dose-dependent effect, thereby creating new therapeutic options.Since in 1984 Setchel www.menopause.org/bioidentical.html).Nowadays, over the counter (OTC) tablet preparations and nutraceuticals with isoflavones extracted from soy and other plants are widespread around the world. These OTC medicines are often used for postmenopausal treatment, like Hormone Replacement Therapy (HRT) with oestrogen and/or progesterone  is most evident in genistein and daidzein and their derivatives. The characteristic way that isoflavones bind to oestrogen receptors (ERs), mainly to beta-receptors (ERs-β), makes them promising molecules in replacing hormones for therapeutic purposes.Very early, in the beginning of the research in this field of study, it became evident that isoflavones were less potent than endogenous and synthetic hormones but it also became obvious that they had fewer side effects. Despite the huge amount of results from many epidemiological trials, it is not possible to make a good correlation between isoflavones and soy extracts being sold today –5.Epidemiological data prove that both genders of Asian population are less affected by hormone-dependent tumours. This fact as been directly related to the cultural diet rich in soy, but other factors could be also involved, such as the low amount of saturated fatty acids ingested, different ways to deal with stress and possible low levels of cortisol, among others, since Indians did not eat much soy and are also protect against these tumours.Since the most active isoflavone, which is also the main isoflavone found in soy seeds, is genistein and its derivatives, we decided to compare OTC tablets containing isoflavones extracted from soy, available in the Portuguese market and the isoflavones extracted from soy seeds supplied by the United States Department of Agriculture (USDA) Germplasm bank. These formulations where all indicated for the treatment of hot-flushes and post-menopausal related problems where the content in isoflavones it was critical for the referred bioactivity. The major conclusion of this comparative study was that important differences existed between the OTC formulations and the content of genistein and other isoflavones in raw soy seeds extracts. The quantification of the isoflavones present in OTC formulations was sometimes lower than the expected levels  –8. TheseIf we consider that it is not yet clear how much of a dose of isoflavones is necessary to observe a physiological effect and if the soy protein has any synergic contribution, we should be concerned about what is really contained in the OTC Tablet preparations of soy isoflavones and what kind of quality control should be established –9. The rDespite the number of clinical trials performed with isolated isoflavones or with isoflavones included in soy or red clover food products, results did not clarify its efficacy or whether they could be used safely as a treatment as it is claimed. On the other hand, the U.S. Food and Drug Administration (FDA) back in 1999 made a statement that soy protein can be used with beneficial results in the prevention of cardiovascular diseases, and recommended that its extracts should be standardised, however the amount of isoflavones that can be on the product was not defined.The OTC tablet preparations of isoflavones extracted from soy that we analysed showed as major bioactive compounds the glycosylated isoflavones genistin, daidzin and glycitin and minor amounts of the malonyl and/or methylated derivatives of genistin and daidzin. The aglycones only appeared in very low amounts. The seeds, supplied from the USDA Germplasm Bank, have a mixture of most of these compounds (conjugated or not) but also have low amounts, some times only traces, of the aglycones –9.The evaluation of the efficacy of several extracts and the different results of clinical trials carried out with soy extracts or isolated isoflavones turns its usage into a very controversial subject. Scientists are now aware of the phenomena. Many are now studying the effects of formulations available to post-menopausal women. Given the difficulty of prescribing such formulations, the aim of the present work was to establish a theoretical calculation suitable to be employed as a way to estimate the “Theoretical Efficacy (TE)” of a mixture of different bioactive compounds in a way to obtain a “Theoretical Efficacy Related to Estradiol (TERE)”. Ultimately, different extracts could be compared, even when the relative amounts present in the extracts are very different.2.hot-flush, menopause, isoflavones, genist-, daidz-, glycit-, clinical trials. We also used the selected papers by a panel of Phytohealth members that had reviewed studies and classified them according to the grading criteria proposed by Harbour and Miller [phytoestrogens, isoflavones, genistein, daidzein, equol, soy (a); cross-referenced with the keywords: post-menopausal, hot-flushes, osteoporosis, bone mineral density, bone metabolism, cardiovascular, endothelial function, vascular reactivity, blood pressure, lipid profile, breast, colon, cognition. In order to make cross comparisons between studies that used a range of sources of isoflavones the doses of isoflavones were calculated as aglycone equivalents.Data from literature and reviews of selected clinical trials: a literature survey was made, using the following search engines: Elsevier-Science Direct, PubMed, SpringerLink, Taylor & Francis, Web of Science (ISI) and B-on. The search included the following keywords: d Miller  and the d Miller  presenteIn this paper we use from the clinical data two important keys to the process; on one hand the relative proportions of the different isoflavones intake and on the other, the efficacy of the treatment in reducing hot-flushes that is one of the parameters more cited in the most of the essays. To do the theoretical calculation  these am3.3.1.The isoflavone content (daidzin and genistin and their derivatives) clearly differs between seeds and OTC tablet preparations extracted from soy. In these OTCs the main compounds are the glycosidic forms, glycitin, daidzin and genistin, but the relative proportions change from one sample to another. From the clinical trials used in the selected reviews, the levels of active compounds used to perform the assays differed significantly and the results are very difficult to compare.We found in literature that there is a consensus that glycosylated and methylated isoflavones have an entero-hepatic absorption where they undergo hydrolysis and afterwards are converted to the sulphonated or glucuronated forms. The aglycones undergo the same metabolization.Daidzein and genistein do not have the same binding affinity to alpha- and/or beta-ERs . Also knHowever, it is also accepted that beta-ERs are mainly located in bones, brain, thymus, bladder, cardiovascular system and its activation by estrogenic compounds, or compounds with the ability to mimic estrogenic molecules, such as phytoestrogens, can improve and prevent conditions like osteoporosis and cardiovascular diseases ,18 and tIn global terms the total efficacy of the TERE will be determined adding these two values. However the amount linked to the alpha-receptors will be consider as a possible risk limitation that needs to be evaluated when the increased dose will induce an improved TERE but the risk assessment for the toxicity can be a handicap.In order to allow an assessment between results obtained from clinical trials and different substrates submitted for therapeutic evaluation, the following calculation is proposed.et al., ERs affinity binding for estradiol for some isoflavones but the some theoretical calculations can be done with other affinities published. Utilising these TERE calculations will be possible to compare results of the bioactivity between various clinical trials or other kind of bio-evaluations.To demonstrate the calculation method, let us consider for example two different clinical trials, both using test formulas containing 100 mg of total isoflavones. In one of them the patients are taking pills with 25 and 75 mg of daidzein and genistein equivalents, respectively, but in the other trial patients ingest 75 mg of daidzein and 25 mg of genistein, which is exactly the inverse of the previous formulation. Looking at Keeping the affinity differences in mind, the ER binding values for daidzein and genistein are a starting point to make the theoretical calculation of the efficacy of both mixtures see . The oveThis is currently the case of the clinical trials conducted with botanical extracts if they are not well characterized and/or not comparable in relation to the relatively amounts of the bioactive compounds. It is very common to see reported in literature that in a given trial was used an extract with bio-compounds without saying exactly which molecules were in the extract.Since isoflavones and other molecules are able to mimic estrogens and they all have a different affinity for the receptors involved in the therapeutic activity, the results cannot be compared. For example, opium has two main alkaloids, morphine and codeine, both with analgesic activity but the first is much more active that the methylated derivative (codeine). The therapeutic efficacy of different mixtures of an opium extract would be therefore dependent on the relative amounts of each compound in them even when calculated with these TE calculations.Applying the same methodology as in i.e., molecules that have a preferential binding to alpha-ERs.For all of them, nevertheless, the risk-benefit relationship is determined as roughly 2% and 98% respectively. The increase of dosage can signify an increase of the amount that can be related to the risk, Once the maximum binding rate of alpha-ERs is determined, the risk of possible tumour cell proliferation by the estrogenic activity of these compounds will be lower and the safety of these OTC tablet preparations of isoflavones extracted from soy, red clover, etc, will be more predictable. This is an example of the application for the TERE.For example, in the first calculations  the deteHighly purified isoflavones, soy foods and soy supplements may stimulate the growth of pre-existing oestrogen-dependent breast cancer tumours. Using an animal model, Ju and colleagues  comparedin vivo potential of equol and flavonoids, such as genistein, equol, apigenin and kaempferol was investigated by Breinholt and colleagues [The lleagues , in immain vivo” estrogenicity of dietary flavonoids.In kaempferol- and equol-exposed mice the cytosolic alpha-ERs concentration was significantly increased when compared to the solvent control, which is speculated to result in an increased sensitivity of the uterus to subsequently encountered estrogens. Oral administration of equol, genistein, biochanin-A and daidzein to 6-week-old female mice revealed a large variation in their systemic bioavailability. Other researchers found similar data. Bioavailability, metabolism, the ability to alter alpha-ERs distribution in the uterus and the estrogenic potential of parent compounds and metabolites may consequently contribute to the differences in “Carcinogenesis, suggests that isoflavone-containing products consumed in the US may have lost many of the biologically active components in soy and, therefore may not have the same health benefits as traditional soy foods.The essays published so far did not reveal yet the full risk assessment of these concentrated extracts. A study reported in the May 2004 online issue of the journal In fact, the profile of the isoflavones is different in soy seeds  and in tet al. [This TERE can be supported by the data collected by Williamson-Hughes et al.  and by Ket al. . They fo4.Much research as been published relating to the issue of “phytoestrogens in human health”, but few recommendations can be made because most of the results seem to be controversial . Maybe, The authors declare that they are not for or against the use of isoflavones in human health applications and that they just wish to attempt to clarify this controversial issue. For instance, the verified estrogenic bioactivity shows an important relationship between genistein dose and the reduction of hot flushes and night sweats. These unpleasant effects observed in post-menopausal women are caused by lower oestrogen levels that fail to regulate body temperature via the hypothalamus. The anti-dopaminergic effect induced by estrogens  can be rIn order to prevent the risks that this therapeutic option can cause in long term use, much research still needs to be done to prove the safety of isoflavones. Fortunately, many of the issues commented here will be under investigation. Studies of the effects of soy isoflavones found in dietary supplements on various parts of the body are under way in various research groups.Some of them are investigating how different doses of isoflavones and the timing of exposure affect breast, brain and adipose tissue, and how the interaction between isoflavones and oestrogen receptors takes place. More information is needed on the biological effects of pure isoflavones and complex mixtures of the various soy isoflavones commonly found in commercial OTC tablet preparations of isoflavones extracted from soy and if the matrix induces changes in the bioability of these compounds.


Rates of non-completion of treatments for personality disorder are high and there are indications that those who do not complete treatment have worse outcomes than those who do. Improving both cost-efficiency and client welfare require attention to engaging people with personality disorder in treatment. A motivational interview, based on the Personal Concerns Inventory, may have the ability to enhance engagement and retention in therapy. Here, we report the protocol for a feasibility study for a randomised controlled trial (RCT).All referrals accepted to the psychological service of Nottinghamshire Healthcare NHS Trust's outpatient service for people with personality disorder are eligible for inclusion. Consenting participants are randomised to receive the Personal Concerns Inventory interview plus treatment as usual or treatment as usual only. We aim to recruit 100 participants over 11/2 years. A randomised controlled trial will be considered feasible if  80% of tThe Personal Concerns Interview as a preparation for treatment of people with personality has the potential to maximise treatment uptake, reduce unfilled places in treatment programmes, and prevent group treatments faltering through non-attendance. Most importantly, it has the potential to improve patient outcomes, helping them to function better and reduce hospitalisation.ClinicalTrials.Gov.UK Identifier - NCT01132976 Personality Disorder: No Longer a Diagnosis of Exclusion [http://www.nice.org.uk). Clearly, there are significant developments in provision for people with personality disorders. One area that needs to be considered when developing treatments and services is that of promoting client attendance and engagement.In the UK in recent years, there has been recognition that people with personality disorders have been poorly served by mental health services, and so, in 2003, the Department of Health issued a directive to develop services for people with personality disorders in a document entitled, xclusion . In 2009In a recent systematic review of non-completion of treatments for personality disorder, McMurran, Huband and Overton  identifiIn a recent systematic review of strategies for reducing drop-out rates in psychotherapy generally, only 15 empirical studies were identified [One promising approach that assists the therapist to motivate people to engage in therapy and effect positive change is based upon identification of valued goals. In evolutionary terms, goals are specific representations of what is needed for survival, and goal pursuit refers to the range of activities employed in the quest for goal attainment . Needs rOne specific theory of motivation in which goal striving plays a central role is the Theory of Current Concerns . Within Although the Personal Concerns Inventory is an assessment of goals and motivational structure, the experience of clarifying one's goals and values can be beneficial in itself, and there is some evidence that engaging in the interview may motivate people to enter treatment . This efThe primary aim of this research is to gather information that will determine whether a randomised controlled trial (RCT) to evaluate the effectiveness of a goal-based motivational intervention called the Personal Concerns Inventory in a community personality disorder treatment service is feasible. Specifically, we aim to  measure This is a feasibility study for a randomised controlled trial (RCT).Approval for the research was given by the Leicestershire, Northamptonshire & Rutland Research Ethics Committee 1 (Ref: 09/H0406/76) and Nottinghamshire Healthcare NHS Trust's Research Management and Governance Section (Ref: CSP/18/05/10 CSP ID 19434).Nottinghamshire Healthcare NHS Trust offers an outpatient service to people with personality disorder. This service has three tiers: 1. information and advice, 2. a 16-week psychological intervention based upon psychoeducation, social problem solving and emotion regulation; and 3. a long-term therapeutic community. All referrals accepted to the psychological intervention are eligible for inclusion. Those who are accepted for treatment are informed about the project and asked if they are willing to meet with the researcher to receive further information. Potential participants are fully informed about the research and given an information sheet. Consent to participate is taken by the individual's clinician at the next appointment. After assessment and psychoeducation, which is the first part of usual treatment, participants are randomised to receive the Personal Concerns Inventory interview plus treatment as usual or treatment as usual only. The Personal Concerns Inventory is completed by the service's therapists, all of whom have been trained in its delivery. The number of people assessed for psychological treatment by the service is 118 per year; we aim to recruit 100 participants over 11/2 years.Randomisation is based on a computer-generated pseudo-random code using random permuted blocks of randomly varying size, created by the Nottingham Clinical Trials Unit (CTU) in accordance with their standard operating procedure and held on a secure server. Treatment allocation for each participant is accessed by means of a remote, internet-based randomisation system developed and maintained by the Nottingham CTU. The sequence of treatment allocations are concealed from the Research Assistant responsible for administering the outcome measures until trial-related assessments are complete.The comparison is between a goal-based motivational interview called the Personal Concerns Inventory plus treatment as usual and and treatment as usual only. Treatment as usual is up to four individual weekly sessions of psychoeducation, based on personality assessment and information exchange , after wParticipants recruited to the Personal Concerns Inventory group receive one or two interviews of maximum total duration of 3 hours after assessment and receipt of the psychoeducation component of treatment. The Personal Concerns Inventory procedure asks participants to identify their goals in 11 life areas , and then prioritise five goals. These five goals are then rated on scales from 0 to 10 assessing five aspects of goal attainment: likelihood of attainment, control over attainment, knowing how to attain it, happiness upon attainment, and commitment to attaining it. Participants are asked to identify obstacles to goal attainment and consider the possibility that therapy could help them overcome these obstacles. This is intended to enhance participants' motivation to engage in therapy.Part of the service's routine assessment is administration of the Personality Diagnostic Questionnaire-4 , a 100-item, self-administered, true/false questionnaire that yields personality diagnoses consistent with the DSM-IV diagnostic criteria for the axis II disorders. Information from this will be used to describe the personality disorder profile of the sample.Within the two weeks prior to the start of the problem solving therapy group, participants in both the Personal Concerns Inventory group and the treatment as usual group are interviewed briefly to assess the goals that they expect therapy to help them achieve. The goals generated by participants will be rated for quality . This information is designed to tell us whether the Personal Concerns Inventory works better than treatment as usual to clarify clients' thinking about their goals and the potential value of therapy in assisting with goal attainments. Throughout the problem solving group therapy, attendance records are kept and at the end of group therapy, therapists rate each participant's level of engagement using the Treatment Engagement Rating Scale . This scale contains items addressing the client's participation, constructive use of sessions, opennness, efforts to change, making sacrifices, goal directedness, and reflection.Information is collected about recent receipt of services throughout using the Client Service Receipt Inventory . The CSRI captures recent use of health and social care. The CSRI is administered at baseline and again at the end of treatment.At the end of treatment, participants in the Personal Concerns Inventory group, both treatment completers and non-completers, are interviewed, either by a researcher or by a service user, to ask for their views on the acceptability and usefulness of the interview. Therapists are also interviewed to assess their opinions of the Personal Concerns Inventory.A randomised controlled trial will be considered feasible if  the recrThe means whereby the Personal Concerns Inventory should work to improve engagement and retention in therapy is by helping the interviewee identify what are his or her important goals, the obstacles to goal attainment, and the relevance of psychological therapy to overcoming obstacles. The end result of therapy should, therefore, be a greater likelihood of attaining important goals and improving life satisfaction.If the Personal Concerns Interview administered in preparation for treatment of people with personality disorder improves engagement and retention in treatment, then this could be an economical way of improving the cost-effectiveness of treatments. It has the potential to maximise treatment uptake, reduce unfilled places in treatment programmes, and prevent group treatments faltering through non-attendance. Most importantly, it has the potential to improve patient outcomes, helping them to function better and reduce hospitalisation.The authors declare that they have no competing interests.MM, WMC, SC, and DW contributed to the design of the study. All authors contributed to the creation of the Manual of Procedures and the study protocol. MM drafted the manuscript. All authors provided a critical review and final approval of the manuscript.


This paper analyzes the impact of population aging on health care expenditures in Korea. Examination of the age-expenditure profile reveals that health care resources are allocated more for the older cohort of population over time, suggesting significant growth of health care expenditures due to population aging. We contend, however, that population aging is considered as a parameter rather than an independent variable to explain rising health care expenditures. This paper shows that population aging is not found to be a significant determinant of health care expenditures according to the econometric analysis using OECD health data and time-series data for Korea. Using the components decomposition method, which measures the contribution of each component of health care expenditure, we estimate that population aging contributes only less than 10 percent. We can observe this from the age-expenditure profile, in which more health care monies are spent on the older cohort of the population. In order to examine the influence of population demographics on health care expenditures within particular countries, researchers have plotted health service use and/or expenditure against age, and used the resulting age-use and age-expenditure curves to quantify the relationship between age and utilization or expenditure. In OECD countries, the average with age ,2.Some studies since 1980s, however, argue that population aging is not a cause or is only a weak factor of increasing health care expenditure. The degree to which increasing expenditures are simply responses to changing demographic variables is small –6. A stuOther studies emphasize that population aging is not a major cause of increasing expenditures, and in fact, the expenditures before death are a major reason behind the high cost for old-age cohorts ,9–14. PrOn the other hand, for the last several decades population aging has proceeded with economic growth in most countries. Many studies which investigate determinants of health care expenditure with comparative data of OECD countries show that some social economic factors, like income, are more significant than population aging. Cross-sectional studies of aggregate national spending levels in several countries found the percentage of the population over age sixty-five to be at best a weak predictor of expenditures –29.Korea has experienced rapid aging, and the forecasts predict that Korea will soon be one of the most aged countries in the world, so population aging is often referred to as a major cause for the ever growing health care expenditures in Korea. The share of people over 65 years of age was 3.1 percent of the population in 1970, 5.1 percent in 1990, 7.2 percent in 2000 and 9.1 percent in 2005. It is predicted to reach 20.8 percent in 2028 and 38.2 percent in 2050, much higher than the 25.9 percent forecasted for other advanced countries . There hThis study shows, first, by using age-expenditure profiles, that health care expenditure in Korea, which experiences a rapid aging, has increased with the aging population. However, this approach simply shows the relationship between age cohorts and health care expenses, and does not count other factors that influence health care expenditures other than the population aging. Thus, secondly, we investigate the determinants of health care expenditure with both cross-sectional and longitudinal data from OECD countries. Such panel analysis has been widely adopted recently. In this approach we control several factors that can influence health care expenditures, and we can then analyze separately the effects of population aging. Next, we analyze the determinants of health care expenditure in Korea using time-series data, and show the difference with the results drawn in the case of the OECD countries. Lastly, this paper measures the contribution of population aging on health care expenditures, using component decomposition method to disassemble the components that constitute the health care expenditure and then analyze how much the change in population aging affects its increase.2.2.1.per capita, by age cohort, were calculated, and thus those constituted the health care expenditure structure with age cohort. This enables us to observe how health care expenditures have changed in accordance to the age structure shifts. We measured the profiles for the years 1991, 1996, 2001, and in addition, measured a profile for 2003. Visiting days, which sum up the annual hospitalized and outpatient days by age cohort, measure the changes in service utilization by age cohort. However, when the health care expenditures by age cohort also include the price changes for services for each corresponding year, it is difficult to separate the effects of aging. Therefore, to observe the health care expenditure in accordance with the genuine change in age structure, it is necessary to find some way of standardization. The method used for this purpose is to calculate the relative indices of health care expenditure by age cohort and observe the structural changes by year. The volume of services used by patients of each age cohort can also be calculated using this method.The age-expenditure profile approach is limited by its need for health care expenditure data, according to age groups. Therefore, this paper uses the data produced from the National Health Insurance (NHI) in Korea. The annual health care expenditures 2.2.per capita is the most influential factor that can explain changes in national health care expenditures, and in addition to income, many other socioeconomic factors and health care system related variables have been discussed in terms of how they have influenced health care costs. The influence of socioeconomic factors and health care system factors on health care expenditures has been estimated in a variety of ways, according to the methods and data used.Researches on the factors that determine the national health care expenditures in the late 1970s and the early 1990s have usually utilized the simple or multivariable regression analysis model based on cross-sectional data. In the late 1990s, researches using various econometric models based on panel data became prevalent. The existing research results point out that the gross domestic product (GDP) In this research we used the longitudinal data on 33 countries during the period between 1970 and 2001. All the countries were members of the Organization for Economic Cooperation and Development (OECD). In addition, analysis based on the time series data of Korea was compared with the analysis of OECD countries, and some implications were found. The analysis in the case of Korea has two time spans: from 1997, the year that national health insurance was introduced, until 2000, and from 1985 to 2000.The following is the full-model used in the analysis:per capita and is used as a dependent variable. Independent variables are classified with socio-economic factors and health system related factors. For the socio-economic factors, we used GDP per capita, the ratio of people older than 65 to the total population, and the ratio of women to the whole work force. For the health system factors, we used government health expenditure, health insurance population coverage, the number of doctors per one thousand people, hospitalization cost, and new medical technology as quantitative variables. Other health system factors, such as the methods of payment to doctors and the existence of gatekeepers are included as institutional variables. These institutional variables are treated as dummy variables. In the model, j denotes the country, and t denotes the year.In this model, NHE represents national health expenditure We note that government health expenditure, which is mostly included in the literature in studying determinants of health care expenditure, does not include social health insurance expenditure. The term government health expenditure refers to investments in public health, which covers prevention and health improvement, prevention of pandemic diseases, public health infrastructure, and other public activities. The underlying logic of using this variable is that government investment for public health will reduce the national health expenditure.The provider payment system shown in Each quantitative variable is converted to natural logarithms to get the elasticity estimate. The logarithm transformation of variables also contributes to mitigate the heteroskedasticity of coefficients. The variables used in the models are defined in 2.3.The increase in health care expenditure can be broken down into several components: the increase in population coverage, the aging of population structure, increased fees for services, and the increased volume of services used. Through this analysis, the effect of population aging can be singled out. The data used in this analysis is the National Health Insurance data of Korea. The health insurance expenditures could be decomposed by the following equation:In capita are likely to be extended longer as people are getting older. The expense per visit day is also supposed to increase according to the population aging. Both the extension of visit days and the increase of expense, however, are not only caused by the population aging. Thus both of them are decomposed of the factor affected from the demographic structure change and the remaining part, such as What we want to know in per capita. In per capita are composed of the effect of demographic structure change on the visit days, which is called “demographic structure change [per capita” in In e change ”, and thThe adjusted expense per visit day is composed of the conversion factor (‘fee’), which converts the score of each service item based on the resource based relative value scale (RBRVS) into price of charge, and the remaining part, such as the We note here that “fee” in a to time point b.We should notice here that “rate of change in fee” and “rate of change in readjusted expense per visit day” include price inflation. Therefore, those rates of change in fee and expense can be expressed in real terms separated from price inflation. The rates of change in demographic structure can be expressed as changes from time point The data for the calculation is provided in j denotes age cohort.The rates of change in demographic structure change from the per capita in Rate of changes in adjusted visit days And rate of change in readjusted expense per visit day can be expressed in two steps. In the first step, change in adjusted expense is separated from the change in demographic structure, as in Three periods of analysis were selected: 1991 to 1999, 1999 to 2003, and 1991 to 2003. The reason we divided the data into three periods is that the separation of prescribing and dispensing drugs was introduced in July 2000, and that policy had a striking impact on the national health care expenditures.3.3.1.As the proportion of older population increases, their health care expenditures tend to increase accordingly, where the health care expenditure represents those accrued in the national health insurance that includes doctors’ service charges and operating expenses, but excludes expenditures for drugs and supplies. The ratio of the health care expenditure of person over 65 to that of person under 65 during the period between 1991 and 2003 is shown in The cause of this phenomenon is that persons over 65 have more health care needs than those under 65. However, the costs of fulfillment of the health care needs of those over 65 can be met as a burden on the population labor force. Thus, as the productivity of the labor force improves and income levels get higher, it becomes easier to fulfill the health care needs of older persons.per capita is high for infants and children; it decreases among the youth, it increases in middle age, and then it increases rapidly in later years. On a graph, this trend is a U-shaped curve, as shown in When we look at the trend of health care expenditure by age groups, we see that the health care expenditure To correct the problem that occurs when comparing with current prices of each year, the relative magnitude of health care expenditures by ages in each year is calculated, as shown in A question that arises is whether the volume of health care services used is following a trend similar to that of health care expenditures. The expense per service unit applied to older people could be increased.Even without these price-related factors, we can observe whether the steep U shaped form could stay the same. As shown in The visit days, with the average growth of visit days subtracted, are shown in per se, but rather by the increase in available national income that implies more resources for health care. In addition, if the extended life span is closely related with the rising national income, the rise of health care expenditures toward older cohorts will be related to the growing national income. Strictly speaking, population aging may not be an independent variable that influences health care expenditures. Population aging progresses in response to improvement in health care, better nutrition, higher education, health awareness, and so on. Therefore, the rise in health care expenditures could be explained by the causes that make population aging possible, rather than by population aging per se.From these observations, is it possible for us to regard population aging as a decisive factor which results in the increase of health care expenditures? The answer is not that simple. So far we have only observed the relationship between population aging and health care expenditures. For instance, as population aging continues, we see health care expenditures increase for people who are 70 years old. However, the causes of the increased expenditures are complicated; as the national income rises, there could be more resources available involved in curing older people, and advances in medical technology could have invested more in health care for them. Since the national income grows accompanied with technological advancement from the perspective of economic history, the phenomenon of rising health care expenditures may not be explained by population aging 3.2.per capita income and women’s participation in the labor force, although the elasticity varies widely because the model is constructed differently.The panel analysis for the OECD countries shows that the results are influenced by the period of analysis chosen and the choice of explanatory variables used. Population aging does not appear to be a significant variable in determining national health expenditures. However, in Model 2, shown in It is curious that the signs of variables “doctor” and “inpatient” are inconsistent in Models 2 and 3 in The results from the time-series data in Korea are shown in It is curious that the increase in the number of doctors has an effect on containing health care expenditures. This result is opposite to that seen in other OECD countries. Korea rejects the supplier-induced demand hypothesis which claims that the increase of doctors is the main cause of the rise of health care expenditures. Therefore, we can conclude temporarily that the consumer’s expanded demand, which was originated by the expansion of the insurance-covered population, is a stronger factor than the supplier-induced demand for health care. However, women’s participation in the work force did not affect health care expenditures significantly. In Model 2 conducted for the recent period, income and health insurance coverage of the population were both significant, but population aging was not.In conclusion, the leading cause of rising health care expenditure is related to the increase in national income and the expansion of the health insurance covered population. The increase in the number of doctors was influential in containing the increase in health care expenditure, and population aging was not significant, as in other OECD countries.3.3.When the period from 1991 to 2003 is selected, the contribution of population aging to the rise in health care expenditure appears to be 6.6 percent, as shown in The results after excluding the price inflation are shown in Population aging contributed less than 10 percent to the increase of health care expenditures. Health care expenditures increased mainly due to the increase in both the volume of utilization and the increasing fees. This implies that the higher level of income and the introduction and/or expansion of health insurance affected the increase in health care utilization, and in turn the increased utilization produced the increase in health care expenditure.4.per se. Therefore, population aging may not be an independent variable that contributes to the rise in health care expenditure. Instead, the factors that make population aging possible such as income, education, and sanitation will be the ultimate determining factors.The objective of this paper was to analyze the impact of population aging on health care expenditures in the case of Korea. We applied three approaches to do this. The first approach using age-health care expenditure profiles showed that, when we look at the profiles closer to the present, the health care expenditures for the older age groups came to increase further. The health care utilization excluding price index, like GDP deflator, was also increasing more rapidly for the older age cohorts. This implies that the health care resources that are allocated to the older age groups are growing, due to the increased resources applied to extend the expected life span that could be generally enabled through the higher national income level, rather than the population aging Some research attributes most of the rise in health care expenditure to the population aging, explaining it by citing the Sisyphus syndrome. This research claims that health care expenditures increase leads to a longer life span (‘provokes aging’) and that the extended life span leads to a higher demand for public health services and finally increases the health care expenditure . The forTo overcome the limitation of neglecting other factors besides population aging in observing the health care expenditure profile by age, we applied the second approach, in which we used longitudinal regression analysis to OECD countries. The result of this analysis shows that in OECD countries, generally population aging was not a significant variable contributing to increased health care expenditures. A similar result was also shown in the case of Korea, though a relatively short period of time-series data was used. The analyses of relatively recent periods, which show a somewhat faster aging, show also that population aging was not a significant factor in the increase of health care expenditures. The main causes of increased expenditures are thought to be both the national income and the expanded application of national health insurance. In the approaches using regression analysis, the effect of higher income on health care expenditure increase could have overwhelmed the influence of population aging in determining health care expenditure. In this approach, we cannot verify, however, of how much the population aging contributes to the increase of health care expenditure.We used an alternative approach, in which we broke down the components contributing to increased health care expenditure and singled out the contribution of the change in demographic structure, most of which is accrued from population aging. During the period of 1991 to 2003, the population aging contributed only 6.6 percent to increasing health care expenditures. However, in real terms excluding price inflation such as GDP deflators, the contribution of population aging was 9.2 percent. In this approach, the contribution of population aging to increased health care expenditures was considered less than 10 percent. The main drivers of health care expenditure increases appeared to be both the increased utilization of volume and the increased fee levels. The real drivers beneath these factors were thought as the higher national income and the introduction of national health insurance. Several studies show that the effects of aging population may be overwhelmed by other factors like the introduction of new technologies and treatments –37; incrIn short, the influence of population aging on the rise in health care expenditures can be viewed as superficial. The reality is that the factors that cause population aging contribute to higher health care expenditure. A study suggested that the fixation on population aging provides an ‘illusion of necessity’ . By makiIn conclusion, population aging is thought to be an endogenous variable rather than an independent variable in how it impacts health care expenditures. It seems to be a parameter or mediator in the process of explaining the causes of increasing health care expenditures. This paper, of course, has some limitation. Time span for the estimation of the determinants of national health expenditure in Korea is not sufficiently long. We need more data for the longer period extending up to date. But when we extend the period, we will have a difficulty to manage in the model, the financial shock that happened in 2001 due to the sudden increase of medical fees that was caused by the sudden introduction in July 2000 of the policy of separating prescribing and dispensing. In the analysis of components decomposition, we took the components which contribute to the increase of health care expenditure as population aging, price, volume, and intensity. But the components can be separated in more detail. Especially the effect of coverage expansion of benefits and the effect of increasing patient  can be separated from the above components. It is, however, technically difficult to separate them in an acceptable manner. How the other important factors, such as cost of dying, diffusion of high technologies, growth of health care provision market are related with population aging will be promising issues of further study in Korea.


Over the last few years the number of immigrants from the non-western parts of the world living in Oslo, has increased considerably. We need to know if these immigrants are satisfied with the health services they are offered. The aim of this study was to assess whether the immigrants' level of satisfaction with visits to general practitioners was comparable with that for ethnic Norwegians.Two population-based surveys, the Oslo Health Study and the Oslo Immigrant Health Study, were performed on selected groups of Oslo citizens in 2000 and 2002. The response rates were 46% and 33%, respectively. In all, 11936 Norwegians and 1102 non-western immigrants from the Oslo Health Study, and 1774 people from the Oslo Immigrant Health Study, were included in this analysis. Non-western immigrants' and ethnic Norwegians' level of satisfaction with visits to general practitioners were analysed with respect to age, gender, health, working status, and use of translators. Bivariate (Chi square) and multivariate analyses (logistic regression) were performed.Most participants were either moderately or very satisfied with their last visit to a general practitioner. Non-western immigrants were less satisfied than Norwegians. Dissatisfaction among the immigrants was associated with young age, a feeling of not having good health, and coming from Turkey, Iran, Pakistan, or Vietnam as compared to Sri Lanka. The attendance rates in the surveys were rather low and lowest among the non-western immigrants.Although the degree of satisfaction with the primary health care was relatively high among the participants in these surveys, the non-western immigrants in this study were less satisfied than ethnic Norwegians with their last visit to a general practitioner. The rather low response rates opens for the possibility that the degree of satisfaction may not be representative for all immigrants. There is a growing number of immigrants from non-western parts of the world in Oslo, the capital of Norway. The number increased from 10.1% to 16.9% of the total population, between 1993 and 2003, and by 01.01.2003 there were 87.472 immigrants living in Oslo [The health problems of immigrants are influenced by culture and beliefs. Additionally, the immigrants' country of origin often do not have the same system of primary health care services as European countries . The heaPrimary health care services are meant to be the foundation of the Norwegian health services . ApproxiTwo former studies in Oslo have shown that non-western immigrants usually thought they had received the health services they needed ,8. HowevIn the present paper we want to compare non-western immigrants' degree of satisfaction with GP services with that of ethnic Norwegians, and how this satisfaction is affected by gender, age, own description of health, and income-producing work.Two studies in Oslo are examined in this paper, The Oslo Health Study and The Oslo Immigrant Health Study. The Oslo Health Study, a population based cross sectional study, was carried out between May 2000 and September 2001 as a collaboration between the Norwegian Institute of Public Health, the University of Oslo, and the Oslo City Council . AltogetThe participants in the Oslo Health Study were divided in groups of Norwegians (born in Norway), western immigrants (born in western countries), and non-western immigrants (born in non-western countries). This categorization was done because of the small numbers of immigrant participants . The parIn 2002 the Oslo Immigrant Health Study was carried out as collaboration between the Norwegian Institute of Public Health and the University of Oslo . InhabitThe two studies followed the same protocol including a physical screening , blood samples, and questionnaires. The Oslo Health Study included a main questionnaire, a first and a second supplementary questionnaire. The immigrant study included a main and a supplementary questionnaire. This article focuses on the answers to the questions in the first supplementary questionnaires in both surveys. The questionnaires can be found with official English translation .In all 18770 persons (46%) participated in the Oslo Health Study. Totally 15282 persons answered the first supplementary questionnaire . All theThe main question we look into in this article is "How satisfied were you with the last visit to a doctor? ". Three answers were possible : Very satisfied, moderately satisfied, and not satisfied. We look into the degree of satisfaction with the last visit to a general practitioner in relation to country of origin, gender, age, own description of health, need of translator, and income-producing work.In order to examine the degree of satisfaction with the last visit to a general practitioner, we used the number of responders who had been to a general practitioner answering the question "What kind of doctor  did you visit on the last occasion?" We also explored how many different general practitioners the responders had been treated by in the course of the last 12 months.Age was divided into "old" (born before 1955) and "young" (born 1955 or later). The state of health was explored by the question "How would you describe your present state of health?" as this independent variable is an indicator of describing the level of health. Possible answers were: "Poor", "Not very good", "Good", and "Very good".We also explored the need for translator "Does anyone help by translating for you when you visit the doctor?" giving five possible answers : "Have not been to a doctor in Norway", "Yes usually", "Sometimes", "No", and "Not relevant (do not need/want such help)".The question "Are you currently employed ?" with the answers : "Yes, full time", "Yes, part time, and "No" was utilized in examining the degree of income-producing work. Persons who are unemployed or outside the labour force are at risk to develop psychological problems, and are therefore in need of health care services ,14.Two additional questions regarding use of health services were also explored: "Do you think that in Norway you have received the medical services you need?" with possible answers "Yes, always", "Yes and no", "No", "Have not needed such help", and "Don't know", and "Do you think the medical service you have received is better or not as good as a Norwegian would have received?" with the answers "Not as good treatment", "Same treatment", "Better treatment", "Have had no need", and "Don't know".Bivariate (Chi square) and multivariate analyses (logistic regression) were performed by using SPSS 13.0. The level of significance was set to p ≤ 0.05. The studies are approved by the Norwegian Data Inspectorate and have been cleared by the Regional Committee for Medical Research Ethics.The Oslo Health Study showed that 9949 people had been to a general practitioner (GP) on the last visit to a doctor. Of the 9829 people who answered the question about the level of satisfaction, 92.3% were ethnic Norwegians and 7.7% were non-western immigrants. In the Oslo Immigrant Health Study 1177 people had been to a GP on their last visit to a doctor, and 1157 people had answered the question about the level of satisfaction.During the last year 82.2% of the ethnic Norwegians, and 82.1% of the non-western immigrants in the Oslo Health Study had visited one or more GPs. Of the Norwegians 46.1% and of the non-western immigrants 38.9% had seen only one GP. In the Oslo Immigrant Health Study 85.5% had been to one or more GPs during the last year, and 39.1% had seen only one GP.The participants' degree of satisfaction with the last visit to a GP according to country of origin is shown in Table Analysis of satisfaction with respect to gender, age, own health, income-producing work, and use of translators are shown in Table Most of the Norwegians were very satisfied, and this was independent of their state of health. The result from the Oslo Health Study showed that most of the non-western immigrants were very satisfied when their health was acceptable and only moderately satisfied when their health was not good. Most of the participants in the Oslo Immigrant Health Study were moderately satisfied, and this effect was independent of their state of health. Analysis by country showed that the when the state of health was "not good", 41.3% of the participants from Turkey were very satisfied, while only 22.2% of the participants from Vietnam were very satisfied.The results of the logistic regression analysis confirmed the bivariate analysis of the Oslo Health Study Table . It showassociated with being non-western, male, young, not in good health, and full time employed or unemployed rather than being part time employed.Results from the Oslo Immigrant Health Study showed that dissatisfaction was associated with being younger, not in good health, and being from Turkey, Iran, Pakistan, or Vietnam as compared to Sri Lanka.The participants in all immigrant groups were moderately satisfied independent of whether they needed a translator or not. Only 13 of the participants in the Oslo Health Study used a professional translator, and 104 of the participants used some other type of translator. Half of the first group were very satisfied with their last GP visit, and 1/3 of the other group were very satisfied. In the Oslo Immigrant Health Study 38 of the participants had used a professional interpreter, and 190 of the participants had used another translator. In the first group 2/5 were very satisfied and in the other group 1/3 were very satisfied with their last GP visit.Of the non-western immigrants in the Oslo Health Study, 63.9% thought they had received the same health services as the Norwegians; 26% did not know. In the Oslo Immigrant Health Study 53.7% thought that they had received the same health services as the Norwegians, and 31.3% answered "don't know".In the Oslo Health Study 42.4% of the non-western immigrants thought they had received the medical services they needed, and in the Oslo Immigrant Health Study 43.1% answered the same.This study focuses on the degree of satisfaction with the visits to general practitioners in Oslo. A substantial proportion of participants were either very satisfied or moderately satisfied with their last visit to a GP. The degree of satisfaction was higher among the ethnic Norwegians than among the non-western immigrants even when factors such as gender, age, own health, and income-producing work were controlled for.The attendance rates for these surveys were rather low, and lowest for the non-western immigrants. The first part of the questionnaires in both surveys contained some rather complex questions concerning eating habits which may have been difficult to answer . This maLow participation rate is a major problem and challenge for most immigrant health studies . Our stuLow attendance rate among non-western immigrants can be due to language problems, cultural differences, and a lesser degree of integration. It seems reasonable to speculate that well integrated immigrants are more likely to participate in health surveys, and that the degree of satisfaction with health services could be dependent on degree of integration. This might imply that the degree of dissatisfaction is underestimated in our study. We found that the participants who described their health as not good were also the most dissatisfied. It might be that people with chronic illnesses, bad health in general, and those who receive disability benefit were less likely to answer the questionnaires as their lives are difficult, and they are less resourceful. This suggests that the percent of persons that were not satisfied with the general practitioner could have been higher, if the response rate had been better.Table Younger people were more dissatisfied than older people. The young patients may be more aware of what they can expect from the health services, while on the other hand, older patients may be more reluctant to complain. The people from Sri Lanka were the most satisfied while the Vietnamese were the most dissatisfied. A study in a multicultural area of London showed that Vietnamese patients stated that they had received better health care in general practice than other ethnic groups. But they also stated that they expected less . ReasonsWe found that 53.7%–63.9% of the non-western immigrants thought they had received the same health services as the Norwegians. These rates are lower than in two previous studies of non-western immigrants in Norway . In a 19One explanation of the lower rates in our study, might be differences in data collection methods : The information in the two former studies were based on interviews.Few of our responders used a translator when visiting a GP. We assume that patients who did not in need a translator either spoke Norwegian or they communicated with a doctor through a mutual language. We also assume that many patients wish to choose a GP who speak their own native language when they do not have a good command of the Norwegian language. In Oslo there are GP's from the non-western parts of the world .In June 2001 the primary health services in Norway were reformed, and the Regular General Practitioner (RGP) Scheme was introduced, based on patient listings and capitation . ParallePrimary health care services shall treat approximately 90% of the enquiries to health service institutions in Norway. The immigrants' countries of origin have different kinds of health care systems. Thus, the immigrants' different cultural backgrounds may lead to expect admission to a hospital or a hospital's outpatient clinic for conditions that in general are treated by general practitioners in Norway. Other immigrants come from countries without an organised health system. They need information on how to utilise our health care system.Healthcare experiences as well as health expectations may vary between ethnic groups. In general practice this is especially relevant . ExpectaOur study has limitations due to small samples. Non-western immigrants are a heterogeneous group, and ethnicity is a complex concept. Belonging to one minority group does not necessarily imply a particular behaviour or a certain health characteristic. Some of the challenges to the health care system include providing services that are sensitive to cultural differences, being able to respond to differences in pattern diseases, and to overcome personal biases .The non-western immigrants in the two surveys were mostly satisfied with their last visit to a general practitioner. The ethnic Norwegians were overall more satisfied than the non-western immigrants. The rather low response rates opens for the possibility that the degree of satisfaction may not be representative for all immigrants.This study invites to further research into the non-western immigrants opinions concerning the quality of the primary health care. The aim of further research will be to better understand the non-western immigrants' special needs so as to improve the health services for these patients.The author(s) declare that they have no competing interests.EL and EOR have contributed to the idea, design, analysis and writing of the paper. PN has contributed to analysis and writing of the paper. All authors read and approved the final manuscript.


High-throughput techniques are somewhat restricted in developing countries. However, computational resources have evolved in recent years to become available to the general public, with greater ability to solve intense computational problems at low cost. Therefore, the vast amount of information that is currently being generated and the need for finding the underpinnings of several issues in biology, have been the impetus of the computational biology area in Latin America. Colombia is no exception, as its rich genetic diversity has convened the attention of several institutions, including both governmental and academic departments, to find how, where, and when these resources could be employed to its benefit. In this review, we introduce the efforts being made throughout the country to spread the word and establish a strong network from a mid- and long-term perspective.In Colombia, computational biology is just starting to be known as a field of research in its own right. Until now, mainly chemists and biologists have used bioinformatics as a tool to try to solve their particular research problems. We start by reviewing the work of some research groups and their projects. Next, we identify the driving forces of computational research and the problems to be faced in the future. This review is not exhaustive and we apologize for any groups that were not mentioned or acknowledged. , Universidad de los Andes. Luis M. Rodríguez-R is a Master's student and bioinformatician at LAMFU; he is also a bioinformatician for the GeBiX project. Roberto Sierra did his Master's studies at LAMFU and is now a research assistant. Roberto also works for the GeBiX project analyzing metagenomic data from 454 sequencing. Alejandro Grajales was formerly a research assistant at LAMFU and was recently accepted as a doctoral student at the American Museum of Natural History in New York. Adriana Bernal is an associate professor at Universidad de los Andes and leads LAMFU with Silvia Restrepo. Emiliano Barreto is a professor at Universidad Nacional de Colombia. Pedro Moreno is a professor at Universidad del Valle. María Mercedes Zambrano is the scientific director of Corpogen and the leader of GeBiX project. Marco Cristancho is the leader of the bioinformatics unit at Cenicafé. Andrés González is a professor at the chemical engineering department at Universidad de los Andes. Harold Castro is an associate professor at the Systems Engineering Department at Universidad de los Andes and a pioneer in grid computing in Colombia.In Colombia, research in computational biology started in a group from pharmaceutical chemistry at Universidad Nacional de Colombia. CBIB, as it is known, was formed in 1998 and has since been headed by Emiliano Barreto. This group has been the Colombian node of the EMBnet (European Molecular Biology network) since 2002 and has been a member of the Ibero-American network of bioinformatics since 2004. It has developed computational biology for research, teaching, and university extension-course purposes. Its participation in educational activities is noteworthy (see below), due to a collaboration with the Swiss Institute of Bioinformatics. It has also developed bioinformatics tools for the storage, handling and analysis of biological data.http://bioinf.ibun.unal.edu.co/servicios/BLEE/) and BLA.id . BLEE was designed by the CBIB in order to organize and systematize information related to an expanded spectrum of beta-lactamases. The BLEE system consists of three modules: (1) an introduction to the basic theory behind the study of the enzymes; (2) a description of the most important biochemical and physico-chemical properties of this group of molecules, as well as the different families they belong to ; and (3) a Website where users can find an online tool developed by CBIB to identify families of an extended spectrum of beta-lactamase(s) by their biochemical properties. BLA.id is an information system that allows for molecular and clinical data-crossing, making possible identification of beta-lactamases from resistant organisms at the intra-hospital level on the basis of their sequences. BLA.id allows users to: analyze sequences; identify them by class, family, or variant levels; build dendrograms; and search/browse related information such as manual and automatic annotation, comments, bibliography, geographical references, alternative names, and source organisms.For a long time, the group has focused on the study of the beta-lactamases, particularly the description of these enzymes and a general understanding of resistance to beta-lactamic antibiotics. Two developments in this area are BLEE, (http://bioinformatics.cenicafe.org/). Initially, they constructed ESTs (expressed sequence tag) and microsatellite coffee databases by means of specialized interfaces that allowed users to search, update, delete, and insert text data, sequences, images, and documents. Their platform, which also includes an in-house–developed LIMS (laboratory information management system), can also be accessed at this same Web address. Moreover, the group maintains a strong collaboration with the Sol Genomics Network (SGN) as the mirror of their site in Colombia. Besides building a very robust platform for research on coffee, Cenicafé has performed such important advances as coffee genomics Beauveria bassianaPlant pathology has been a key area for the development of computational biology in Colombia because of the country's commitment to agriculture, with plant pathology and the breeding of crops being a national priority. Coffee has historically been the main agricultural export product of Colombia, accounting for 17% of the agricultural production in 2008, and giving employment to more than 560,000 coffee-growing families Phytophthora infestans, a destructive pathogen of potato crops. The study of this pathogen's genome has led to the development of bioinformatics and molecular tools that are useful in characterizing this oomycete's populations Phytophthora infestans genome Xanthomonas axonopodis pv. manihotis, and have become one of the teams participating in the annotation of three Xanthomonas genomes. LAMFU's Web site (http://bioinf.uniandes.edu.co/) allows access to and exploration of the microsatellite database, PhytoSSR, of three Phytophthora species P. infestans, the team successfully reconstructed the metabolomics of the diseased potato by a systems biology approach based on our own microarrays data , led by Adriana Bernal and Silvia Restrepo, maintains an active field of computational biology research in to two diseases of crops relevant to third world countries: potato and cassava. On one hand, the group had been studying the oomycete pathogen Located at Universidad del Valle in Cali, Colombia, Pedro Moreno has developed a scalar theory that tries to explain population repertoires of cells during humoral immune response Pseudomonas aeruginosa biofilm removal from abiotic surfaces with interesting results Bacillus thuringiensis using bifurcation analysis. Based on a deterministic model, they found that B. thuringiensis could also exhibit a bistable response during sporulation, and that the transition from planktonic to sporulated state is strongly influenced by noise within the cell. Interestingly, they proposed a novel scale-down in silico approach to determine cellular reactions to periodic variations in oxygen tension by analyzing the effects of amplitude and frequency of cells on the distribution of the population and protein frequency based on Fast Fourier Transform analysis P. aeruginosa that is capable of predicting deletions or overexpression of genes in order to optimize the production of the electron shuttle molecules and therefore increase power density Escherichia coli without external electron acceptors using a similar genome-scale model. Rational product design is also being carried out in his lab with a systems engineering approach. In particular, the team, in collaboration with LAMFU, is developing algorithms that can predict mutations in specific lipases that degrade the quorum-sensing signal of the commonly known plant pathogen Ralstonia solanacearum. These algorithms are built on ab initio protein models of molecular mechanics and dynamics [20].The systems biology team inside the Grupo de Diseño de Productos y Procesos (GDPP) at Universidad de los Andes, led by Andrés González, is applying systems biology tools to product design and biological system optimization from an industrial perspective. For example, they are assessing gene expression noise in quorum-sensing–regulated gene networks by stochastic modeling. Once the evolution of the signal in time is obtained, they can introduce optimization strategies to find adequate doses of quenchers to minimize signal concentration, and hence the pathogenic phenotype fails to evolve in the host cell. These algorithms have been applied to B. thuringiensis deterministic model could be built using the grid infrastructure.The group at the Universidad del Valle is not the only team collaborating with engineers. At Universidad de los Andes, biologists work with systems and computer engineers to build a robust computational infrastructure. Harold Castro's group is designing and implementing a grid infrastructure that utilizes the entire computational capacity of the University to help solve scientific problems. It includes not only dedicated clusters, but also computer rooms scattered across the campus. This solution is based on virtualization and allows researchers to use both opportunistic and dedicated resources, with great independence of the platform. Users build an image of their machine  and deploy a virtual cluster on the physical machines available or required. This strategy allows researchers to work on the platform of their choice while taking advantage of resources provided by any collaboration grid in which the institution participates. Actually, the Nowadays, Colombian researchers are studying Colombian biological diversity as a means of responding to worldwide concern about the loss of diversity due to global climate change and the need for alternative sources of energy. Diversity is explored at different levels. The CBIB group at Universidad Nacional created ENKI-DB http://www.gebix.org.co). GeBiX, in collaboration with LAMFU, is building and implementing pipelines for the analysis of the metagenomics molecular data. The most remarkable feature of GeBiX is that it constitutes the first effort to bring together most of the main players in computational biology in the country to establish a nationwide platform for research in bioinformatics.Two metagenomic efforts are being conducted in Colombia. The first, conducted by a consortium of institutes and universities, is exploring the microbiota present in potato-cultivated soils. For this purpose, CBIB created software to design probes for a microarray that can determine the presence of microorganisms and their metabolic activities in cultivated soils. A second metagenomics project aims to study the microbiota present in soils and water reservoirs of a national park . This program is being conducted by GeBiX, the Colombian Center for Genomics and Bioinformatics of Extreme Environments , Cornell University, and the University of Arizona. Scientists from a broad spectrum of Colombian research centers and universities have participated in these courses.http://bioinformate.uniandes.edu.co.In an effort to expand the field of bioinformatics in Colombia, the Universidad de los Andes developed a virtual learning environment (VLE) in the bioinformatics field. The VLE is called Bioinfórmate and can be accessed at Investment in overall research and development in Colombia is not large and is ranked below many other Latin American countries The implementation of governmental policies to support interdisciplinary courses and graduate degrees in universities around the country to train young scientists in computational biology;The establishment of special funding by local funding agencies or agreements with the information technology and communication (ITC) industry to support bioinformatics research;The development of a national grid for the analysis and sharing of bioinformatics tools and genomic data as well as improvements to the current computational capacity;The foundation of a Colombian national society in computational biology and bioinformatics that can organize annual meetings, gather information, and identify people currently working in computational biology, among other activities.Many challenges lie ahead for Colombian scientists. Apart from continual efforts needed to study, analyze, and catalog its notable genetic diversity, agricultural research must be sustained as a key area of investment for improving the productivity and competitiveness of Colombia's agricultural sector


Smoking remains a major public health problem; developing effective interventions to encourage more quit attempts, and to improve the success rate of self-quit attempts, is essential to reduce the numbers of people who smoke. Interventions for smoking cessation can be characterised in two extremes: the intensive face-to face therapy of the clinical approach, and large-scale, public health interventions and policy initiatives. Computer-based systems offer a method for generating highly tailored behavioural feedback letters, and can bridge the gap between these two extremes. Proactive mailing and recruitment can also serve as a prompt to motivate smokers to make quit attempts or to seek more intensive help. The aim of this study is to evaluate the effect of personally tailored feedback reports, sent to smokers identified from general practitioners lists on quit rates and quitting activity. The trial uses a modified version of a computer-based system developed by two of the authors to generate individually tailored feedback reports.A random sample of cigarette smokers, aged between 18 and 65, identified from GP records at a representative selection of practices registered with the GPRF are sent a questionnaire. Smokers returning the questionnaire are randomly allocated to a control group to receive usual care and standard information, or to an intervention group to receive usual care and standard information plus tailored feedback reports. Smoking status and cognitive change will be assessed by postal questionnaire at 6-months.Computer tailored personal feedback, adapted to reading levels and motivation to quit, is a simple and inexpensive intervention which could be widely replicated and delivered cost effectively to a large proportion of the smoking population. Given its recruitment potential, a modest success rate could have a large effect on public health. The intervention also fits into the broader scope of tobacco control, by prompting more quit attempts, and increasing referrals to specialised services. The provision of this option to smokers in primary care can complement existing services, and work synergistically with other measures to produce more quitters and reduce the prevalence of smoking in the UK.Current Controlled Trials ISRCTN05385712 Mortaliho start . Developho start .Smoking cessation services are currently high on the NHS agenda, with strong drive to deliver a variety of interventions in primary care. Interventions for smoking cessation can be characterised in two extremes. The treatment model of the NHS services is based on the clinical approach, offering intensive support and focusing on individual face-to-face treatment. As a result of government initiatives , the numA large number of studies of tailored feedback have been published demonstrating positive results. This trial uses a modified version of a computer-based system developed by two of the authors (HG and SS) to generate individually tailored feedback reports designed to encourage and help smokers to quit. The smoker first completes a paper-based Smoking Behaviour Questionnaire (SBQ). The SBQ data are scanned into a database, and the computer program generates a feedback letter that is highly tailored to the individual's responses.n = 1164), this intervention significantly increased 1-month prolonged abstinence rates from 11.3% in the control group to 16.4% in the intervention group (p < 0.02). These findings are consistent with previous studies, which have demonstrated a positive effect of individually tailored printed self-help material on smoking cessation [The efficacy of our tailored feedback was evaluated as an adjunct to telephone counselling  in a randomised trial of 1508 participants . Resultsessation , and sugessation , in contessation ,19. A Coessation  reportedTwo exceptions to this are recent UK general practice based studies that failed to demonstrate an increase in cessation rates for tailored feedback compared with an untailored letter  or with Since our previous study with the Quitline,  we have Smoking cessation literature has been criticised in the past for being written at a level beyond the literacy skills of many smokers , leadingIn addition, the acceptability and feasibility of the delivery of this modified feedback in general practice using a proactive recruitment strategy has been assessed in a pilot trial . QuestioThe results of the pilot trial also indicate that a high proportion of the respondents are not planning to quit in the next six months . It is eThe aim of this study is to test the hypothesis that personally tailored feedback reports, based on an assessment of individual needs and tailored to levels of reading ability, sent to smokers identified from general practitioners lists with varying levels of motivation and readiness to quit, will increase quit rates and quitting activity over and above that found with standard self help and usual care received from the practice. The study objectives are 1) to compare the effectiveness of sending personalised computer tailored feedback reports to smokers with sending standard self-help materials 2) to explore the effectiveness of tailored feedback reports by socio-economic status to determine their effect in more deprived groups 3) to determine the characteristics of smokers who are prompted to change their behaviour after receiving tailored feedback reports.The study is a randomised controlled trial of cigarette smokers identified from GP records and sent a questionnaire. Smokers returning the questionnaire are randomly allocated to a Control Group, to receive standard help, or to an Intervention Group to receive tailored feedback reports. The trial is conducted as a collaboration between UCL and University of Cambridge, and is co-ordinated from UCL. The study has been reviewed and approved by the Northern and Yorkshire MREC, and has received R&D approval from all participating PCTs.The research has substantial potential to benefit participants, by improving health through a positive change of lifestyle. The information leaflet also informs participants that while there is no guarantee that the information they receive will help, they may find that they learn more about themselves by answering the questions. The aim of the intervention is to help participants to stop smoking, it is therefore unlikely that there will be any adverse effects. However, anyone experiencing distress as a result of the assessment or intervention, is advised to discuss it with their GP or a counsellor.The MRC General Practice Research Framework (GPRF) is a network of 1100 practices scattered throughout the UK. We are recruiting 100 GPRF practices, selected to represent high and low socio-economic areas to maximise the generalisability of the results. Practices generally identify 13% to 22% of their patients as smokers, depending on the characteristics of the patient population, and the accuracy and completeness of the records . A mediuAll current cigarette smokers aged 18 to 65 able to read English are eligible for inclusion in the study. Exclusion criteria are minimal because the aim is to recruit all smokers. However, any patients selected who are considered by the GP to be unsuitable for the project, e.g. people with severe mental impairment or severely or terminally ill, are excluded.Those willing to be contacted for future assessment return the completed questionnaire, together with a signed consent form, to the research team at University College London. Randomisation is at the level of the study participants. Upon receipt of the completed questionnaire eligible participants are randomly assigned to one of the two conditions, according to an externally constructed randomisation plan. The general practices represent a clustering variable and to reduce any confounding by practice we are using block randomisation, using blocks of eight (within which the order of assignment will be random), within each practice to allocate patients to each condition to closely balance the numbers. In a large trial such as this, we expect the conditions to be balanced on important predictive factors such as dependence.However, any imbalances will be controlled for in the statistical analysis. While it is not possible to blind participants to the receipt of a feedback letter, in order to ensure that the researchers in all cases are blind to the allocation of the participant, the feedback is generated by a service administrator. To avoid bias in the outcome assessment, when conducting follow-up interviews by telephone for non-responders the interviewer will be blinded to the allocation of the respondent.Participants are sent materials according to their randomisation, immediately after returning the questionnaire. Participants allocated to the Control Group are sent standard non-tailored information (the NHS 'SMOKEFREE' booklet), as well as receiving the usual care offered by their general practice. To eliminate any variation in the care offered, usual care is defined from the results of the pilot study, and we attempt to ensure that all recruited practices offer the same protocol. Participants allocated to the Intervention Group are sent a computer-tailored feedback report based on the information obtained at baseline, in addition to the standard non-tailored information and receipt of the usual care offered by their general practice. The Intervention Group are also sent an additional assessment to generate a further personal progress report one-month after the baseline.The baseline assessment questionnaire (SBQ) assesses demographic characteristics , intention to quit, motivation, dependence, previous quit attempts, perceived advantages and disadvantages of quitting, self-efficacy and social environment. The baseline data are scanned and entered using FORMIC data capture software, simultaneously creating an SPSS file containing data for analysis, and a data file for producing feedback letters. A computer program temporarily combines these data with the personal data of participants allocated to the Intervention Group, selecting the correct messages from the message library to produce a feedback report. Once the report is produced the file is deleted, in accordance with the Data Protection Act. Participants are informed of this possible use of the data.Participants in the Control group receive the standard self-help immediately after returning the questionnaire. Participants in the Intervention group also receive the additional help in the form of a personal feedback letter immediately after returning the questionnaire, and a further one-month assessment for generating a personal progress report. The time schedule for the mailing of assessment and follow-up questionnaires, and intervention materials is presented in Table Outcomes are to be measured by postal questionnaire. Non-respondents to questionnaires will receive one postal reminder. Non-respondents to the reminder will be contacted by telephone. In order to estimate the accuracy of self-reports, a random sample of 20% of the participants who report abstinence will have their status validated by salivary cotinine sample, obtained by post.Long term abstinence has been thought of as the gold standard for evaluating smoking cessation interventions, but has been criticized as failing to measure other possible benefits of treatment, such as repeated quit attempts and shorter periods of abstinence . Recent The Primary Outcome Measure is Prolonged abstinence for 1 month and for 3 months at the 6-month follow-up.Secondary Measures are 24 hr and 7 day point-prevalence abstinence, quit attempts, changes in motivation and intention to quit, and in cognitions measured at baseline, use of NRT or Zyban, and any contact with advice services or health professionals , use of NHS resources and other smoking cessation aids for economic analysis.Process measures are adherence to advice, perceptions of the feedback reports, perceived personal relevance of the feedback reports.Performance figures against target figures set by PCTs before and after the intervention will be obtained from General Practices as indicators of activity.Spontaneous cessation is difficult to estimate, but population cessation rates suggest that it is between 0.5% and 3%  and 4.9%The Cochrane review  of sevenBased on our previous studies, we expect approximately 20–25% attrition ,40. For Chi-squared tests will compare binary outcomes between the intervention and control groups (e.g. for prolonged abstinence of 4 weeks), with logistic regression to take into account any chance imbalance in important baseline characteristics between the groups. Continuous variables (e.g. cognitive changes) will be compared with the two-sample t-test, with multiple regression to account for other important characteristics. Odds ratios and 95% confidence intervals for differences in means or medians (as appropriate) will be quoted.To address drop-out, the primary analysis will assume that non-responders continue to smoke. Multiple imputation methods will be used as a sensitivity analysis, where predictors of drop-out will be used to impute likely outcomes (SOLAS software).Because benefits of interventions may differ by general practice, and patients within practices may demonstrate more similarity in their outcome than patients in different practices, multi-level models will be applied to take into account general practice effects (MLwiN software).Participants will be categorised by socio-economic status, social deprivation and different educational level to explore the effectiveness of the intervention in these groups.The incremental cost-effectiveness of the individual feedback compared to the control condition will be assessed from the NHS perspective in line with methods recommended by NICE . The cosIn accordance with NICE technical appraisal guidelines , we are Small groups of smokers recruited via the Quitline commented on the original questionnaire and feedback letter, which were modified accordingly. The smoking cessation counsellors at the Quitline also provided input. Ongoing research using Focus Group discussions with smokers have explored consumers' views on the acceptability of this approach to encourage and support smoking cessation. Follow-up questionnaires sent to all participants in the study will evaluate users' perception of the materials. Participants will have the opportunity to request a report of the results. A lay summary will be prepared and sent to all participants requesting one.In the UK there are 450 new smokers every day . At thisIt is important to offer a range of interventions that appeal to different individual needs and preferences . ComputeReaching and changing the behaviour of smokers, particularly heavily dependent smokers and those from lower socio-economic groups is a challenging task, and the effect of any intervention likely to be small. However, contrary to common assumptions, the proportion of hardcore smokers (defined by cigarette consumption and time from waking to first cigarette), forms a lower proportion of all smokers than in 1996 . AlthougBrief advice from GPs has been shown to increase quit rates , and thiEQ-5D: EuroQol 5D; ESCAPE: Effectiveness of computer-tailored Smoking Cessation Advice in Primary Care; GP: General practitioner; GPRF: General Practice Research Framework; MLwiN: Multilevel modelling for windows; MRC: Medical Research Council; MREC: Main Research Ethics Committee; NHS: National Health Service; NICE: National Institute for Clinical Excellence; NRT: Nicotine replacement therapy; PCT: Primary Care Trust; R&D: Research and Development; SBQ: Smoking Behaviour Questionnaire; SOLAS: Software Tool for Analyzing Incomplete Data; SPSS: Statistical Package for the Social Sciences; TTM: Transtheoretical model; UCL: University College London; UK: United Kingdom.The authors declare that they have no competing interests.HG conceived of the study, was involved in the development of the intervention and questionnaires, drafted the protocol and is the principal investigator.SS is a co-investigator, and was involved in the conception and design of the study, in the development and adaptation of the intervention, and contributed to the writing of the protocol.IN is a co-investigator with expertise in primary care research, was involved in the design of the study, contributed to the writing of the protocol, and is advising on the management and co-ordination of the trial, particularly the liaison with the GPRF.RM is a co-investigator and trial statistician, and contributed to the protocol in matters relating to randomisation and statistical analysis.CG is a collaborator, has commented on the protocol and contributed to matters relating to the analysis and reporting of economic and quality of life issues.All authors read and approved the final protocol.