The epidemiology of obesity in primary care populations has not been thoroughly explored. This study contributes to filling this gap by investigating the relationship between obesity and different sources of personal stress, mental health, exercise, and demographic characteristics.A cross-sectional survey using a convenience sample. Five hundred women who attended family planning clinics were surveyed and 274 provided completed answers to all of the questions analyzed in this study. Exercise, self-rated mental health, stress, social support, and demographic variables were included in the survey. Multiple logistic regression analysis was performed.After adjusting for mental health, exercise, and demographic characteristics of subjects, analysis of the data indicated that that being having a large family and receiving no support from parents were related to obesity in this relatively young low-income primary care sample, but self-reported stress and most types of social support were not significant.Obesity control programs in primary care centers directed at low-income women should target women who have large families and who are not receiving support from their parents. Many variables may influence eating behavior and therefore may also influence obesity, including depression, anxiety, stress, social support, race, ethnicity, education and income -8. WhileStudies of stress as a risk factor for obesity are limited. In fact, few epidemiological studies have been reported in primary care journals. An exception is found in a report by Sammel et al, who included a stress index in their study of weight gain among women in their late reproductive years (ages 35–47) . Three hStress can be measured in different ways. The personal circumstances experienced by individuals might be expected to have a direct effect on depression, anxiety, and general health status. After all, when conflict arises within a family, the psychological consequences can be dramatic. Even though the relevance of various sources of personal stress to obesity has not previously been examined in the community health literature, their potential importance is worthy of investigation.The purpose of the study reported here was to investigate the importance of personal stressors in determining obesity. The sample was drawn from a low-income female population: women using a family planning clinic for primary care. Exercise, social support, mental health and other personal characteristics were measured and held constant in order to determine the independent effect of different sources of personal stress on obesity.A cross-sectional survey of primary care patients (adult non-pregnant women) attending one of five Planned Parenthood clinics in the Panhandle of Texas was conducted. The Amarillo Institutional Review Board granted exempt status to the study because no protected health information was collected. Planned Parenthood provide a valuable and unique sampling frame because it supplies basic primary care to low-income women in this area, including birth control, but not abortions.Eligibility for the study was limited to patients who were over age 18 and not pregnant. Questionnaires were placed on a table in waiting areas, with a poster inviting participation. Clinic staff also handed out survey forms. Subjects placed the completed forms in a sealed box. Sealed boxes containing survey forms were returned to Texas Tech for data entry. Microsoft Access was used for data entry.Five hundred forms were distributed. Twenty surveys were returned by persons ineligible for study participation and were excluded from the sample. The final data set was comprised of 345 subjects. Computing the response rate as completed returns divided by eligibles (345/(500-20) produces a participation rate of .719. Complete cases were available from 274 subjects for the multivariate analysis.The dependent variable was obesity. Body mass index (BMI) was computed as weight in pounds times 703 divided by height in inches squared. BMI greater than 30 was classified as obese, and made up about 20 percent of the sample. Cases with missing heights and weights were dropped.Independent variables were stress, social support, age, race/ethnicity, education, income, number of persons in the home, exercise, marital status, anxiety, and depression. Key instruments are discussed below.Health items were taken from the Duke Health Profile . Mental Stress and social support items were taken from the Duke Social Support and Stress Scale (DUSOCS). The DUSOCS contains items addressing personal support from various sources. A person who stresses the respondent is defined as one who causes problems or makes life more difficult . RespondExercise was measured in terms of times per week . Age, number of persons in the home, race/ethnicity , marital status, and educational level  were used to control for demographic differences among subjects. The median age was 25. Age was categorized as 18–21, 21–30 or 31 or over. Breaks in the age distribution were made at the first and third quartile.Chi-square tests were used to test for the relationship between each independent variable and obesity. Variables that were significant at p < .10 in univariate tests were included in a multiple logistic regression analysis. EpiInfo 3.2.2 was used for data analysis.Nearly half of respondents were classified as being obese (47.8 percent). About half of the respondents reported 'a lot or some' stress from parents or a spouse. 'A lot or some' stress from a child was experienced by about 40 percent. More than three-fourths of respondents said they receive 'a lot or some' support from a spouse or parent. About sixty percent received 'a lot or some' support from a child. Over 90 percent reported 'a lot or some' support from a friend.Table The sample was comprised of relatively young women, with most being under 30 years of age. Most respondents lived with two or more other people and most had high school degrees. More than one-fourth of respondents were married. Over one-fourth were Hispanic and over half were non-Hispanic White. Most had incomes under $30,000 per year. Over 35 percent got no exercise at all.Table 'Some' or 'a lot; of nervousness was reported by about one-third of respondents, while over one-third said they were depressed 'some' or 'a lot'. Neither depression nor anxiety was retained for use in the multivariate model, since significance levels were below .10.Variables that were significant at p < .10 were included in the multiple logistic regression model  stress with objective  measures of stress in this population group are unknown. Consistent with the findings of our study, Sammel et al did not find stress to be related to obesity in their study of women aged 35–47 .Exercise was not significantly related to obesity in our data. Interestingly, Sammel et al also found no relationship between exercise and obesity 1]. Kaplan et al reported that physical activity was related to obesity in older Canadians, but their sample was quite large  thus giving them more statistical power .Obesity rates increased with age in our univarate analyses. This is consistent with what has been reported by other investigators ,3. We foWe could not show self-assessed depression to be predictive of obesity. Several other investigators have examined this issue, with some seeing obesity as a consequence of depression and others regarding depression to be a result of obesity. In a large study by Carpenter et al , increasThe reasons why large families increase the risk of obesity are not entirely clear. One obvious mechanism is that, since women traditionally prepare meals, they may have more frequent opportunities to consume food and households with large families are more likely to have greater volumes of food available.The research question for this paper was about the risk factors for obesity in a low-income female population in a single community. Our study differs from some other studies of obesity by its inclusion of several types of personal stress as well as social support and mental health measures. We were able to show that personal stress, as defined and measured in this study, was not an important risk factor for obesity in this population group.A limitation of this study is that it does not address occupational stress. Work-related stress has been shown to be related to the health of employees -14. HoweDespite these limitations, our findings have significance for public health practice related to weight control. Health promotion programs that seek to educate and encourage healthier eating behaviors in low-income female populations should focus on women who are not receiving support from their parents and have large families of their own. In addition, income and eligibility for food assistance may affect dietary practices in unexpected ways, so primary care providers should explore this issue.None declared.JR planned the study, organized the survey, and wrote the first draft of the results. BR wrote the section addressing mental health and obesity.The pre-publication history for this paper can be accessed here:


About half of all newly presented episodes of shoulder complaints (SC) in general practice are reported to last for at least six months. Early interventions aimed at the psychological and social determinants of SC are not common in general practice, although such interventions might prevent the development of chronic SC.The Education and Activation Programme (EAP) consists of an educational part and a time-contingent activation part. The aim of the EAP is to provide patients with the proper cognitions by means of education, and to stimulate adequate behaviour through advice on activities of daily living.The article describes the design of a randomised clinical trial (RCT) to evaluate the effectiveness and cost-effectiveness of an EAP in addition to usual care, compared to usual care only, in the prevention of chronic SC after six months. It also describes the analysis of the cost and effect balance. Patients suffering from SC for less than three months are recruited in general practice and through open recruitment. A trained general practitioner or a trained therapist administers the EAP.Primary outcome measures are patient-perceived recovery, measured by self-assessment on a seven-point scale, and functional limitations in activities of daily living. Questionnaires are used to study baseline measures, prognostic measures, process measures and outcome measures.st 2003. Data collection is to end in June 2004.The inclusion of patients in the study lasted until December 31 Shoulder complaints (SC) have been defined by Sobel & Winters  as pain SC are characterised by pain in the area between the base of the neck and the elbow, at rest or when elicited by movement of the upper arm Fig. .Musculoskeletal disorders, of which SC constitute the second largest group after low back disorders, account for the second largest share in healthcare costs and represent the largest group of work-related diseases in the Netherlands .The point prevalence of SC in the general population in the Netherlands has recently been estimated at 21% . In a BrThe International Association for the Study of Pain (IASP) regards persistent or recurring pain lasting less than three months as acute pain, whereas more than three months of persistent or recurring pain is considered to be chronic pain . The stuThe Dutch College of General Practitioners provides clinical guidelines for the treatment of SC . These gTo date, early interventions aimed at the psychological and social determinants of SC are not common in general practice, although such interventions in the early stages of the SC might prevent the development of chronic complaints .We hypothesised that an intervention concentrating on psychological and social determinants in the early stages of SC would prevent the development of inadequate cognitions and maladaptive behaviour, ensuring that such inadequate cognitions and behaviour do not play a role in the development of chronic SC later on.The term cognitions refers to the way patients think about their pain and what the pain means to them, in terms of thoughts, beliefs, attitudes and self-efficacy expectations , whereasPatients' cognitions and behaviour should thus be influenced so as to become adequate cognitions and adaptive behaviour. A relatively brief treatment in the early stages of SC, administered by a trained therapist, may be expected to be effective in preventing the development of chronic SC. The Education and Activation Programme (EAP) that formed the subject of the present study is such an early intervention.This paper describes the design of a study to evaluate the clinical effectiveness of an early EAP aimed at using psychological and behavioural factors to prevent chronic SC. In addition, the study is to evaluate the balance between costs and effects. EAP in patients with acute SC is to be compared with treatment according to the Dutch College of General Practitioners guidelines. The Medical Ethics Committee of the Institute for Rehabilitations Research in association with Rehabilitation Foundation Limburg has approved the design of the study presented here. Funding was obtained from the Netherlands Organisation for Scientific Research.This paper describes also the rationale and content of the EAP.Previous studies have indicated that cognitive behavioural therapies aimed at bio-psychosocial factors are promising instruments for the prevention of chronic musculoskeletal pain . The EAPThe aim of the EAP is to prevent the development of inadequate cognitions and maladaptive behaviour in patients with acute SC.Education is used to maintain or induce adequate cognitions by providing information that is tailored to questions that patients have about their SC. Health care educators frequently assume that giving information equals comprehension, which should automatically translate into changed behaviours as the knowledge is applied . AccordiSince inadequate cognitions and maladaptive behaviours are not yet fully developed in patients with acute SC, the focus of the EAP is not on restructuring inadequate cognitions or modifying maladaptive behaviour, but on maintaining or inducing the proper cognitions by education and on maintaining or inducing adequate behaviour by giving advice on activities of daily living. Adequate behaviour is considered to be behaviour in which the patient remains active. A comprehensive description of the EAP is given in the Design section.Patients are recruited by GPs and in the open population by advertising in local newspapers.Patients are eligible for inclusion in the Randomised Clinical Trial (RCT) if they consult their own GP or respond to adverts in a local newspaper with a new episode of SC that has lasted no longer than three months, at rest or when elicited by movement in the shoulder area.Patients are included if they are 18 years or older and living in the south of the Netherlands. Only newly presented episodes of SC are considered, that is, patients who have not consulted their GP and have not been treated for their SC in the preceding three months. Additional exclusion criteria are given in table A Randomised Clinical Trial (RCT) with a six-month follow-up is used to evaluate the effectiveness and cost-effectiveness of an EAP to prevent chronicity in patients with acute SC, compared to usual care.A computer-generated random sequence table is used to randomise the patients to EAP or usual care. Neither the patient nor the GP, nor the trained therapist, can be blinded for the allocated treatment. The trained therapist is also the researcher coordinating the RCT and conducting the data analysis, but is blinded for treatment allocation during the data analysis. The allocation code will be revealed only after the data analysis has been completed.Usual care (UC) is applied according to the Dutch College of General Practitioners guidelines for SC version 1999)[99[19]. MThe focus of the EAP is to maintain or induce the proper cognitions by education and to stimulate adequate behaviour by means of advice on activities of daily living. Table The EAP consists of a minimum of two sessions and a maximum of six follow-up sessions over a period of six weeks. Each session may last up to 20 minutes. The first and second sessions are organised in the general practice setting by the trained GP, or at the patient's home by the ambulant EAP therapist. The other sessions are provided by telephone.The first part of the EAP has an educational purpose, and focuses on information about the origin, nature and prognosis of the SC, possible interventions and their effects, the impact on activities of daily living and its consequences and the patient's own possibility to contribute to recovery. This information is tailored to the patients' questions and needs and is based on the information available in the Dutch College of General Practitioners guidelines for SC.In addition, the effect of cognitions and behaviour on the perpetuation of the SC is clarified to the patient by an example. If possible, this example refers to a condition or circumstance the patient has experienced, such as a broken bone or back pain. The patient is helped by the trained GP or the trained therapist to explore whether his or her thoughts about the SC are justified. Negative patterns of thinking are modified into adequate and accurate thoughts.The second part of the EAP consists of a time contingent activation programme, based on the principles of operant learning. It focuses on gradually increasing activities of daily living, despite the pain.Potential avoidance of activities is countered by reinforcement of continuation or resumption of usual activities.Positive reinforcement is used to stimulate patients with a normal activity pattern, in spite of their SC, to continue their activities. This positive reinforcement may be enough to achieve continuation of the desired activities . These pPatients who have reduced their normal activities are helped to identify up to three frequent activities of daily living that they have reduced as a result of the SC. These activities are stepwise gradually increased to the desired level of activity in a time-contingent manner. The desired level of activity and the magnitude of the increases are determined and agreed upon by the EAP therapist and the patient.The patient and the EAP therapist also plan a progress evaluation, which is used to positively reinforce the patient's behaviour if the gradual increase has been correctly implemented or to adjust the magnitude of the increases if the original objectives prove too optimistic.The first outcome measure is the perceived recovery of the patient. Patients are considered to be recovered when they report to be much improved or fully recovered, on an 7-point ordinal scale, after six months.The second outcome measure is that of functional limitations in activities of daily living. This variable is assessed by a 16-item questionnaire, the shoulder disability questionnaire (SDQ), with a The statistical analysis will be carried out according to the 'intention-to-treat' principle. Differences between groups, with 95% confidence intervals, will be calculated for each outcome measure. The study groups will be compared by an independent samples t-test for changes since baseline for continuous outcome variables and the chi-square test for categorical outcome variables. In addition, the corresponding baseline value for each continuous outcome will be used as a covariate.The analysis will be repeated taking any loss-to-follow-up into account by applying a sensitivity analysis in which all patients who are lost to follow-up are first considered to show the largest observed improvement and then the largest observed deterioration in outcome measures.The analyses of the difference in change for the outcomes at three and six months will account for the repeated measures character of the data. Baseline characteristics that are a priori considered to be possible prognostic factors for outcome variables, as well as post-randomisation differences between the groups, will be handled as potential confounders. Their influence will be evaluated by means of multivariable regression analyses. In the case of confounding, adjusted effect estimates will also be reported.About half of all newly presented episodes of SC in general practice are reported to last for at least six months. A number needed to treat of 4.5 after six months is considered clinically relevant. This implies an absolute reduction of 22% of the proportion of patients with SC after six months. With a two-sided alpha of 0.05 and a statistical power (1-β) of 0.80, 70 patients per treatment group are needed to detect a difference in favour of the EAP compared to usual care after six months.This RCT is part of the Dutch Shoulder Disability Study, a comprehensive prognostic cohort study on SC, with randomised controlled interventions in subcohorts. The Dutch Shoulder Disability Study is funded by the Netherlands Organisation for Scientific Research .There are several reasons to publish a study design before the results are available. The main reason is that it provides an opportunity to counteract publication bias, that is, the phenomenon whereby a study producing positive results is more likely to be published than a study showing no difference between the study groups , [23]. HAnother reason is that it gives researchers the opportunity to reflect upon the study design independently of the results. When results run counter to the researchers' expectations, methodological flaws are usually examined. But when the results are in line with expectations, methodological flaws are more likely to be overlooked. The third reason arises from the tendency among randomised controlled studies to deviate from their original designs, mainly because of practical problems. Such deviations from the study design may affect the study results. Publishing the study design forces researchers to test its implementation and to answer for any deviations from the design.Finally, this article offers us an opportunity to describe the rationale and content of the intervention in greater detail than the methods section of an article reporting the results of the RCT would do [24].The EAP is a brief intervention that can easily be administered by GPs in addition to the usual care according to the guidelines. This might give GPs an instrument to prevent the development of chronic SC in the early stages of the complaints by focusing on psychological and social determinants.st 2003. Data collection will be completed in June 2004. Currently, 108 patients have been included and are being followed up.The inclusion of patients in the study lasted until December 31SC: Shoulder ComplaintsGP: General PractitionerIASP: International Association for the Study of PainEAP: Education and Activation ProgrammeRCT: Randomised Clinical TrialUC: Usual CareCDB: Camiel De BruijnSDQ: Shoulder Disability QuestionnaireNWO: Netherlands Organisation for Scientific ResearchThe author(s) declare that they have no competing interests.CDB participated in the design of the study, will provide the EAP as an ambulant therapist, coordinate the data collection, will perform the statistical analysis and publish the results. RDB participated in the design of the study and will participate in the statistical analysis. JG, MG, WVDH and G-JD also participated in the design of the study. AK participated in the development of the education and activation programme and will conduct the training of the general practitioners that will give the education and activation programme. GVDH conceived of the study, and participated in its design. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


The Millennium Ecosystem Assessment focuses on the benefits people obtain from ecosystems and aims to improve ecosystem management and contribute to human well-being and poverty alleviation Nobody questions the importance of good scientific information for sound environmental decision-making. But designing mechanisms to link scientific research to the decision-making process is no easy matter. Research and decision-making often seem to operate in different worlds. Policy-makers' needs for applied findings and best judgment typically clash with scientists' pursuit of basic research and statistical significance.Despite this challenge, as needs for scientific input into decision-making arise, a number of institutions have been established to help bridge the science–policy divide. Regulatory agencies like the United States' Food and Drug Administration have met this need in areas of public health, for example, and Environmental Impact Assessment procedures have helped to introduce better science into project-level decisions. At the scale of global environmental challenges, highly regarded mechanisms have been established such as the Scientific Assessment of Ozone Depletion, which has guided decisions by governments, the private sector, and nongovernmental organizations (NGOs), and the Intergovernmental Panel on Climate Change, which has become the authoritative source of policy-relevant information on climate science.But a significant gap remains in the landscape of institutions designed to link science with policy-making: no mechanism has existed to provide decision-makers with authoritative information on the causes and consequences of changes in the planet's ecosystems and on the options for response.Human well-being and progress toward sustainable development are vitally dependent upon improving the management of Earth's ecosystems to ensure their conservation and sustainable use. The benefits that human beings extract from nature are the foundation of all economies and the basis of major industries, are sources of knowledge, and are central to many cultures. While demands for ecosystem services such as food and clean water are growing, human actions are at the same time diminishing the capability of many ecosystems to meet these demands. And while many of the changes to ecosystems, such as increased agricultural production, have greatly enhanced human well-being, many others have not. World fisheries are now declining due to overfishing, for instance, and some 40% of agricultural land has been degraded in the past half-century. Other human-induced impacts on ecosystems include alteration of the nitrogen, phosphorous, sulfur, and carbon cycles, causing acid rain, algal blooms, and fish kills in rivers and coastal waters, along with contributions to climate change.The benefits that human beings extract from nature are the foundation of all economies and the basis of major industries, are sources of knowledge, and are central to many cultures.www.millenniumassessment.org) was launched one year later, in 2001. More than 700 authors from 80 countries are now involved in the expert working groups preparing the global assessment; 100 experts will serve on the Editorial Review Board; more than 1,000 experts will be asked to review the materials, and hundreds more are undertaking subglobal assessments as part of the MA.Recognizing the growing scale of these problems, United Nations Secretary General Kofi Annan, in his 2000 Millennium Report to the General Assembly, called for a Millennium Assessment of Global Ecosystems to provide definitive information on the consequences of ecosystem change for human well-being. With further authorization received through three international conventions  and with financial support from the Global Environment Facility, the United Nations Foundation, the David and Lucile Packard Foundation, and the World Bank, the Millennium Ecosystem Assessment (MA) (The MA focuses on ecosystem services (the benefits people obtain from ecosystems), how changes in ecosystem services have affected human well-being, how ecosystem changes may affect people in future decades, and response options that might be adopted at local, national, or global scales to improve ecosystem management and thereby contribute to human well-being and poverty alleviation .Ecosystems and Human Well-Being: A Framework for Assessment—was published in 2003 and describes the approach and methods used in the MA. The four main assessment volumes—Conditions and Trends, Scenarios, Response Options, and Subglobal Assessments—began the first of two rounds of peer review in January 2004, and the final assessment reports will be published in early 2005.The first report—Unlike previous global scientific assessments, the MA is a “multiscale” assessment. Assessments at subglobal scales are needed because ecosystems are highly differentiated in space and time and because sound management requires careful local planning and action. Local assessments alone are insufficient, however, because some processes are global and because local goods, services, matter, and energy are often transferred across regions. The MA subglobal assessments will directly meet needs of decision-makers at the scale at which they are undertaken, strengthen the global findings with on-the-ground reality, and reinforce the local findings with global perspectives, data, and models.In Southern Africa, for example, a series of community-level assessments are being conducted using the MA conceptual framework. The findings from these assessments inform, and are informed by, assessments underway in the Gariep and Zambezi river basins. These local and river basin assessments, in turn, are linked to a regional assessment encompassing the countries in the Southern African Development Community. Other subglobal assessments are now underway in such regions as São Paulo, Brazil; coastal British Columbia, Canada; the Caribbean Sea; western China; Colombia; the Sinai Peninsula, Egypt; several regions within India; Indonesia; the Laguna Lake Basin, the Philippines; Portugal; and Sweden.The ultimate impact of the MA will depend on its credibility, legitimacy, and utility. To ensure its scientific credibility, the assessment involves leading scientists from around the world and has established an independent peer-review process. To ensure the political legitimacy, all of the stakeholders—governments, the private sector, and NGOs—have a role in governing the process, and governments themselves have approved the process through decisions in international conventions. And, to ensure its utility, ongoing interactions with stakeholders are designed to ensure a focus on their questions and issues.The scientific information now available concerning ecosystems and human development holds the promise of significantly improving the choices that the public and decision-makers take concerning the environment. But for that promise to be fulfilled, a bridge needs to be built between the research community holding this information and the decision-makers seeking it. The MA is an attempt to establish that bridge.


This study uses cigarette price elasticity to evaluate the effect of a new excise tax increase on cigarette consumption and to investigate responses from various types of smokers.Our sample consisted of current smokers between 17 and 69 years old interviewed during an annual face-to-face survey conducted by Taiwan National Health Research Institutes between 2000 to 2003. We used Ordinary Least Squares (OLS) procedure to estimate double logarithmic function of cigarette demand and cigarette price elasticity.In 2002, after Taiwan had enacted the new tax scheme, cigarette price elasticity in Taiwan was found to be -0.5274. The new tax scheme brought about an average annual 13.27 packs/person (10.5%) reduction in cigarette consumption. Using the cigarette price elasticity estimate from -0.309 in 2003, we calculated that if the Health and Welfare Tax were increased by another NT$ 3 per pack and cigarette producers shifted this increase to the consumers, cigarette consumption would be reduced by 2.47 packs/person (2.2%). The value of the estimated cigarette price elasticity is smaller than one, meaning that the tax will not only reduce cigarette consumption but it will also generate additional tax revenues. Male smokers who had no income or who smoked light cigarettes were found to be more responsive to changes in cigarette price.An additional tax added to the cost of cigarettes would bring about a reduction in cigarette consumption and increased tax revenues. It would also help reduce incidents smoking-related illnesses. The additional tax revenues generated by the tax increase could be used to offset the current financial deficiency of Taiwan's National Health Insurance program and provide better public services. One of the problems in controlling tobacco in Taiwan is that cigarette prices are lower in Taiwan than in most countries ,2. In InThe smoking population increased to 4.5 million persons  in 2002 . One outBecause high excise taxes on cigarettes have been found able to reduce cigarette consumption -8, such The government should take elasticity of demand into consideration when deciding whether to increase or add an excise tax levy. If there is a price elasticity below 1, a tax increase brings about a decline in consumption and an increase in total tax revenues. Since Hsieh, Hu and Lin (1999) found that figure to be -0.6 in Taiwan, it can be reasonable to assume that a tax increase would be more likely to reduce cigarette consumption more significantly in Taiwan than in other countries with lower price elasticities at least in the short-term and medium term . Higher Taiwan's Tobacco and Wine Tax Law is currently under review in the Legislative Yuan of Taiwan. Some legislators are seeking to increase the Tobacco Health and Welfare Tax by NT $3 per pack, raising it from NT $5 to NT $8 per pack. Just as they have done in the past, cigarette sellers will probably shift the tax increase to the consumers letting them be responsible for the increase. The effect of the price increase on demand depends on cigarette price elasticity – the larger the elasticity, the larger the reduction in consumption. Therefore, an estimation of price elasticity for domestic cigarettes could be a very important indicator of the possible effect a "Tobacco Health and Welfare Tax" would have on cigarette consumption and could be used to adjust Tobacco Health and Welfare Tax accordingly.Price elasticity of cigarette in Taiwan has been mostly estimated using time-series data ,13, thouThis study uses data on current smokers from 17 to 69 years of age during years 2000 to 2003. First, the demand function of the current smokers was established. Respondents who answered "everyday" or "some of the days" to the question how often you smoke were classified as "current smokers". Then, we used a random sampling of how they consumed and how much they paid for it between 2000 to 2003 to calculate cigarette price elasticity. We then analyzed differences in cigarette price elasticity in smokers categorized according to gender, age, education, income standard, and how much they smoked.Cigarette demand function was estimated by OLS and expressed by double logarithm function. The estimated demand function we used was:Qig = α0 + β1 ln Pig + γ2 ln Iig     (1)ln whereig is i'th current smokers' logarithm representing monthly amount smokers consumed per person in group g. Current smokers were categorized according to age, gender, education, monthly income, and amount smoked. lnPig is i'th current smokers' logarithm representing cigarette price per pack (NT$) for smoking characteristics group g. lnIig is i'th current smokers' logarithm representing income per capita (NT$) for various categories of smokers in group g.lnQα0, β1, and γ2 are parameters to be estimated. In order to measure how price change might affect cigarette consumption, the determination of price elasticity was particularly important. Price elasticity of demand for cigarettes is defined as the percent change in consumption resulting from a price increase. Cigarette price elasticity of demand β1 and income elasticity of demand γ2 can be derived from logarithmically differentiation (1) according to price and income.The Using an annual face-to-face survey on cigarette consumption from 2000 to 2003 by Taiwan National Health Research Institutes, we collected data on how many packs current smokers consumed, how much they paid for a pack of cigarettes, how much they earned per month and how much they spent on cigarettes per month. Current smokers were categorized into gender, age, education, income, and amount smoked. Calculations of cigarette price were based on the average retail price of the top 3 most consumed cigarettes, calculations of number of packs smoked per month were done by dividing the monthly cigarette consumption by the average retail price. Calculations of income were based on personal monthly income.Certain background characteristics are listed in Table Cigarette consumption, retail price and personal monthly income were used in equation (1), the OLS method, to calculate cigarette price and income elasticities. The overall cigarette price elasticity was negative, less than one, indicating that cigarette consumption or demand in Taiwan was inelastic during the study period Table . Taken iAfter Taiwan's accession to WTO in 2002, Taiwan's first Tobacco Health and Welfare Tax added NT $5 the price of cigarettes, resulting in an increase in cigarette retail price from NT $35.2 in 2001 to NT $42.2 in 2002, about an NT $7 increase. In 2001, smokers 15 years old or older consumed an average 126.52 packs/person . In 2002However, the tax has been in force for two years, and a significant reduction in consumption has been shown to date. Cigarette taxes accounted for 40% of the retail price in 2002. Although forty percent sounds high, this proportion is still rather low when, as mentioned earlier, comparing it with the 66% or more of the retail price going for cigarettes prices in high-income countries (with the notable exception of the United States). ConsequInter-party negotiations at the Legislative Yuan resulted in changes to Tobacco and Liquor Tax Law which led to a NT $3 rise in the health tax levied on cigarettes, from NT$5 to NT$8 per pack. The cigarette industry is likely to pass the tax increase in the form of higher prices on to the consumer. A price increase of 3 NT per pack in cigarette would reflect a consumption reduction of 2.47 packs per capita, totaling 44.7 million packs, 2.2% per capita, in cigarette consumption. Cigarette consumption would be reduced to 2 billion packs (based on a population count of 2003), and the government tax revenue would be 33.46 billion, including the Health and Welfare Tax of 16 billion. We estimate that with a Health and Welfare Tax increase from 5 NT to 8 NT per pack, there would be a 6 billion NT increase in revenue from the Health and Welfare Tax.In 2000 and 2001, the cigarette price elasticities of the current smokers were -0.3134 and -0.3684, respectively. In 2002, it had reached its maximum of -0.5274, indicating that as cigarette prices increased, so did the price elasticity. Consumers responded to the higher prices by cutting consumption. Then in 2003, after Taiwan's accession to WTO, cigarette price elasticity then lowered to -0.309, indicating that the effect of a cigarette price hike can diminish over time.Two sets of previous data concerning the cigarette consumption, retail price and personal monthly income of the current smokers obtained during 2000–2001 and during 2002–2003, were made available to us. Using the OLS method and the rise of cigarette price in 2002 as the baseline, we computed the cigarette price and income elasticities for these two sets of data. Table Cigarette price elasticity for the male smokers reached statistically significance (5%), which was higher than the price elasticity of the female smokers, indicating that men were more responsive to price elasticity than the women. The cigarette price elasticity of the male smokers in 2002–2003 was -0.393, which was higher than -0.3107 male smokers in 2000–2001. The income elasticity of male smokers in 2002–2003 was 0.0194, reaching statistical significance (5%). There was no statistical difference found in estimated cigarette price and income elasticity of smokers among the different age sub-groups, though, according to some reports in foreign countries, teenagers are more sensitive changes to cigarette prices than adults -17.Education level seemed to make a difference. The price elasticity smokers with junior high school educations was -0.5766 in 2000–2001, which was higher than that of senior high school level smokers, -0.2772. In 2002-2003, the price elasticity of college level smokers was -0.7007, which was higher than that of the smokers of senior high school level, -0.5369. Therefore, between 2000 and 2001, the more educated group had a larger price elasticity, though the less educated group had the higher coefficient in 2002–2003. Our findings cover two time spans and are different from those reported by foreign researchers who have found that consumers at lower education levels respond stronger to the change of cigarette price . In our In this study, we evaluate the effect of a new tax on the consumption of tobacco by calculating the cigarette price elasticities of various kinds of smokers and comparing those values with their reactions to an increase cigarette, and then using knowledge gained from that study, we assess the possible effect of another increase on consumption. We found that the new tax scheme implemented after Taiwan joined the WTO reduced cigarette consumption by 13.27 packs/person (10.5%). We estimated that an additional NT $3 increase in Taiwan's Health and Welfare Tax would reduce cigarette consumption here by 2.47 packs/person (2.2%).In this study, cigarette price elasticity was less than one, meaning that in addition to reducing cigarette consumption, an additional tax would also generate additional tax revenues. Continuing price increases should reduce cigarette consumption significantly. Provided that the tax increases are proportionately larger than the resulting reduction in cigarette consumption, cigarette tax revenues will increase and can be used to reduce current National Health Insurance deficits and possibly reduce the damage and death caused by smoking related diseases.Based on estimated cigarette price elasticities for various kinds of current smokers, we found that male smokers without income and light smokers were more sensitive to changes in cigarette prices. Teenagers (17 – 24 years old), however, were not found to be significantly influenced by the change in cigarette price, which means it will take more than just tax increases to decrease consumption among our youth. Schools will need to commit to preventive education by inculcating the students with the knowledge of tobacco hazards. Only through early preventive education starting from their childhood can we expect to see significant reduction in cigarette consumption.Finally, the R-squared statistics of the each empirical estimation was below 0.1 for probably sake of to calculate elasticity and exclude variables like advertisement. Future research should also attempt to include these factors with cigarette demand function.The author(s) declare that they have no competing interests.JML performed physical measurements, collected data, and drafted the manuscript. TCH reviewed the manuscript. CYY and SHC carried out the statistical analysis and participated in data collection. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Our sense of taste begins with taste buds and ends in the brain. Researchers are beginning to unravel the mechanisms and connections that lie in between The ability to taste food is a life-and-death matter. Failure to recognise food with a high enough caloric content could mean a slow death from malnutrition. Failure to detect a poison could result in near-instant expiration. And now, as researchers begin to understand some of the nuts and bolts of taste perception, it seems that the sense of taste may also have more subtle effects on health.At the front line of the taste sensory system are the taste buds—onion-shaped structures on the tongue and elsewhere in the mouth . Up to 1Taste is the sense by which the chemical qualities of food in the mouth are distinguished by the brain, based on information provided by the taste buds. Quality or ‘basic taste’, explains Bernd Lindemann, now retired but an active taste researcher in Germany for many years, is a psychophysical term. Large numbers of people describe different tastants and then statistical analyses are used to define the important tastes. ‘The number of taste qualities has varied over the years’, says Lindemann. ‘We are now settling at around five, though I would not be surprised if some additional qualities pop up’.The five qualities that Lindemann refers to are salty, sour, bitter, sweet, and umami, the last being the Japanese term for a savoury sensation. Salty and sour detection is needed to control salt and acid balance. Bitter detection warns of foods containing poisons—many of the poisonous compounds produced by plants for defence are bitter. The quality sweet provides a guide to calorie-rich foods. And umami (the taste of the amino acid glutamate) may flag up protein-rich foods. Our sense of taste has a simple goal, explains Lindemann: ‘Food is already in the mouth. We just have to decide whether to swallow or spit it out. It's an extremely important decision, but it can be made based on a few taste qualities’.Taste has been actively researched for many decades. During the 20th century, electrophysiologists and other researchers worked hard to understand this seemingly simple sense system. Then, in 1991, the first olfactory receptors were described. These proteins, which are exposed on the surface of cells in the nose, bind to volatile chemicals and allow us to detect smells. This landmark discovery, in part, encouraged many established taste researchers to investigate the molecular aspects of taste.The olfaction results also enticed researchers from other disciplines into the taste field, including collaborators Charles Zuker  and Nick Ryba . About six years ago, explains Zuker, who previously worked on other sensory systems in flies, ‘there was a disconnect between our understanding of sensations in the case of photoreception, mechanoreception, touch, and so on and what we knew about taste’. There was evidence, says Ryba, that a class of protein receptors called G-protein-coupled receptors (GPCRs) were involved in sweet and bitter taste, ‘but the receptors weren't known, so we started to look for them …. These molecules are intrinsically interesting, but more importantly, they provide tools with which we can dissect out how taste works’.The bitter receptors fell first to the onslaught of the UCSD–NIDCR team and other molecular biologists. In 1999, the ability to taste propylthiouracil, a bitter tasting compound, had been linked to a locus on human Chromosome 5p15. Reasoning that this variation might be due to alterations in the coding sequence for a bitter receptor, the UCSD–NIDCR researchers used the draft of the human genome to search for sequences that resembled GPCRs on Chromosome 5p15. ‘That was how we found T2R1, the first bitter receptor, and, subsequently, a whole family of T2Rs’, says Zuker.Researchers want to know: how is taste coded?All these receptors, says Zuker, are coexpressed in bitter taste receptor cells, a result that contradicts other research showing that different bitter-responsive cells react to different bitter molecules. ‘To me’, says Zuker, ‘it makes sense that all the bitter receptors would be expressed in each bitter taste cell. We just need to know if something is bitter to avoid death’, not the exact identity of the bitter tastant.Sac locus, which determines the ability of mice to detect saccharin, and T1R3, a third member of the T1R family. The UCSD–NIDCR team subsequently showed that the T1R2 and T1R3 heterodimer (a complex of one T1R2 and one T1R3 molecule) forms a broadly tuned sweet receptor, responsive to natural sugars and artificial sweeteners, and that a homodimer of two T1R3 molecules forms a low-affinity sugar receptor that responds to high concentrations of natural sugars only. All sweet detection, concludes Zuker, is via the T1R2 and T1R3 receptors.The sweet receptor story started in 1999 with the identification of two putative mammalian taste receptors, GPCRs now known as T1R1 and T1R2. In early 2001, four groups reported an association between the mouse And umami? A truncated glutamate receptor was identified as an umami receptor by researchers at the University of Miami  School of Medicine in 2000. Zuker, however, believes that the one and only umami receptor is a heterodimer of T1R1 and T1R3. In October 2003, Zuker and his coworkers reported that mice in which either T1R1 or T1R3 has been knocked out show no preference for monosodium glutamate (MSG), an umami tastant. However, other researchers reported in August 2003 that T1R3 knockouts retain some preference for MSG. ‘We believe this is due either to the truncated glutamate receptor or another unknown receptor’, says lead author Sami Damak . Damak says he does not know why the two sets of T1R3 knockout mice behaved differently, but the UCSD–NIDCR researchers suggest that the residual response to MSG seen by Damak et al. is a response to the sodium content of MSG. Damak is not alone, however, in thinking there may be more than one umami receptor .Commenting on these recent discoveries, taste expert Linda Bartoshuk  says that ‘it is lovely to see all these details, especially as they confirm what we already believed conceptually’. For example, she says, it is no surprise that there are many bitter receptors but probably only one sweet receptor. ‘There are so many poisons and it makes perfect sense to have lots of receptors feeding into a common transduction pathway. Sweet is a different problem. In nature, there are many molecules with structures similar to sugar that we must not eat because we cannot metabolise them. So I would have predicted one or at most a few highly specific sweet receptors’.The salty and sour receptors may be very different from the GPCRs involved in bitter, sweet, and umami perception, which bind complex molecules on the outside of the cell and transmit a signal into the cell. For salty and sour perception, the taste cell only needs to detect simple ions. One way to do this may be to use ion channels—proteins that form a channel through which specific inorganic ions can diffuse. Changes in cellular ion concentrations could then be detected and transmitted to the nervous system.Physiologist John DeSimone  says there are at least two ion channel receptors for salt in rodent taste receptor cells. The first of these is the epithelial sodium channel, a widely expressed channel that can be blocked specifically with the drug amiloride. In rats, says DeSimone, only 75% of the nerve response to salt can be blocked by amiloride, so there is probably a second receptor. This, he says, seems to be a generalist salt receptor—the amiloride-sensitive channel only responds to sodium chloride—and may be the more important receptor in people.Sour tastants are acids, often found in spoiled or unripe food. DeSimone's current idea is that strong acids enter taste cells through a proton channel (probably a known channel present on other cell types) while weak acids, like acetic acid (vinegar), enter as neutral molecules and then dissociate to lower intracellular pH. DeSimone believes that he has identified the proton channel involved in sour taste as well as an ion channel that could be the second salt receptor, and he plans to do knockout experiments on both. If these channels are essential elsewhere in the body, as DeSimone suspects, to avoid lethality he will need to construct conditional knockouts in which the channel is lost only in the taste receptor cells.Zuker, meanwhile, is not convinced that the current ion channel candidates for salt and sour perception are correct. And, he says, GPCRs could also be involved in these modalities. ‘There is a precedent for that’, he claims, noting that extracellular calcium is sensed by a GPCR.With many taste receptors now identified, researchers are turning to a long-standing question in taste perception: how is taste coded? When we eat, our tongue is bombarded with tastants. How is their detection and transduction of information organised so that the appropriate response is elicited? Taste physiologist Sue Kinnamon  explains the two theories of taste-coding. In the ‘labelled-line’ model, sweet-sensitive cells, for example, are hooked up to sweet-sensitive nerve fibres that go to the brain and code sweet. If you stimulate that pathway, says Kinnamon, ‘you should elicit the appropriate behavioural response without any input from other cell types’. In the ‘cross-fibre’ model, the pattern of activity over many receptors codes taste. This model predicts that taste receptor cells are broadly tuned, responding to many tastants. Support for this theory, says Kinnamon, comes from electrical recordings from receptor cells and from nerves innervating the taste buds that show that one cell can respond to more than one taste quality.Zuker and Ryba's recent work strongly suggests that taste-coding for bitter, sweet, and umami fits the labelled-line model in the periphery of the taste system. Their expression data show that receptors for these qualities are expressed in distinct populations of taste cells. In addition, in early 2003, they reported that, as in other sensory systems, a single signalling pathway involving the ion channel TRPM5 and PLCβ2, a phospholipase that produces a TRPM5 activator, lies downstream of the bitter, sweet, and umami receptors. When the UCSD–NIDCR researchers took PLCβ2 knockout mice, which did not respond to bitter, sweet, or umami, and engineered them so that PLCβ2 was only expressed in bitter receptor-expressing cells, only the ability to respond to bitter tastants was regained. These data, says Zuker, support the labelled-line model.The latest data supporting the labelled-line model came last October when Zuker and colleagues described mice in which a non-taste receptor—a modified κ-opioid receptor that can only be activated by a synthetic ligand—was expressed only in cells expressing T1R2, sweet-responsive cells. The mice were attracted to the synthetic ligand, which they normally ignore, indicating that dedicated pathways mediate attractive behaviours. The researchers plan similar experiments to see whether the same is true for aversive behaviours.Even with all these molecular data, the cross-fibre model of taste-coding still has its supporters—just how many depends on whom one talks to. Both Damak and Kinnamon, for example, believe that there is at least some involvement of cross-fibre patterning even in the taste receptor cells. But, says neurobiologist and olfaction expert Lawrence C. Katz , ‘the onus is now on people who believe otherwise [than the labelled-line model] to provide compelling proof for the cross-fibre theory because now, at least at the periphery, the evidence is compelling for a labelled line for bitter, sweet, and umami’. Bartoshuk also says the debate is decided in favour of the labelled-line model in the periphery. The crossfibre model is an interesting historical footnote, she comments.Whether this putative link between taste perception and health can be confirmed and whether it will be possible to manipulate food preferences to improve health remain to be seen. However, it seems certain that, as in the past five years, the next five years will see large advances in our knowledge of many aspects of taste, a fascinating and important sensory system.The periphery of the taste sensory system has yielded many of its secrets, but relatively little is known about the transduction pathways in taste, how taste cells talk to the nervous system, or about events further downstream in the brain. How are signals from taste receptors integrated with those from olfactory receptors to form a representation of complex food flavours, for example? With their expanding molecular toolbox, researchers can now delve deeper into these aspects of taste perception. This may tell us not only about taste but about how the nervous system in general is put together, says Ryba.But understanding taste is not just an academic exercise. It has practical uses too. DeSimone suggests that by understanding salt receptors, it may be possible to design artificial ligands to help people lower their salt intake. As Kinnamon succinctly puts it, ‘Can you imagine eating potato chips and not having the salty component?’ An artificial salt receptor ligand could make salt-free foods a palatable option for people with high blood pressure. Lindemann also sees a great future in artificial ligands for taste receptors. The sense of taste is partly lost in elderly people, he says, so better tastants—effectively ‘chemical spectacles’—might give them back their pleasure of eating and thereby improve their quality of life.Finally, some aspects of taste may be inextricably tied up with general health, says Bartoshuk. Many people who can taste propylthiouracil are also ‘supertasters’—they have more fungiform papillae, structures containing taste buds, on their tongues than non-tasters . Superta


The Mammalian Phenotype (MP) Ontology enables robust annotation of mammalian phenotypes in the context of mutations, quantitative trait loci and strains that are used as models of human biology and disease. The Mammalian Phenotype (MP) Ontology enables robust annotation of mammalian phenotypes in the context of mutations, quantitative trait loci and strains that are used as models of human biology and disease. The MP Ontology supports different levels and richness of phenotypic knowledge and flexible annotations to individual genotypes. It continues to develop dynamically via collaborative input from research groups, mutagenesis consortia, and biological domain experts. The MP Ontology is currently used by the Mouse Genome Database and Rat Genome Database to represent phenotypic data. Mammalian phenotypes are complex and the term itself is imprecise. Generally, we use the word phenotype in referring to the appearance or manifestation of a set of traits in an individual that result from the combined action and interaction of genotype and environment.Because mouse is the premier model organism for the study of human biology and disease, the goal of comparative phenotyping and building new animal models through genetic engineering holds great promise. The mouse has distinct advantages for studies that translate to humans. It is a small, short-lived mammal with a fully sequenced genome in which all life stages can be accessed, and for which myriad tools are available for precisely experimentally manipulating its genome. Further, the large collection of inbred strains of mice and the controlled environment in which the animals live provides the ability to confirm phenotype observations and to systematically perturb environmental factors and genetic input to measure effects under defined conditions. Current international efforts to 'make a mutation' for every gene through mutagenesis  and geneMammalian phenotypes are frequently genetically complex. Mutation of even a single gene almost always produces pleiotropic effects. Conversely, non-allelic mutations can produce indistinguishable phenotypes. Modifier genes and epistatic interactions can markedly alter the phenotype. Combining different allelic combinations of different genes can produce unique phenotypes not found in the single-gene mutation genotype. Imprinting of genes can dramatically affect phenotype. Mutations expressed in different inbred strains of mice can manifest as an increase or decrease of severity or penetrance of the corresponding phenotype. Quantitative trait loci (QTL) can contribute in complex nonlinear ways to the phenotype. In addition, mutations that are 'genomic' in nature, either disrupting or deleting multiple genes or occurring in intergenic regions, can produce distinct phenotypes and challenge us to think beyond gene effects to genomic effects. The outcome of these complex interactions can be dissected and reproducibly examined by characterizing inbred strains that represent the combined phenotype of the 'whole-genome' genotype in its environmental context.The Mouse Genome Database (MGD) at the Mouse Genome Informatics website ,5 servesWritten descriptions of phenotypes in higher organisms reflect the complexity of the subject, the richness of language, and the phenomenal diversity that these data represent. While text descriptions are commonly used in publications describing phenotype, and have been the basis of electronically accessible phenotypic descriptions   and the Consider the example in Table A further detriment to database text records is their difficulty to update and maintain. As new information is learned about a phenotypic mutant, the record must be continually rewritten. Although this practice might be sustained for a small number of records, it does not scale when thousands of mutant records are considered. The alternative of simply adding on another paragraph to existing text records becomes confusing, with potentially conflicting information and different writing styles appearing in one textual description, and unwieldy, with more and more text that may no longer represent a logical synthesis.Formal nomenclatures for genes, mutant alleles and inbred strains of mice have existed since the 1940s ,9. The MBeyond nomenclatures, which are key to object identities and relationships, are vocabularies that can be used to describe broader concepts and categorizations. Vocabularies can take many forms, including simple lists of controlled terms, such as the cytogenetic band designations used to name the bands defined by chromosome staining or the classes of genetic markers, such as gene, pseudogene, expressed sequence tag (EST), and so forth.The annotation of complex biological data and concepts requires more than lists and simple vocabularies. Ontologies, or 'descriptions of what there is', contain both concepts, with precise meanings, and relationships among those concepts. As such ontologies are able to support descriptions of complex biology and are useful in making these data more amenable to computational analyses. The first widely used ontology developed and adopted in the biological domain is the Gene Ontology (GO) -13 whichAlthough the need for vocabularies as key components to consistent phenotype annotations for mammals has been recognized for some time , and manOur goal is to describe the richness of phenotypes as precisely as they are known, recognizing that phenotype data are by nature complex and usually incomplete. Taking advantage of structural properties of a DAG, we have the ability to annotate phenotypes to the level of data resolution available, whether general or very specific and the ability to query with a high-level term, returning all phenotypes containing annotations to that term or to terms more specific than the query term. Thus, one can query for 'respiratory signs/symptoms' and retrieve all phenotypes annotated to this term and its hierarchical 'children' , or specifically request annotations to any of these sub-terms.The top level terms of the MP Ontology include physiological systems, behavior, developmental phenotypes and survival/aging. Physiological systems branch into morphological and physiological phenotypes at the level immediately below. A browser to view the ontology is available at  Figure . In thisEach MP ontology term has a unique identifier, a definition and synonyms. In the term detail pages, these data and the number of hierarchical paths of the vocabulary where the terms appear are displayed. A plus sign following the term indicates that children of this term exist. In this figure, displayed next to the term, is a link indicating the number of annotation instances in MGD using this term or children of this term. This feature, due to be publicly available in early 2005, will greatly improve phenotype-centric searching in MGD.To initiate the vocabulary, we first developed a high-level categorization of phenotypes consisting of approximately 100 terms, such as heart/cardiovascular dysmorphology and skeletal axial defects. As we used this list for annotations, terms were refined and general organizing principles for the MP vocabulary were developed.An important component of our approach has been to address two practical implementation questions. From the biologist's perspective, the question is what term would be used to describe a specific phenotypic trait. From the curation perspective, we ask what terms reflect biological reality and maximize curator productivity.From a purely ontological perspective, every trait could be broken down into a core object, such as 'cornea' or 'gastrulation', defined by anatomical, behavioral or physiological terms, and a series of attribute vocabularies that describe the quality, quantity and character of a trait. For the practical reason of needing robust terms to describe phenotypes up-front to speed curation and the problem of losing biological meaning, particularly for clinical or dysmorphology terms, when terms are completely deconstructed , we have chosen to use compound terms in the MP Ontology. A few examples of terms where it is difficult to preserve the full biological meaning once they are deconstructed are shown in Table pheno@informatics.jax.org.Three major strategies are being pursued to further develop the vocabulary itself. First and most important is through the ongoing process of curating phenotype data. As new phenotypic traits are described and published, the need for new terms is recognized. New terms added in this way may be a simple addition to an existing hierarchical path or may result in the addition of entire new branches in the hierarchy. Second, collaborative efforts between the MGD phenotype curators, the mouse mutagenesis centers and the rat genetics community identify new specific terms and suggest improved organization of terms within particular hierarchical branches. Third, we are recruiting individuals with expertise in specific biological domains to review and evaluate sections of the vocabulary for accuracy, completeness and systematic arrangement. The MP Ontology is a work in progress and remains incomplete in some areas. We welcome the participation of the mammalian research community so that the most useful, definitive and universally applicable terms will be included. Information can be obtained by sending e-mail to While common pathological and clinical terms are used in the MP Ontology, considerations for term placement within the structure and for precise terminology is often derived from comparison with other open biological ontologies (OBO) . RecentlThe MP Ontology was built as a DAG using the DAG-Edit software written by John Richter and Suzanna Lewis . The MP Phenotypes are described in the MGD relative to the genotype of the individual. Genotype objects specifically consist of one or more allele pairs describing mutations or QTLs and the genetic background strain(s) where the phenotype was observed. Each phenotype annotation associates a MP Ontology term with a genotype/strain and the reference or data source supporting this assertion. Additional modifying text may be annotated to describe detail that is not easily standardized. Examples include experimental conditions, age of onset and incidence, and trait penetrance, among others. The annotation note may also include specifics of the phenotype where such details are deemed to be too case specific to be a MP term. In addition, genotypes are associated with OMIM where a particular mouse genotype is a model for human diseases and syndromes. Figure The MP Ontology and annotation schema was designed to minimize curatorial time, yet remain precise enough to describe phenotypic data. It supports robust phenotypic annotations and querying capabilities for mouse phenotype data. While this vocabulary is far from complete, we have designed strategies for its continued development as a collaborative effort for supporting the representation of existing mutations and those that continue to be created.As of 1 November 2004, over 11,150 phenotypic alleles representing mutations in 5,214 unique genes had been catalogued in MGD. For these alleles, 9,696 genotype records exist, with 21,556 phenotypic annotation instances. The MP Ontology is also used in phenotypic data annotations at the RGD . As our


In the recent years, several cytokines have been associated with Alzheimer's disease (AD) development and progression and many studies have correlated this risk with polymorphisms in the genes encoding these molecules. Also the type 1 cytokine interferon (IFN)-γ belongs to a cytokine class that affects the immune function; in fact it plays a major role in defence against viruses and intracellular pathogens but also in the induction of the immune-mediated inflammatory response. The aim of this study was to evaluate the role of IFN-γ in AD by studying the association of +874T→A IFN-γ gene polymorphism with AD. We included in this study 115 AD patients  and 90 sex and age-matched healthy controls  from northern Italy. Genomic DNA was extracted with the salting-out method from whole blood of all subjects; the genotyping at IFN-γ loci was assessed with ARMS-PCR. The data obtained from the +874T→A IFN-γ gene polymorphism analysis of AD patients and HC lack of any statistically significant differences also when stratified according to gender. In conclusion these results confirm the previous shown lack of association between +874T→A IFN-γ gene polymorphism and the risk of AD. However, other polymorphisms have been demonstrated to influence IFN-γ transcription and since natural killer cells of AD patients show higher production of the cytokine, further analysis will be necessary to clarify the role of this gene in the pathogenesis of the disease. In the human brain several cell types are responsible for initiating and amplifying a specific inflammatory response. In Alzheimer disease (AD) signs of an inflammatory activation of microglia and astroglia are present both inside and outside amyloid deposits. Cell cultures and animal models suggest an interactive relationship between inflammatory response activation, reduced neuronal functioning and amyloid deposition. Furthermore cells associated with extracellular plaques within AD brains can produce a variety of cytokines, chemokines and other related proteins that influence plaque and tangle formation . For the


The TM4SF10 gene encodes a putative four-transmembrane domains protein of unknown function termed Brain Cell Membrane Protein 1 (BCMP1), and is abundantly expressed in the brain. This gene is located on the short arm of human chromosome X at p21.1. The hypothesis that mutations in the TM4SF10 gene are associated with impaired brain function was investigated by sequencing the gene in individuals with hereditary X-linked mental retardation (XLMR).The coding region (543 bp) of TM4SF10, including intronic junctions, and the long 3' untranslated region (3 233 bp), that has been conserved during evolution, were sequenced in 16 male XLMR patients from 14 unrelated families with definite, or suggestive, linkage to the TM4SF10 gene locus, and in 5 normal males.Five sequence changes were identified but none was found to be associated with the disease. Two of these changes correspond to previously known SNPs, while three other were novel SNPs in the TM4SF10 gene.We have investigated the majority of the known MRX families linked to the TM4SF10 gene region. In the absence of mutations detected, our study indicates that alterations of TM4SF10 are not a frequent cause of XLMR. Caenorhabditis elegans VAB-9 protein, a protein that has recently been shown to be involved in the control of cell adhesion and epidermal morphology [Brain Cell Membrane Protein 1 (BCMP1) cDNA was fortuitously isolated from a thyroid cDNA library [rphology . The proInitial Northern blot analysis of TM4SF10/BCMP1 gene transcripts distribution in adult dog tissues revealed very high expression in the brain, and lower but clearly detectable levels of expression in most of the tissues examined  confirmeInitially, the TM4SF10 gene was assigned to Xp11.4 . Recent Blood genomic DNA was collected from 16 patients (14 unrelated) and 5 unrelated healthy volunteers using a standard procedure . The patPCR reactions were performed in a final volume of 100 μl containing 200 ng of genomic DNA, 1 μg of each primer  on an Applied Biosystems 3100 automatic DNA sequencer. The sequences of the primers are given in table rd base of the codon Arg59, where a C residue was present in half of the sequences and a G residue in the other half. Individual single nucleotide polymorphism (SNP) data are shown in table The human TM4SF10 gene is composed of 3 exons and produces a 4 kb-long mRNA. The short coding region (543 bp) is interrupted by 2 introns and the last and the largest exon also contains a 3 233 bp-long 3'UTR (see Figure The long 3'UTR sequence of the TM4SF10/BCMP1 transcript is highly conserved, with an overall score of 72% when human, dog, mouse and rat sequences are compared. As the 3'UTR of mRNAs may contain regulatory sequences that participate in the control of gene expression, we decided to screen this part of the gene as well. The entire region, including the sequences around the polyadenylation site, was subdivided into four overlapping fragments of approximately 1 kb in length (3'UTR F1–F4, Figure TM4SF10 sequence was obtained from 16 patients and 5 controls. Four SNPs were identified in the non-coding part of the gene: 3 of them were located in the 3'UTR of the mRNA while the fourth one was located downstream of the polyadenylation site (Figure In this study, we have investigated the majority of the known MRX families linked to the TM4SF10 gene region. In the absence of mutations detected, our results indicate that alterations in the transcribed region of TM4SF10 are not a frequent cause of XLMR. Although the gene promoter has not been identified and screened yet, it appears very unlikely that all mutations would be there.This work also identified three novel SNPs in the TM4SF10 gene, which adds to our knowledge of SNP occurrence within this gene.None declared.CCH performed/managed the PCR and sequencing reactions, and analyzed the DNA sequences. FK, JG, MJA, EHF and CS provided the DNA samples. These authors also participated in the writing of the manuscript. DC conceived and supervised the study, and drafted the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Chemical reactions lie at the heart of many biological processes, from photosynthesis and respiration to cell signaling and drug metabolism. Thanks to an atmosphere rich in oxygen, many organisms use oxygen to carry out these life processes. But oxygen metabolism produces highly toxic by-products called reactive oxygen species. When oxidation outpaces detoxifying reactions, oxidative stress occurs, and accumulating reactive oxygen species are free to wreak havoc on cellular machinery.PLoS Biology, Lars Leichert and Ursula Jakob describe a novel method to monitor thiol modifications in proteins subjected to varying redox conditions in a living organism, the bacteria Escherichia coli. This technique is capable of providing a global snapshot of the redox state of protein cysteines during normal and oxidative stress conditions in the cell.Cysteine, one of the 20 different amino acids that make up proteins, contains a thiol group, which can be modified upon oxidation. A thiol group can stabilize protein structures by forming covalent disulfide bonds and can mediate cysteine-regulated redox reactions. At the same time, however, the high reactivity of thiol groups makes them also particularly vulnerable to nonspecific reactions during conditions of oxidative stress. Over the past few years, an increasing number of proteins have been discovered that use oxidative thiol chemistry to regulate their protein activity. In E. coli periplasm (the region between the cell's membrane layers), and they were.To detect proteins that have the ability to undergo stress-induced thiol modifications, Leichert and Jakob differentially labeled the thiol groups of thiol-modified and non-thiol-modified proteins. The proteins were then separated on two-dimensional gels based on their charge and molecular weight. If the technique worked, most thiol-modified proteins should be detected in the oxidizing environment of the E. coli periplasm—was targeting. In E. coli mutant strains that lack DsbA, Leichert and Jakob identified a number of proteins with either substantially less or no thiol modification as compared to wild-type (non-mutant) strains, suggesting that these proteins are indeed DsbA substrates.After proving the method's ability to detect proteins whose thiol groups were oxidized, the next logical step was to determine what proteins DsbA—the enzyme that catalyzes disulfide bond formation in the E. coli cytoplasm contains several reducing systems. When the researchers tested a mutant strain that lacked the gene for the reducing enzyme thioredoxin, they found that a large number of proteins accumulated in an oxidized state. Many of these proteins have cysteines and require a reduced thiol status for their activity. These results demonstrated that under normal growing conditions, many proteins contain cysteine residues that are vulnerable to even small amounts of reactive oxygen species and so require the constant attention of detoxifying enzymes.In contrast to the periplasm, the In a final set of experiments, Leichert and Jakob discovered a number of proteins whose thiol groups get specifically modified in the presence of reactive oxygen species. These results start to explain some of the many metabolic changes that occur in oxidatively stressed cells.Leichert and Jakob's technique should be applicable to many different cell types and organisms and can be used to investigate the in vivo thiol status of cellular proteins exposed to virtually any physiological or pathological condition that is accompanied by oxidative stress. The next step will be to investigate just how thiol modifications mediate the various functions of redox-regulated proteins.


Science, Stuart Kim, a Stanford developmental biologist, made the case for laying down the broad strokes of a complex physiological process before defining its mechanisms. “A powerful, top-down, holistic approach,” he wrote, “is to identify all of the components of a particular cellular process, so that one can define the global picture first and then use it as a framework to understand how the individual components of the process fit together.” To get a broad view of gene expression in the aging nematode, Kim's lab turned to DNA microarrays and functional genomics. In a new study, Kim and colleagues apply this same approach to the decidedly more complex problem of human aging and “present a molecular portrait” of the aging kidney.Four years ago in Scientists have identified a wide range of molecular pathways and mechanisms associated with aging. Many have been found in evolutionarily distant organisms, suggesting they have been conserved and could shed light on human aging. Yet other studies suggest that since few animals reach old age in the wild, any aging-related physiological changes aren't likely to impact the fitness of a population and so aren't likely to be conserved. Consequently, aging pathways in worms, for example, would have little bearing on humans. To investigate the molecular pathways associated with human aging, the authors focused on human tissue—in this case, the kidney.Kidneys came from 74 patients, ranging in age from 27 to 92. Samples were extracted from donated kidneys or “meticulously harvested” from kidneys with localized disease to ensure only normal tissue was taken. Two structures that are critical to kidney function (removing toxins from blood) were removed from each sample: the renal cortex, which filters plasma, and the medulla, which alters urine composition to maintain fluid balance. Both deteriorate with age. An extensive clinical history was noted for each sample to account for any potentially confounding medical factors.Kim and colleagues then isolated RNA transcripts from the samples to determine the activity of every gene, broken down by age and kidney section, through microarray analysis. Looking for differences in gene expression across the genome, they identified genes that showed a statistically significant change in expression as a function of age. Of 33,000 known human genes on the microarray, 985 showed age-related changes, most showing increased activity. These changes are truly age-regulated, the authors conclude, since none of the medical factors impacted the observed changes in gene expression.Although cortex and medulla have different cell types and perform different functions, their genetic aging profile was very similar, suggesting a common aging mechanism operates in both structures. In fact, these mechanisms may function broadly, as most of the age-regulated kidney genes were also active in a wide range of human tissues. Other organisms appear to lack these changes, however, prompting the authors to argue that understanding aging in humans will require human subjects.Most importantly, the genetic profile of the tissue samples correlated with the physiological and morphological decline of an aging kidney. An 81-year-old patient with an unusually healthy kidney had a molecular profile typical of someone much younger, while a 78-year-old with a damaged kidney had the profile of a much older person. Using the power of functional genomics, this study has identified a set of genes that can serve as molecular markers for various stages of a deteriorating kidney and predict the relative health of a patient compared to their age group. These gene sets can also serve as probes to shed light on the molecular pathways at work in the aging kidney, and possibly on the process of aging itself.


Although the poles are less diverse than the tropics, this decline shows substantial asymmetries between the hemispheres, suggesting that responses to environmental change may differ substantially in the north and the south. Penguins have been receiving a lot of bad press lately. They are considered somehow counter, spare, strange. Unlike most plant and animal groups, they do not show a peak of species richness towards the equator and a decline towards the poles. This more conventional spatial pattern is conveniently known as the latitudinal diversity gradient because of the strong covariance of richness and other measures of biodiversity that it describes. It is one of the most venerable, well-documented, and controversial large-scale patterns in macroecology . EquatorAlthough spatial patterns in biodiversity, and particularly the latitudinal gradient, are increasingly well documented for a range of taxa, the proposed mechanisms underlying these gradients remain controversial. In essence, the multitude of mechanisms proposed to explain diversity gradients can be reduced to three categories: historical, ecological, or null. Most significant in raising the temperature of recent discussions is the question of the relative importance of each of these major categories. Historical mechanisms are those that suggest that earth history  and phylogenetic history have played major roles in generating current patterns in diversity, and tend to emphasise regional  differences therein . ExplanaNonetheless, juxtaposing these three major mechanisms raises several questions that could substantially inform the debate in many ways, but have enjoyed far less attention than debating the relative merits of each of them. The geometric constraints model suggests that, to the extent that there is symmetry in the continuity of land (or water) about the equator, declines in richness from the tropical peak should also be symmetrical, with any asymmetries in the latter matching those in the former. Indeed, most texts and reviews dealing with latitudinal diversity gradients only briefly mention hemisphere-related differences and focus instead on the general decline of diversity away from the tropics in both directions e.g., . HoweverThe last 100 million years have seen both a substantial steepening in latitudinal diversity gradients and the fragmentation of continental land masses . By 15 mMean annual precipitation is spatially more complex. Overall, precipitation is slightly higher in the south than in the north, at least below 60° latitude. However, much of this precipitation falls over the ocean in the south, leaving the more temperate parts of the southern continents as dry as their northern counterparts . SpatialClearly, the spatial complexity of climatic variation is much greater than the present overview would suggest. However, these broad brush strokes capture the hemisphere-related variation that might be most significant from a biological perspective.If differences in climates do cascade upwards to influence individuals, species, and broader scale patterns in diversity, their influence should be readily detectable at the level of species' life histories and distributions. In birds, large-scale geographic variation in life history variables, such as the incidence of cooperative breeding, extent of parental care, survival, and the timing of reproduction, has been studied for at least the past 50 years, and the mechanisms underlying this variation have been much debated. Taking phylogeny and the idiosyncrasies of the Australian avifauna into account, southern species typically lay small clutches and have long fledging periods, and it is often difficult to predict their date of first laying or, indeed, whether they will lay in a particular year at all . By contThese kinds of differences extend to other taxa. Thus, although the variation of metabolic rate with latitude is becoming increasingly well known for a variety of groups, Insect life histories also show hemisphere-related variation. Low-temperature-related diapause is virtually absent in southern species e.g., , and metNorth–south asymmetries also show up in snowlines, treelines, the frost tolerance of trees, and the proportion of winter deciduous species . Indeed,In the years since By contrast, it appears that proximate ecological correlates of diversity gradients differ considerably between north and south. Although both historical and ecological factors have led to variation in the numbers and identity of species across the globe , climateOf course, biodiversity is not just species richness, but also encompasses the ecological complexes of which species are a part. Although potential north–south asymmetries in interactions have not been widely explored, recent work is providing tantalising glimpses of such variation. Thus, it appears that on the basis of a straightforward  comparative analysis, specialisation in plant–pollinator relationships is much greater in the south than in the north. European and North American orchids are typically visited by five species of insects, whereas in southern Africa the median is a single pollinator species per species of orchid  Figure . Insect–Despite considerable spatial complexity, there do seem to be regular north–south differences in species life histories and patterns of range size variation that are consistent with disparities in the climates of the two hemispheres . These dFirst, both phylogenetically independent and non-independent comparisons of life history traits and physiological variables across a variety of groups are required. Contrasting these approaches will provide considerable insight into how much of the signal is based on phylogenetic patterns, and how much on current ecological responses. Whilst in some cases data may be obtained from the literature, it is likely that new work will have to be undertaken, especially in the southern hemisphere, where the number of past investigations of such traits is generally much lower than in the north. Moreover, replicated studies using similar methods might substantially improve the signal-to-noise ratio, which can be weakened in “macrophysiological” or large-scale life history and physiological comparisons by the fact that different methods often lead to different outcomes.Second, there is much to be said for the application of similar methods to investigations of large-scale, hemisphere-related patterns of species interactions. Differences like those in plant–pollinator systems discussed here might extend to other interactions in marine and terrestrial systems. Contrasting phylogenetically independent and non-independent comparisons are likely to provide much insight into the reasons for those asymmetries that are found.Finally, comparisons of latitudinal gradients and their underlying correlates in the two hemispheres for the same taxon, sampled using similar methods, and investigated with methods that take cognisance of likely confounding effects are required. This approach will provide a means of determining whether asymmetries in the climates of the two hemispheres really do translate into differences in biodiversity patterns. Such an approach goes to the heart of the question of the processes underlying the latitudinal gradient in species richness, and could go a considerable way to teasing apart the importance of historical, ecological, and null explanations, and identifying the mechanisms that underlie them.In our view, clarifying these issues is of considerable importance. What is at stake is not a set of arcane ecological questions, but rather questions that are central to determining whether ecological and conservation lessons learnt in one area can be applied more broadly. For example, it has been suggested that climate change will cause substantial extinctions in the near future . Indeed,