The field of therapeutic focused ultrasound, which first emerged in the 1940s, has seen significant growth, particularly over the past decade. The eventual widespread clinical adoption of this non-invasive therapeutic modality require continued progress, in a multitude of activities including technical, pre-clinical, and clinical research, regulatory approval and reimbursement, manufacturer growth, and other commercial and public sector investments into the field, all within a multi-stakeholder environment. We present here a snapshot of the field of focused ultrasound and describe how it has progressed over the past several decades. It is assessed using metrics which include quantity and breadth of academic work , funding trends, manufacturer presence in the field, number of treated patients, number of indications reaching first-in-human status, and quantity and breadth of clinical indications. The first publication to demonstrate focused ultrasound's potential therapeutic use appeared in 1942 . At thisThe Food and Drug Administration (FDA) first approved a focused ultrasound (FUS) device in 1988 ,5. This In the 1950s, Vallancien et al. reported clinical results with a new system that employed ultrasound imaging for guidance and a thermocouple for thermal measurements. This system was used to treat patients with bladder cancer . This leMagnetic resonance imaging (MRI)-guided focused ultrasound devices were introduced in the early 1990s -14, withThe development of multielement transducers ,16 allowTo date, a significant amount of work has been performed using various ultrasound (US)-guided and MRI-guided systems for the treatment of symptomatic uterine fibroids ,34; braiTo date, more than 80,000 patients have been treated globally using a variety of ultrasound-guided and MRI-guided therapeutic high-intensity focused ultrasound devices.In order to evaluate the growth of the field of focused ultrasound, and to shine a spotlight on its current level of development and clinical adoption, two primary areas have been assessed, namely historical progress in financial support and general awareness of focused ultrasound, and the health impacts of the field.The financial support and general awareness of focused ultrasound can be assessed by tracking the amount of research funding provided to focused ultrasound projects, the number of publications in peer-reviewed journals, and general awareness metrics such as visits to specific focused ultrasound websites, including its Wikipedia page.The impact of focused ultrasound on the health of the global community can be gleaned through examination of the number of clinical indications reaching first-in-human stage and of how many patients have been treated.For this evaluation, several metrics and data sources were used including the annual number of publications (Medline) and citations (Thompson Reuters Web of Science); the number of abstracts presented in meetings dedicated to focused ultrasound , the biennial meeting organized by the Focused Ultrasound Foundation (FUSF—founded in 2006), and the European Focused Ultrasound Working Group (EFUS—founded in 2011)); the clinical indications that have reached the level of human feasibility trials (obtained from literature review and communications with relevant researchers); the number of annual treatments administered (from manufacturers' reports); manufacturer growth within the field; and the amount of National Institutes of Health (NIH) funding allocated to focused ultrasound research. In addition, the number of hits on the FUS Foundation website and FUS Wikipedia page were used as indicators for general awareness of and interest in the field. This data was used to evaluate the historical progress and current status of FUS as a treatment modality for a variety of clinical indications.The annual number of publications was obtained using the Medline trends online tool, with the search term ‘focused ultrasound’ which is inclusive for most other terms used in this field. The Thomson Reuters Web of Science was used to assess the number of citations per year, with the same search criterion.Organizers of focused ultrasound-specific scientific meetings were contacted in order to assess the number of abstracts presented at these meetings. Where these organizers could not be reached, the number of publications listed in the Proceedings for these conferences was used.Manufacturer count and type were obtained by requesting information from industry executives, online research, and information collected through focused ultrasound symposia registration and sponsorship data. Only manufacturers developing an image-guided, non-invasive device using focused ultrasound for therapy or pre-clinical research, including systems solely for animal research, were included in these metrics.The number of patients treated was acquired for each clinical indication by contacting the relevant device manufacturers. To identify the time point at which each clinical indication reached a feasibility clinical trial, the authors surveyed researchers in the relevant clinical field, reviewed articles, and conducted specific literature searches.NIH funding allocation to focused ultrasound research was obtained using the NIH RePorter database. The terms ‘high intensity focused ultrasound,’ ‘focused ultrasound therapy,’ ‘ablation,’ ‘drug delivery,’ and ‘HIFU’ were searched for separately, but the data was aggregated and duplicates were eliminated. Search results were further refined based on the relevance of the listed projects. Data were analyzed and presented by year, total HIFU annual funding, and funding as a percent of the total NIH budget. Total annual NIH research spending was extracted from NIH annual reports. In this work we present only NIH funding and not funding from sources in Europe and Asia because these data were not publicly available in a single location. We assume the NIH funding could be considered as a surrogate for government funding worldwide.The visits to the FUS Foundation website were analyzed using Listrack and Google analytics. The number of Wikipedia page views was collected using stats.grok.se with the key word ‘high-intensity focused ultrasound.’ These general awareness metrics data were analyzed and are presented by month or quarter, with significant events highlighted on the timeline.The data collected and the search terms apply to therapeutic focused ultrasound, with the majority on it being for high-intensity focused ultrasound, and thus distinct from non-focused therapeutic ultrasound that is used for physiotherapy or other indications.As shown in Figures Figure As shown in Figure The data presented shows evidence of progress in the field of focused ultrasound. This is demonstrated by the number of clinical indications explored, which has increased from 1 to 21 since 1950, or by the increase in the amount of research as indicated by the steady increase in the number of publications. In addition, the number of abstracts at focused ultrasound events and symposia is also on the rise, indicating a higher level of activity . Publications and citations for focused ultrasound have also been increasing yearly and by a greater percentage than the total number of medical publications, indicating that focused ultrasound research is growing faster than medical research overall. A similar trend of growth could be seen also in the increase in funding allocated to focused ultrasound and by web traffic in sites dedicated to this topic.This data, however, continues to pose important questions about metrics and data collection. How can the community measure progress in a field that is developing globally across many different clinical indications? Should progress be measured using translation and application or technological capability metrics? How can public awareness be measured and correlated with adoption?Collection of relevant data remains a challenge for the focused ultrasound community. Most funding data is publicly available only for programs in the USA. This means that some global impacts cannot, as yet, be measured or compared. Additionally, research site, manufacturer, and clinical site information is collected only for the organizations that actively participate in the focused ultrasound community and regularly submit their information on a voluntary basis. This means that it is harder to collect data from some regions than others, skewing the geographic representations of the focused ultrasound field. The Focused Ultrasound Foundation would like to invite the community to engage with its business development team to enable better data collection and increased global awareness.The field of therapeutic focused ultrasound has been steadily growing since its inception in the 1940s. The results presented here, obtained using quantitative metrics and publically accessible data sources, offer a snapshot of the progress in the development and clinical adoption of this technology. Data indicates that there is widespread progress in scientific and clinical research which may lead to increased adoption of the technologies for the benefit of patients worldwide.This data, however, continues to pose important questions, particularly for the Focused Ultrasound Foundation. How can future growth potential be identified and our resources mobilized to maximize progress in this area? How can we overcome the barriers along the pathway from idea conception to successful patient treatment, to catalyze the process and bring this non-invasive therapy to patients faster?The Focused Ultrasound Foundation may be the most appropriate organization to continue to track the field's progress. If so, it needs input and guidance from the focused ultrasound community to strengthen these efforts. Suggestions for further metrics relevant to the development of the field and the sharing of information in the areas currently being monitored would be welcomed.progress@fusfoundation.org.The FUS Foundation aims to provide the most accurate information. If you have more current information, please send it to


Current projections of the scale of the coming dementia epidemic assume that the age- and sex-specific prevalence of dementia will not vary over time, and that population ageing alone (increasing the number of older people at risk) drives the projected increases. The basis for this assumption is doubtful, and secular trends  are perfectly plausible.We carried out a systematic review of studies of trends in prevalence, incidence and mortality for people with dementia, conducted since 1980.We identified nine studies that had tracked dementia prevalence, eight that had tracked dementia incidence, and four that had tracked mortality among people with dementia. There was some moderately consistent evidence to suggest that the incidence of dementia may be declining in high-income countries. Evidence on trends in the prevalence of dementia were inconsistent across studies and did not suggest any clear overall effect. Declining incidence may be balanced by longer survival with dementia, although mortality trends have been little studied. There is some evidence to suggest increasing prevalence in East Asia, consistent with worsening cardiovascular risk factor profiles, although secular changes in diagnostic criteria may also have contributed.We found no evidence to suggest that the current assumption of constant age-specific prevalence of dementia over time is ill-founded. However, there remains some uncertainty as to the future scale of the dementia epidemic. Population ageing seems destined to play the greatest role, and prudent policymakers should plan future service provision based upon current prevalence projections. Additional priorities should include investing in brain health promotion and dementia prevention programs, and monitoring the future course of the epidemic to chart the effectiveness of these measures. Almost all current projections of the scale of the coming dementia epidemic, including those published by Alzheimer’s Disease International (ADI) –3, assumIt should be noted that trends in the two indicators may not move in the same direction; for example, reductions in incidence might be accompanied by increases in duration of survival with dementia, or vice versa, the one effect tending to cancel out the other in terms of their overall impact on prevalence. Secular trends may vary among world regions, and among different population subgroups within one country. Experience with changing rates of cardiovascular disease, obesity, diabetes and cancer shows this clearly. Geographic or year of birth variations in adult disease occurrence can be explained by differential exposure during different epochs in life, since as early as conception. Hence, the considerable variability in secular trends for these chronic diseases reflects different degrees of progress in improving public health and access to healthcare, and in strengthening health systems and services to better detect, treat and control these conditions.A decline in age-specific incidence of dementia, at least in high-income countries, is theoretically possible, driven by changes in exposure to suspected developmental, lifestyle and cardiovascular risk factors for dementia . The 201Secular trends in survival with dementia are difficult to measure. Because dementia has a long and highly variable latency period, estimates from clinical services are confounded by time of diagnosis. If diagnosis is being made at an earlier stage in the disease process, then duration of dementia may appear to be increasing, whereas this may signify only that people with dementia are in contact with services for a higher proportion of the overall disease duration. Trends in cause of death on death certificates provide information on secular changes in the attribution of dementia as a cause of death, but not on the all-cause mortality rate among people with dementia . A propeFinally, it should be noted that one of the indications of successful dementia risk reduction may be that the incidence of dementia is deferred to older ages. Thus, the average age of onset may increase over time. Under these circumstances, age-specific or age-standardised mortality for people with dementia may not change, but overall, for all people with dementia, mortality may be higher and survival with dementia shorter, reflecting that onset is occurring closer to the ‘natural’ end of life. Langa has described this phenomenon as ‘the compression of cognitive morbidity’ , a desirAt the time of the 2009 World Alzheimer Report, what very few data were available from certain high-income countries did not suggest any clear pattern of a decline or increase over time in either the incidence or prevalence of dementia , 22, 23.Studies of secular trends since 1980 in the prevalence or incidence of dementia or Alzheimer’s disease within defined populations were identified from the systematic review of studies of dementia prevalence and incidence conducted by the Global Observatory for Ageing and Dementia Care for the World Alzheimer Reports of 2009 , and froWe identified nine studies that had tracked changes in dementia prevalence over time Table . In one Nine studies had tracked dementia incidence over time Table . StatistIn only four of the studies did the researchers take the opportunity to study or report changes in mortality and/or survival among people with dementia, or the ratio of mortality rates between those with and without dementia Table . In the Another approach to estimating secular trends involves combining evidence from all studies conducted within a particular country or region, using a meta-analytical approach and meta-regression to estimate the effect of time of study upon prevalence. This approach was used in the 2009 ADI World Alzheimer Report to estimate secular trends in dementia prevalence in Europe . One proEast Asia is the one other world region with sufficiently numerous prevalence studies to permit meta-regression and estimation of secular trends in dementia prevalence. A study of secular trends in Japan (part of the adjacent Asia Pacific high-income region) reported a tendency towards increasing prevalence, but this was based on only eight data points, including the four waves of the Hisayama study , and didDiagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III), the DSM-III-R, or the International Classification of Diseases, Tenth Revision, which then tended to record a lower prevalence of dementia than those more recent studies that used DSM-IV dementia, 10/66 dementia criteria or Geriatric Mental State Examination (GMS)-Automated Geriatric Examination for Computer Assisted Taxonomy (AGECAT) criteria. For the purposes of estimating current dementia prevalence, whether the higher estimates for the most recent period are explained by real underlying secular trends or the use of more up-to-date and valid diagnostic criteria, or both, is immaterial. However, for the purposes of forecasting future trends in prevalence and numbers in the region, the distinction is clearly crucially important [The most important potential confounder appeared to be the choice of dementia diagnostic criteria. Older studies tended to use criteria from the mportant . As prevmportant , a trendmportant . The premportant . Rapid dmportant . A recenmportant . The relWe have updated our recent work on the global burden of dementia and reviewed the entirety of the current global evidence on trends in the prevalence, incidence, and survival with or mortality due to dementia, using data from studies in which investigators had monitored these indicators over time in defined populations with fixed survey and dementia ascertainment methodologies. We also reviewed regional meta-analyses in which researchers had sought to estimate regional trends in prevalence across studies, conducted in various sites and using diverse methods. The present review is the most comprehensive such study to date.There is no clear evidence from this review to justify a departure from the current position of assuming constant age-specific dementia prevalence when making projections of the numbers likely to be affected in the future . The eviThe future course of the global dementia epidemic through to 2050 is likely to depend, at least to some extent, upon the success or otherwise of continuing efforts to improve public health , 25. ThoWhether declining incidence is accompanied by a decline in the age-specific prevalence of dementia will depend upon any coincident changes in survival and/or mortality patterns of people living with dementia, which are difficult to predict on the basis of current data. If the onset of dementia occurs close to the end of the natural lifespan, fewer years may be lived with dementia. Two studies suggest that decline in incidence may be greater in younger age groups, suggesting that the incidence of dementia may be being deferred into older age , 52. ThiOther factors, such as improvements in standards of health and social care for people with dementia as well as provision or withholding of life-prolonging critical interventions, might also be expected to have an influence on mortality rates among people living with dementia. In well-resourced, advanced healthcare settings, there is growing awareness that critical interventions should not be withheld simply because someone has dementia when these would improve quality of life. At the same time, in the context of end-of-life care, the focus should be on palliation to improve quality of life, and interventions that merely prolong life with risk of harm to the patient should be withheld . In low-Studies that use fixed methodology to estimate changes in dementia prevalence, incidence and mortality over time, in defined populations, are uniquely valuable assets. It is important that more such studies be commissioned. The most valuable will be those that track all three parameters over time, which none of the studies reviewed in this paper did. Surveys with nationally representative samples will have the greatest generalisability and the greatest potential to both inform and track the impact of national policies. Where trends are observed, it will be important to relate these to compositional changes in the population, particularly to changes in levels of exposure to critical risk factors. However, in very few studies have researchers made a comprehensive assessment of such compositional factors and their changes over time, and in only three studies did investigators attempt to attribute changes in dementia frequency to changes in risk factor exposure , 37, 38.In previous modelling exercises, researchers have sought to predict what might happen to the future prevalence of dementia, given our best estimates of risk associations and possible changes in those risk factor profiles over time , 50. In Lancet editorial [The projections of the ADI report for 2050 are alarming, but it is important to bear in mind that they are just that – projections.... The opportunity is here to ensure that the grim outlook for dementia in 2050, especially in low-income and middle-income countries, becomes nothing more than a work of fiction.The best available evidence suggests that the age-specific prevalence of dementia is unlikely to change significantly in coming years, even if the incidence of dementia falls in response to secular improvements in public health in high-income countries. This conclusion remains provisional, given the limited data available on secular trends and the heterogeneity in study findings. Prudent policymakers should exercise due caution, being swayed neither by individual studies nor by Pollyannaish statements, such as expressed in a recent ditorial :The projFuture projections  may actu


Music is a potent mood regulator that can induce relaxation and reduce anxiety in different situations. While several studies demonstrate that certain types of music have a subjective anxiolytic effect, the reported results from physiological responses are less conclusive. Virtual reality allows us to study diverse scenarios of real life under strict experimental control while preserving high ecological validity. We aimed to study the modulating effect of music on the anxiety responses triggered by an immersive virtual reality scenario designed to induce fear of heights. Subjects experienced a virtual scenario depicting an exterior elevator platform ascending and descending the total height of its 350 meters tall supporting structure. Participants were allocated to either a group that experienced the elevator ride with background music or without, in a between-groups design. Furthermore, each group included participants with different degrees of fear of heights, ranging from low to high fear. Recordings of heart rate, galvanic skin response, body balance, and head movements were obtained during the experiments. Subjective anxiety was measured by means of three questionnaires. The scenario produced significant changes in subjective and physiological measures, confirming its efficacy as a stressor. A significant increase in state anxiety was found between pre and post-assessment in the silence group, but not in the music group, indicating that post-stress recovery was faster in the musical group. Results suggest that music can ameliorate the subjective anxiety produced by fear of heights. Anxiety is an adaptive and complex emotion consisting of physiological, cognitive, and behavioral components  resulted in an increased feelings of relaxation and a reduction in state anxiety, when compared to groups who sat in silence or listened to heavy metal music . The resHowever, a series of studies have demonstrated that music can also prevent significant increases in physiological responses due to anxiety. Additionally, other studies have demonstrated that music can facilitate recovery from a psychologically stressful task by modulating the post-stress responses of the hypothalamic pituitary adrenal axis and cardiovascular system. Researchers found significant decreases in salivary cortisol and systolic blood pressure in subjects who recovered from a laboratory stressor with relaxing background music in comparison to silence . Along tOne of the major problems in psychological research is that of trying to link ecological validity to experimental control . The majin vivo exposure therapy in the treatments of acrophobia, fear of flying, or post-traumatic stress disorder  can evoke the sense of presence, which refers to behaving and feeling as if we were in a virtual world created by computer displays . The building had a total of nine floors. To add realism to the experience we included a background noise of an elevator moving and stopping through each floor, in both conditions. In order to take baseline measures we also created a neutral virtual setting on the ground floor that depicted a terrace with tables and chairs.The virtual environment used for this experiment depicted an exterior elevator platform ascending and descending the total height of its supporting structure -350 m tall  and after the VR exposure (postSTAI) to assess possible differences between conditions in the post-stress recovery response. The measure of interest, is the difference between the post-experiment total score and the pre-experiment total score (dstai = Poststai-Prestai). The more negative the values, the less anxiety experienced after the virtual scenario. Participants also answered the trait anxiety subscale before going through the VR experience.The State Trait Anxiety Inventory-Form Y (STAI-Y) is a self-report survey containing two independent 20-item scales that measure state and trait anxiety. This inventory was developed by dAPQ = PostAPQ-PreAPQ). The more negative the values, the less physiological self-awareness during the VR experience.The Autonomic Perception Questionnaire (APQ) is a 24-item visual analog scale used for the assessment of self-awareness of physiological activation . High scores in APQ indicate greater awareness of bodily sensations and correlates positively with anxiety, heart rate and skin conductance response . In the Table 3 summarizes the specific items included in this questionnaire. This type of information is useful in VR research since it provides further data to understand how people react in virtual environments. A similar strategy was used in With the objective of taking into account the degree of presence that participants experienced during this study, we included a 7 point Likert-type questionnaire that subjects had to fill in at the end of the session. The physiological measures recorded in this experiment were electrodermal activity (EDA) and electrocardiogram (ECG). EDA responses are widely used as indirect measures of emotional arousal through changes in skin conductance, since they are strongly related to sympathetic responses. In this study, we measured and analyzed skin conductance level (SCL) which is related to a person’s overall arousal .From the ECG signal the main measurement analyzed was heart rate, defined as beats per minute (bpm). Past studies have shown that HR is a reliable measure of stress in response to a threating situation in virtual reality and real environments . To carrThe physiological recordings were over each of the first 30 s after the subject arrived at each floor. Also during this time he had to judge his or her level of anxiety while looking down. In total there were 20 trials per subject, including: baseline, each individual floor, which was visited twice (while ascending and descending), and a last trial taken on the ground floor. Furthermore, to eliminate within group variability in arousability, we analyzed the percentage of change from baseline in HR and SCL rather than absolute values. Normalization was carried out based on the literature using the following formula: Percentage of change = 100 × [/baseline] .With the aim of measuring behavioral parameters related to fear of heights we used a force platform (see above) to register center of pressure (CoP) coordinates. It has been demonstrated that significant changes occur in CoP displacements or postural stability as a result of anxiety and fear induced by standing on the edge of an elevated surface and also that individuals suffering from acrophobia might have prior abnormalities in balance control . FurtherAs with physiological measures, the analysis was done over 30 s windows, with a total of 20 trials per subject, and to control for within-group variability, normalization of the data was carried out following the same formula as above.Figure 1B). A 2-min baseline measurement was taken in a neutral virtual scenario, located on the ground floor. Afterward, the actual experiment started with the elevation of the virtual platform to the top of the building, stopping at all floors on the way. The elevator then followed the reverse path to the ground floor. Subjects remained for an average of 40 s on each floor during which a beep sound prompted them to state out loud their SUDS score. Finally subjects were asked to again complete the post-experiment questionnaires of the STAI and APQ. They also completed a questionnaire that gave basic demographic data such as age, gender, nationality, computer literacy, programming literacy, medication intake, alcohol intake, and presence or absence of any medical condition. Finally, they filled in a questionnaire to assess their perception of the virtual experience.Each participant was asked to sit down in a quiet room and read a brief explanation of the experiment. They were requested to sign a consent form if they were willing to participate. In the brief explanation, participants were told that they could withdraw from the experiment at any time without explanation. Upon agreement, we first administered the STAI and then the APQ. Participants were also instructed in how to report their Subjective Units of Discomfort (SUDS). After participants had finished answering the pre-questionnaires they put on the physiological devices, shutter glasses and a microphone to communicate with the experimenter. Subsequently, participants entered the Cave system. They were instructed to stand on the Wii Board with the toes of their feet protruding from the edge  and the Acrophobia Questionnaire (AQ) as a covariate in order to control for participants’ different degrees of fear of heights. Ordered logistic regression is the appropriate method for the analysis of ordinal scales from questionnaire data since the assumptions of the standard general linear model (regression and ANOVA) that the responses be on an interval scale and normally distributed are obviously violated.The Subjective Units of Discomfort, Heart Rate, Skin Conductance, and Balance Parameters, were analyzed using a mixed effects model with fixed effect Group (music and no music) and Direction (ascending and descending). The random effects were defined within individuals. In this analysis, we included the “Floor Level” as a covariate. The floor level could potentially influence the degree of anxiety since participants tend to report increased levels of anxiety on higher floors.Finally, for analyzing the State Trait Anxiety Inventory and Autonomic Perception Questionnaire responses, a one-way ANCOVA was carried out. In this analysis, AQ was also included as a covariate in order to control for the degree of fear of heights.n = 19 in the music condition and n = 20 in the no music condition.One participant from the music condition was excluded from the analysis, since she was an outlier in some questionnaire responses and we realized that she was not a native Spanish speaker. This left a total sample of Figure 2 summarizes the boxplots for the different questions included in the virtual reality experience questionnaire (see questions in Table 3). In order to assess possible differences between the conditions, we ran an ordered logistic regression analysis on each questionnaire item, including Group (music and no-music) as a fixed factor and AQ as a covariate. For the questions presence, realism, real vs. virtual, and attention to scene, no main effects of Group  or AQ  were found.p < 0.01, Odd Ratio (OR) = 1.14) and of Group  on the stressful questionnaire item. This result indicates that higher AQ scores are related to greater cumulative scores in the stressful question. Furthermore, this result also shows that subjects in the music condition have lower cumulative scores on the stressful question in comparison to the no-music group. We also found a significant main effect of AQ on the fear of falling  and attention to beep  questions. However, we did not find a significant effect of Group in these questions . This indicates that higher AQ scores are related to a higher degree of fear of falling and to more attention paid to the beep sound during the virtual experience. Finally, we found a significant main effect of Group, but not for AQ (p = 0.50), on the attention to elevator  question. This shows that participants in the music condition have lower cumulative scores on the level of attention paid to the virtual elevator in comparison to the no-music condition.However, we found a significant main effect of AQ (no-music condition in comparison to the music condition. In order to test this we ran a mixed effects model with fixed effects Group (music and no-music) and Direction (ascending or descending) over SUDS. The random effects were over the individuals. Furthermore, AQ and Floor Level were added as covariates in this analysis.We hypothesized that the increase of self-reported SUDS would be significantly higher in the F = 1.16, p = 0.29]. However, there was a significant effect for AQ , Direction  and Floor Level  on SUDS. This shows that a higher degree of fear of heights, shown by the AQ scores, predicted higher degrees of self-reported anxiety during the virtual experience. Furthermore, as shown in Figure 3, SUDS scores were significantly higher when participants ascended in the elevator in comparison to when they descended. Similarly, reported SUDS scores increased significantly when participants ascended to a higher floor.We found no significant effects for Group  and AQ . However, when we ran the analysis excluding these two outliers, Group  remains significant with a higher effect size, while AQ  is not significant anymore. This result indicates that while participants in the no-music condition had a significant increase in state anxiety after the virtual experience , those in the music condition did not have a significant increase in their state anxiety and in some cases this anxiety was even reduced .Our prediction was that state anxiety would increase significantly in the dAPQ (PostAPQ-PreAPQ) was defined as the dependent variable. In order to control for the level of fear of heights, the AQ scores were included as a covariate in this analysis. No significant effects were found for Group and AQ.In order to identify possible changes associated to the presence or absence of music in the Autonomic Perception Questionnaire, the analysis of data was carried out using one-way ANCOVA were Group (presence or absence of music) was included as the independent variable and Two mixed effects models with fixed effects Group (music and no-music) were carried out in order to analyze HR responses as subjects ascended or descended through the elevator, respectively. The random effects were over the individuals. Furthermore, AQ and Floor Level were added as covariates in this analysis. We predicted that heart rate would be significantly higher in the no-music in comparison to the music condition, and also that it would be significantly influenced by the degree of fear of heights.F = 0.61, p = 0.44] and Floor Level . However, there was a significant effect of AQ  on HR. This indicates that higher degrees of fear of heights are related to increase HR as subjects ascend through the virtual elevator. No significant effect for Group , Floor Level , or AQ  were found in HR measures recorded when subjects descended. As it can be seen on Figure 5, AQ scores positively influenced average HR when subjects ascended in the virtual elevator.For HR measures recorded when subjects ascended, no significant effects were found for Group . However, no significant effect were found for Group  or AQ . Furthermore, no significant effect on Group , Floor Level , or AQ , was found in skin conductance when subjects descended.For skin conductance measures recorded when subjects ascended, we found a significant effect of Floor Level , Direction , Floor Level , and AQ , were found for media-lateral sway. Concerning anterior-posterior sway, we found a significant effect for Floor Level , but not for Group , Direction , and AQ . This means that as subject’s moved through the different floors of the building, the anterior-posterior sway increased.No significant effect of Group [The results obtained in this experiment indicate that music can to some extent facilitate post-stress recovery in subjects with different degrees of fear of heights. This was true in an immersive virtual reality experience that depicted a virtual platform moving up and down a building of 350 m. However, we could only observe the anxiolytic effect caused by music in subjective responses taken after the experience, and not in self-reported anxiety scores during the experience or physiological measures. These results are in line with those obtained by In contrast, our results partially corroborate the results obtained by A possible explanation for the diverse effects of music on modulating induced stress may be due to the control or not of the prior level of anxiety that the different types of stressors caused the experimental subjects. For example, one can employ the task of doing an exam or preparing a public talk, but these activities are not necessarily stressful to all people. In the current study we thoroughly controlled for the prior level of fear of heights that subjects experienced and analyzed to what extent the degree of fear influenced the dependent variables. The virtual reality scenario had an observable effect on all levels of responses since we observed significant differences in subjective units of discomfort, heart rate, electrodermal responses, and mean sway velocity, between the baseline (ground level) and top floor. However, a plausible explanation for the lack of results of music on SUDS and physiological responses might be that the virtual situation ended up being so stressful that the effect of music was not sufficient to affect the participants during the experience, but only afterward when recovering from stress. One could argue that experiencing oneself over a platform at 350 m gives rise to a deeply rooted life-threatening fear. The fact that the event is virtual does not eliminate anxiety when faced with a stressful situation, as long as subjects feel present in the virtual environments, which has been consistently demonstrated . Another limitation is that we did not screen participants for possible comorbid psychopathology and groups were not balanced by gender. Future studies should control for possible comorbid psychopathology with the use of a standardized questionnaires, as well as control for and analyze the influence that gender can play on anxiety responses and the possibly differing effects of music on people of different genders. Finally, our 30s physiological measures  were enough to detect changes at different heights, but did not allow assessing a possible enhancement of parasympathetic activity through music. Future studies should consider recording physiological signals, such as electrocardiography (ECG) for longer time periods in order to analyze responses such as the Respiratory Sinus Arrhythmia (RSA) which has been linked to parasympathetic activity.SS, MVSV, FV, and MS conceived of the project; SS with the help of MVSV, MS, IB, AP, and JP designed the experiments; AP, IB, and JP programmed the experimental scenario; SS performed the experiments with the help of IB; SS with the help of MS and IB analyzed the data; SS wrote the paper with the help of all authors; all authors read and approved the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


This paper provides empirical evidence that helps to answer several key questions relating to the extent of urban sprawl in Europe. Building on the monocentric city model, this study uses existing data sources to derive a set of panel data for 282 European cities at three time points . Two indices of urban sprawl are calculated that, respectively, reflect changes in artificial area and the levels of urban fragmentation for each city. These are supplemented by a set of data on various economic and geographical variables that might explain the variation of the two indices. Using a Hausman-Taylor estimator and random regressors to control for the possible correlation between explanatory variables and unobservable city-level effects, we find that the fundamental conclusions of the standard monocentric model are valid in the European context for both indices. Although the variables generated by the monocentric model explain a large part of the variation of artificial area, their explanatory power for modelling the fragmentation index is relatively low. Europe has one of the world’s highest densities of urban settlement, with over 75% of the population living in urban areas. Despite Europe’s relatively low rate of population growth, there continues to be an uneven expansion of urban areas across the continent. The size of many European cities is increasing at a much faster rate than their populations. This trend towards reduced population densities began in the early 1970s, most prominently in medium-sized European cities. There is no sign that this trend is slowing down and, as a result, the demand for land around cities is becoming a critical issue in many areas .The phenomenon of increasingly large urban areas taking up a greater proportion of the available land area is often termed urban sprawl. Various studies such as The literature on urban sprawl incorporates the work of economists, geographers and planners. Surveys of important issues underlying this research can be found in, among others, Despite the increasing interest in urban sprawl in Europe, relatively few empirical studies have been undertaken at the continental scale. The heterogeneity of the European urban context and limitations with the availability of data are probably the main reasons for this lack of interest. That is not to say that there has not been an effort to study the process of urban sprawl in Europe. Various studies, including 1 They noted the lack of a standard definition of the city or metropolitan area in Europe and highlighted the difficulties inherent in attempting a systematic cross-national comparison of European cities owing to the limited availability of data. Despite these limitations, their study provided some evidence on the extent of urban sprawl in cities in the European Union. However, their study did not address the measurement of urbanised areas per se and instead concentrated on identifying factors that influence population density. In their study, The main objective of our paper is to explore the relationship between urban sprawl and a set of variables that urban economic theory and the empirical literature suggest may be correlated with the phenomenon. Thus, rather than attempting to determine the causal factors behind urban sprawl we adopt a heuristic approach and seek to test competing hypotheses on the impact of various determinants. To this end we identify and gather existing data that can be used to identify the key determinants of urban sprawl across a large sample of European cities. Analysis is based on the well-known monocentric city model, which identifies population, income, commuting costs and the value of land as essential drivers of sprawl. In addition to these economic variables, the impacts of other geographical, socio-cultural and climatic factors, suggested by the literature, are also considered.Our study makes two main contributions to the literature on urban sprawl. The first concerns the measurement of sprawl and provides some observations about the data that are available for this purpose in Europe. Two complementary indices of sprawl are used in this paper, the first reflecting a change in spatial scale and the second the degree of fragmentation that is observed when large urban areas grow. Here, the term fragmentation is used to describe an aspect of urban morphology reflecting the spatial pattern of urban development, and in particular whether such development is compact or scattered in various fragments separated by open spaces. The extent of sprawl increases as development becomes more dispersed and further non-contiguous fragments are added to the urban area. The processes underlying the scattered development of urban areas have been discussed by By considering these two indices, we seek to ascertain whether or not the factors associated with the expansion of urban areas are also linked to an increase in fragmentation, with the city becoming less compact as the distances between adjacent patches of urban land increase. Both indices are calculated using Corine Land Cover data sets for three reference years . Several data sources are used to build a wide-ranging and consistent set of explanatory variables for a sample of 282 European cities. To our knowledge this is the first time that a study of this magnitude and scope has been conducted in the European context.The second important contribution of this study is related to the econometric techniques used in the estimation of the indices. Unlike previous studies, a comprehensive analysis of panel data is conducted to account for unobservable individual heterogeneity and to determine the best estimation method for each index. Several tests were used to choose between alternative panel data estimators. Specifically, a modified random effects-type model (the Hausman–Taylor model) is used, which allows us to control for endogeneity bias while, simultaneously, identifying the estimates for the time-invariant regressor.The fundamental theory in urban economics relevant to urban expansion is the monocentric city model . Within There are four main predictions of the monocentric city model. First an increase in the urban population should increase the distance to the edge of the city and raise the population density, since more people need to be housed. Second, an increase in income increases housing demand and leads to an extended city with a lower population density. Third, an increase in commuting cost lowers disposable income at all locations, reducing housing demand and leading to a more compact city with higher population density. Fourth, increasing the agricultural land rent raises the opportunity cost of urban land and makes the city smaller and denser.This basic version of the monocentric city model cannot explain the scattered development observed in some cities, where some parcels of land are left undeveloped while others, further away, are built up. One way of accounting for scattered development is to assign an amenity value to public open space, so that individuals may be willing to incur the additional commuting costs associated with living further away from the CBD in order to have open space near their home . SimilarSeveral studies have tested the empirical validity of the monocentric city model. In independent studies of the US context, In addition to the key variables of the monocentric city model, a study by In a developing country context, These studies confirm that the monocentric city model is empirically robust. The economic variables identified by this literature explain the majority of variation in the sizes of cities in different contexts. Moreover, many other geographical variables have also been found to play an important role in explaining urban expansion.It should also be noted that some models have included variables that measure the ethnic composition of the population e.g.  and crimOur paper contributes to this literature by explicitly considering the multidimensional nature of sprawl. Although there is evidence that urban sprawl is a multidimensional issue that should be measured in a particular way, each of the previous empirical studies examines only a single dimension of sprawl, i.e. either the urbanised area or the population density. In contrast, Based on the theoretical and empirical literature, we seek to explain differences in urban sprawl in Europe across space and time. The approach taken here is mainly based on the monocentric city framework and conceptually the empirical model is given by:This study considers two indices of sprawl that reflect the spatial scale of cities and urban morphology. By considering these indices, we examine the extent to which the determinants of urban expansion are linked to the fragmentation of urban areas. As independent variables, both indices will be estimated using the same explanatory variables. In this section we specify the sources and extent of the data used in this study before discussing the methodological features of sprawl measurements and the choice of explanatory variables.2 Here, all cities are defined at three scales: the Core city, which encompasses the administrative boundaries of the city; the Large Urban Zone (LUZ), which is an approximation of the functional urban region centred around the Core city; and the Sub-City District, which is a subdivision of the LUZ (We focus on a sample of European cities obtained by combining various existing data sources. Our starting point was the complete set of 320 cities used in the Urban Audit (UA) database. the LUZ . We conc3 Derived from Corine Land Cover, UMZ data covers the whole EU-27 at a 200 m resolution for those urban areas considered to contribute to urban tissue and function , compiled by the EEA, which contains spatial information for three years .function . Geospat4While the UA database covers 320 cities, the publicly available UMZ data does not include information for the UK, Cyprus and Finland for 1990 and for Greece and Cyprus for 2006. Taking this into account, the sample used in this study comprises the 237 LUZs where, for 1990, 2000 and 2006, complete information is available on artificial area and the number of urban fragments. Two indices of urban sprawl are constructed. The first index aims to measure the spatial scale of each city by considering the total artificial area in square kilometres (ArtifArea) as a proxy for all urbanised land in each LUZ. These areas were obtained directly from the spatial UMZ data according to Corine Land Cover nomenclature. This simple measure reflects the evolution of urban land cover in a given area without any prejudgment on internal composition or urban morphology, i.e. the scattered nature of the urban area.The second index reflects urban morphology, and the spatial patterns of residential land development, in particular, whether residential development is scattered or compact. A simple scattering index is adopted, measuring the degree to which urban development is spread across land in different fragments. We use the following expression:Frag represents the number of urban fragments  within a specific LUZ. This index reflects how scattered urban development is across the whole urban region and sprawl is identified as a higher number of different fragments. Since larger urban areas would be expected to have more fragments than smaller ones, this size effect is corrected by dividing Frag by the artificial area within each LUZ.where 5 When combined, these data sources provide a set of explanatory variables covering a broad sample of European cities.The UA database provides a wide range of variables, including those commonly used in the monocentric city model . However, data are missing for some cities, which makes the use of some variables unfeasible. Therefore, the UA data are supplemented by data obtained from the European Observation Network, Territorial Development and Cohesion (ESPON).6 and total population (POP).7 GDP per capita (GDPcap) is used as a proxy for income. All of these variables are defined for the three reference years  for 282 cities across Europe. However, no direct measures of transport costs or agricultural land rents exist for the whole of Europe over the relevant time periods. Similarly, there are no European data sets relating to agricultural land markets or transport costs at the city level. Based on the empirical studies cited earlier, proxies were identified that provide adequate measurements of these variables. First, to account for agricultural land rent, the ratio of agricultural added value to the area of agricultural land (Agriprox) was calculated. Data on agricultural added value were available from ESPON, and the agricultural land area for each LUZ was calculated. The rationale for including this proxy is that this ratio could explain different levels of agricultural productivity. Normally, higher agricultural productivity should be capitalised into land rent. Similarly, highway density (Highway) data from the Eurostat regional data set was used as a proxy for transport costs. The assumption here, is that investments in highways make travelling faster and more convenient, which reduces the time and the costs of commuting.The ESPON database provides comprehensive data for each LUZ on Gross Domestic Product (GDP) adjusted for Purchasing Power Standards2 (NO2) as a good indicator of air pollution. A terrain variable, median city centre altitude above sea level (MedAlt), is also included. This variable is a partial indicator for the ruggedness of the terrain in the LUZ, as this may have an impact on the potential for urban growth.Following In addition to the economic and geographical variables of interest, other social and cultural variables are considered. First, data on recorded crime (Crime) from the UA is used to account for the security situation in the central city. As mentioned previously, Preliminary analysis of the data shows that on average, over the period 1990–2006, the urbanised area increased by 18.4%, while population density fell by 9.43% and the Scattering index decreased by 9.07% . In geneIn summary, sprawl shows different trends depending on the index used to measure it and the region within which cities are located. Southern cities show the fastest growth of urbanisation and the highest decrease in density, but their morphology tends to be more compact. Despite their relatively low levels of urban growth, northern cities experienced a relatively large decline in both density and scattering. From this it can be deduced that rapid urbanisation is not necessarily accompanied by a decrease in density. Also, that urban areas within cities where density is declining do not necessarily become more scattered.To illustrate the interdependence between these three indices of urban sprawl and the time-varying explanatory variables (Population and GDP per capita), the sample of LUZs is divided into two groups depending on the rate of growth of each index. The first group corresponds to the bottom quartile (relatively slow growth) and the second group corresponds to the top quartile (relatively high growth). All changes in urban areas and density are in the directions predicted by the monocentric city model. Furthermore, the growth of population and GDP per capita are negatively correlated with the evolution of scattering.Panel data analysis is adopted to deal with observations from multiple cities over three periods. Given the variables discussed above, the estimating equation of sprawl indices is given by:i and t stand for cities and time periods, respectively. The dependant variable ArtifArea or Scatt).8 There are two time-varying regressors, Population (POP) and GDP per capita (GDPcap). 9where 10 Rather than use OLS in this case, it is more appropriate to use random and fixed-effects models both of which are commonly applied to panel data. Both models take account of unobservable individual heterogeneity and the distinction between them is whether or not the individual-specific time-invariant effects are correlated with the regressors. The fixed-effects model offers consistent estimators but does not allow us to estimate time-invariant variables since it is based on the within operator . The random- effects model increases the efficiency of estimations but imposes a strong assumption that individual effects are not correlated with explanatory variables.Furthermore, in order to improve on some of the shortcomings of these two models, the Hausman-Taylor instrumental variable estimator can also be applied here . The Hau11The model selection process follows The Hausman and Taylor method can be represented in its most general form as follows:1, Z1], where Q is the within transformation matrix with where truments . If the 12A Hausman test is used to discriminate between fixed and random-effects approaches. Under the null hypothesis of the Hausman test, the estimators from the random-effects model are not systematically different from those from the fixed-effects model. If the null hypothesis cannot be rejected (probability of the test higher than 5%), we consider the estimators from the random-effects model to be consistent. Otherwise, if the null hypothesis is rejected (probability lower than 5%) only the fixed-effects model is consistent and unbiased. In the case of this model, Hausman test results show that the random-effects hypothesis is rejected in favour of the fixed-effects estimator when ArtifArea index is the dependent variable. However, when the Scatt index is considered as the dependent variable, the random-effect regressor is consistent. The results of the Hausman test are reported in the bottom of ArtifArea index. Although the fixed-effects estimator is not an option in our study, since it does not allow the estimation of the coefficients of the time-invariant regressors, it is still useful in order to test the strict exogeneity of the regressors that are used as instruments in the Hausman-Taylor estimation. Thus, when strict exogeneity for a set of regressors is rejected, others must be considered to act as instruments in the estimation. Once the second Hausman test has identified which regressors are strictly exogenous, they are subsequently used as instruments in the Hausman-Taylor estimation.Some qualifications need to be made regarding the use of the Hausman-Taylor estimator, in the case of the POP as endogenous, while GDPcap and all time-invariant variables are exogenous. Only this configuration allowed us to obtain estimates close to the fixed-effects for time-varying variables. In addition, the Hausman test confirms the consistency of the Hausman-Taylor estimator  and (2)). The second configuration adds all of the explanatory variables selected in this study (columns (3) and (4)). Furthermore, year and regional dummies are used to control for time-specific changes in the sprawl indices caused by other factors.All the coefficients of the main independent variables emerge as significant with the expected signs (columns (1) and (2)). The Population coefficient is significant and positive, ranging between 0.288 and 0.329. The GDP per capita coefficient is also significant with a positive sign, varying between 0.168 and 0.281. The sign on the coefficient of Agriprox, the proxy for agricultural land values, is negative as predicted by the monocentric model. The higher the agricultural land value, the slower the expansion of artificial area. The coefficient on the transportation cost proxy (Highway) is positive which is also as expected. When transportation networks are dense, the cost of travel is low and the artificial area is relatively large. As other explanatory variables are added, the main variables of the monocentric model remain significant with the expected signs. This is still true with or without the dummies for years.Interestingly, this study highlights the importance of agricultural productivity in limiting the expansion of urban areas. Unlike previous studies, a relatively high coefficient is observed for the agricultural rent proxy, ranging from −0.265 to −0.279. This means that agricultural productivity can be a genuine barrier to urban sprawl in Europe. This reflects the fact that in Europe, agriculture at the urban fringe is often highly intensive, offering relatively high yields and profits.Rain and Temperature) have a significant and negative effect, which reflects the tendency towards urban sprawl in temperate climates. The connectivity of cities to the rest of the world, measured through the relative importance of the nearest airport (AccessAir), is also significant and positive. Generally, cities with a major airport attract significant economic activity and therefore expand. The coefficient of the variable NO2 is significant and positive. Thus, pollution recorded in the central city tends to encourage households to move to suburban areas, promoting sprawl. The cultural attractiveness of the city, approximated by the number of cinema seats, is significant and negative, suggesting that attractive cultural amenities in the centre of the urban area discourage outward sprawl that makes those amenities less accessible. The coefficients of the variables Crime and MedAlt are not significant, but show the expected signs. A high crime rate in the central city promotes urban expansion, encouraging households to settle in suburban areas. As expected, increasing altitude acts as a brake to the expansion of cities.The climatic variables  and (2) includes the main variables of the monocentric city model, while Columns (3) and (4) add the other explanatory variables.Returning to the R2 values and non-significance of several variables, show that fragmentation is not necessarily influenced by the same set of variables that determines spatial scale. In all cases, coefficients for POP and GDPcap are negative and significant suggesting that larger populations and higher income levels in an urban area may be linked to lower rates of fragmentation. Therefore increases in population and per capita income are associated with cities that are both larger and more compact. This reflects the strong demand for land in more affluent LUZs and the associated levels of population growth. Such demand may lead to a reduction in the number of urban fragments, as discrete settlements start to expand and merge with each other, or with the central city. Such phenomena can be influenced by urban planning policies, which may be designed to encourage development within these interstitial spaces rather than around the fringes of the LUZ.The results reported in columns (1) to (4) in NO2 and MedAlt were significant in the models. The pollution proxy has a negative impact on scattering, reflecting a tendency towards greater fragmentation in cities experiencing higher levels of air pollution. However, the effect of altitude is positive; thus cities located in urban areas at higher altitudes are likely to be more fragmented, possibly as a result of the local terrain.Furthermore, the coefficient of the agricultural land value proxy is also negative but not always significant. As might be expected, high agricultural land productivity should constrain urban fragmentation by limiting the amount of land available for development. The opposite might be expected for less productive land provided that other factors (e.g. topography or drainage) are favourable to development. The results reported here, suggest some level of heterogeneity in the agricultural activities within each LUZ, resulting in complex land-use patterns specific to each area. The transport cost proxy also had a negative coefficient, and again this was not always significant. Of the other explanatory variables, only POP and GDPcap) in explaining changes in the sprawl index, can be ranked according to the magnitudes of their elasticities. However, this criterion can be misleading, because the total effect of one factor on another over time, depends on both the magnitude of the elasticity and the change in the variable.The relative importance of variables that vary over time . Where data on potential explanatory variables were not available, a suitable proxy variable was constructed.Data were obtained for these variables over three reference years . The use of panel data allows unobservable individual heterogeneity to be controlled but also means that a simple OLS estimator is unlikely to be suitable, as this would not account for such unobservable heterogeneity across cities. Several different estimators were considered and statistical tests were performed to determine the ability of each to account for the specific structure of the panel data for the two aspects of sprawl measured by the study. The Hausman-Taylor estimator was used in the case where sprawl is measured in terms of changes to the urban  area, but where the dependent variable is an index of fragmentation (i.e. scattering) a random-effects estimator was adopted.Our results are robust and when urban sprawl is approximated by the spatial scale, i.e. changes to the artificial area within the LUZ, they clearly confirm the predictions of the monocentric city model. Thus, the coefficients of the main explanatory variables in the model are significant, with the expected signs. In addition, the significance of these variables does not change when other explanatory variables are introduced. While increasing income per capita and population growth are clearly associated with the expansion of urban areas, the models reported in this paper also suggest a possible link between the productivity of adjacent agricultural land and a more restricted outward growth of cities. High productivity maintains or increases land values and makes development on the urban fringe more expensive and therefore less attractive. This economic restriction to the supply of available land may be supported by planning regulations, which limit the availability of land in the urban fringe for development, while the value of agricultural land close to urban areas might be increased owing to proximity to markets for some high-value products such as soft fruits and salad vegetables.There is less obvious correlation between the fragmentation of urban areas and the growth of income and population. Other factors, such as altitude or terrain, are shown in the model to be associated with fragmentation but much of the variation is left unexplained. It is suggested that urban planning policies and land availability may be particularly influential in determining the level of fragmentation, along with any other factors that reduce the outward growth of cities and therefore encourage in-fill development in the interstices between fragments.Some limitations to this study must be acknowledged, such as our current inability to include variables relating to important political and institutional factors (e.g. land supply and zoning), that are likely to affect both urban scale and fragmentation. The model also omits information on some specific geographical features therefore limiting our ability to explore the variation in urban sprawl indices more deeply. It is also possible that there may be complex interactions between some environmental factors  and urban sprawl, that are not accounted for in our model.Although we have not accounted explicitly for the role of land-use policies (mainly because of the lack of data), our study may provide some possible insights into the design of policies seeking to control sprawl. While environmental and landscape protection are important aims, such policies should not ignore the important economic mechanisms that can drive urban sprawl. This research suggests that in many cities, urban sprawl may be associated with increasing wealth. Therefore policies that limit the expansion of urban areas may risk restricting economic growth, as house prices within the LUZ increase, development land becomes scarce and individuals and businesses decide to relocate to other cities where there is still room for new development on the periphery.Policy makers reluctant to place regulatory restrictions on sprawl but who are concerned about the loss of environmental quality or amenity from the development of the urban fringe, may wish to consider other policies that use the market to discourage the outward expansion of cities. Our results suggest that agricultural productivity, and by extension profits, can restrict development by driving up land prices around cities. Therefore the adoption of policies that have a positive impact on farm incomes on the urban periphery could have a direct effect on reducing the likelihood of outward sprawl, while at the same time potentially encouraging the development of non-urban areas within the LUZ boundary, thus reducing urban fragmentation and making the city more compact.


The World Health Organization promotes salt reduction as a best-buy strategy to reduce chronic diseases, and Member States have agreed to a 30% reduction target in mean population salt intake by 2025. Whilst the UK has made the most progress on salt reduction, South Africa was the first country to pass legislation for salt levels in a range of processed foods. This paper compares the process of developing salt reduction strategies in both countries and highlights lessons for other countries. Like the UK, the benefits of salt reduction were being debated in South Africa long before it became a policy priority. Whilst salt reduction was gaining a higher profile internationally, undoubtedly, local research to produce context-specific, domestic costs and outcome indicators for South Africa was crucial in influencing the decision to legislate. In the UK, strong government leadership and extensive advocacy activities initiated in the early 2000s have helped drive the voluntary uptake of salt targets by the food industry. It is too early to say which strategy will be most effective regarding reductions in population-level blood pressure. Robust monitoring and transparent mechanisms for holding the industry accountable will be key to continued progress in each of the countries. Globally, the prevalence and impact of hypertension and diets high in sodium increased between 1990 and 2010 ,4. In thlutenica (a vegetable relish), and Argentina has legislated salt levels for a range of products, including bread and processed meats [The most recent estimates showed that in 2010, global mean salt intake was around 10 g per person per day, so around twice the WHO recommended amount. The East African Region had the lowest salt intake, at just over five grams per person per day, while the Central East Asia Region had the highest at around 13 g . The Unied meats ,17.The South African government recently adopted a more comprehensive legislative approach by passing legislation for salt levels in a wide range of processed foods. The initial salt level standards will become mandatory as of 30 June 2016, with more stringent maximum levels coming into place from 30 June 2019 .This article provides a review of the historical processes, the establishment of the evidence bases and the subsequent advocacy and lobbying in the UK and South Africa that led to the adoption of their different salt reduction strategies. Narrative documentation of the author’s own experiences, supplemented through relevant scientific papers, campaign materials and evaluations, as well as consultation responses, provided the basis for a comparative analysis of UK and South African approaches.Prior to the UK government’s Food Standards Agency (FSA) making salt reduction a public health priority in 2003, debates about salt between government, the food industry, the Salt Manufacturer’s Association and health advocacy groups had been running for decades ,20. The Subsequent government reports made no strong recommendations until the early 1990s, when dietary targets for salt were set and the government made clear recommendations for reductions in the sodium levels of manufactured foods ,25,26. TFollowing a change in the UK government in 1997, salt reduction was once again placed on the agenda, and a further review of the evidence was commissioned by the newly established Food Standards Agency. The Scientific Advisory Committee on Nutrition (SACN)’s report on Salt and Health, published in June, 2003, provided a comprehensive up-to-date overview of the research evidence and confirmed the need for action, stating that, “Key to achieving a sustained salt reduction for public health benefit is the engagement of the food industry” . This reIt was estimated that 15% of salt consumed in the UK was added during cooking and at the table and that 5% was naturally occurring in foods, with the remaining 80% coming from processed foods . ExistinThis salt model was used to calculate how much salt would need to be removed in each food category to reduce the salt content of the food supply by 40%, which  would move average population intake from 9.5 g of salt/day to 6 g of salt/day. It was acknowledged that very large reductions in some of the main product categories would be difficult to achieve; therefore, the model highlighted the need for a broad-based approach that sought to achieve some reduction in almost all food categories.The salt model was the first step towards establishing category-specific targets in the country and was used as the basis for negotiating actual targets with the food industry, taking into account both the technical feasibility related to food safety and processing mechanisms, as well as consumer acceptability of reduced salt foods. The salt model was published for public consultation in 2003, and at the same time, a broad program of food industry engagement was instigated.The approach of the UK FSA in engaging the food industry has been well documented  see Fig.Following the publication of the SACN report in June, 2003, a high-profile stakeholder forum was convened jointly between the FSA and the Department of Health in November, 2003 . The forThe different sectors of the food industry were engaged in a number of ways, including through written consultations, working groups with representatives from multiple companies and face-to-face meetings with individual companies. Individual company commitments and action plans were negotiated and published on the agency website. Trade associations were used to communicate issues to a range of companies or a particular sector. Retailers, for example, were engaged through the British Retail Consortium and food manufacturers through the Food and Drink Federation. Separate strategies were developed for communicating to small businesses and the catering sector to ensure that they had the required information and technical support to make reductions in parallel with the market leaders .Cross-industry collaborative groups were established on bread, breakfast cereals and soups and sauces to encourage corporate collaboration between companies and to agree on commitments to salt reductions in their respective products. For example, the bread and breakfast cereal manufacturers initially agreed to work towards annual reductions of 10% for three consecutive years from 2003. Many of these manufacturers have since continued making reductions beyond the initial target . A similOnce industry stakeholder engagement had been established, targets for maximum levels of salt in each food category were developed, taking into account technical, safety and consumer acceptability issues. The targets were designed to be challenging enough to ensure that they would impact on population salt intake and population health. At the same time, they were set at a level that had already been achieved by the lower salt products in the category, demonstrating technical feasibility. Progress towards achieving the targets was monitored through both industry self-report and the establishment of a database of salt levels in the top food categories that contribute to salt in the diet . In 2009The UK salt reduction strategy is multi-faceted, comprising work with industry, as well as a social marketing campaign to change consumer behaviour, accompanied by clearer food packaging labelling of salt content. At the outset of the campaign, the government promised the food industry that in return for their efforts to reduce salt in foods, the FSA would launch a high profile campaign to inform consumers that salt was bad for health and that they needed to try and reduce salt in their diets, thus driving consumer demand for the newly reformulated reduced salt foods. At first, food companies did not want to alert consumers to the fact that salt was being reduced in their products, for fear of consumer rejection of the reformulated versions. Salt was therefore reduced gradually and in silence.Meanwhile, the FSA launched its famous “Sid the Slug” campaign to raise awareness that salt was bad for health. The multimedia campaign included advertising billboards, television commercials and internet coverage and was based on the premise that salt kills slugs, and can harm humans, too. The campaign infuriated the Salt Manufacturers’ Association (SMA), who complained to the Advertising Standards Authority that the information was misleading. Following an extensive review of the evidence base, the Advertising Standards Authority rejected the SMA complaint in its adjudication. Ironically, the controversy resulted in extensive media coverage, which added considerably to the reach of the campaign, and at no extra cost. Evaluation after the first stage of the campaign revealed that within a year, the proportion of people that knew the dietary target for salt had increased from 3% to 34% .The second stage of the FSA awareness campaign focused on behaviour change. The slogan, “Is your food full of it?” was launched, together with a series of targeted TV advertisements and other campaign materials to encourage consumers to check food labels and select products with the lowest salt content. At this stage, the food industry started to recognize that people were becoming increasingly interested in consuming a low salt diet. One multinational company supported the FSA campaign by including the slash “Check out our salt levels” on the front of its premium brand products, whilst an upmarket supermarket chain displayed in-store posters saying, “We’re reducing salt in our foods faster than you can say sodium chloride”. For the first time in decades, the government, health advocacy groups and, now, even the food industry were presenting a united salt reduction message. Subsequent evaluation of the social marketing campaign has demonstrated an impressive impact in terms of reported changes in consumer behaviour .The campaign reported a reduction of about a gram of salt per person per day in 2008 . By 2010In 2012, South Africa established a daily salt intake target of less than five grams per person by 2020. However, like the UK, the benefits of salt reduction were being debated in South Africa long before it became a policy priority. Whilst salt reduction was gaining a higher profile on the international policy agenda, the availability of local, context-specific, domestic costs and outcome indicators proved crucial to influencing the legislation. Research conducted in the mid-2000s followed by extensive academic engagement with the South African Government and non-governmental organizations, such as the Heart and Stroke Foundation, led to the introduction of government policy directives on salt reduction.The South African Medical Research Council (MRC) produced a policy brief , which sThe legislative process in South Africa came about through international political pressure coinciding with new local evidence and embraced by political opportunism. In September, 2011, influential leaders gathering at a United Nations high-level meeting on non-communicable diseases (NCD) in New York reached consensus on the global priority action needed to prevent and treat these conditions  and idenResearch to understand the contributions of different foods to salt intakes in South Africa informed the legislation. Repeated 24-h urinary collections in different population groups provided estimates of usual total sodium intake. A study in Cape Town reported ethnic differences in average daily salt intakes, equating to 7.8, 8.5 and 9.5 g/day in black, mixed ancestry and white individuals, respectively . DietaryHaving established that 54% of the salt in the diet came from processed foods, the next step was to identify which other foods were contributing to salt in the diet. The diverse ethnic groups in South Africa have markedly different eating patterns and are at different stages in the nutrition transition . These At that time, there were no nationally representative dietary studies that had been conducted in South African adults. A secondary analysis of four dietary surveys that used a 24-h recall method was undertaken to assess quantities and food sources of sodium intake. This included two studies of rural black subjects ,52,53,54boerewors, a seasoned beef sausage, meat pies, processed meats, such as polony, vienna, salami, ham and other sausages), as well as soup powders and brick margarine. The practice of adding monosodium glutamate-based flavour enhancers  and stock cubes to staple foods  during preparation is common in South Africa, particularly in disadvantaged communities, and contributes to the high sodium intake in the black, majority population. The relative contributions of these different foods by different ethnic groups are summarized in A fifth study that included three repeated 24-h dietary recalls in a multi-ethnic sample in Cape Town also helped to identify sources of salt in the diet . As wellmaas) and the substitution of table salt with a salt substitute (SOLO™) lowered blood pressure by a clinically significant magnitude in community-dwelling, hypertensive patients (p = 0.021) was similar to that shown by the use of diuretic therapy. However, additional benefits were observed, over and above standard pharmacotherapeutic approaches, as all participants had a diagnosis of hypertension and were receiving standard care according to primary care clinical guidelines. The outcomes of the study showed that many of the beneficial nutrients obtained through the adoption of a DASH (Dietary Approaches to Stop Hypertension) diet could be obtained simply by modifying existing commonly consumed food items to contain higher amounts of potassium and magnesium and lower amounts of sodium [Once evidence about food sources of salt was available, researchers worked with food industry partners that included R & D staff, food technologists, consumer affairs and marketing managers to develop sodium-reduced variants of bread , margaripatients . The magf sodium ,60.Final decisions about the maximum levels of salt to be allowed in foods were driven by the food industry-partnered research on the development of reduced sodium bread , as wellPublication of the draft regulations was followed by a three-month open public consultation process. After review, the Ministry made adjustments to timelines and adjusted the salt content of some of the food categories, as published in the final government gazette dated 20 March 2013 , and shoIt is notable that many of the maximum permitted levels of salt allowed in food categories are much higher than the current UK targets, particularly for processed meats, savoury snacks, such as crisps, and breakfast cereals. It is difficult to compare targets for dried soup powders and stock cubes, as the UK targets specify levels of salt in the products as consumed. Due to the common practice of using these products as condiments to flavour staple maize meal dishes in South Africa, the South African targets report levels as purchased in the dry form. The more stringent targets that are stipulated for 2018 for these dry goods reflect a period of adaptation for consumer taste preferences.A further difference between the South African and the UK targets is that the UK has established both maximum levels, which all companies are encouraged to try and achieve, as well as average levels, which are usually much lower and which represent the average for the product category as a whole. The idea is to reflect the often wide variations of salt levels in products, even within a specific product category, and still ensure that levels are reduced by as much as possible. In addition, monitoring of salt levels is also weighted by sales to account for the fact that even relatively small reductions in salt levels in products with a large share of the market will have a significant impact on population salt intake levels. Conversely, large reductions in salt levels in products that have a small share of the market will have limited impact. Whilst the combination of maximum and average targets is likely to be a more effective approach, the challenges associated with monitoring against average targets means that many countries prefer to stipulate maximum levels.It is obviously too early to assess any impact of the South African salt reduction strategy. The fact that a large proportion of salt in the diet is added during cooking and at table meant that, in addition to working with the food industry to reduce salt in processed foods, any salt reduction strategy in South Africa would also need an accompanying social marketing campaign to target changes in individual consumer behaviours. Ahead of the legislated targets for salt reduction coming into place in mid-2016 and mid-2018, an advocacy group called SaltWatch has been established to complement government legislation by developing a national salt awareness campaign , which mThe same evidence-based approach that was used to establish the legislation is now warranted for the monitoring and evaluation of the effectiveness of the legislation. Whilst the efforts of advocacy groups, such as SaltWatch, are important, government funding also needs to be allocated to ensure that robust monitoring mechanisms are in place by the time the legislation comes into effect in June, 2016. This includes monitoring of the salt content of foods and shifts in population-level salt intake and blood pressure distribution, as well as evaluation of compliance of the food industry sector with the salt targets and the impact of the consumer awareness campaign.n = 3842, as well as a smaller comparative sample of 385 individuals aged 18–49 year. Wave 0 was completed in 2004 and Wave 1 in 2008. Wave 2 is currently interviewing respondents, and Wave 3 is planned for 2016. Wave 2 data collection will include 24-h urinary sodium analyses in a sub-sample in order to provide representative baseline measures of salt intake against which to monitor the progress and effectiveness of the new South African legislation. The SAGE study is also taking place in Ghana, which will provide a comparative African country that does not have a policy to influence the sodium levels in the food environment, but that has similar levels of hypertension and increasing obesity and which can therefore act as a control to the South African study. Additionally, all six SAGE countries will include a set of standard questions on salt behaviours [In the meantime, one proposal for monitoring changes in salt intake and blood pressure is to leverage data from existing surveys and to include measures of 24-h urinary sodium excretion in these surveys. An example is the multi-country WHO Study on global AGEing and adult health (SAGE) in South Africa, a cohort study that collects comprehensive longitudinal information on the health and well-being of adult populations and the ageing process . The surhaviours , providiHypertension, or high blood pressure, is a common risk factor for stroke, coronary heart disease and kidney disease and is the leading preventable risk factor for death in the world ,67. TherIn terms of similarities, both strategies were initiated as a result of new or updated, culturally appropriate evidence. The comprehensive review and update of salt reduction evidence by the Scientific Advisory Committee on Nutrition in the UK was an important tool to galvanise the political support required for the UK to launch its salt reduction strategy in 2003. This confirmed that existing evidence was strong enough to necessitate action and was translated into a consumer-friendly format to help obtain public support. Likewise, experience from our review of the South African experience has also clearly demonstrated that original data ,48,57,58Another striking similarity is the importance of continued advocacy by academics and/or non-governmental organisations to influence policy agendas. CASH in the UK was a key driving factor for government action on salt reduction in that country, while academics in South Africa have played an important role in persuading the government to act by strengthening the evidence and highlighting the cost effectiveness of taking action. Once salt reduction strategies are in place, academics and advocacy organisations need to continue their activities to ensure independent monitoring of the implementation and hold both government and the food industry to account.In both the UK and South Africa, the action taken by government was fairly bold. The UK was the first country to launch a comprehensive national salt reduction strategy in the face of continued industry-fuelled controversy over the evidence. One of the drivers for this in the UK was the establishment of the Food Standards Agency, which was at arms-length from government. However, with a remit to protect the interests of consumers in relation to food, this Agency had the capacity and political independence to take on the salt reduction campaign in a much more targeted and dynamic way than typically pursued by government health departments.Another similarity between the UK and South Africa is the adoption of multi-pronged approaches to reduce population salt intake. Population-based approaches to disease reduction need inter-sectoral collaboration, underpinned by stronger leadership from policy makers, advocates and health professionals. The pragmatic CVD-Risk Management package developed by the World Health Organization (WHO) to facilitate cardiovascular risk assessment and management in low-resource settings ,76 proviThe effectiveness of salt reduction strategies is based on their potential to change the food environment. Such an approach requires not only buy-in from the food industry to reformulate food products, but commitment from government to support co-ordinated programs to change consumer behaviour. This is particularly true for South Africa where, in contrast to the UK, a high proportion of salt consumed still comes from salt added during cooking or at the table. Behaviour change programs can include the promotion of food-based dietary guidelines , but neeClearly the main difference between the UK and South African programs is the introduction of legislation in South Africa. Whilst the voluntary approach of the UK is undoubtedly having an impact, some experts claim that voluntary processes are unlikely to be sustainable for most countries and that legislation is required . Whilst The introduction of legislation on salt targets in foods was driven by an urgent need in South Africa to address the increasing burden of disease related to chronic diseases. Unlike the UK, where communicable diseases are fairly well controlled, South Africa faces a quadruple burden of disease, which includes, HIV and tuberculosis, and high maternal and infant mortality, in addition to non-communicable diseases and injuries . In the Micronutrient deficiencies still exist in some sectors of the population in South Africa. Since 1995, universal salt iodisation (USI) has successfully eradicated iodine deficiency in the country , with suAs with all public health issues, translation from research to policy requires advocacy and lobbying from respected coalitions, along with strong governmental leadership. Variations on this process were followed in both the UK and South Africa for the implementation of their salt reduction campaigns. It remains to be demonstrated whether mandatory legislation is more effective than voluntary target-setting in reducing population-level salt intake. Ongoing monitoring of the food supply in both of these countries is essential to measure impact, while data on trends in health outcomes is needed to inform outcome evaluation. The experiences from these two countries provide guidance for other countries that are in the process of developing salt reduction strategies to address the burden of cardiovascular disease.