Extramammary Paget disease of the vulva (EMPV) is a rare skin disorder commonly seen in postmenopausal Caucasian females that appears clinically as red, eczematous, pruriginous, and sometimes painful lesions. Although most cases are noninvasive, EMPV may be associated with an underlying or distant adenocarcinoma. EMPV has a chronic and relapsing course. The reference treatment is based on local surgical excision with negative margins. However, disease frequently extends far from the visible lesion, and surgical margins are frequently positive. Topical photodynamic therapy (PDT) is an established treatment modality for various dermatooncologic conditions. For example, red light irradiation with the Aktilite CL 128 and Metvixia  as a photosensitizing molecule is a conventional protocol approved and widely used in Europe for PDT treatment of actinic keratosis, but this treatment is not yet widely used for EMPV because it has never clearly been demonstrated and is very painful.The aim of the study is to investigate the efficacy and safety relating to the medical device PAGETEX as a new painless PDT device using Metvixia in the treatment of vulvar Paget disease. The primary end point is the disease control rate at 3 months in 30% of the patients included, defined as stability, partial response, or total response, considering the extent of the lesion. Secondary end points are the disease control rate at 6 months, patient quality of life, level of pain experienced by the patient at each PDT session, severity of erythema, presence of protoporphyrin IX in Paget cells after each PDT session, and overall satisfaction level of the patient.The trial is an interventional, exploratory, simple group, nonrandomized, and single center  study. Twenty-four patients will be included according to Simon’s optimal plan. Therapeutic procedure is based on a cycle of two PDT sessions with the PAGETEX medical device at 15-day intervals . At the assessment session, 3 months after inclusion, if the control of the disease is partial or null, the patient will complete another cycle of two PDT sessions. A final evaluation will be performed in all patients at 6 months. Analyses will be performed using SAS version 9.4 software (SAS Institute Inc). The characteristics of the patients at baseline will be described; qualitative variables will be described by numbers and percentages, and quantitative variables will be described either by the mean and standard deviation for Gaussian distribution or by the median and interquartile range . The normality of the distributions will be tested by a Shapiro-Wilk test and checked graphically by histograms.First patient was included in September 2019 and clinical investigations are planned until August 2022. The final results of this study are expected to be available in January 2023.This clinical trial aims to evaluate the efficacy and safety of a new PDT protocol for the treatment of EMPV. The PAGETEX device could become the treatment of choice if it is effective, painless, and easy to implement and use in hospitals.ClinicalTrials.gov NCT03713203; https://clinicaltrials.gov/ct2/show/NCT03713203PRR1-10.2196/15026 Extramammary Paget disease of the vulva (EMPV) is invasive in 20% of cases. If the invasion is less than 1 mm, the evolution is the same as that of noninvasive lesions. Beyond 1 mm, or when there is an underlying carcinoma, the prognosis is worse with a risk of remote lymph node metastases . The investigator must ensure that subjects are informed clearly and fully about the purpose, potential risks, and other critical issues regarding clinical studies in which they volunteer to participate. Freely given written informed consent must be obtained from each subject prior to clinical study participation, including informed consent for any screening procedures conducted to establish subject eligibility for the study. The rights, safety, and well-being of the subjects are the most important considerations and should prevail over interests of science and society.Patients or the public were not involved in the conceptualization or carrying out of this research. Concerning treatment of personal data, this study is in compliance with the French methodology of reference (MR0001), which is a simplified declaration of data from medical research to the French National Data Protection Authority. The only persons authorized to access data and modify files generated by the study will be persons directly involved in the study. The participants will have access to the data and be able to modify them at any moment through one of the referring investigators of the study. The sponsor affirms the patient’s right to protection against invasion of privacy.The first patient was included in September 2019. Evaluation of disease control in the first 8 patients will determine the study's continuation (early 2020). The final visit of the last patient is expected to August 2022. Analysis of the results is scheduled for the end of 2022, and results are expected to be published at the beginning of 2023.PDT using 5-aminolevulinic acid has been employed sporadically to treat EMPV even if it is not the common treatment of this pathology ,16. MAL-


If people were asked whether income changes influence self-rated health and morbidity, they would probably answer yes. Indeed, previous studies validated this assumption, but most of them used cross-sectional data and only considered self-rated health as the decisive factor. On the other hand, there are a few studies using longitudinal data, which found a much smaller association between income and self-rated health. In order to give a conclusive overview of the current study situation, this review summarizes and examines studies which use only longitudinal data. In addition to self-rated health, the effects of income on the objective factor of morbidity were also investigated. The review includes a total of 14 papers that use data from seven different countries. It concludes that there is a small, statistically significant, positive impact of increased income on self-rated health, but a negative association between income growth and morbidity. Taking the limitations of confounders, attrition, and selection bias into account, the results may even be insignificant.  From a macrosocial point of view, health is an important factor contributing to longevity, successful aging, or satisfaction with life. Therefore, there is a widespread interest in finding possible influencing factors and their interactions with health to gain a better understanding of the determinants of health.Income is generally regarded as such a factor. Most people would intuitively claim that higher income improves health. Indeed, research shows clear evidence for a statistically significant, positive relationship between income and health. However, most studies use only cross-sectional data to examine this relationship ,2,3. AnaA systematic review from 2011 investigated the relationship between change in income and change in self-rated health (SRH) using only longitudinal data. It was found that only a small number of studies met the inclusion criteria, as the number of existing studies with longitudinal data was small. They concluded that there is a statistically significant, small, and positive relationship between income and SRH, and that once controlled for any bias, the result would no longer be found .Since the research was carried out in January 2010, these results are now almost 10 years old. The aim of this review therefore is to include the research done in the last 10 years to bring the scientific findings concerning the relationship between income and health up to date. A further aspect was added by also investigating an objective factor, morbidity, to obtain holistic view on the relation between income and health, although there are even fewer studies on this subject. This systematic narrative review analyzed studies with longitudinal data in order to find some evidence for the relationship between income change and SRH and morbidity, asking the question: “What effect does a change in household income have on SRH and morbidity when examining longitudinal data?”. To be more precise, the effect of income change on a subjective measurement parameter for general health and the effect on the objective outcome morbidity was examined. Furthermore, the effect of exogenous positive income shocks in the form of lottery winnings or the German reunification was analyzed. Longitudinal data to investigate the relationship between income and health over time;income in an individual/absolute form, rather than as a measure of income inequality;SRH or a similar measurement parameter for subjective general health ORseveral, but at least three, different chronic conditions for the variable of morbidity; andhealth as:a wide age range with only adults included. The age of the working population (15–65 years old) was considered the best cohort.The criteria for being included in this review were use of:The search was started in September 2018 with the parameters of income, SRH, morbidity, and longitudinal data. The variables SRH and morbidity were linked with “OR”, while income and longitudinal data were linked with “AND”. Furthermore, SRH and morbidity were linked to the other parameters via “AND”. This combination resulted in the identification of 285 articles via the PubMed database. After scanning the titles and abstracts, 272 papers were excluded for not meeting the inclusion criteria. The remaining 13 papers were analyzed by reading the whole text. Seven papers were excluded following this, with a total of six papers included in this review. Another search was carried out in March 2019 with the exact same parameters and combinations. It resulted in one additional paper being included in this review.One of the aforementioned papers is a systematic review . This paThe last step of the search strategy was to analyze the references of the included papers. This analysis identified another two papers for inclusion in this study.In total, 14 papers met the inclusion criteria and provided the basis for the subsequent analysis.Both dependent and independent variables were defined in different ways in many of the papers, but some papers had some definitions in common. One independent and two dependent variables are defined below.The independent variable income was often defined as individual household income per annum. This includes employment earnings, government benefits, pensions, investments, and interests . EquivalIn 11 of 14 papers, SRH was based on the answer to the question “In general would you say your health is excellent, very good, good, fair, or poor?” The other papers use different approaches. One paper did not include any measure of self-rated health .The other possible outcome of morbidity was included in only four papers and they all defined it in different ways. One study combined 48 health symptoms to the Standardized Index of Bad Health . AnotherAs described above in “Dependent and Independent Variables”, income as well as SRH and morbidity were defined in different ways. In particular, morbidity was defined differently in each of the four papers.The time of measurement also varies across the papers with dates between 1967 and 2015. The papers analyzed a total of nine different panel survey data sets from seven countries. Furthermore, the statistical methods differ to some extent. A regression model was used by every paper except one ,16.Looking at all these variations, it is not possible to conduct a meta-analysis. The scope of this paper is therefore limited to a narrative review.In total, 14 papers met the inclusion criteria and could be included in the review .The included papers analyzed survey data from seven different countries . In the following section of this paper, the findings will be presented according to country, alongside summaries of the panel surveys used in each the papers to ensure better comparability. Following this, the systematic review of Imlach Gunasekara et al., which included studies from four different countries and five different panel surveys, is considered separately. One paper analyzed the Chinese population with the help of the National Health Services Survey (NHSS) and China Health and Retirement Longitudinal Study (CHARLS).The NHSS started in 1993 and is conducted every five years, and includes questions about socioeconomic characteristics, health status, satisfaction rate and health insurance, among other things. In total, the survey contains data from about 300,000 adults (>15 years) from 93,600 households .The CHARLS began in 2011 and is repeated every two years covering topics like socioeconomic status and chronic diseases. The information was collected from 17,000 older adults (>45 years) living in 10,000 households .The paper dealt with the relationship between socioeconomic status and morbidity in China. For the analysis, data was collected from the NHSS in 1998, 2003 and 2008 and from the CHARLS in the first four waves (2011–2015). The NHSS and the CHARLS allow a statement to be made as to whether the relationship exists both in the all-age cohort and in the older only cohort. The authors analyzed three morbidity outcomes  and two factors of socioeconomic status (income and education) using individual fixed effect regression models and individual random effect models. It was found that the relationship between income per capita and morbidity is quadratic negative and non-linear. Furthermore, morbidity decreases by growing per capita income until a turning-point level is reached, whereby morbidity begins to increase with continuing income growth .There is just one paper analyzing the German population employing the German Socio-Economic Panel (GSOEP). The GSOEP is a survey which used a sample of initially 12,000 West German adults (>17 years) in 1984. 4400 adults of East Germany were included in the sample from 1990. The data has been collected every year since then [The authors examined the effect of income change on health satisfaction in both West- and East Germany after the reunification in 1990. They used data collected in the years 1984 to 2002. Adding a fixed-effects ordinal estimator and a causal decomposition technique to account for attrition bias, the results show a small, significant and positive effect of income change on health satisfaction in only East German males. While there is no significance for East German females, a small, significant effect was found in West German males and females. Furthermore, a downward trend in health satisfaction for both East and West was found by analyzing the data through 13 years since reunification .Three papers included in this review looked at Great Britain. The British Household Panel Survey (BHPS) was used by all these studies to investigate the possible relationship between income and health.This longitudinal survey started in 1991 with a sample of about 10,000 adult people (>16 years) from about 5500 households. It was continued with annual interviews covering several topics like individual and household demographics, mental and physical health, labor-force status, employment. In more recent waves, the sample size has grown to 16,000 people from 9000 households [The first study examined the association between household income, income inequality, relative income and self-reported health using the first 12 waves 1991–2004) of the BHPS. In total, the paper applied three differently ordered probit regression techniques resulting in supporting the absolute income hypothesis. In other words, the absolute household income had a significantly positive effect on SRH. On the other hand, no evidence was found to support either the relative income hypothesis or the income inequality hypothesis [ of the BThe second paper collected data from the first 11 waves starting in 1991 to investigate the relationships between income, relative deprivation and SRH. The use of parametric and semiparametric panel data models allowed the authors to account for misspecification and heterogeneity. It was found that household income affects self-assessed health in a small but statistically significant, positive way. It also showed that large changes in income lead to small changes in SRH. The correlation was characterized as non-linear .The third and last paper using the BHPS data estimated the effect of lottery prizes as a proxy for exogenous income shock on four different health outcomes . The collected information included health data from 1996 through 2008 (wave 6–18), lottery prizes data from 1997 until 2008 (wave 7–18) and they were analyzed using three different individual fixed effects regression models. The results show statistically insignificant coefficients for the lottery prizes. To be more precise, no positive relationship between exogenous income shocks and self-rated health or physical health problems was found .Altogether, three papers investigated the effect of income on health in citizens of New Zealand and all of them used the NZ Survey of Family, Income and Employment (SoFIE).The SoFIE is a nationally representative panel survey of the resident population for a period of eight years (October 2002–September 2010). The annual interviews included adults (>15 years) from a total of 11,500 households. About 22,000 people interviewed in the first wave were followed over time. Additionally, the number of residing children in each household was identified (about 7000 at wave 1) .The first paper focused on the relationship between income change and SRH and how this relationship is modified by baseline health or poverty. The methods included data from four waves of the survey (2002–2005) and a fixed-effects ordinal logistic regression model. Analyzing the variables showed a small, positive, but non-significant association between annual household income and SRH. To be more precise, an increase in income of $10,000 in one year improved the chance of reporting better SRH by 1%. The only significant modification of this relationship was caused by poor baseline health, while poverty or deprivation had no influence .The second study collected information from seven waves (2002–2009) of the survey to investigate the effect of In-Work Tax Credit (IWTC) interventions on SRH. The variables of eligibility for IWTC and the amount of IWTC and SRH were analyzed using fixed effects regression analyses, allowing for the consideration of time-invariant and measured time-varying confounders. The findings showed that becoming eligible for IWTC as well as a great increase in the IWTC amount caused no difference in SRH. In addition, it was found that an increase by $1000 in the IWTC amount improved SRH by only 0.003 units, which means there is no significance in the relationship [The last paper used the exact same sample with the same methods and similar variables to find out whether an unconditional tax credit for families (FTC) affects the SRH. Using eligibility for FTC and the amount of FTC as measurement parameters, the analysis resulted in a small and insignificant change in SRH in becoming eligible for FTC or receiving a $1000 increase in the FTC amount. In other words, there is no substantial effect of unconditional tax credit for families on SRH. To summarize this second and last study, it can be said that there is no difference between the effect of unconditional and employment-conditional tax-credit on SRH .The Swedish population was examined by two different papers using the Swedish Level of Living Surveys (LNU). The surveys investigated a random sample of adult population (15–75 years) starting in 1968 and repeated in 1974, 1981, 1991, 2000, and 2010. The interviews included questions with regard to health, education, and working conditions and combined the answers to register information of household income .The first paper analyzed the effect of positive income shocks measured as monetary lottery prizes on health and mortality. Poisson as well as Ordinary Least Squares regression were used on the collected data from waves in 1968, 1974, and 1981. It found out that increased income causes better health. A lottery win of about SEK 100,000 in a 13-year period improves SRH by 3 percent. In addition, there is a negative association between income shocks and poor mental health, cardiovascular diseases, and headaches [The second study examined income changes over time and their relationship with SRH. The longitudinal income data has been collected from the income register of 1995 to 2000 and was connected to the cross-sectional data on self-rated health of the LNU in 2000. Using logistic regression models, the findings show that decreases in absolute income have a stronger effect on SRH than income gains do. The loss of income causes adverse effects on health while an increase in income shows heterogeneous results. In summary, the study found that income instability in both ways leads to inimical effects on health .The three papers studying the residents of the USA used three different panel surveys. The first study investigated the effect of income on health with the help of the first National Health and Nutrition Examination Survey (NHANES) and Epidemiologic Follow-up Study (NHEFS). The first survey was conducted from 1971 to 1975 starting with a sample size of 14,407 adults (25–75 years) .The aim of the paper was to examine the associations between individual income, income inequality, SRH, morbidity, and mortality. In addition to the collected baseline data from the first National Health and Nutrition Examination Survey, follow-up data including data about SRH from 1982 through 1984 were also used. Using cumulative logistic regression models, there was a much stronger correlation between individual income and biomedical morbidity than was the case with income inequality. Also, the same connection to baseline and follow-up SRH was found [The second paper used the Panel Study of Income Dynamics (PSID), which started in 1968 with nearly 5000 households. Every year, the study collected information about income and employment experiences until 1997. Data has been collected every two years thereafter. SRH-data was only gathered between 1984 and 1997 [This paper focused on the impact of income variations on SRH using health data from 1984–1997 and labor income data from 1978–1994. After individual-specific fixed-effects regression analysis was carried out, the results show that positive income shocks improve health and at the same time adverse income shocks cause the opposite effect. In addition, health is improved by moving from the bottom or the top of the income distribution to the middle. The turning point between improvement and deterioration of health was found to be the 75%-percentile of income distribution .The most recent paper looked at a specific part of the population using the Mexican American Cohort Study (MACS). Mexican Americans (>18 years) were recruited between July 2001 and April 2004. The information covered, among other things, demographic characteristics, medical history, level of acculturation, and social habits .The study investigated the prediction of SRH before and after imputation of the missing variable yearly household income. Data was collected between 2002 and 2005 and four different methods were used to impute the missing variable income. Using a logistic regression analysis, it was found that the variable yearly household income is a good predictor for SRH. To be more precise, an increasing income of $5000 improves the odds of SRH as good or better by 11%. On the other hand, people with a good or better SRH have a significantly greater income than those with a fair or poor SRH .The review analyzed 13 studies, which used five different longitudinal panel surveys altogether. The BHPS, GSEOP, as well as the PSID have already been summarized (see above). The remaining surveys concern the US and Australia and are called the Health and Retirement Study and the Household, Income and Labour Dynamics in Australia (HILDA). The Health and Retirement Study is a biennial study that started with 22,000 adults from the US (>50 years) in 1992. The focus of this study was the employment and health transition in older people [The HILDA survey began in 2001 with 7683 households including nearly 14,000 individuals (>18 years) from all over Australia .The aim of the review was to find the possible relationship between change in income and change in SRH in adults. All the studies used in the review were conducted either in Great Britain, USA, Germany or Australia. Most studies found a positive, small, and statistically significant association between income and self-rated health. Three of these studies found no significant associations among women. After consideration of unmeasured confounders and measurement error, the association was no longer found .Before starting the research, we expected the relationship between income and self-rated health to be significant, namely that income would have a clear, positive effect on self-rated health as shown in several cross-sectional studies before . We thouIn summary, most of the analyzed papers found clear evidence for a significant, positive relationship between income and both SRH and morbidity. Surprisingly, this association was very small and would likely be rendered insignificant, once adjusting for confounders and bias. It was even more surprising that two studies characterized the relationship as non-linear and presented a specific turning-point. Reaching this turning point, the studies suggest that SRH or morbidity starts to worsen while income continues to grow ,21.In total, there are nine studies and one systematic review examining the effect of income on SRH or some similar variables for self-rated health. Therefore, this issue has been most frequently explored in the 14 analyzed papers. To sum up, five studies found a significant, positive association between income and SRH, but only a very small one. Two of these papers only covered a short time period of three or four years, while the other three covered a longer period of 11 or 13 years. Having similar results, the duration of the measurements seems to be irrelevant for the results. At this point, it would be interesting to find out whether this irrelevance is also present when investigating much longer time periods as for example a whole life. There is currently no such data available. Four studies found either no significance or inconsistent results in relation to the effect of income on SRH. Two of them examined employment-conditional or unconditional tax-credits as income shocks and found a small but insignificant association between income shocks and SRH ,16. ThisThe other papers presenting a significant positive association between income and SRH also include factors that limit their explanatory power. The most common problem of these studies were unmeasured confounders. The income–health association is quite complex due to many variables which can possibly modify this interaction. Some studies ignored important confounders such as employment status, social support and family structure ,8.The aim of all papers was to investigate the pathway from income to health in order to analyze the relationship between income and health. Therefore, the occurrence of the opposite pathway  called reverse causality was mentioned as another limitation ,25. Selection bias should also be mentioned. Two papers stated this bias as their limitation. One study included a greater number of women in its sample (87%). Consequently, these findings may not be generalizable to the whole population . AccountIn summary, the results of the studies are the same as in the analyzed systematic review of Imlach Gunasekara et al. Most of the studies in the analyzed systematic review as well as in this review showed a small, statistically significant, and positive relationship between income and SRH . This reOnly two studies investigated the relationship between income and morbidity. The reason for this may be that the common variable SRH considers all aspects of health. Therefore, morbidity is also included in measures of SRH. Nevertheless, SRH and morbidity should be distinguished, because SRH is a subjective variable whilst morbidity can be examined objectively. Both studies found a significant negative association between income and morbidities ,14.Due to very different ways of measuring morbidity, it is quite complicated to compare these studies with each other. One study used biomedical morbidity measured through physical examination and classified according to the severity of the condition . The othThe main difference between this study and almost all the other studies is the definition of income. Mostly, the other studies, in particular the paper analyzing the relationship between income and morbidity, used household income, while this study used income per capita . This adHowever, in previous literature, the negative association between income and morbidity was also found in Europe and the USA ,27. On tIn summary, the two analyzed papers do not present new evidence, but they can confirm the results of previous literature.There are three studies examining a special form of income change. They investigated the effect of exogenous positive income shocks on SRH and morbidities either in the form of lottery winnings or as the result of the German reunification.Two studies using lottery prizes as income shocks showed inconsistent results. One paper found statistically significant association between these income shocks and SRH as well as morbidity , while tThere are some differences between the two studies, which may explain the conflicting results. Firstly, the analyzed surveys come from different countries (Sweden and Britain) and the sample size was different. The small sample in the Swedish survey of about 3000 adults may be less meaningful than the British sample of about 16,000 people. Secondly, analyzing the Swedish data, the authors defined their outcome differently from the British study by using the number of poor mental health symptoms. Interestingly, the results of the British study also found a significant positive effect on mental health. In this case, the results are consistent, only leaving a difference in the effect of income shocks on morbidity ,13.There is a major advantage, but also disadvantage, in using lottery winnings as a proxy for income changes. On the one hand, lottery winnings as exogenous income shocks are better suited to investigate the causality of the relationship due to the unexpectedness of income growth. On the other hand, the generalizability is questionable, since only those willing to take risks are included in the sample .The analysis of the German reunification showed a significantly positive effect of income change on self-assessed health satisfaction for males only. The authors also found a downward trend of health satisfaction for both East and West over a 13-year period after reunification, suggesting the positive effect is a short-term effect. The main strengths of the study cover the exogeneity of reunification and the use of fixed-effects models. The exogeneity allows a greater chance to examine the causality between income and health and, due to the fixed-effects models, they are able to account for individual heterogeneity. However, only 26% of East Germans were interviewed in all waves, which means that the sample has suffered a large decrease in the number of participants over time (panel attrition) [All three studies are forms of natural experiments collecting data at least over 10 years.Apart from the strengths of such natural experiments in terms of determining the causality of the relationship between income and health, one major problem should also be considered. Namely, the health outcomes of these studies may not be comparable to those studies that presuppose a permanent increase in income. The same individual may be affected in different ways in cases of an exogenous income shock or permanent income change . Thus, iFirst, there were only a few papers which met the inclusion criteria and could be included in the review. In contrast to the large number of available cross-sectional analyses, there are still few studies using only longitudinal data on this topic. The advantage of using longitudinal data is to be able to consider any unobservable individual effects, which may be important disruptive factors for the relationship between income and health . The review mostly considered the same dependent and independent variables, same age span, and at least similar sample sizes. Nevertheless, the differences between short-term and long-term observations and between fixed-effects and non-fixed effects in the reviewed studies cause significantly diverging results . This laLooking at the countries from which the data was analyzed, it is noticeable that these are exclusively industrialized countries. The results for developing countries may differ from those for industrial countries due to the different living conditions. It therefore can be hypothesized that the living conditions of people from industrialized countries with a certain wealth might not be as strongly influenced by an increase in income as might be the case with people from, for example, developing countries. There are therefore many research opportunities in this area. Since only one database (PubMed) was used for research, possible suitable studies from other databases were not considered.Another source of error could have occurred during the search for suitable studies. When scanning titles and abstracts, papers might have been excluded erroneously from the review due to poorly worded abstracts . Finally, publication bias is a problem of every systematic review. There is always the possibility that analyses remain unpublished and obviously cannot be found . In total, 14 studies with data from seven different countries and 11 panel surveys were analyzed in this review. The results did not meet our expectations. Overall, the majority of the papers did indeed find a small, but significant positive effect of income change on some measurement parameter for general self-rated health. In addition, the association between income and morbidity was found to be significantly negative. That means that growing income reduces morbidity. However, accounting for all the disruptive factors as for example family structure and employment status, reverse causation and selection bias, these results may not be significant. This means that the initial expectations were only fulfilled to a limited extent. There is a positive relationship between income and self-rated health, but it is unexpectedly small.◦the multitude of possible disruptive factors,◦the presumably different responses to exogenous income shocks and permanent income increases, and◦the different research methods producing various results, it becomes clear that the association between income and health is very complex and needs further examination. Looking atBecause there could be only a few papers included in the review and longitudinal surveys are superior to cross-sectional analyses, there should be more research done with longitudinal data. Particularly, there is a lack of literature using long-term observations over 13 years or data from developing countries. There is the possibility that studies from low-income countries may found a different characterization of the relationship between income and health. More work is therefore needed, especially in low to middle-income countries.Moreover, to date the relationship between income and morbidity has not been sufficiently investigated. Since this objective measurement parameter probably causes less recall bias than SRH, further research should also be done in this area.Intuitively, one may assume that income changes have a big effect on self-rated health and morbidity. Most people tend to assume that an increase in income automatically means an increase in health as well. Personal health and public policy decisions may be influenced by this assumption.However, and quite unexpectedly, the findings of our study suggest that there is only a hardly recognizable positive impact of increased income on health. The relationship between income and health seems to be more complex than generally assumed. This indicates that decisions based on the previously mentioned assumption might not be as substantiated as thought before.


Tobacco control policies rely heavily on law and are steeped in litigation. Examining the creation of tobacco control laws in the European Union, this article lays out the potential costs and benefits of legalism for public health practitioners and advocates. Legalism is a form of governance that relies heavily on the authority of law to settle political disputes, with consequences for the ways in which governments make, and advocates push for, public health policies. To the extent that legalism creates procedural problems and distortions in the content of public health policy, then the content of law and its making is a public health problem. On the other hand, litigation can also be a public health tool, and an enforceable, justiciable right to health is a powerful political and legal weapon in its own right.  Public health often works through law, regulating industries and individuals and punishing specific actions. It is impossible, therefore, to understand contemporary public health without understanding legalism and its politics.Legalism is a mode of governance characterized by a strong emphasis on the formulation and enforcement of legal rules over less formal policies, frequent court cases, legal expertise and a multiplicity of formal policymaking structures (such as public consultation or impact assessment) that can help policymakers to manage legal risks.Officials, researchers and advocates working to address public health problems can benefit from understanding the causes and consequences of legalism, which has become a well-established way of working in several health-related policy areas and looks likely to become the new norm in others. Tobacco control measures rank among the most successful policies in public health. But they are also subject to some of the most intense legal scrutiny and industry use of legal challenges seen by any public health interventions. Examining tobacco control regulations is therefore an excellent way to examine the development of legalism in public health policymaking and its consequences.Legalism is frequently thought of as a purely American phenomenon. When we think about lengthy, expensive court cases involving tobacco companies, smokers and governments, we are likely to think about the USA. Indeed, until the 1990s, little tobacco-related litigation took place in countries other than the USA. From the 1990s onwards, however, the number of tobacco-related court cases outside of the USA has increased dramatically. In line with this trend, as European Union (EU) institutions began to craft collective tobacco control laws, the number of legal challenges seen in Europe began to increase. In recent years, we have seen a number of highly significant tobacco-related cases involving EU member states. This paper reviews these cases and the surrounding politics in order to shed light on the development and consequences of legalism.Legalism is a form of governance that occurs when the law is viewed as a highly important, or even dominant, form of authority. In a legalist paradigm, societies rely heavily on law and judges to address political conflicts. Politicians, bureaucrats, advocates, business interests and other stakeholders view laws and regulations, courts and the formal bureaucratic procedures that accompany them as essential (and sometimes preferable) parts of the political environment. All actors anticipate legal challenges and act accordingly: politicians prioritize legislation and rulemaking over informal negotiations, bureaucrats oversee the formulation of rules and attempt to manage legal risks, judges interpret policy and policymaking and interest groups formulate and use legal arguments. ‘Soft law’  exists, but remains in the shadow of hard law.Legalism can arise as a result of competing demands in highly contentious political spaces, particularly where other forms of interest aggregation  are weak or absent. In those circumstances, actors may begin to demand better protection under the law, or seek out legal redress more readily.,adversarial legalism, characterized by frequent and costly court cases, highly complex regulations that emphasize enforcement, judges that exist outside of state hierarchical controls, and highly mobilized legal actors. Some continental European countries, in contrast, have a long tradition of bureaucratic legalism, relying on interpretation of bodies of rules by state-appointed bureaucrats to solve political disputes.Researchers observing legal systems in different countries note that states have different varieties of legalism based on their domestic institutions and dominant values.,EU member states may have different legal styles, but political scientists argue that global forces acting upon them are causing a degree of convergence. In particular, deregulation, followed by the proliferation of legal rules designed to promote and manage cross-border markets, creates ideal conditions for legalism.Eurolegalism.The EU institutions are a case in point, having developed their own variety of legalism, Beginning in the 1980s, European states embarked on an ambitious project to create a single market. In doing so, they granted authority to the European institutions to address regulatory barriers to the smooth operation of a fully-integrated market for goods, services and capital. The EU institutions began to pass more, and more detailed, legal rules to govern areas such as environmental policy and public health that could potentially be barriers to the single market. The EU’s supranational court, the European Court of Justice (ECJ) (which later became the center of an EU court system) played an active role in settling disputes about EU-wide regulations. Over time, the EU’s legal institutions have responded to a whole host of competing demands, not just for or against economic aspects of market integration, but concerning the fundamentals of a variety of social policies and citizenship rights.In EU tobacco control policy, competing demands for market integration and calls for stronger public health protections have been formalized in law, resulting in a policy environment strongly shaped by market regulations and the risks and opportunities inherent in legal actions.The Single European Act (SEA) signed in 1986 was a fundamental treaty that laid out the path to the creation of a European single market. The SEA authorized the European Commission to take actions to facilitate market integration and recognized that the Commission could address regulations designed to protect health in that context.The Commission acted quickly to capitalize on its new authority. The first EC-wide laws addressing tobacco control, designed to harmonize policies among member states, banned television advertizing of tobacco products (89/552/EEC), addressed health warnings on tobacco packaging (89/622/EEC), set maximum levels of tar in cigarettes (90/239/EEC), extended the labeling directive  and required minimum taxation levels for tobacco products .,Although the implementation of the labeling directive in Italy was challenged in court (C-222/91), it was a further, more ambitious Directive that caused the most trouble for the Commission. Directive 98/43/EC banned all tobacco advertizing across the EU. It took almost 10 years to pass, in some part thanks to the lack of a clear legal base in the treaties, and upon passage was immediately challenged by Germany in the ECJ on the grounds that the rules went further than necessary to promote the smooth operation of the single market. In a blow to the aspirations of tobacco control advocates, the Court annulled the advertizing directive in 2000 but also went further to suggest how the problem could be addressed.Several factors contributed to the fragility of EU tobacco control policy in this early period. The EU Commission, often characterized as the ‘policy engine’ of the EU, did not have a dedicated health directorate until DG SANCO was established in 1999. Public health interest groups were also a comparatively weak presence in Brussels, and so decisions on the first round of directives were made in relative isolation by EU officials.,Crucially, a number of key member states that initially opposed the formulation of a comprehensive tobacco control law at the EU level , 2001/37/EC) weakened their opposition.After the annulment of Directive 98/43/EC, legal activity increased, arguably becoming more adversarial than before. Between 2000 and 2004, 10 EU member states sued tobacco companies over smuggling in American courts, eventually resulting in a $1.25 billion dollar settlement in favor of the European states. The EU’s new TPD quickly faced a legal challenge from industry (C-491/01). But this time, the challenge failed. This happened, in part, because officials had gone further in the text of the Directive to frame the law as driven by market integration, highlighting the role of the directive in harmonizing disparate rules across member states. The Court determined that the TPD did indeed aim to facilitate market integration, and that having the protection of public health as a ‘decisive factor’ driving the law did not mean that the measure could not also support market integration. This thinking made its way into a subsequent string of jurisprudence and also influenced future actions taken by EU officials.At this time, the EU and its member states also played a key role in facilitating the first international agreement on tobacco, the WHO Framework Convention on Tobacco Control (FCTC). The FCTC places binding (if not particularly enforceable) obligations on states to adopt more stringent tobacco control policies. Despite its lack of teeth, the agreement presents, in a legal form recognizable to courts, an international, evidence-based consensus in favor of a specific set of tobacco control policies. The European Community and all 28 EU member states are parties to the FCTC.The involvement of the EU in facilitating the FCTC made a significant difference in the latest round of legal disputes that began in 2014. After five years of intense lobbying, corruption allegations and bargaining, the EU passed a revised version of the TPD in 2014 . The new TPD augmented the powers of the EU on tobacco control in specific areas including the regulation of e-cigarettes, the prohibition of characterizing flavors including menthol, a requirement for larger mandatory warnings on packs. It also contained language emphasizing member states’ ability to go beyond the directive and implement plain packaging. The revised TPD thus demonstrates the extent to which the EU’s political institutions—particularly DG SANCO and the European Parliament—have developed political capacity in the area of public health since the early days of EU tobacco control policy. The text of the revised TPD is much less vulnerable than that of the original advertizing directive to challenges via the Court of Justice of the EU (CJEU), reflecting understanding on the part of the drafters of the difficult balance between of market harmonization and public health protections in EU law.The TPD was swiftly challenged in European courts by tobacco firms, involving domestic courts in the UK, Ireland and France as well as the CJEU . The challenges focused on labeling measures in the context of certain member states’ decisions to implement plain packaging, provisions on e-cigarettes, the ban on characterizing flavors and the ban on sale of snus as well as questioning the purpose and appropriateness of the entire Directive.In its responses, the CJEU ruled that the TPD is valid, supporting the EU’s authority to act in this area and rejecting claims that the measures were not appropriate to achieve the goals of the Directive. Significantly, the Court’s judgments refer extensively to the FCTC as a core part of the legal context. The Court uses FCTC obligations instrumentally to demonstrate an international political and scientific consensus in support of specific tobacco control policies, demonstrating just how important the FCTC is to global tobacco control efforts.and is an appropriate measure for ensuring a high level of protection of human health.Further to supporting the EU’s ability to pass tobacco control regulations in general, the judgments thoroughly endorse the EU’s specific approach on some tricky issues. On e-cigarettes, an issue that countries around the world are addressing in very different ways, the Court found that a two-tier regulatory framework with different rules for cigarettes and e-cigarettes was appropriate given the different levels of risk that the two categories of products represent. On labeling, the Court affirmed the EU’s decision to allow member states to go beyond the TPD and introduce plain packaging. On characterizing flavors, the Court did not see a disconnect between the goal of market integration and that of protecting human health. Rather, the judgment affirms that the directive both achieves the goal of bringing different national rules into line with one another But public health officials and advocates should not grow complacent in the face of these recent victories. Friction between the goals of market integration and public health protection still exists. In October 2014, an Italian law introducing minimum pricing for cigarettes was successfully challenged via the EU’s court system, with the CJEU determining that the law violated an EU Directive that sets an EU-wide tobacco excise duty .Conflicts of interest: None declared.Legalism is a form of governance that relies on the authority of law to settle disputes.Tobacco control measures are heavily influenced by legalism.While legalism can support public health, it can also create procedural problems and distortions that derail public health policy.


Procambarus clarkii and the burrowing behavior in the secondary digging crayfish P. acanthophorus.Melatonin (MEL) is an ancient molecule, broadly distributed in nature from unicellular to multicellular species. MEL is an indoleamine that acts on a wide variety of cellular targets regulating different physiological functions. This review is focused on the role played by this molecule in the regulation of the circadian rhythms in crayfish. In these species, information about internal and external time progression might be transmitted by the periodical release of MEL and other endocrine signals acting through the pacemaker. We describe documented and original evidence in support of this hypothesis that also suggests that the rhythmic release of MEL contributes to the reinforcement of the temporal organization of nocturnal or diurnal circadian oscillators. Finally, we discuss how MEL might coordinate functions that converge in the performance of complex behaviors, such as the agonistic responses to establish social dominance status in  N-acetyl-5-methoxytryptamine (melatonin or MEL) is a phylogenetically well-preserved molecule, broadly distributed from unicellular to multicellular species. Despite differences in biosynthetic pathways between taxonomic kingdoms, this molecule has remained unaltered throughout species evolution and presents the same chemical structure in all species studied so far [N-acetylserotonin [d so far . In eukad so far ,2 and ind so far . Afterwaerotonin ,4.MEL is an amphiphilic molecule that, after being synthetized, can passively diffuse across the plasma membrane to the interstitial space and blood circulation. This capability was demonstrated by detecting the indoleamines undergoing efflux through amperometry, fluorescence, and optical quenching . MEL alsMEL’s roles in physiology are pleiotropic and encompass broad time and space scales. Regarding space, this indoleamine could be accumulated in subcellular organelles or cross membranes to act locally as an efficient free radical scavenger in the mitochondrial and/or directly modulate the activity of intracellular proteins in the cytoplasm . MoreoveThis review will focus on the role of MEL as a chemical messenger involved in the functioning of circadian systems in crayfish. First, the importance of circadian systems in the physiology will be described to contextualize and highlight the importance of MEL in health maintenance. In subsequent sections, evidence will be shown and discussed in the context of MEL’s participation in regulating the circadian rhythms in crayfish.In organisms, a collection of heterogeneous oscillating functions coexists that requires precise synchronization to maintain homeostasis and health . Almost Another substantial feature of this system is its capability to synchronize the internal time with the period of cyclic environmental cues named “zeitgebers”. Adjustment is accomplished by several pathways and this plasticity allows organisms to predict regular external changes with different periods, such as tide variations, day-night cycles, lunar cycles, and seasons ,24. InteThe circadian system is constituted by hierarchically organized structures that differ among species . In geneMEL is one of the output signals that conveys the information about the dark phase of photoperiodic regimen (scotophase) to synchronize the system with the day-night cycle. In vertebrates, MEL is synthesized in the pineal gland and in peripheral organs . MEL migProcambarus clarkii, P. bouvieri, and P. digueti have been used to define the circadian properties and the elements that compose the circadian system in crayfish [Crayfish are nocturnal decapods that inhabit a wide variety of freshwater aquatic habitats, including lotic and lentic environments. These organisms have been used as a model to study circadian rhythm mechanisms because they are less complex than vertebrates. Although the genetic core of the circadian clock in decapods has not been determined yet, crayfish ,40,41. Icrayfish . Also, tcrayfish .Drosophila melanogaster, Leucophaea maderae, or Gryllodes sigillatus [In both invertebrates and vertebrates, the pacemaker has been proposed to be in the central nervous system (CNS), i.e., in the protocerebral optic lobes in insects such as gillatus ,45,46 angillatus ,48,49. Rgillatus ,50,51,52Complementary evidence obtained by measuring the circadian rhythms mentioned above supports the hypothesis that the intercommunication of brain structures from the lateral and median protocerebrum establishes the pacemaker functioning in crayfish, as was proposed by the group of Fanjul-Moles ,50. MoreThe ERG rhythm persists in isolated eyestalks , and theP. clarkii crayfish that had their eyestalks removed from their base after severing the connection between the lateral and median protocerebrum. Crayfish activity was recorded with a videomex system, as described in detail by Fanjul-Moles et al. [To confirm the former hypothesis, we measured the locomotor activity rhythm in male s et al.  and De ls et al. . Locomots et al. . The numIn the late 70’s, Page and Larimer  analyzedConcerning circadian outputs, it has been suggested that the rhythms in crayfish are coordinated by a neuro-endocrine feedback loop established between the protocerebrum and the sinus gland ,51,63. TDrosophila, whose photoreceptors from the eyes and ganglion are required for appropriate synchronization [The mechanism underlying synchronization of the crayfish circadian system with zeitgebers has been extensively studied with regards to the photoperiodic cue and the ERG rhythm because its oscillations are very stable in period. This is also because the rhythm phase, that also has an adequate stability, is relatively easy to define. The phase is an important parameter to determine the strength of a disturbance induced by a specific cue or signal in the oscillators, a requirement to re-entrain the circadian system during the synchronization process. In this context, in crayfish, three different groups of photoreceptors (inputs) can send sensory information to the circadian pacemaker about the light perceived. The principal pathway to detect light during the photophase is through the retinal photoreceptor cells. However, two alternative groups of photoreceptors might contribute to the circadian input; one is in the cerebroid ganglion  and the nization .As previously mentioned, ERG rhythm is nocturnal and peaks at the middle of the scotophase ,63. ThisCrayfish maintained under constant darkness expressed an ERG rhythm with a period shorter than 24 h ,53,69. WIt is important to mention that, in crayfish maintained under light-dark cycles, the endogenous MEL and PDH are released following a circadian rhythm with an opposite phase. Whereas MEL has a nocturnal peak , PDH preIn addition to the effect of a chronic daily injection of the hormones on ERG rhythm, which requires several days to be observable, a single dose of exogenous MEL or PDH induces an acute  effect on the excitability of neuronal cells in both the pacemaker of the ERG rhythm  and the structures where this rhythm is expressed . MEL reduced the number of spontaneous electrical potentials (firing rate) recorded from the cerebroid ganglion at four different time points, whereas PDH increased the firing rate of neurons from this structure ,59. ConcP. clarkii, the rhythm of light sensitivity (ERG rhythm) under a photoperiodic regimen is nocturnal, whereas the rhythm of the number of spontaneous potentials recorded from the cerebroid ganglion is diurnal [Evidence suggests that MEL and PDH are hormones exerting opposite effects but, interestingly, their actions depend on the temporal dynamics followed by the structures affected . That is, the circadian increase of endogenous MEL- or PDH-release, which are opposite in phase, modulates the functioning of the neuronal structures involved in the expression and control of the ERG circadian rhythm , which also oscillate 180° out-of-phase . In this diurnal . Additio diurnal   and were acclimated to laboratory conditions for at least two weeks. They were maintained under a light-dark cycle  and fed with pellets for shrimps. An intracardiac injection of either MEL (0.0316 µg/20 g of body weight) or vehicle was applied during the middle of photophase or scotophase, and the activity of paired crayfish opponents was recorded with a video camera. Videos were then analyzed to quantify the occurrence of the agonistic behavior, in particular the number of agonistic confrontations or encounters. The data were compared using a one-way ANOVA test. No differences were detected in animals injected with MEL during scotophase and in vehicle-administered crayfish . In contAdditional evidence has shown that agonistic behavior depends on the release of amines with a neurotransmitter function, such as tyramine , octopamP. acanthoporus. This is a secondary burrower crayfish that spends much of its lifetime in the shelters they built themselves, annually, during the months of the dry season. This species digs complex tunnels with chimneys in the field but also under laboratory conditions. The persistence of this behavior in captivity has allowed us to study the circadian rhythm properties in the burrowing activity but also the influence of soil as an ecological resource with high-perceived value [Another example regarding the influence of MEL on the expression of behavioral patterns is the burrowing activity of ed value .P. acanthoporus maintained under a photoperiodic regimen shows a clear nocturnal circadian pattern in their burrowing activity, with a period of 24 h [P. acanthoporus. The effect exerted by soil availability was evaluated by keeping animals in aquaria with sediment to build refuges or in aquaria with water but without sediment. At the beginning of the experiments, crayfish were synchronized for four days, alternating intense illumination for 12 h with dim light intensity for another 12 h. Under this condition, the activity followed a clear circadian rhythm of 24 h with oscillations of the same amplitude. Then, from the 5th to the 10th day, animals were subjected to constant light to determine the true circadian nature of this rhythm and to have lighting enough to detect crayfish movements with a video camera. Nocturnal-active animals progressively reduce their activity and increase the period of their rhythm under constant light (L-L) [P. acanthoporus maintained in constant illumination with water but no soil in their aquaria, the amplitude of the rhythm (level of activity) diminished progressively over days. Surprisingly, the amplitude of the rhythm in the aquaria with available sediment to excavate remained at the same level and, in all cases, deep tunnels were built, suggesting that crayfish maintain the same level in their burrowing activity [ of 24 h . Therefoht (L-L) ,60. In Pactivity .It seems that the available sediment in aquaria induced the burrowing behavior, and the performance of this motor behavioral pattern modified both the mean period and the amplitude of the oscillation of the rhythm of activity under constant illumination. This evidence indicates that this ecological factor—that, in appearance, does not mark a progression in the daily cycle—had a deep impact on the circadian system. When the pacemaker and peripheral oscillators lose communication, a reduction of the rhythm amplitude may be caused by their progressive uncoupling. Therefore, it could be hypothesized that sediment might be a reinforcing factor for the coupling of oscillators. A possible mechanism for this coupling could be the consolidation of communication between the pacemaker and peripheral oscillators, reflected in the maintenance of the oscillation amplitude.P. acanthophorus. However, more experiments are needed to determine the role of PDH and MEL in modulating the level of the burrowing activity under a photoperiodic regimen and the pathways triggered by these hormones at organismal and/or cellular levels.Since circadian rhythms in crayfish are coordinated by a neuro-endocrine feedback loop between the cerebroid ganglion and the sinus gland , the perception of the available sediment and the performance of the motor program might impact the release pattern of these hormones. In this way, they might modulate the temporal organization and the rhythm of burrowing behavior in The examples presented in this section concern two crayfish species that display complex behaviors, comprised by a sequence of stereotyped movements and postures. In these behaviors, several limbs are used simultaneously (considering that they are decapods), together with other sections of the body such as the entire abdomen or just the telson. These limbs follow a well-defined motor program. In addition, these behaviors converge in the increased overall activity level induced by exogenous MEL or by the soil. Moreover, in both examples, the effect could be observed hours after the stimulus and was apparently maintained for several days, suggesting a change in the state of the organism. The level of activity could be determined by the strong relationship between the following elements: (1) the mechanisms to control the behavioral program ; (2) the level of metabolic processing by which enough energy is supplied to perform a sustained behavioral program; and (3) the mechanisms to internally detect the program’s performance or the pathways to perceive external factors that trigger the behaviors . Each of these elements have a specific level, and they could establish a feedback-loop that would allow a change of the organism’s state if one of them suffers a modification (up- or down-regulation). In this context, MEL might facilitate the adequate acquisition of each of these functions to be upgrading them to their optimal states. This is not only with regards to the needs of the organism during the performance of a determined behavioral pattern but also with regards to synchronizing it to the specific time of the circadian cycle in which the behavior needs to occur. This proposal opens interesting therapeutic potentials, for instance, the simultaneous administration of MEL and a specific drug that restores the release of a neurotransmitter that was lost because of neuronal dysfunction . Thus, MIn summary, MEL is an endocrine signal that might act on at least two different levels in the organization of the crayfish circadian system. Evidence suggests that MEL is involved in the synchronization process which directly informs the pacemaker and peripheral oscillators about the beginning of the scotophase and the progression of internal and external time. Importantly, the MEL signal resets the time of the clock, and this modification is persistent after daily treatment with a dose of this hormone. This fact suggests that its action could be exerted on the genetic core of the clock.Additionally, MEL has an acute effect in the modulation of neuronal cell excitability, which might correspond with an action on the pacemaker’s outputs. Moreover, peptidergic signals, such as PDH, could represent MEL’s counterpart in the circadian system, suggesting that these endocrine signals are involved in the synchronization process detecting the opposite phases of the photoperiod. Moreover, they might reinforce the coupling of oscillatory structures to coordinate the temporal order in crayfish. With this in mind, it appears that MEL organizes the different functions that need to converge to perform complex behavior performance, such as agonistic encounters, to establish social dominance status and possibly burrowing. Both are dependent on different chemical messengers, circuits, neural structures, and peripheral organs.It is worth mentioning that, in humans, some anomalies occurring in physical or mental disorders correlate with the uncoupling of the circadian oscillatory structures, which affect behavior performance and cognition . In this


The health professions have progressed and evolved considerably over the last few decades in response to demographic, technological, societal and political changes. They continue to do so as the volume and complexity of population health needs steadily increase. Role boundary expansion is among the key changes to the health professions, including podiatry to meet demand. Nonetheless podiatry’s role boundary expansion has not been achieved swiftly or without resistance from neighbouring and dominant professions. This paper seeks to explain the nature of this resistance with respect to the sociology of the professions literature and to shed light on some of the factors and processes at play when role boundary changes arise in health care.Taxonomic, Marxian, Bourdieusian, Foucauldian, Boundary Work and Neo-Weberian paradigms.Six of the most contemporaneously relevant sociology of the professions theories are summarised: This review highlights that some paradigms are more relevant than others in the current socio-political landscape. It also illustrates that there is a common theme underlying each approach to defining the professions and their boundaries: competition. This may help health professionals, including podiatrists, to understand and manage the challenges and resistance experienced when professions attempt to expand role boundaries to meet increasing and changing population health needs. The healthcare landscape has changed significantly over the last few decades. Increased pressure on health services to provide efficient, high quality services in an uncertain economic climate that meet population health needs has prompted innovative changes to the organisation and provision of health care , 2. FurtA key measure proposed to improve the efficiency of health services involves increasing the flexibility of the health care workforce by breaking down traditional role boundaries , 3. IncrWhile the advent of professional role flexibility is recognised as a key measure to optimise the efficiency and utility of the health care workforce, some professions perceive that this approach may threaten, even erode their established role boundaries , 15. ProIn cases of professional role boundary expansion in health care, the outcomes tend to favour the longer established professions . What isThe professions are commonly perceived to hold special, higher level knowledge , 17–19 wThis paper explores some of the more pertinent and contemporaneously relevant theories, perspectives or approaches to defining the professions. It is important to take an historical perspective on this subject and consider the foundations laid down by earlier, albeit outdated, theories as well as more prominent ones related to the sociology of the professions.The taxonomic approach emerged in the 1950s and is considered the earliest theoretical attempt at defining professions. It has two divisions: the trait and the functionalist. The trait approach to defining the profession was based on a list of core traits and characteristics which distinguished professions from lay occupations . Under tMarxian perspectives of the professions are based on capitalist relations of production . MarxistBourdieu’s conceptualised the social world as a symbolic system made up of different lifestyles and status groups. The social world is perceivably double-structured: (1) when viewed objectively, the world appears to be socially structured, with some agents  and groups of agents in more advantageous positions than others, due to particular properties, traits or characteristics they exhibit; (2) from a subjective point of view, the construction of the world is based on the perceptions and appreciation of the relative power held by different agents. With these two forms of structure, the social world appears to be a natural, stable and common-sense space .Bourdieu objectifies the position of the agents relative to one another within the larger social space , 35. TheThe term ‘capital’ represents resources of potential value or power, which when mobilised or converted, confer social advantage . BourdieIn the health professions setting, access to and mobilisation of social capital is particularly useful for reproducing existing power dynamics. For instance medical doctors by virtue of their status within the hospital setting have more powerful social networks and other forms of social capital than nurses as shown Huby et al. . Podiatrhabitus is what produces the outward characteristics, traits, cultural tastes and practices by which an agent’s position within the social space can be determined. For example, one might be classified on the basis of their accent, the clothes they wear, foods they eat, sports they play, occupation, workplace and so on. The production of a class of habitus or a particular lifestyle is the natural consequence of agents living in close proximity and sharing similar qualities and characteristics. Habitus also provides frames of reference for the perception and appreciation of practices constitutive of a habitus. It therefore acts in a cyclic manner to allow both self-classification and the classification of others and contributes to the making of a world which is self-evident, or as summarised by Bourdieu [The social space and the agents within it are influenced and defined by their access to the various forms of capital , 35. OneBourdieu , ‘HabituThe nature of the social world and the relativity of agents’ positions within it indicate that perspectives of the space depend entirely on the point from which the view is taken leaving no scope for an absolute or universal vision of the social world. The social world therefore is a continuous space with no clearly defined boundaries . While tSymbolic power struggles occur when efforts are undertaken by agents or groups of agents to legitimise and impose upon others, particular perspectives of the social world, in which they are seen to hold more power or be of a higher status. These power struggles are considered symbolic because those engaged in them are armed with symbolic capital . The symbolic capital an agent or groups of agents can access has been accumulated through previous power struggles and has dictated their current position within the social space. Power struggles therefore tend to reinforce the relations of power within the social world .Some forms of symbolic capital, especially cultural capital, are universally recognised. An educational qualification for instance, is a form of cultural capital that can confer a socially recognised title such as ‘doctor’ or ‘surgeon’. These titles are considered to be true titles of symbolic capital and the threat of symbolic power struggles over them is minimal. Moreover, titles that have been legally sanctioned are perceived to be absolute or official and free from the relativity and indeterminacy typical of the social world . SecurinFoucault has made broad and monumental contributions to many aspects of social theory. His work is considered diverse, complex and because of the many different readings and interpretations of Foucault has wide application , 39. ForFoucault  describegaze, which describes how medicine perceived the body by the way it looked or seemed. The gaze also refers to the technique by which the medical profession attained knowledge of the body, the internal organs and tissues, norms and variations [medical cases upon which medicine could act autonomously [Foucault’s account of the conception of medicine is based in part on the medical riations . The sysnomously .For Foucault, knowledge was an important technique of power as it provided a basis for the regimes of truth upon which the balance of power is based , 39. As In Nettleton’s , 44, 45 Foucault’s conceptualisations of disciplinary power, power techniques and power-knowledge are still significant to contemporary studies of the professions where power is exerted on the basis of disciplinary or profession-specific knowledge. Podiatry’s supreme knowledge of the foot appears insufficient to gain the level of power over this anatomical area as that held by dentistry over the mouth and teeth. While the establishment of podiatric biomechanics has contributed to podiatry’s disciplinary power, it has been difficult to demonstrate that the foot has the same level of significance as the mouth and teeth , 47.boundary work as a two-part process: the constitution of a self-defined and independent knowledge base and then the labour of division to construct and maintain the profession’s role boundaries. By delineating an independent and self-contained area of knowledge, professions construct a field which appears to have a natural basis. The aspiring professions then claim expertise in the field, exercising authority and exclusivity. This field needs to be defined by clear boundaries that are expandable with time and ongoing effort [Fournier  describeg effort , 21. FouThe second component of boundary work is the ongoing effort to create and maintain professional boundaries. For this part Fournier  drew upoThe second boundary location is between the profession and the client. These boundaries rely upon the profession creating a degree of dependence of the client on them or their service. Professions can achieve this is by ensuring that only those with relevant educational credentials can access and decipher it professional knowledge . In JamoThe third boundary lies between the profession and the market. This boundary relies on the notion that the professions are concerned with contributing to public good, rather than self-interests, and that their services are provided rather than sold. Owing to their unique scientific knowledge, professions are accountable to internal standards, such as codes of ethics, rather than to the market or the government. This internal accountability contributes to the creation of boundaries that separate and effectively protect professions from the market .Boundary work as a concept remains relevant to studies of the professions in the current socio-political climate. Key aspects of podiatry’s boundary work have been in distancing itself from its ancestor, chiropody, and in emphasising its clinical subspecialties such as the diabetic foot, biomechanics and surgery , 47.social closure is employed to describe how aspiring and established professions secure and protect their role boundaries and the benefits associated with their professional status by monitoring and limiting entry into their occupational group [Neo-Weberian perspectives of the professions emerged in the late-1960s. The concept of al group , 53, 54.al group , 54, 55.al group , 54.occupational closure [Among the many proponents of Weber’s  social c closure  which he closure ).s. Larson also drew upon Jamous and Peloille’s [Larson , 61, dreloille’s  indetermloille’s ), cannotloille’s .occupational imperialism which refers to the inter-occupational dynamics evident as the occupations attempt to secure their status and ‘mould the division of labour to their own advantage’ . In the’ (p.15, . Larkin Abbott  emphasisParkin  describeIn Witz’  analysisStrategies of occupational closure can be broadly categorised as credentialist and legalistic in nature , 50, 60.The relevance of knowledge to the definition of the professions has been discussed by a number of neo-Weberian authors. Abbott  elucidatLegalistic strategies of exclusion are considered the most powerful , 54, 65.Medical Registration Act of 1858 marked the birth of the modern medical profession in the United Kingdom and the beginning of its exclusive relationship with the Government, in which it benefited from unequivocal legitimacy [Medical Registration Act which gave legal substance to the term, qualified medical practitioner ([The most common and visible legalistic strategy of closure is professional licensure or registration which is achieved only upon securing government support. Licensure legitimises professional boundaries and facilitates the exclusive access for eligible individuals to work in a particular role and use the associated title . The medgitimacy , 50, 65.itioner (, 38. Theitioner (, 37, 65.itioner (, 22, 62,Neo-Weberian approaches can facilitate enlightening empirical studies of the professions. It allows for empirical investigation of the current state of the professions as well as an exploration of the history and socio-political context in which the professions emerged . A neo-WTaxonomic and Marxist approaches have been widely criticised and therefore not used in contemporaneous studies of the professions. Bourdieu’s conceptualisation of the social world, Foucault’s power-knowledge concept, Fournier’s boundary work and neo-Weberian social closure theory each illuminate two phenomena: the dynamic nature of the professions and their boundaries, which are susceptible to changing social influences and processes; and the inevitability of role boundary competition. Whether referred to as symbolic power struggles as in Bourdieu [This paper has briefly summarised six of the most comprehensively documented approaches to defining and exploring the professions. Bourdieu , boundarBourdieu , disciplBourdieu  or for tBourdieu , there iUnderstanding the relevance of role boundary competition and contestation in the context of health care may help the health professions, such as podiatry, rationalise the struggles inherent in their quests to either work to full scope or expand scope of practice. It is acknowledged that the health professions are primarily genuinely interested in maximising the workforce and its capacity to meet the ever-increasing population health demand however battles to secure professional jurisdiction are inevitable. With this knowledge, professions may be less discouraged in the face of interprofessional resistance and better able to negotiate role boundary issues at the macro, meso and micro levels.


Batrachochytrium salamandrivorans , in mainland Europe in 2010 and prior to its detection in captive amphibians in the United Kingdom (UK), we tested archived skin swabs using a Bsal-specific qPCR. These samples had been collected in 2011 from 2409 wild newts from ponds across the UK. All swabs were negative for Bsal. Bayesian hierarchical modelling suggests that Bsal was absent from, or present at very low levels in, these ponds at the time of sampling. Additionally, surveillance of newt mortality incidents, 2013–2017, failed to detect Bsal. As this pathogen has been shown to be widespread in British captive amphibian collections, there is an urgent need to raise awareness of the importance of effective biosecurity measures, especially amongst people with captive amphibians, to help minimise the risk of Bsal spreading to the wild. Continued and heightened wild amphibian disease surveillance is a priority to provide an early warning system for potential incursion events.Whether an infectious disease threat to wildlife arises from pathogen introduction or the increased incidence of an already-present agent informs mitigation policy and actions. The prior absence of a pathogen can be difficult to establish, particularly in free-living wildlife. Subsequent to the epidemic emergence of the fungus,  Batrachochytrium salamandrivorans  is a recently-discovered, emerging pathogen causing epidemic mortality and population declines of urodele amphibians  in The Netherlands, Belgium and Germany2. The detection of Bsal in archived specimens exclusively from Asia and its widespread presence in China and Vietnam in the absence of disease, suggests that this pathogen is likely to have originated from Asia and was recently introduced into Europe4. In addition to the index site of emergence in Europe in a population of wild fire salamanders  on the Belgium/Netherlands border, the pathogen has recently been identified in wild amphibians in Germany5. Whereas no evidence of Bsal infection has been found on screening captive pet salamanders in the United States of America6, or on limited testing in Canada7, the pathogen has been detected in urodeles sampled from zoological and hobbyist collections in Europe, including in the United Kingdom (UK)10.The chytrid fungus, 11. There are three native species of urodele in the UK: the great crested newt (Triturus cristatus), the smooth newt (Lissotriton vulgaris) and the palmate newt (Lissotriton helveticus). Whilst all three newt species are present across Great Britain , only the smooth newt is present in Northern Ireland. The great crested newt is a Biodiversity Action Plan priority species, is listed on Appendix II of the Bern Convention and on Annexes II and IV of the EU Natural Habitats Directive, and is known to be susceptible to lethal infection with Bsal11. Infection with Bsal has been documented in smooth newts at multiple sites in mainland Europe5. In contrast, experimental challenge of the palmate newt with Bsal demonstrated resistance to infection in this species2. The alpine newt , which is susceptible to fatal chytridiomycosis following experimental challenge with Bsal, and which has been found to be infected in the wild in mainland Europe5, is an invasive species in the UK with naturalised populations widely distributed across England and in parts of Scotland and Wales12. As all wild urodeles in the UK are newts, we use the latter term from here on to refer to these species.Although this newly-discovered pathogen can infect anurans, it is only known to cause disease in urodeles, albeit with huge variance in infection outcome amongst species, ranging from tolerance to deathIn this study, we capitalise on existing sample archives and on disease surveillance to evaluate the likelihood of Bsal presence in wild newts in the UK, with the aim of informing mitigation strategies and contingency planning to prevent the incursion and impact of this pathogen on UK wildlife.B. dendrobatidis (Bd) infection in wild amphibians in the United Kingdom13. Ponds were opportunistically selected to obtain a wide geographical coverage across the UK. As far as possible, sampling effort was stratified by region, with the number of sampled ponds commensurate with county size; easily accessible ponds were often preferentially selected. Non-invasive skin swabs were collected in the field by trained herpetologists and field ecologists and were tested in the laboratory for Bd using qPCR13. This study was approved by the Zoological Society of London’s Ethics Committee (WLE534) and all methods were performed in accordance with the relevant guidelines and regulations. Extracted DNA samples were archived at −80 °C and were consequently available for the current study. All available DNA extracts from both native and introduced newt species were tested using Bsal-specific qPCR as described by Blooi et al.14.A survey was conducted in 2011 to investigate the spatial distribution of The results of the Bsal qPCR analyses were pooled across all four newt species and were used to develop a Bayesian hierarchical model to estimate the infection prevalence in newts and ponds in the UK, as follows:Let 15). To complete the Bayesian specification, we use the following prior distributions15). Of course, there may be some differences between this laboratory experiment and field sampling, and hence we explore a range of options, but for which we think that the lower bound of these choices will correspond to a highly conservative estimate for The number of positive swabs is then modelled as:mentclass2pt{minim16, in the sense that it uses hierarchical structures to share information between different sampling sites. The complexity of our model is limited by the available data; the model could be extended, e.g. to analyse differences in infection prevalence between species, if more detailed data become available from future studies.Bayesian hierarchical modelling is a flexible framework, and our model is similar, in essence, to more complex occupancy models17, and the model was fitted using the freely available WinBUGS package18. All code necessary to repeat the analysis and to produce the figures and tables can be found in the Supplementary Methods. The raw data file can be found in the Supplementary Worksheet.The data analysis and visualisations were conducted in R19. A post-mortem skin swab from each animal was examined using Bsal-qPCR.Disease surveillance of wild amphibians was conducted across Great Britain, 2013–2017 inclusive. Reports of sick or dead amphibians, regardless of the perceived cause of illness or death, were solicited from members of the public. Carcasses were retrieved for post-mortem examination when the state of preservation permitted and these were examined using a systematic inspection protocol of the internal and external systemsL. vulgaris, L. helveticus & T. cristatus) and one invasive species  were sampled; all tested qPCR negative for Bsal.Archived samples of extracted DNA from skin swabs collected in 2011 from 2409 newts at 103 sites . This is given by the parameter mentclass2pt{minimSince we did not find any Bsal-positive swabs, the differences in the estimated posterior probabilities of infection for individual ponds correspond to differences in the number of samples analysed, with larger estimated values corresponding to ponds with low numbers of samples, which in turn corresponds to a higher probability of missing infection if it was indeed present in that pond. For ponds where smaller numbers of samples were taken, there is more uncertainty as to whether a pond was infected or not, which translates to higher estimates of the posterior probabilities of infection.These results suggest that even with highly conservative estimates of the test sensitivity, the available data provide strong evidence that the proportion of Bsal-infected ponds is, at worst, very small . The use of vague prior distributions also means that the uncertainties in the posterior distributions will be larger than if we used more informative prior distributions, adding more weight to our conclusions that Bsal is unlikely to have been present in any of the ponds sampled, or if present at all, only present at very low levels. The posterior mean estimate for the proportion of infected ponds in the population is 1.1% in the worst-case scenario, and within the individual ponds sampled the largest posterior probability of infection was around 0.7%.L. vulgaris, 7 T. cristatus, 1 I. alpestris and 3 unidentified species) from 18 sites were examined post mortem and their skin swabs were analysed. None were qPCR-positive for Bsal.We received 60 reports of wild newt mortality (+/− morbidity) from 40 sites in Great Britain, March 2013–December 2017 . Of these, 43 animals , our results indicate that Bsal is either not present in wild amphibians in the UK, or that its presence is localised and/or at low prevalence, consistent with a recent introduction. Given these results, for the purposes of disease mitigation and management strategy development, it is appropriate to adopt the precautionary principle and develop plans based on the assumption that wild amphibians in the UK are currently Bsal-free.It is unusual to be able to examine such a large and relevant dataset prior to the detection of an emerging infectious disease in free-living wildlife. Our results demonstrate the value of disease and pathogen surveillance22. Equivalent models do not yet exist for the UK. However, given that at least one UK native species (T. cristatus) is known to be susceptible to lethal infection with Bsal2, a strategy to prevent human-mediated introduction is a priority23. Crucially, this includes implementation of biosecurity measures24 within captive collections  and adequate quarantine and testing of imported amphibians (to avoid importing infection from new sources such as private collections or the amphibian trade). In addition, continued surveillance of wild populations is essential for early detection of incursion to enable mitigation protocols to be implemented in a timely manner to ensure maximum likelihood of success. Experience from mainland Europe, and efforts to develop treatment options for individuals and sites, should be used to help inform potential future control measures26.Modelling studies for Bsal in wild urodele populations in mainland Europe, where fire salamanders occur, suggest that disease outbreaks may occur at very low host population densities and can lead to the local extirpation of susceptible species within a few months10, the risk of incursion of this pathogen into UK wildlife is likely to continue. The European Commission recently implemented controls to prevent the spread of Bsal within the European Union (EU)27, but the small-scale trade of urodeles amongst hobbyists is unregulated and the introduction of costs and other hurdles associated with complying with the new EU regulations might direct more amphibian trade along unregulated pathways. Thus, raising the profile of Bsal within the hobbyist community and providing guidance on developing and maintaining Bsal-free collections is of key importance to minimising the risk of Bsal infection to both captive and free-living amphibians.In summary, whilst Bsal infection is known to be present in captive amphibians in the UK, we currently have no evidence of infection in free-living populations in this country. Since captive amphibians, including urodeles, continue to be imported into the UKSupplementary MethodsSupplementary Worksheet