The clinical doses of cannabidiol are sufficient to occupy the functional D2High sites. it is concluded that the dopamine partial agonist action of cannabidiol may account for its clinical antipsychotic effects.Although all current antipsychotics act by interfering with the action of dopamine at dopamine D2 receptors, two recent reports showed that 800 to 1000 mg of cannabidiol per day alleviated the signs and symptoms of schizophrenia, although cannabidiol is not known to act on dopamine receptors. Because these recent clinical findings may indicate an important exception to the general rule that all antipsychotics interfere with dopamine at dopamine D2 receptors, the present study examined whether cannabidiol acted directly on D2 receptors, using tritiated domperidone to label rat brain striatal D2 receptors. It was found that cannabidiol inhibited the binding of radio-domperidone with dissociation constants of 11 n In addition, a recent report by P. McGuire et al.3 found that 1000 mg per day cannabidiol added to the ongoing antipsychotic treatment significantly improved schizophrenia in a study on 88 patients. Because there are no known reports of cannabidiol acting directly on dopamine D2 receptors, the important findings by Leweke et al.2 and McGuire et al.3 may indicate that cannabidiol is the first apparent exception to the general rule that all antipsychotics either block or interfere with dopamine at brain dopamine D2 receptors.5Although currently used antipsychotics for schizophrenia all interfere with the neurotransmission of dopamine,et al.3 went so far as to state that the antipsychotic target for cannabidiol was not dopaminergic. Furthermore, the report by Leweke et al.2 did not attribute the antipsychotic action of cannabidiol to any particular set of receptors in the brain. For example, it is possible that cannabidiol may act on one or more types of receptors to exert its clinical action. Such possible targets include fatty acid amide hydrolase, serotonin-1 receptors, GPR55 receptors and transient potential vanilloid-1 receptors.8In fact, McGuire 9Cannabidiol is an active cannabinoid found in high concentration in the cannabis plant (up to 40% in the extract). Cannabidiol has many possible uses in a variety of medical illnesses, especially in certain types of epilepsy and possibly in treating psychosis.et al.3 and Leweke et al.2 Such an investigation was considered essential in order to test the basis for the commonly known dopamine hypothesis of psychosis,5 especially as it is known that the potent cannabinoids HU210 and Win 55,212-2 cause behavioral dopamine supersensitivity and elevated D2High receptors.5 That is, should there be no effect of cannabidiol on dopamine D2 receptors, despite having a clinical antipsychotic action, the dopamine hypothesis underlying psychosis would need to be modified.Although dopamine D2 receptors are a main common target for antipsychotic drugs, it was essential, therefore, for this present study to examine whether cannabidiol had any direct action on dopamine D2 receptors that might account for the clinical antipsychotic effects observed by McGuire m Tris-HC1 (pH 7.4 at 20 °C), 1 mm EDTA, 5 mm KCl, 1.5 mm CaC12, 4 mm MgC12 and 120 mm NaCl. The homogenate was not washed, centrifuged or preincubated because our previous work found that 30–50% of the D2 receptors were lost by these procedures.10Rat striatal tissues were used as a source of dopamine D2 receptors. The rat striata were from carbon-dioxide-killed Sprague-Dawley rats or from frozen rat brains . The brain (stored at −70°) was partly thawed and the striata removed. The striata were homogenized in buffer (4 mg frozen tissue per ml buffer), using a teflon-glass homogenizer (with the piston rotating at 500 r.p.m.) and 10 up-and-down strokes of the glass container. The buffer contained 50 m3H]domperidone ]domperidone; 41.4 Ci mmol−1; made by Moravek Biochemicals and Radiochemicals, Brea, CA, USA). Each incubation tube  received, in the following order, 0.5 ml buffer , 0.25 ml [3H]domperidone, and 0.25 ml of tissue homogenate. The tubes  were incubated for 2 h at room temperature (20°), after which the incubates were filtered using a 12-well cell harvester  and buffer-presoaked glass fiber filter mats (Whatman GF/C). After filtering the incubate, the filter mat was rinsed with buffer for 15 s (7.5 ml buffer). The filters were pushed out and placed in scintillation minivials . The minivials received 4 ml each of scintillant , and were monitored 6 h later for tritium in a Beckman LS5000TA scintillation spectrometer  at 55% efficiency. The specific binding of [3H]domperidone was defined as total binding minus that in the presence of 10 μmS-sulpiride.The dopamine D2 receptors in the rat striatal tissue were measured with domperidone, as indicated in the results. The form of the Cheng–Prusoff equation used was Ki=IC50%/(1+C*/Kd), where C* was the final concentration of the radioligand and Kd was the dissociation constant of [3H]domperidone (Kd=0.5 nm), as determined directly by the saturation binding of [3H]domperidone  to the striatal homogenate. Reagents and compounds were obtained from commercial sources .Independently, the Cheng–Prusoff equation  that occupied about 82% of the D2 receptors.  or 2.3 nm/(2.3 nm+0.5 nm)).The competition between cannabidiol and [3H]domperidone at the brain dopamine D2 receptors. Cannabidiol inhibited the binding of [3H]domperidone at the high-affinity component (at dopamine D2High receptors) with 50% inhibition occurring at 66 nm . In addition, cannabidiol inhibited the low-affinity component of binding (at dopamine D2Low receptors) with 50% inhibition occurring at 2800 nm (n=5).The results for the competition are in 11 the cannabidiol dissociation constants  were 11 nm at D2High and 2800 nm at D2Low.Using the Cheng–Prusoff relation,m guanilylimidodiphosphate, the binding of [3H]domperidone to the high-affinity site (at D2High receptors) was completely abolished. All the dopamine D2High receptors had converted to their D2Low state in the presence of the guanine nucleotide.Furthermore, in the presence of 200 μ3H]domperidone, there was no such biphasic competition when cannabidiol competed against the binding of [3H]raclopride (data not shown). In fact, cannabidiol inhibited the binding of [3H]raclopride with only a single dissociation constant of 4900 nm at the dopamine D2Low receptors (with an IC50% concentration of 9000 nm). Such a phenomenon was also previously seen with dopamine, which competed in a biphasic manner versus [3H]domperidone but in a monophasic manner at D2Low receptors when using [3H]raclopride.14In contrast to the reproducible biphasic pattern of cannabidiol competition versus the binding of [3H]domperidone in two phases, corresponding to dopamine D2High and D2Low dopamine receptors. This biphasic pattern only occurs with dopamine agonists, as consistently found with hallucinogens15 and the commonly used anti-Parkinson agonists.16The data in 12 which is a partial agonist 13 Brexpiprazole and cariprazine are relatively new compounds and have not yet been examined in this assay.Such a biphasic pattern does not occur with any of the antipsychotics, except for aripiprazole,3H]domperidone, in exactly the same way as aripiprazole, indicates that cannabidiol may act clinically as a partial agonist at the dopamine D2 receptors, similar to the clinical antipsychotic action of aripiprazole.Therefore, the biphasic pattern of cannabidiol in inhibiting the binding of domperidone at the D2 receptors. However, the following important points indicate that such an indirect action through CB1/D2 heteromers is unlikely.It may be argued that the present m effectively inhibited the binding of [3H]domperidone to the D2High site . A similar situation occurred with dopamine,14 as mentioned above. It is possible that the two different [3H]ligands have a different mode of attachment to the dopamine D2 receptor, based on the fact that domperidone has a pKa of 7.9, whereas raclopride has a pKa of 8.97, resulting in a different proportion of charged and uncharged species of the two ligands, where the charged nitrogen atom of domperidone and raclopride is expected to be the main point of attachment. The fact that [3H]raclopride was not competed by cannabidiol at D2High precludes the ready measurement of cannabidiol versus the binding of [11C]raclopride in possible studies in humans.It is not known why cannabidiol inhibited the binding of [or sites , yet inhin vitro in the present work may possibly account for some of the clinical side-effects of cannabidiol such as somnolence, diarrhea, decreased appetite and fatigue.27 Moreover, because it is well known that the partial dopamine agonist aripipazole can sometimes elicit psychotic signs and symptoms in patients,28 it is entirely possible that long-term use of marijuana can lead to an accumulation of the cannabidiol partial agonist in some individuals and cause a psychotic episode. This is unlikely, however, because cannabidiol has been reported to protect against the effects of tetrahydrocannabinol.30The apparent partial agonist action of cannabidiol


Associations of SFA, monounsaturated FA (MUFA), n-3 polyunsaturated FA (n-3 PUFA) and n-6 PUFA, with changes in low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TAG), and total cholesterol to HDL ratio (TOTAL:HDL), were assessed by linear regression. Substitution models assessed isocaloric replacements of SFA with MUFA, n-3 PUFA, n-6 PUFA or CHO. Higher SFA intakes were associated with decreasing TAG. No associations were observed for fatty acid intakes with LDL, HDL or TOTAL:HDL. In females, replacing SFA with CHO was associated with increasing LDL, TAG and TOTAL:HDL. Our findings confirm observations in adults, although sex-specific determinants seem relevant in our adolescent population. Overlooking the nutrient context when limiting SFA intakes might have detrimental consequences appreciable as early as adolescence.The relevance of dietary fatty acids (FA) for blood lipids should be assessed in the context of substituting nutrients. Such evidence is lacking for adolescents. This study describes prospective associations of dietary FA with changes in serum lipids during adolescence, and considers the theoretical isocaloric replacements of saturated FA (SFA) with other FA or carbohydrates (CHO). Children from the GINIplus and LISAplus birth cohorts, with data on FA intakes (at age 10 years) and serum lipids (at age 10 and 15 years), were included ( Since the first appearance of evidence suggesting a detrimental role of saturated fatty acids (SFA) in the development of coronary heart disease ,2, the aIt is currently well established that CVD risk factors progress from childhood and adolescence into adulthood . ResultsThe current study therefore aims to describe the prospective associations of fatty acid intakes during childhood with changes in serum lipid concentrations during adolescence. Furthermore, we are interested in observing how associations with SFA may depend on the choice of substituting nutrient. We therefore consider changes in blood lipids following the theoretical reduction of SFA in the context of different isocaloric replacements with other fatty acids or with carbohydrates.The present study used data from the 10- and 15-year follow-up assessments of the ongoing GINIplus  and LISAplus (Influence of Lifestyle-Related Factors on the Immune System and the Development of Allergies in Childhood plus the Influence of Traffic Emissions and Genetics) birth cohort studies. Healthy full-term newborns were recruited from obstetric clinics in four German cities. Information was collected using identical questionnaires and at physical examinations. The study designs, recruitment and exclusion criteria have been described previously ,27. For n-6 and n-3 PUFA, protein, carbohydrate and alcohol were calculated  based on the German Food Code and Nutrient Database (BLS) version II.3.1 [Dietary intake data were collected at the 10-year follow-up assessment, using a self-administered food frequency questionnaire (FFQ) designed to assess food and nutrient intake over the past year in school-aged children, and validated to estimate energy, fatty acid and antioxidant intake . In brien II.3.1 . Each nuBlood samples were obtained during the 10- and 15-year follow-up physical examinations. The concentrations (mmol/L) of total cholesterol, LDL, HDL, and triglycerides (TAG) were measured in serum using homogenous enzymatic colorimetric methods on a Modular Analytics System from Roche Diagnostics GmbH Mannheim according to the manufactures instructions. External controls were used in accordance with the guidelines of the German Society of Clinical Chemistry and Laboratory Medicine. The ratio of total to HDL cholesterol (TOTAL:HDL) was calculated by dividing total cholesterol by HDL.t-test. Participants with complete data on FA intakes at age 10 years, serum lipids at age 10 and 15 years, and all adjustment variables were included in the study . To test2-test for categorical variables. Differences in characteristics between males and females at each assessment were tested using Wilcoxon signed rank test for continuous variables and χ2-test for categorical variables (Fisher’s exact test for binary variables). Changes (∆) in lipid concentrations and in TOTAL:HDL ratio were calculated by subtracting each measurement at the 10-year follow-up from its respective measurement at the 15-year follow-up. Statistical analyses were carried out in the total population and stratified by sex. Subject characteristics at ages 10 and 15 years were described by medians  or counts (%). Differences from 10 to 15 years were tested using paired Wilcoxon signed rank test for continuous variables and McNemar’s χn-3 PUFA or n-6 PUFA) with the different blood lipid parameters . Through this prospective approach, we aim to avoid any misleading findings emerging from the possible bidirectional relationship between fatty acid intakes and blood lipids assessed at a single time-point only. Second, substitution models were fit to observe the effect of replacing SFA with other fatty acids  or with CHO, on the different blood lipid parameters . These models included the exposure nutrient of interest as well as all other energy-bearing nutrients except SFA (the nutrient being “replaced”). In this way, energy intakes of protein, carbohydrate, alcohol and other fats are held constant; and by additionally including total energy intake in the model it is possible to interpret the resulting coefficients for each nutrient as its theoretical substitution for an equal amount of energy (%EI) from saturated fat, being the only energy-bearing nutrient not accounted for in the model. All models were adjusted for potential covariates in two steps. First, we adjusted for basic covariates (MBASIC): study , recruitment region , sex —not in sex-stratified models—exact age at 10-year blood sampling (years), fasting status at blood sampling (not fasted (46%); fasted at one assessment (45%); fasted at both assessments (9%)), BMI (kg/m2) at age 10 years, screen-time  at age 10 years, total energy intake  at age 10 years, and lipid concentration (mmol/L) at age 10 years. In a second step, models were further adjusted for other potential confounders (MADJ): parental education level  and pubertal onset at age 10 years . Given the high intercorrelation typically present amongst dietary components [RESID and CHORESID), which were uncorrelated with each other [RESID was included in place of MUFA, along with all other covariates, and vice versa). Results from the linear regression analyses are presented as regression coefficients (β) per interquartile range (IQR) increase in the relevant exposure variable, along with their 95% confidence interval (95% CI). A two-sided α-level of 5% was considered significant for the total population analyses. For the sex-stratified analysis we corrected for multiple testing using Bonferroni correction: the α-level was divided by 2 (2.5%) as the dataset was analyzed by sub-groups of two levels . Statistical analyses were conducted using R (www.r-project.org), version 3.3.0 [Using linear regression, two modelling approaches were applied. First, single nutrient models were fit to observe the changes in blood lipids when increasing habitual intakes of a single nutrient at a constant energy intake. Intakes of different fatty acids assessed at age 10 years were considered as the exposures of interest. Separate regression models were run for each exposure . Differences in descriptive characteristics between participants included in the analyses and participants lost to follow-up are presented in the n = 64). Clear outliers in blood lipid concentrations (n = 10), or adjustment variables (n = 1) were visually identified using descriptive plots and excluded from the analyses. Basic characteristics of the study population at age 10 and 15 years are described in The present analyses comprised of 1398 participants . The derivation of the study population is presented in BASIC) and fully adjusted models (MADJ). The resulting β-coefficients indicate the changes in blood lipid concentrations (mmol/L) per IQR increase in the %EI of a given fatty acid, while maintaining total energy intake constant. A significant inverse association was observed between the intake of SFA (IQR increase in %EI) at age 10 years and the change in TAG concentrations from age 10 to age 15 years , p-value = 0.042). A similar association was observed in females only, which was borderline statistically significant when corrected for multiple testing , p-value = 0.025). No associations were observed for any of the fatty acid exposures with the other assessed blood lipid parameters. The prospective associations of dietary fatty acid intakes (in %EI) at age 10 years with changes in serum lipid concentrations from age 10 to age 15 years are described in BASIC) and fully adjusted models (MADJ). Coefficients (β) obtained from these models represent an isocaloric substitution, i.e., the change in blood lipid concentrations when theoretically replacing the intake of SFA with another (specific) fatty acid or CHO, while maintaining total energy intake constant. A direct association was observed in the basic model for the substitution of CHO (IQR increase in %EI) for SFA with ∆LDL , p-value = 0.05). Sex-stratified analyses indicated significant associations in females only, after correction for multiple testing: direct associations were observed for the substitution of CHO (IQR increase in %EI) for SFA with ∆LDL , p-value = 0.019), ∆TAG , p-value = 0.014), and ∆TOTAL:HDL , p-value = 0.024).The present study used data from two large German birth cohorts to assess the prospective associations of fatty acid intakes with changes in blood lipid concentrations during adolescence. We found that higher intakes of SFA at age 10 years were associated with decreasing TAG between ages 10 and 15 years. Furthermore, we observed that the consumption of CHO at the expense of SFA in females was associated with increasing LDL, TAG and TOTAL:HDL. p-value = 0.068). Although the evidence for an association of SFA with LDL has been widely accepted, recent studies in adults have emerged, reporting no association between SFA and CVD risk [r = 0.77), and also presented strong negative correlations with CHO (r = −0.81), which limits the ability to disentangle the individual effects of SFA [Our findings regarding the prospective association of SFA intakes with reduced TAG concentrations are in line with existing literature in adults . The obsCVD risk . Nonethes of SFA . In lighs of SFA . This has of SFA .Results from our substitution analyses showed that replacing SFA with CHO was associated with increasing LDL, TAG and TOTAL:HDL in females. Our findings are in line with studies in adults which report a detrimental effect on blood lipids when substituting CHO for SFA . HoweverComparison of our results with existing evidence in adolescents is restricted due to the absence of studies carried out during this life period. One similar study observed theoretical effects of substituting MUFA or PUFA for SFA, and total fat for CHO from ages 8 to 11 years . The stuOne of the main strengths of this study is its focus on the prospective role of dietary fatty acids on blood lipids during adolescence, a life period not often addressed and becoming increasingly relevant in terms of later disease development. Furthermore, we consider isocaloric replacements of SFA, which can contribute toward better understanding its independent role in the context of other nutrients. For our analyses, we benefited from a large homogenous population of females and males, providing data covering a five-year period from childhood to adolescence. The longitudinal nature of this study is a key aspect which allows us to add to the limited knowledge regarding fatty acid intake and prospective changes in markers of cardiometabolic risk during adolescence. Given the observational nature of the study, causality cannot be implied; nevertheless, the prospective analysis offers a temporal component which provides stronger grounds for a causal interpretation. Whether the observed effect sizes in this study can be considered clinically relevant might be a point for discussion. Furthermore, considering that children in the present study are not a high risk population and present normal blood lipid levels, the observation of associations at this stage provide only an indication of a possible early role of dietary nutrients in the long-term development of CVD risk factors. Nevertheless, given the increasing evidence for the progression of risk factors from childhood to adulthood, preventive measures might already consider this age group. Our findings provide a relevant indication of possible dietary targets which could support the development of recommendations for early disease prevention.A main drawback in nutritional epidemiology is the high intercorrelation amongst different nutrients, which, if overlooked, can lead to incorrect conclusions. The use of substitution models can provide additional insight through the adjustment for other nutrients. However, the method can result in multicollinearity within statistical models, again generating misleading associations . In our In conclusion, our findings suggest that higher SFA intakes might lead to reductions in TAG concentrations during adolescence. We highlight that observed associations in this context are not independent of other correlated nutrients. Furthermore, replacement of SFA with CHO in female children is associated with increasing levels of LDL, TAG and TOTAL:HDL during adolescence. Our findings confirm observations in adult populations, where detrimental aspects of increased consumption of CHO at the expense of SFA have been reported. Sex-specific determinants may however play a greater role during adolescence. It is important that recommendations to reduce SFA intakes do not overlook the possible effects of other nutrients consumed in their place.


Disease maps are important tools in the management of disease. By communicating risk, disease maps can help raise awareness of disease and encourage farmers and veterinarians to employ best practice to eliminate the spread of disease. However, despite the importance of disease maps in communicating risk and the existence of various online disease maps, there are few studies that explicitly examine their usability. Where disease maps are complicated to use, it seems that they are unlikely to be used effectively. The paper outlines an attempt to create an open access, online, searchable map of incidents of bovine tuberculosis in England and Wales, and analyzes its usability among veterinarians. The paper describes the process of creating the map before describing the results of a series of usability trials. Results show the map to score highly on different measures of usability. However, the trials also revealed a number of social and technical limitations and challenges facing the use of online disease maps, including reputational dangers, role confusion, data accuracy, and data representation. The paper considers the challenges facing disease maps and their potential role in designing new methodologies to evaluate the effectiveness of disease prevention initiatives. Disease maps are important tools in the management of disease. On the one hand, disease mapping is used to detect relationships between human and animal diseases , diseaseDespite the apparent importance of using maps to communicate animal disease risks, there are few attempts to examine their use. Where disease maps have been created, it seems that they are complicated to use, require extensive training and only used by those responsible for data entry , 12. TheThe paper examines the development and usability of the ibTB disease map through a series of usability trials with veterinarians. In doing so, the paper also explores the social and technical limitations and challenges facing the use of online disease maps to enhance and encourage greater levels of biosecurity on cattle farms.www.ibtb.co.uk) hosted data of all “ongoing” and “closed” bTB incidents since 2010 in England and Wales. Farms without a bTB history are not visible. The only data associated with individual incidents are their start and end date. Other information such as farm type and herd size is not displayed. The website is hosted in the cloud using MS Azure technology. It is a “3 tier application”—comprising data, service, and application tiers. To create the data tier ibTB utilizes data from the Animal and Plant Health Agency’s (APHA) “Sam” system which records bTB testing details. Data from this system are downloaded on a monthly basis, cleaned, re-formatted, and geo-referenced and then uploaded to the ibTB back-end SQL Server database. Other data utilized by the system are as follows: Ordnance survey’s Codepoint—used for the postcode search facility and the base maps  which are freely available ESRI products. Technologies utilized in the service and application layers included ASP.Net, HTML, C#, JavaScript, and ESRI JavaScript API. ESRI code was used to cluster breakdowns and display them as one of three categories .In order to make bTB incident data available, a searchable website was designed.A series of usability trials were conducted to assess the ease of use of ibTB and users’ perceptions of the role ibTB could play in managing bTB. Usability is defined in ISO 9241-11 as comprising three key dimensions: satisfaction , efficiency , and effectiveness  , 21. A cTo assess the usability of ibTB, a task-based approach was adopted in which users were asked to complete five different tasks reflecting a range of activities that ibTB could be used for, varying in difficulty and geography  were noted, along with the number of mistakes made during the task and the time taken to complete it. These were cross-checked with separate observation notes taken during each usability trial. On three occasions Silverback failed to record screen and/or audio activity. In a further two cases, there was no accessible WiFi or 3G signal available to connect to ibTB. Instead, the participant’s own computer was used to conduct the usability tests, but without the ability to record using Silverback. These users are excluded from the analysis of task completion. Responses to open-ended questions were recorded using a digital voice recorder. Transcripts were prepared and analyzed thematically to draw out shared uses, concerns and limitations relating to ibTB. Survey data were entered into SPSS to calculate the SUS scores, and conduct descriptive analysis and statistical tests of association and difference.Veterinarians were asked about their use of maps and computers in their daily work. Use of computers was rated as very frequent  and veterinarians generally responded that they felt comfortable using a computer . Veterinarians’ use of maps (mean 3.92) and online maps (mean 3.68) was less frequent.(a)Reassurance: Veterinarians commented that ibTB could be used to show farmers that they are not the only ones with bTB in their area, thereby helping to reduce the stigma of a bTB incident on their farm. For example, one vet commented: “There’s a lot of stigma about TB in this area. It can be an issue. But if they see they’re not the only ones with it, that could help.”(b)Advising: Veterinarians argued that farmers can frequently be unaware of the bTB situation in their local area. While farmers may claim to know who has bTB, often this knowledge is based on rumor. As one vet said: “Often, when you go out on a farm, they don’t know who else has got TB. Sometimes they say they do, but they’re wrong.” However, private veterinarians acknowledged that farmers can sometimes have a better knowledge of bTB than themselves. ibTB was seen as providing a valuable factual resource that effectively democratized information on bTB. As a result, some veterinarians argued that they were in a better position to provide advice to farmers on best practice such as biosecurity and cattle movements as each could know the “true” incidence of bTB in their local area.(c)Epidemiological knowledge: Related to the second reason, private veterinarians argued that for too long they had been excluded from easy access to bTB data. Finding out the bTB status of a farm neighboring a client’s but registered to a different veterinary practice involved convoluted conversations with other veterinary practices in which client confidentiality meant that disclosing disease status was often problematic. ibTB therefore avoided these problems, but could also allow veterinarians to build up a picture of bTB in their local area and understand its spread.All veterinarians welcomed the development of ibTB. Private veterinarians in particular were pleased to be able to see these data, suggesting that the information was vital for them to work with their clients to help them manage bTB. These veterinarians argued that previous data restrictions reflected a perceived lack of trust in private veterinarians’ epidemiological skills by Government, but that ibTB could now help them engage with farmers and government veterinarians on an equal footing. In democratizing bTB information, veterinarians therefore saw three clear uses for ibTB:(a)Nosiness: Reflecting academic studies of farmer behavior (behavior  veterina(b)Explaining tests: The regulations around bTB testing can be complicated for farmers. Veterinarians argued that often farmers can be confused about why they have to test their herd so soon after their last herd test (this can be due to a new bTB incident on a nearby farm). Veterinarians reasoned that farmers could use ibTB to check local bTB to help explain any unexpected tests.(c)Farm biosecurity: Some veterinarians suggested that farmers might use ibTB to identify whether they should improve their on-farm biosecurity (because of a nearby bTB incident) or assess the riskiness of potential stock purchases from an area or specific farm. However, many veterinarians were skeptical about the extent to which farmers would use ibTB to do this, suggesting that farmers’ purchasing habits were difficult to change. As one vet pointed out: “Most stock decisions we can’t change: traders will always trade; closed herds want to stay closed; there’s not many in the middle.”Veterinarians also commented on the potential use of ibTB among farmers. While opinions varied on the extent to which farmers would use ibTB and the impact it would have on their behavior, the following three main uses were identified:Results of the usability trials are shown in Table The average time to complete a task was 126 s. Task 2 was completed quickest on average, while Task 3 had the slowest average although was completed by all participants. It is worth pointing out that variation in the time taken to complete the tasks was also due to the users’ level of interest in bTB. For example, some users were keen to explore in detail the incidence of bTB in surrounding herds for some tasks  in order to form epidemiological judgments.There were few visible signs of frustration among participants. Mouse circles were counted on 19 occasions, and double clicking on 29. One sign of frustration not recorded but which became evident during testing was respondents rapidly zooming in and out of the map. Sometimes this was due to poor mouse control but it also occurred when users were trying to find a specific location (such as during Tasks 3 and 5). One problem with the use of ESRI maps was that place names could disappear at different magnification levels making navigation awkward.Mistakes were made by 17/20 users, although only a total of 28 individual errors were recorded across all five tasks. Twelve mistakes were recorded for Task 1. This could have been due to the fact that this was the first task. A common mistake was the incorrect use of the search function. On being asked to search for a farm using its CPHH, veterinarians frequently left out the final part of the code, resulting in a failed search. Task 3 also had a significant number of mistakes due to inappropriate searches. On being asked to search for a specific place, 10 users attempted to search by typing the place name into the search box. When this failed to work, users completed a Google search to find a postcode with which to search. The remainder navigated to the location where they thought the town was located before finding it. These mistakes highlighted the importance of including a place name search function in future versions of ibTB.r = −0.514, p = 0.021). Users who rated themselves as more frequent computer users also completed tasks quicker than less frequent users . However, there was no relationship between experience with maps and time or ease of task completion.When asked to rate the ease of completing each task, all responses were positive. The average ease of completion for the five tasks was rated at 5.3 out of 7. Task 1 was rated easiest despite having most mistakes. Tasks 2 and 3 were rated lowest. In both cases, users experienced problems of identifying which farm they had searched for because of a failure of ibTB to show a placeholder for all farms. Users who rated the tasks as easy were also more likely to complete the tasks in less time  but the relationship between the SUS scores and time taken to complete tasks was not significant . There was also no relationship between SUS scores and users’ declared proficiency in using a computer or online maps. When different dimensions of usability are considered separately, users who completed the tasks quickly were more likely to rate ibTB as highly learnable . All other relationships were not statistically significant.Overall, ibTB scored highly on the System Usability Scale , but both scores indicated above average usability. The lower scores for government veterinarians are likely to be due to the fact that other bTB resources are available to them. While private veterinarians were generally enthused by the availability of “new” data, veterinarians working in APHA commented that other mapping and data management software was more suitable.(a)Reputational dangers: Most veterinarians accepted that ibTB could function as a means to improve biosecurity and cattle purchasing decisions. However, not only were they skeptical about the extent to which farmers would change their behavior as a result of ibTB, but they also raised concerns about their role in passing on information about bTB status. For private veterinarians, the idea that they could now pass on previously confidential data about another farmers’ bTB status was troubling. Some veterinarians commented that they would be reluctant to tell farmers about others’ bTB status. Instead, they said that they would tell them to go and look on ibTB themselves, or direct them to an administrator in their practice who could look up the information for them. These actions were due to two concerns related to avoiding reputational damage to the practice or their career. The first was the need to avoid giving out inaccurate data that could threaten veterinarians’ business. Given that ibTB has a time lag of one month, this was seen as a real possibility. The second was a concern to be seen as an “informant.” One vet referred to this as a “TB Grass,” commenting that “The last thing I want is a reputation for going round telling people that so and so has TB.”(b)Role confusion: While private veterinarians were concerned about their reputation, APHA veterinarians were concerned about how ibTB changed their role in bTB management. Because of the confidential nature of disease status, government veterinarians have been trained not to reveal the bTB status of neighboring farms to other farmers. That this information was now publicly available challenged this role, and veterinarians were unsure what it would mean for them in future. During the tasks, APHA veterinarians asked if they were allowed to tell farmers what ibTB said about farmers’ neighbors. Just like private veterinarians’ coping strategy, these veterinarians also suggested they would simply tell farmers to go and look on ibTB for themselves. In the minds of both private and public veterinarians, ibTB challenges their role as a neutral arbiter or a “bTB confidant” that they believed contributed to forging a trusting relationship with farmers. For policy makers, the lesson is that the social context of disease management affects how information on disease status is interpreted and distributed.(c)Accuracy: The accuracy of data was a widespread concern. It was frequently stated by veterinarians that while the tasks were easy to complete, their accuracy was open to question. As noted above, one concern was the ability to identify a farm without a placeholder on the map. Although veterinarians could use local knowledge or assume their location, it remained a concern because as one vet described “it matters because I would give different advice depending on which one it is.” More broadly, veterinarians complained that the maps in ibTB did not show field boundaries which were important in attempting to make an epidemiological assessment of the riskiness of a farm they had searched for: “It doesn’t tell you where the breakdown occurred—it could have been miles away. That could affect your opinion on whether it was risky.” Others also pointed out that this assessment should also take into account the precise location of the breakdown given that herds are split into epidemiological groups that can be located in different parts of a farm. As one vet commented: “I wouldn’t rely on it too heavily for factual accuracy—for me, you don’t want to get it wrong in public—it isn’t quite good enough for that.”(d)Data absences: In relation to data accuracy, veterinarians also pointed to other forms of data that ibTB could display that would also assist in making an informed epidemiological risk assessment for any given farm. These included the need to display all farms whether they had ever had bTB or not. This was mentioned often in relation to Task 5 where only a handful of cases were evident, but veterinarians wanted to get a sense of disease prevalence as well as incidence. Related to this was the absence of county boundaries on the map (these were only displayed at high magnification). While veterinarians accepted that disease “knew no boundary,” these could still be useful in getting a sense of prevalence in areas that were not familiar to veterinarians. Other data requested by veterinarians included: herd size; herd type; the number of reactors and inconclusive reactors in a breakdown; and the number, interpretation and type of tests used. Private veterinarians were also keen to learn the cause of the breakdown held in APHA records, and some argued that information from wildlife surveys and the M. bovis genotype should be shown on the map. The purpose of showing these data was to help inform their own epidemiological assessment of a farm and/or area, but some veterinarians also suggested it could be important in demonstrating to the public the need for wildlife controls to prevent the spread of bTB.(e)Data representation: Many veterinarians commented that some aspects of the visual display could be improved to help interpret the maps better. Important place names could disappear at different levels of magnification. The clustering of breakdowns was also criticized. First, the 3-point scale was seen to be ineffective, and second, clusters could move when uses zoomed in and out of the map. This had the effect of changing users’ assessment of the level of bTB in an area. The zoom function could also change users’ perceptions of an area in other ways. When searching for a CPHH , the default zoom level could portray a different disease picture compared with a wider zoom level. It was noticeable that among those veterinarians that took the time to zoom out there was often a change in their perception of the incidence of bTB in the area searched for, once they realized that there were many other breakdowns nearby. Finally, some veterinarians commented that it would be better to see how many years each farm had been free from bTB. This was perceived to be more positive than current breakdowns which as one vet suggested could look like “a map of doom.” Years of freedom is also familiar to farmers as a metric used in risk based trading mechanisms for bTB and other diseases ; and making changes to the search facility. The website has also been made fully compatible with mobile devices. Technical limitations have meant that the ability to search for place names—one of the main problems faced by users—has not been included.The usability trials demonstrated that veterinarians had high levels of satisfaction, could complete tasks easily, and rated ibTB highly on the SUS. However, despite the high levels of usability, veterinarians still identified key technical and social challenges that affected their use of ibTB. For some, these challenges suggest the need for further research on the way maps represent and communicate disease data. The usability trials suggested the need for a broader consideration of how different representations of bTB can influence farmer and vet behavior. Studies on behavior change argue that the way a phenomenon is framed can impact upon subsequent behavior. For example, research suggests that avoiding losses is often a greater behavioral driver than winning . FramingOn the other hand, thinking about how disease maps represent data should also direct disease mappers to consider the underlying assumptions and power relations within their maps. Veterinarians’ responses to ibTB revealed tensions within the assumption that they should play an important in using and promoting disease maps to farmers. For example, while previous research has highlighted the importance of veterinarians in encouraging farmers to implement biosecurity or advise them in animal health , discusshttps://web.archive.org/web/20150910011759/http://badger-killers.co.uk/culling-increases-btb/). While farmers’ groups have called for access to ibTB to be strictly controlled . AM is employed by the Animal and Plant Health Agency (APHA), an agency of Defra. Interpretation of the results of the usability trial rests with the authors. The reviewer DD and handling Editor declared their shared affiliation.


Spontaneous eye blink rate (EBR) has been proposed as a noninvasive, inexpensive marker of dopamine functioning. Support for a relation between EBR and dopamine function comes from observations that EBR is altered in populations with dopamine dysfunction and EBR changes under a dopaminergic manipulation. However, the evidence across the literature is inconsistent and incomplete. A direct correlation between EBR and dopamine function has so far been observed only in nonhuman animals. Given significant interest in using EBR as a proxy for dopamine function, this study aimed to verify a direct association in healthy, human adults. Here we measured EBR in healthy human subjects whose dopamine D2 receptor (DRD2) availability was assessed with positron emission tomography (PET)-[18F]fallypride to examine the predictive power of EBR for DRD2 availability. Effects of the dopamine agonist bromocriptine on EBR also were examined to determine the responsiveness of EBR to dopaminergic stimulation and, in light of the hypothesized inverted-U profile of dopamine effects, the role of DRD2 availability in EBR responsivity to bromocriptine. Results from 20 subjects  showed no relation between EBR and DRD2 availability. EBR also was not responsive to dopaminergic stimulation by bromocriptine, and individual differences in DRD2 availability did not modulate EBR responsivity to bromocriptine. Given that EBR is hypothesized to be particularly sensitive to DRD2 function, these findings suggest caution in using EBR as a proxy for dopamine function in healthy humans. However, PET is costly, labor intensive, exposes participants to radiation, and many research institutes do not have the facilities to conduct human dopamine PET. Spontaneous eye blink rate (EBR) has been proposed as an inexpensive, noninvasive biomarker that can serve as a proxy for dopamine function. Here we present evidence that EBR is not a valid proxy for general dopamine functioning in healthy humans, but it remains to be determined whether EBR can index specific aspects of dopamine functions.Dopamine is critical for cognitive and reward functions, and dopamine dysfunction is linked to neuropsychiatric disorders including addiction, Parkinson’s disease, and schizophrenia. In humans, direct in vivo assessment of the dopamine system is achieved through positron emission tomography . PET together with different radioligands has provided valuable information about different aspects of dopamine function such as receptor density, dopamine release, and dopamine synthesis capacity , or a history of using drugs known to affect the dopamine system  and EBR in drug-naive monkeys . In the in vivo in healthy humans. The focus on DRD2 stems from previous results suggesting that EBR is more strongly associated with D2 than D1 receptors  who had undergone PET-[18F]fallypride for a separate study in our lab were recruited to have their eye blinks recorded for this study, once in a placebo condition and once after bromocriptine administration. Participants were recruited from the Nashville, TN metro area. Exclusion criteria included any history of psychiatric illness on a screening interview . The scanner had an axial resolution of 4 mm and in-plane resolution of 4.5- to 5.5-mm FWHM at the center of the field of view. [18F]fallypride ((S)-N-[methyl]-5-(3[18F]fluoropropyl)-2,3-dimethoxybenzamide) was produced in the radiochemistry laboratory attached to the PET unit, following synthesis and quality control procedures described in United States Food and Drug Administration IND 47,245. [18F]fallypride is a substituted benzamide with very high affinity to D2/D3 receptors  were obtained for each participant to aid coregistration and spatial normalization of PET images.ND images were calculated using the simplified reference tissue model, which has been shown to provide stable estimates of [18F]fallypride BPND (SCR_007378). Limited PET spatial resolution introduces blurring and causes signal to spill onto neighboring regions. Because the cerebellum is located proximal to the substantia nigra and colliculus, which both have DRD2, only the posterior 3/4 of the cerebellum was included in the region of interest (ROI) to avoid contamination of [18F]fallypride signal from the midbrain nuclei. The cerebellum ROI also excluded voxels within 5 mm of the overlying cerebral cortex to prevent contamination from cortical signals. The bilateral putamen ROI, drawn according to established guidelines (SCR_002823). Emission images from the three PET scans were merged temporally into a 4D file. To correct for motion during scanning and misalignment between the three PET scans, all PET frames were realigned using SPM8 to the frame acquired 10 min after injection (RRID:SCR_007037). Model fitting and BPND calculation were performed using the PMOD Biomedical Imaging Quantification software (PMOD Technologies). BPND images represent the ratio of specifically bound ligand  to its free concentration.Voxelwise D2/D3 BPide BPND . The ceride BPND . The ceridelines  on the MND in the striatum, which has the highest concentration of postsynaptic DRD2 in the brain, and the midbrain, the site of dopamine neurons on which presynaptic DRD2 are located, were extracted and regressed on EBR . Five minutes has been proposed as the standard time period for EBR assessment based on tests of reliability and is consistent with the EBR-reading literature from the 1930s and 1940s, where EBR was often reported over a 5-min period . Eye bliSubjects were asked to remove contact lenses before the recording of eye blinks if they wore contact lenses. Placebo/bromocriptine session order, blind to both the subject and the researcher, was counterbalanced across subjects. Eye blinks were visually counted with interrater and intrarater reliability above 95%. EBR was defined as the number of eye blinks per minute. EBR data from the bromocriptine condition were not available for two subjects: data from one subject were lost due to a technical failure, and data from another subject were excluded from analysis because the subject reported eye irritation after removing contact lenses and blinked excessively during the recording of eye blinks. Eye blink recording for one subject in the bromocriptine condition inadvertently terminated at 4 min, and thus EBR was calculated using 4 min of data for this session.ND on EBR; standardized beta coefficients (correlations), t statistics, and p values for the relations between [18F]fallypride BPND and EBR from these regressions are reported in Results.An average of 17 months (range: 3–32 months) separated the PET-[18F]fallypride scan from the recording of eye blinks. The time lag reflected that the majority of subjects were recruited for the EBR and bromocriptine study after having already completed the PET study, and the expense of PET data collection did not allow collection of a new cohort of participants. Time difference in data acquisition along with age and sex were entered as covariates in all regressions of [18F]fallypride BPr3 = 0.98, p = 0.002)a, providing evidence that 5 min was sufficient to capture spontaneous EBRs reliably. In the second approach, we separately calculated EBR for the first and latter half of each subject’s placebo and bromocriptine session’s 5-min EBR recording. The two EBR measures correlated very strongly in both the placebo b and bromocriptine c conditions. Results in this study observed using EBR calculated over 5 min still held when EBR was calculated in half that time window, showing that EBR was very stable and can even be assessed in under 5 min d and the bromocriptine condition e. All subjects were therefore included in primary analyses. To correct for multiple comparisons of four ROIs, results were considered significant at p < 0.0125.As expected, there were significant individual differences in spontaneous EBR . The Dixon’s test for outliers confirmed that there were no outliers in the placebo condition f, putamen g, ventral striatum h, or midbrain i i , Table 1r16 = 0.83, p < 0.0001)k l m in the present data (EBR in the bromocriptine condition was highly correlated with EBR in the placebo condition (0.0001)k A, indica 12.6])l B. Becausent data C.ND on the difference in EBR between the placebo and bromocriptine conditions. Bromocriptine effects on EBR were not significantly predicted by BPND in the caudate n, putamen o, or midbrain p. Ventral striatal BPND had the largest association with bromocriptine-induced changes in EBR out of the four ROIs but was not statistically significance even at the uncorrected level q, ND. Bromocriptine effects on EBR also did not relate to BPND in any ROI when changes in EBR were calculated as the percentage change from EBR in the placebo condition .ND on bromocriptine-induced changes in EBR. There was no significant parabolic relation between [18F]fallypride BPND and changes in EBR: caudate r, putamen s, ventral striatum t, or midbrain u, The influence of dopamine on behavior has been proposed to have an inverted-U profile in which individual differences in baseline dopamine function nonlinearly affect individual responses to dopaminergic stimulation. To examine this hypothesis in our data, we performed quadratic regressions of [18F]fallypride BPThe present results showed no relation between EBR and DRD2 availability in healthy human subjects. EBR also was not responsive to mild dopaminergic stimulation by bromocriptine in a consistent manner across subjects, and individual differences in DRD2 availability did not substantially modulate EBR responsivity to bromocriptine. Given that EBR is hypothesized to be particularly sensitive to DRD2 , these fMost studies that have reported a relation between EBR and dopamine function observed the association in atypical populations  or under a neuropharmacological manipulation . EBR andIt is worth noting that several studies employing neuropharmacological approaches have reported no effects of dopaminergic drugs on EBR . Also arND and EBR, we cannot dismiss the possibility that there may have been changes in dopamine function during this time that altered the relation between DRD2 availability and EBR in a manner not accounted for by the time difference. Published data on the long-term stability of [18F]fallypride binding is lacking at present. However, individual differences in D2-like receptor availability as measured by [18F]fallypride are stable across time periods of a month or more and thus appears to provide a reasonably stable index of individual differences in striatal dopamine D2-like function , [18F]fallypride BPND is also influenced by endogenous dopamine levels . The observation of low EBR in Parkinson’s disease patients suggests that EBR might correlate with tonic dopamine levels, which are more closely indexed by PET tracers for dopamine synthesis rather than dopamine receptor availability. Future studies assessing the relation between EBR and dopamine synthesis might clarify this possibility. We additionally note that [18F]fallypride binds to both D2 and D3 receptors and weakly to D4 receptors. If EBR is specifically mediated by a particular type of dopamine receptor, the nonspecificity of [18F]fallypride within the D2 family of receptors might obscure the relationship between EBR and [18F]fallypride BPND. However, it should be noted that we did not observe different patterns of association across striatal regions despite their differing levels of relative D2 and D3 expression.We note that although [18F]fallypride BPIn conclusion, the present findings suggest that EBR is not a valid proxy for general dopamine functioning in healthy humans, but it remains to be determined whether EBR can index specific aspects of dopamine functions.


Patients increasingly use online health communities to exchange health information and peer support. During the progression of health discussions, a change of topic—topic drift—can occur. Topic drift is a frequent phenomenon linked to incoherence and frustration in online communities and other forms of computer-mediated communication. For sensitive topics, such as health, such drift could have life-altering repercussions, yet topic drift has not been studied in these contexts.Our goals were to understand topic drift in online health communities and then to develop and evaluate an automated approach to detect both topic drift and efforts of community members to counteract such drift.We manually analyzed 721 posts from 184 threads from 7 online health communities within WebMD to understand topic drift, members’ reaction towards topic drift, and their efforts to counteract topic drift. Then, we developed an automated approach to detect topic drift and counteraction efforts. We detected topic drift by calculating cosine similarity between 229,156 posts from 37,805 threads and measuring change of cosine similarity scores from the threads’ first posts to their sequential posts. Using a similar approach, we detected counteractions to topic drift in threads by focusing on the irregular increase of similarity scores compared to the previous post in threads. Finally, we evaluated the performance of our automated approaches to detect topic drift and counteracting efforts by using a manually developed gold standard.Our qualitative analyses revealed that in threads of online health communities, topics change gradually, but usually stay within the global frame of topics for the specific community. Members showed frustration when topic drift occurred in the middle of threads but reacted positively to off-topic stories shared as separate threads. Although all types of members helped to counteract topic drift, original posters provided the most effort to keep threads on topic. Cosine similarity scores show promise for automatically detecting topical changes in online health discussions. In our manual evaluation, we achieved an F1 score of .71 and .73 for detecting topic drift and counteracting efforts to stay on topic, respectively.Our analyses expand our understanding of topic drift in a health context and highlight practical implications, such as promoting off-topic discussions as a function of building rapport in online health communities. Furthermore, the quantitative findings suggest that an automated tool could help detect topic drift, support counteraction efforts to bring the conversation back on topic, and improve communication in these important communities. Findings from this study have the potential to reduce topic drift and improve online health community members’ experience of computer-mediated communication. Improved communication could enhance the personal health management of members who seek essential information and support during times of difficulty. To illustrate the importance of addressing topic drift in online health communities, consider the case of Anne who was curious about a side effect she was experiencing with a newly prescribed medication for attention deficit hyperactivity disorder (ADHD). She was worried that the side effect would get worse and wanted to hear about other people’s experiences. She started a discussion regarding the drug and side effects in an online discussion group. Other online community members joined the discussion and shared their experiences as ADHD patients. When someone mentioned taking medication to prevent being fired from work, the topic of conversation changed to ADHD and work performance, including a discussion of the Americans with Disabilities Act (ADA) and legal advice. Ultimately, the conversation ended when one member repeatedly posted about his negative experience obtaining ADA assistance. Anne’s specific question regarding her medication side effect was never answered, and she decided to stop taking the drug. If she had learned how others dealt with the side effect and that it did not get worse, she might have continued the treatment. What could Anne, moderators, or the online community have done to get Anne’s questions answered?Anne experienced topic drift , where tPrevious studies on topic drift have focused on different domains and CMC methods, including email-based newsgroups , online Analyzing topic drift can shed light on the overall community experience. For example, Lambiase found that emotionally aggressive postings led discussion away from the original topic and led participants to unsubscribe or remain inactive . SimilarAccording to Hobbs, 3 conversational devices attributed to topic drift in dialogues are semantic parallelism, chained explanation, and metatalk . SemantiMany manual analyses of topic drift ,7,11 havWho provides this counteracting effort to topic drift in topically focused communities is unknown. Furthermore, automated techniques have the potential to detect both topic drift and counteracting efforts but are unexplored in online health communities. Answering these open issues is important to inform support that helps valuable online health communities thrive.Returning to our motivating scenario, people like Anne openly discuss and seek information and support in online health communities, such as WebMD ,24. ThesThe data for this study consist of posts from moderated, disease-specific WebMD communities. WebMD is one of the most popular health information sources for health consumers , thus weWe selected 7 WebMD communities: (1) attention deficit hyperactivity disorder (ADHD), (2) breast cancer, (3) diabetes, (4) heart disease, (5) multiple sclerosis (MS), (6) pain management, and (7) sexual health . We downThe University of Washington Institutional Review Board determined this study exempt from review.gradual or abrupt topic drift, determined by the degree of topical change from the previous post to the current post in a thread (RQ1). Gradual topic drift refers to small degrees of topical change in which the current topic is related to the previous topic. We considered a complete change of topic as well as topic domination as abrupt topic drift. Topic domination was measured through previously identified tactics—using a high volume of messages ”) or community nomenclature , (3) the keywords had a modifier to indicate lesser degree , (4) the keywords were used in meta-discussion about off-topic discussions, or (5) the keywords were used to start new off-topic threads . These were stricter criteria than RQ2 because this also removed global topic drifts along with the posts that described OT and lesser degreed local topic drifts.We evaluated our automated topic drift detection technique with self-identified topic drift and “on-topic” posts. First, we used posts from RQ2 that contained key terms: “hijack” or “off topic” as positive cases that our detection system should recognize as low in similarity measurement, given that members explicitly indicated the off-topic nature of the post. Because the interpretation of topic drift can be subjective , we reli“this is not off topic”) or (2) community members had shown intention to bring topics back to the original post . Because there were only a few negative cases, we added 70 manually selected “on-topic” posts with little or no topic drift that the detection system should recognize as high in topical similarity from the RQ3a qualitative analyses. We made these selections and adjustments prior to the evaluation process without any information on their similarity scores.To identify negative cases, we first used posts from RQ2 if (1) the posts negated the keyword  and then the results of quantitative analyses (RQ3b-RQ5) for the 7 moderated online health communities.gradual topic drift —in which topics remained in the discussion while few topics were newly introduced or neglected . This gradual change occurred among posts in nearly every thread. However, threads generally  stayed within the global frame of community topics, including symptoms, treatments, side effects, insurance issues, and emotional support for the specific community. On average, threads started with 3.44 topics and 1.05 topics were carried from post to post, while 1.58 topics were newly introduced. The following are themes associated with the severity and sources of topic drift.We manually analyzed 416 posts from 50 threads. Our systematic analysis showed that in most threads, the topic changed gradually— Abrupt topic drift occurred in 22% (11/50) of manually examined threads. The following is an example thread (Example Thread 1) from the Heart Disease community that showed abrupt topic drift, in which Poster_C controlled and changed the topic to their personal experience—topic domination. The thread ends as Poster_C repeatedly posted about their personal experience to control the topic and caused abrupt topic drift.I have heard that minutes makes a difference concerning a stroke, could seven hours make a difference with a blood clot beginining in the uppper leg traveling down?Poster_A: I don’t know how long it takes for tissue to die, but I would not wait 7 hours. But more important the clot can breakup and go to the lungs.Poster_B: My mother died waiting for 7 hours, before she was taken to hospital. She was refused transport by ambulance service, because of misdiagnosed by Paramedic.Poster_C: It could - the longer tissues are deprived of blood and oxygen, the greater the risk of having permanent damage. Always better to seek medical attention earlier when there are concerns of a stroke or of other similar types of issues.MD_Poster_D: Thanks Dr. [Name], I feel she could have been saved, if she had gotten treatment sooner. The doctors will not say one way or the other, they afraid of being ask to testify in court.Poster_C: I’m so sorry to hear about your loss – it’s really helpful for other people in this forum to hear about your experiences - so thank you for sharing them with us.MD_Poster_D: Dr. [Name], Thanks for your welcome response. You seem like a caring and knowledgeable Doctor. I would like to talk to you further about this situation, My email address is [email address] (Example Thread 1 from Heart Disease community)Poster_C: We observed that sharing personal experience pertaining to the main thread topic was commonly practiced. Although personal narratives can provide powerful information , they caAnother source of abrupt topic drift was requests to MD moderators. Many community members asked MDs personal questions in the middle of the threads, similar to Poster_C in Example Thread 1 above. Other causes of abrupt topic drift included jokes or the inability of community members to use the online interface. For example, members started new conversations or sent personal messages from within the thread, then excused themselves for changing the topic: “Hi guys, it maybe kinda off topic. I actually don’t know how to post my own topic  […]”.Sexual Health CommunityAbrupt topic drift occurred from multiple sources, including members’ desire to joke, share personal stories, or interact with MD members as well their inability to use the interface. Although complete prevention of abrupt topic drift may not be possible, some can be addressed through better design (see Discussion).We found 185 posts from 168 unique threads: 53 posts in which community members used the key term “hijack” and 132 posts in which community members used the key term “off topic”. We also found 2894 posts from 373 threads that contained either key term in the title. However, we did exclude the latter from analysis. Both members and moderators used the terms. After applying these criteria, only 118 posts from 114 unique threads were considered in this analysis.“Hijack” was associated with local topic drift whereas “off topic” was used to indicate both local and global topic drift. The types of topic drift were not mutually exclusive .Two major themes emerged from qualitative analysis and are presented below. First, we found evidence of a posting culture in members’ reactions towards abrupt topic drift . Second, contrary to previous research, we found that members supported having off-topic discussions .The following was a canonical example of how a community member believes threads should start and unfold in WebMD communities.It is usually best to start your own discussion if you have questions or are seeking support. Certainly, you can share your own experiences and that is encouraged here. […] Elaborating too much is sometimes considered “hijacking a thread” in internet message board lingo. Many times this happens in these discussions - they take many tangents with different twists and turns. […] Regardless of how a discussion evolves, I always pray that we all can find the answers and relief we need.Pain Management communityAs shown in the example post above, the community member was aware of topic drift and described it with the term “hijacking.” According to the member, hijacking could occur when a member elaborates too much or otherwise dominates a thread. Dominating the conversation has been associated with topic control and topic drift in previous studies ,21,29 be“Why do my post always get treated as if I am posting something none  needs to know I do not think I will post here anymore, :angry: [name]”.Diabetes communityAccording to Lambiase , off-top“I am sorry I hijacked your thread, [name]. That is a bad habit of mine. Your post IS valuable. […] Truly, [name], I didn’t mean to hurt your feelings. I am sorry.”Diabetes communityBecause WebMD members showed an intuitive understanding of the thread’s main goals, members worked to counteract topic drift by bringing the conversation back to the original purpose of the thread as shown in the following example post: “Since your question seems to have gotten hijacked by a debate about the economy and the merits of various forms of education, I’ll try to get it back on track […]”.Sexual Health communitychained explanation  ”.Sexual Health communityThe posts above show how community members reacted negatively to local topic drift and its negative effect on the main topic. These examples of topic drift often occurred in the middle of threads as conversations evolved. In contrast, members described starting off-topic discussions with regard to goals of the specific community  positively, which we describe next.Although members reacted negatively towards local topic drift in the middle of the thread, they reacted positively to off-topic stories  when shared separately in new threads. The following posts show the reaction of moderator and user member towards global topic drift.To all re your comments about staying on point....if this community were being taken over with off-topic and/or “fun” discussions, that would be one thing. But that’s not the case in this community or even on this thread. Yes, on any board there are newcomers and lurkers. They get good information and support here. But, to me, a bit of fun can also add to creating a community where someone would like to stay for a while.Diabetes community moderatorPersonally, if all that was discussed in any community on WebMD was the main topic, I would cease to be involved. I enjoy sharing with others and getting to know them by discussing what is happening in their lives other than the main health concern.Diabetes community memberOT or off topic in the title was suggested or practiced in 5 communities  as shown in the quote: “‘OT’ means ‘off topic.’Members showed support for having off-topic discussion because it could build rapport and bring members closer. However, members also suggested ways to indicate that the topic of the thread was unrelated to the health condition of the specific community. For example, adding either It lets people know the subject won’t be MS. Otherwise, someone will click on it expecting to find MS info, then they may get upset when they find that it’s not what they wanted.”MS communityP=2.69e-05, r=.13). Our findings suggest that members reacted negatively towards local abrupt topic drift and topic control similar to previous studies Poster_B: Bradycardia means a low heart rate, usually less than 60 beats per minute. A pacemaker can be recommended when bradycardia is symptomatic, or if there is another underlying electrical problem with the heart that increases the risk of the heart slowing even more or even stopping. Pacemakers work very well […]MD_Poster_C: Dear Dr. [Name], My mother is 73 years old, and had a pacemaker placed 2 years ago at the, Mayo Clinic. She is doctoring in her home town now. They are having trouble contoling her comidon levels, it has been 2 weeks now, and still do not have the levels controled. Is this unusual to have it take so long to adjust her levels?Poster_D: Thanks for your reply. One more question. How does all of this associate with the stints and I forgot to mention that my friend has had two heart attacks this past year. Can we possibly look forward to my friend having a long and somewhat healthy life if the pacemaker and his new medication, Coreg, do what they are supposed to do? I realize that I am asking you to look into a crystal ball, but surely you have an educated guess? (Example Thread 2 from Heart Disease community)Poster_A: In Example Thread 2, Poster_A is the original poster who started the thread with multiple questions including (1) bradycardia and (2) possible outcomes and expectations. Both Poster_B and MD_Poster_C focused on bradycardia and treatment options . Poster_D, however, changed the topic to Poster_D’s personal question and attempted to engage in a side discussion with the MD_Poster_C. The original poster, Poster_A, counteracted this drift by bringing the topic back to the unanswered question by elaborating on their situation. The 2 most common ways original posters counteracted topic drift were (1) focusing the discussion to the remaining unaddressed issues and (2) correcting the discussion trajectory .“I urge you to start another discussion”).In our manual analysis, we found that original posters put in the most counteraction effort. Other users and members with defined roles  also counteracted topic drift. However, they also went along with the current topic of conversation at times. Similar to original posters, MDs, moderators, and other users counteracted topic drift by (1) addressing unanswered questions after topic drift had occurred or (2) discouraging abrupt topic drift . When we compared counteraction effort among roles, we found a significant difference  showed promising results as an application to track topic drift. Next, we evaluated our automated technique for detecting counteraction to topic drift using our manual assessment of 50 posts as the gold standard. Our findings shed light on how topic drift unfolds in online health communities, how members of these communities react to topic drift, and who brings topics back to the original intent of threads through counteraction. We also address gaps in previous literature by illustrating possible benefits of having off-topic discussions, highlighting counteraction provided by different types of community members, and applying an automated method to detect topic changes at the thread level.Topic drift occurred in our online community data at 2 levels: global  and local . Previous studies associated topic drift from global goals with incoherence  and descOT or off topic titled threads that purposely discussed off-topic issues. Both power users and moderators supported these off-topic discussions representing global topic drift. The off-topic discussion supporters, however, advocated that the off-topic nature of threads be indicated in the title so that the threads would not interfere with other discussions that pertained to the global goals of the community. The supporters voiced the opinion that off-topic discussions could build rapport and bring members closer. Such support might not be representative of reactions towards topic drift more generally because we focused only on self-identified topic drift threads.However, in the online health communities we analyzed, we found topics generally stayed within the global level  with the exception of OT in the title. Given this confusion, we suggest that designers and administrators of online health communities consider other structured ways to have off-topic discussions (see further discussion below).We found that having off-topic discussions, as indicated by global topic drift, positively affected online health communities. For instance, many off-topic discussions were lively and humorous, which was in direct contrast to the melancholy and serious tone of many on-topic discussions. Moreover, off-topic discussion threads  had higher levels of participation. However, we did not find evidence that regular users supported off-topic discussions in our manual assessment. We suspect that either our sample size was not large enough or that only experienced members  were aware of the culture of sharing off-topic discussions. We reached this conclusion because we observed posts that asked about the meaning of Although power users and moderators supported off-topic discussions at the global level, most members reacted negatively towards abrupt local topic drift. We observed 2 types of local topic drift: gradual topic drift and abrupt topic drift. Gradual topic drift, in which only a fraction of topics changed through a semantic parallel, occurred most frequently. This change is common and expected in any conversation . MembersMany online communities use moderators and even community members to regulate the content of posts. Manual efforts of monitoring posts have been shown to miss or misjudge important posts . Our autMoreover, moderators could use automated methods as a supplement to reduce the burden of keeping discussions on track. Automated methods could alert moderators of abrupt topic drift occurring in the middle of threads. An immediate alert could allow moderators to provide timely support and minimize negative impacts. As for the community, similar automated methods could provide the basis for filtering spam or abusive content, while keeping relevant on-topic content available to the community.Expanding these topic-oriented automated methods could further enhance online health communities by (1) locating topically relevant posts  in threaWe also offer design considerations based on our findings. Our findings suggest that facilitating off-topic discussions could benefit members who desire emotional connection and lighten the mood of the community. The popularity of off-topic discussion threads also suggests that support for limited off-topic discussions could contribute to sustained participation, which is a prominent challenge for online communities ,51.We discovered that some members expressed a reluctance to change topics completely but did so anyway because starting a new thread or sending a private message was not an intuitive process. An intuitive interface supporting the creation of new topics or branching off a new side conversation might reduce abrupt topic drift.One limitation in our qualitative analyses was that we had a single analyst and a dataset with 7 communities within the WebMD platform. Therefore results may not be generalizable to other communities. We recognize the limitation of using a single analyst. However, a previous study illustrated that the interpretation of topic drift can be subjective , thus weWe also considered observations within the unit of analysis  as independent; nevertheless, correlation could exist in the counteraction effort a member provides when acting in different roles. However, both qualitative and quantitative analyses showed consistent results in a diverse group of online health communities in WebMD. Findings could indicate that original posters have a higher stake in keeping the thread on topic than other members. This finding, however, could also be due to differences in the responsibilities of moderators and other types of community members.From previous research, we expect moderators to recruit new members, temper discussions, and create an engaging and respectful community culture . AlthougOur findings suggest that topic drift occurs despite apparent differences in health aspects  and representative demographics  of different communities. Understanding how these differences affect topic drift could deepen our understanding in future work. Although our term-based similarity metric was not developed to analyze conversations, our study showed its practical application for analyzing CMC through consistent results across the seven diverse WebMD communities. An extended evaluation using a large gold-standard dataset could investigate the effectiveness of this as well as other sophisticated similarity measurements, such as knowledge-based  and corpWe provide new insights into topic drift by illustrating possible benefits of having global topic drift in online health communities, identifying sources of abrupt local topic drift, highlighting considerable counteraction provided by original posters, and creating automated methods to detect topic drift and counteraction at the thread level. Our findings suggest that members react negatively towards local topic drift in the middle of the thread but advocate sharing globally off-topic stories to build rapport and bring members closer. Although many members counteract topic drift, original posters appear to provide the most effort to keep their threads on topic. Finally, we demonstrated automated techniques to detect both topic drift and counteraction. Based on these findings, we have contributed practical suggestions for designing online health communities to better facilitate online discussions. Findings from this study have the potential to reduce topic drift and improve online health community members’ experience. Such experiences could improve the personal health management of members who seek essential information and support during times of difficulty.


There is a persistent shortage of underrepresented minority (URM) faculty who are involved in basic biomedical research at medical schools. We examined the entire training pathway of potential candidates to identify the points of greatest loss. Using a range of recent national data sources, including the National Science Foundation’s Survey of Earned Doctorates and Survey of Doctoral Recipients, we analyzed the demographics of the population of interest, specifically those from URM backgrounds with an interest in biomedical sciences. We examined the URM population from high school graduates through undergraduate, graduate, and postdoctoral training as well as the URM population in basic science tenure track faculty positions at medical schools. We find that URM and non-URM trainees are equally likely to transition into doctoral programs, to receive their doctoral degree, and to secure a postdoctoral position. However, the analysis reveals that the diversions from developing a faculty career are found primarily at two clearly identifiable places, specifically during undergraduate education and in transition from postdoctoral fellowship to tenure track faculty in the basic sciences at medical schools. We suggest focusing additional interventions on these two stages along the educational pathway. Science benefits from diversity, and in this regard, there have been many reports that reflect a recognition of the inherent value of a more diverse workforce,2. IndeeIndividuals classified as underrepresented minority (URM) are scientists who self-identify with a racial or ethnic minority group “underrepresented in science”  to increase diversity in this area. The synThirty years ago it was accurate to state that URM trainees were being lost at every stage in the process. However, this analysis of currently available US national data sources indicates that the diversions of URM scholars from the goal of developing a faculty career specifically in biomedical research are found primarily at two highly identifiable places, (1) during undergraduate education, and (2) in transition from postdoctoral fellow to faculty. As a secondary question, we looked at the broader trends among biomedical education and how the field is growing. While there had been a large increase in biomedical PhD students from 2000–2008, after this date the numbers of matriculating and graduating doctoral students are no longer increasing.This study focused on the students and postdocs who contribute to diversity specifically in those areas of basic biomedical research that are substantially supported by grants from the NIH. URM trainees are defined as individuals who self-identified as belonging to one or more of the following racial or ethnic groups: Black or African-American, Hispanic or Latino, and American Indian or Alaskan Native. “Other” students refers to US citizens who have self-identified with two or more races or ethnic groups, or those who have chosen not to identify with any ethnic group, or those whose ethnicity is unknown to those conducting the survey. In the national data sources those who identified as Native Hawaiians or Pacific Islanders are grouped under the Asian American or Asian category which made it impossible to track them as a unique group underrepresented in science. Additionally, the appendix tables available from the NSF’s surveys did not report students with physical disabilities nor those who came from an economically disadvantaged or rural background. Therefore, we focused our study on those URM groups that have data consistently available across all national sources.We sought to identify the points of diversion in the pathway to tenure track URM faculty, which extends from graduating high school seniors to the stage of securing tenure track faculty positions in biomedical research. We used two methods to examine the pathway to faculty positions . The synthetic cohort method, similar to that used by Garrison et al, was useTo study the demographics of the later stage educational pathway, we used available national historical data from 2000–2013. This second method examines the demographics of those following a traditional trainee trajectory from undergraduate, to graduate student, through postdoctoral fellowship to a tenure track faculty position over this time period. The data sources are clearly identified in Digest of Education Statistics . In. In22]. As reported by the NSF, the number of URM full-time faculty in the life sciences has increased from 2,000 in 1993  to 5,200 in 2013 (7.3%) . We are A summary of the increasing levels of participation by URM students and postdoctoral fellows in the academic environment leading to tenure track faculty positions is shown in In this paper we have examined the various checkpoints where URM individuals are lost from the pathway leading to faculty positions. This analysis reveals there are two times that persist as areas of concern, in addition to three checkpoints where minimal losses occur. We discuss these various checkpoints in order of their occurrence.The first major interruption in the pathway to faculty is during the stage of undergraduate education. Over the last fifteen years there has been an increasing number of degrees awarded to URM students, which is clearly an accomplishment; however, the graduation rate is below expectations based upon the number of incoming undergraduate URM students who express an interest in graduating with a biological sciences degree. This poor retention rate likely reflects nation-wide attrition from college, which has been shown to be higher among minority groups and economically disadvantaged students ,26.Similar to our findings, the NCES released a report that found that attrition rates in non-STEM fields were as high or higher than those in STEM fields in their defined cohort. Additionally, their study found that nearly one-half of the students in their STEM cohort did not complete a degree in STEM ,26. Six Although it is possible to increase college completion rates by looking at a cohort of students six years after matriculation rather than four years, the relative outcomes of the different populations of students are not widely different enough to justify moving our analysis to examining our cohort at 6 years past matriculation into a bachelor’s degree. Both the NCES’s longitudinal cohort and our broad synthetic cohort all show that URM undergraduate attrition is an area of great loss of human capital to our field of interest in biological sciences, as well as to every other STEM and non-STEM field. Because this study is pseudo-longitudinal and does not follow the same sample of people, limitations exist. The cross-sectional data do not capture students who matriculate into an undergraduate or graduate institution after being out of school for an extended amount of time or students who take a leave of absence during their education. The data do not account for individual differences, such as individuals who may have participated in intervention programs targeted for underrepresented minorities. Despite these limitations, the national data available to us strongly demonstrate that URM undergraduate attrition is a major diversion of candidates from a trajectory leading ultimately to faculty positions. There is a critical need for interventions focused on improving retention of all students at the undergraduate level.After the significant loss of URM students during undergraduate studies, our study reveals three checkpoints of minimal loss in the pathway to faculty. These checkpoints are matriculation into a doctoral program, receipt of a doctoral degree, and acquisition of a postdoctoral position. Considering that URM students are earning roughly 18% of the bachelor's degrees in biological sciences in 2013, we are encouraged that 15% of the doctoral students and 13% of the doctoral graduates are URM. These strong rates of persistence are promising to those who have worked hard to design interventions targeting persistence from graduate school matriculation to graduation. Similar to doctoral graduation persistence, we see comparable URM retention at the postdoctoral level. In 2013, URMs made up 11% of the postdoctoral fellows employed at academic institutions in the life sciences which also demonstrates that URMs are interested in pursing a postdoctoral fellowships at a similar rate to White doctoral graduates. Clearly, overall, one of the major positive outcomes detected by this study is the observation that the fraction of URM trainees is steadily increasing at every stage in the analysis over the entire 13 years (2000–2013).We credit several successful interventions for reinforcing the integrity of the educational pathway for a URM trainee. An almost certain factor in this trend is the success of a range of programs devised by the NIH and NSF, such as the MARC, PREP, IMSD, minority summer programs, and especially the T32 programs at the NIH. By requiring intentional recruitment of and participation from diverse trainees on all T32 grants, the NIH plays a major role in increasing diversity at the graduate and postdoctoral level. A recent National Research Council study showed that an institution’s minority student population increases in an environment supported by NIH training grants .Although minority participation increased in graduate training and in doctoral receipt from 2007–2013, the overall student and graduate numbers  in the biomedical sciences field remained constant. This is an extremely important observation as there is a popular misperception that the number of PhDs awarded in biomedical science graduate programs is increasing vigorously. In a recent article the statement was made that for the life sciences, “the number of doctoral recipients shows no signs of leveling off” . While iThe second major interruption in the pathway to faculty in the basic sciences occurs immediately after a trainee’s postdoctoral fellowship. Compared to their non-URM peers, far fewer URM postdoctoral trainees transition into faculty positions in AAMC basic science departments, which is in agreement with a recent report from Gibbs et al on all STEM fields . This laIdeally, one would like the demographics of the faculty in biomedical sciences to closely match those of the US population, which would result in at least a 30% URM composition. The NIH strives for more diversity within its scientific community believing that better ideas and discoveries will come from diverse groups ,28. HoweIn conclusion, within the last decade we see that minimal losses occurred during the transition into graduate school doctoral programs, attainment of a doctoral degree, and when securing a postdoctoral position. These are encouraging results; however, we remain profoundly concerned that URM trainees divert substantially from a biomedical faculty career during (1) undergraduate education and (2) in the final transition from postdoctoral fellowship to tenure track faculty position. Thus, as NIH, universities, and other institutions are committed to increasing diversity at the faculty level, they will need to focus their attention on the contributing factors to stages where major losses occur.S1 FigFor all ethnic groups, there is an increasing amount of interest in the biological sciences upon matriculation into college. Black, Latino, and White students express similar interest in this area.(TIFF)Click here for additional data file.S2 FigAs seen in the synthetic cohort, Whites who express an interest in biological sciences are nearly twice as likely to complete a bachelor’s degree in biological sciences four years later than URM students.(TIFF)Click here for additional data file.S1 Table(PDF)Click here for additional data file.