Over recent years, studies have demonstrated links between risk of cardiovascular disease in adulthood and adverse events that occurred very early in life during fetal development. The concept that there are embryonic and fetal adaptive responses to a sub-optimal intrauterine environment often brought about by poor maternal diet that result in permanent adverse consequences to life-long health is consistent with the definition of “programming”. The purpose of this review is to provide an overview of the current knowledge of the effects of intrauterine growth restriction (IUGR) on long-term cardiac structure and function, with particular emphasis on the effects of maternal protein restriction. Much of our recent knowledge has been derived from animal models. We review the current literature of one of the most commonly used models of IUGR , in relation to birth weight and postnatal growth, blood pressure and cardiac structure and function. In doing so, we highlight the complexity of developmental programming, with regards to timing, degree of severity of the insult, genotype and the subsequent postnatal phenotype. The importance of maternal nutrition to growth of the foetus has long been recognised with inadequate maternal nutrition, as a result of undernutrition and/or malnutrition, linked to induction of intrauterine growth restriction (IUGR) and potential adverse impacts on lifelong health of the offspring. Importantly, over recent decades both epidemiological and experimental studies have shown an association between IUGR and an increased risk of cardiovascular disease later in life ,3,4,5,6.It is now well established that events occurring during early life can also impact on long term levels of blood pressure and cardiovascular health ,9,10,11,In 1977, Forsdahl was the first to report a close correlation between increased rates of death from ischaemic heart disease and poverty in childhood and adolescent years in Norway . SimilarSince then, there have been many epidemiological studies in many populations worldwide that have confirmed these observations ,33,34,35Negative correlations between birth weight and levels of blood pressure in adult life are also now well established ,42,43,44The “catch-up” growth or “postnatal accelerated growth” hypothesis was proposed approximately fifteen years ago by Alan Lucas and Atul Singhal ,54. ThisIt is well established that postnatal weight gain is an important indicator for the programming of adult disease . AccelerLow birth weight is defined as birth weight below 2.5 kg , irrespeIn clinical practice IUGR is generally assigned to small for gestational age infants with a birth weight and/or birth length below the 10th percentile for gestational age . It occuIn general, growth restriction commencing from early pregnancy leads to proportional or symmetrical growth restriction, whereas in infants where there is mid-trimester or third trimester growth restriction there is disproportionate or asymmetrical growth restriction . When thIUGR is not a specific disease per se but a manifestation of many maternal and foetal factors leading to poor foetal growth. There are many causes of IUGR including environmental and genetic factors. In general, IUGR usually results from nutrient and/or oxygen deprivation to the foetus, often due to both maternal and foetal factors . ExperimThe concept that there are embryonic and foetal adaptive responses to a suboptimal intrauterine environment that result in permanent adverse consequences is consistent with the definition of “programming” ,81. “ProPotential programming effects on tissue structure and on the number of functional units formed in vital organs.Adverse environmental factors acting during the developmental period have the potential to disturb the processes of cell proliferation and differentiation . The vul(1)Nephron number has been observed in offspring in response to a maternal prenatal low-protein diet in the rat ,94, mous(2)Total cardiomyocyte number in the offspring of rats exposed to maternal protein restriction or placental insufficiency during pregnancy  and in l(3)The numbers of secondary muscle fibres has been reported in the young offspring of a variety of species, including rats , pigs 1 and shee(4)Total pancreatic weight, islet cell mass and the relative proportion of β-cells within the islets  has beenFor example, a reduction in:Furthermore, it has been shown that the vasculature undergoes permanent changes in reactivity as a result of maternal nutrient restriction . In addiMuch of our knowledge relating to the short term and long-term effects of IUGR has been derived from animal studies. A number of animal models of poor maternal nutrition and/or placental insufficiency have been developed over recent years to investigate the causes and consequences of IUGR. A variety of species have been studied, including: rodents, sheep and primates; and both, maternal dietary manipulations or surgical interventional techniques have been employed ,113,114.In our laboratory over the past decade we have comprehensively examined the cardiovascular phenotype of rat offspring following maternal protein restriction. However, as our studies have progressed, it has become clearly apparent, that the cardiovascular and metabolic phenotype of the offspring using this model differs between different laboratories, which likely relates to subtle differences in study design. This in turn, makes comparison of the findings between studies difficult. For example, there are differences in the strain of rats studied, levels of maternal protein restriction in the diet, timing of administration of the diet to the dams and postnatal differences in body growth and levels of blood pressure of the offspring. These differences are highlighted in In our studies, Wistar-Kyoto (WKY) female breeder rats are fed a low protein diet for two weeks prior to birth to get the dams accustomed to the diet, then during pregnancy and for two weeks during lactation as the rodent organ systems are still developing in the early postnatal period. To avoid a high mortality rate in the offspring  we have In the following sections we compare our findings with others; in doing so, we highlight differences in the maternal protein restriction model, which may account for conflicting findings between laboratories .In accordance with our findings, many laboratories worldwide have shown that administration of a protein restricted diet to rat dams during pregnancy leads to growth restriction in the offspring . Given tWhy there are differences in postnatal growth in the offspring between studies is unknown. It is conceivable that it may be the prolonged maternal protein restriction after birth for two weeks during lactation in our studies that leads to the persistent attenuation of body growth in the LPD offspring. In our studies, we have chosen to feed the rat dams the specialized diets (LPD and NPD) for the first two weeks of lactation as rats are an altricial species and are born at a time when their organs are very immature. For instance, in the heart maturation of cardiomyocytes, which occurs late in gestation in humans, occurs in the first two weeks after birth in the rat . LikewisIn addition, there is another important difference in relation to the dietary feeding regime to the rat dams in our studies, compared to many other studies. In our studies, the dams commence the diet 2 weeks prior to mating, in order to get the dams accustomed to the specialised diets. In contrast, in the majority of studies utilising the maternal protein restriction model, they have commenced feeding the diet to the dams at the beginning of pregnancy. Hence, it may be the feeding of the low protein diet to the dams during the periconceptional period that has led to the long-term attenuation of postnatal growth and to some of the other differences in findings, compared to other studies using the maternal protein restriction model. Indeed, there have been a number of recent studies demonstrating long-term effects on the offspring, as a result of insults; including impaired nutrition, experienced by the mothers at around the time of conception ,171,172,Over recent decades there have been many epidemiological studies that describe a direct link between being born small with an elevation of blood pressure in adulthood ,176,177.The findings in relation to the effects of IUGR on blood pressure later in life using animal models differs widely amongst studies; some studies report no effects on blood pressure, whereas others report an elevation in blood pressure in adulthood . In our An alternative explanation for the differences observed in levels of adult blood pressure may relate to whether the protocols used to measure blood pressure leads to stress in the animals. Indeed, there have been a number of studies suggesting that it is an elevated stress response in IUGR offspring that subsequently leads to the elevation in blood pressure rather than a direct etiological effect ,184,185.−1, 1228 cm−1, 1038 cm−1 bands, respectively. However, the protein, lipid and proteoglycan spatial distribution was similar within the myocardium of the left ventricular free wall and interventricular septum of the LPD and NPD adult offspring [−1, which is due to the presence of proteoglycans. Importantly, in this regard it has been shown that an increase in proteoglycan deposition can ultimately affect cardiac performance [In our analyses of the adult hearts of the IUGR LPD offspring we have no evidence of overt structural abnormalities in the myocardium of LPD offspring compared to NPD offspring in early adulthood (18 weeks of age) as assessed by echocardiography  and therffspring . Interesformance ,192. Theformance ,194. We formance , which dformance .Although no differences in myocardial collagen were observed between LPD and NPD offspring at 18 weeks of age we have detected an increase in interstitial fibrosis in LPD offspring at 24 weeks of age  and at 3Over recent years we have tested the hypothesis that IUGR acts as a primary insult to the heart, rendering the heart susceptible to secondary postnatal insults, such as hypertension, high salt diet and hyperglycaemia. It is well known that hypertension leads to left ventricular hypertrophy ,198,199 Contrary to our initial hypothesis, when hypertension was induced as a secondary cardiac insult, the response to hypertension was not exacerbated in the IUGR offspring. The cardiac hypertrophic growth response to Ang II infusion, as assessed using echocardiography, was not different between the IUGR and non-IUGR offspring; however, there were differences in cardiac tissue structure. Unexpectedly, in the Ang II infused IUGR adult offspring the levels of interstitial collagen in the left ventricle myocardium was markedly reduced when compared to the non-IUGR offspring (unpublished observations from our laboratory). Hence, our findings do not support the concept that the IUGR heart is necessarily more vulnerable to hypertension in adulthood and importantly, our findings suggest that in some circumstances the IUGR heart may be somewhat protected from adverse remodelling. Further studies are required to elucidate the mechanisms for the reduced deposition of collagen.In other studies in our laboratory we have examined the effects of induction of diabetes in adulthood, as a secondary postnatal insult, on the growth of the IUGR and non-IUGR heart . SimilarThere have been a number of studies that have examined the effect of a high salt diet administered postnatally, as a secondary lifestyle insult, on blood pressure in IUGR offspring ,202,203.In summary, the findings of this review highlight the importance of maternal diet on the long-term cardiovascular outcomes of the offspring. Upon comparison of the findings between different laboratories using rat models of maternal protein restriction we highlight the many differences in the cardiovascular phenotype of the offspring between studies, which may relate to the rat strains studied, severity of the dietary protein restriction and the timing of the diet administration. In addition, this review emphasizes the complexity of the mechanisms relating to the developmental programming of heart disease and highlights directions for future research that are required to establish the importance of the periconceptional, pregnancy, lactational and post-weaning windows in life-long developmental programming.


This paper draws on household data to examine the prevalence of female genital mutilation (FGM) in Senegal and the effectiveness of the country's anti-FGM law in dealing with actual breaches and providing protection to the victims. The 2010–2011 Senegal Demographic Health Survey and Multiple Indicators Cluster Survey (SDHS-MICS) covers 14,228 women and their daughters. Logistic regression was used to investigate the geographic distribution of FGM across regions. For the enforceability of anti-FGM, desk research was used. Overall prevalence among women and daughters was 28.1% and 6.2%, respectively. Significant factors were sociodemographics, ethnicity, and region. This analysis shows both advantages and vulnerabilities of the anti-FGM law in relation to the issue of enforcement. It indicates that the law falls short of offering adequate protection to potential victims. FGM is a cultural and social norm imbedded predominantly in rural settings and as such, drives resistance to jettisoning FGM. Legislation has been one of the driving forces behind the eradication of the practice. Female genital mutilation (FGM) has widely been described as female genital cutting (FGC) and refers to practices involving the partial or complete ablation of the external female sexual organs on non-medical grounds. The World Health Organization (WHO) distinguishes among four types of FGM based on the invasiveness of the intervention, and these are described elsewhere.7Likewise, on the side of the law, it is suggested that no amount of legislative measures would be sufficient to completely eradicate FGM. This is because FGM, once performed, is irreversible.In other words, public health burdens of FGM include both consequences for mother or daughter mortality and ongoing morbidity concerns throughout their lifespans. As a potentially life-threatening procedure, FGM is now widely condemned as a violation of human rights and a criminal offense in many national jurisdictions.2Various studies give many reasons for practicing FGM around the world. One overriding reason in Africa and elsewhere is that marriage does not come easily without the female having to prove her virginity.24This paper examines the geographic variation of FGM and the effectiveness of an anti-FGM law in Senegal. The intention is to provide information for specific and targeted intervention in that country. Existing research does not sufficiently reflect on household data to determine the degree of prevalence of such a practice. It also suggests that the anti-FGM law has largely failed to secure meaningful prosecutionBefore exploring how Senegal has tackled FGM, we first provide some background information about Senegal and then present a small situation analysis of the prevalence of FGM in the country. In essence, the Republic of Senegal is located on the coast of western Africa with a population of about 13 million, of which 94% are Muslims, 4% are Christians, and 2% belong to traditional religions. There are about 20 different ethnic groups distributed across 14 provinces. The largest ethnic groups are the Wolof, the Fulbe and Toucouleur, the Serer, the Fulani, the Diola, and various Mandingo groups. Women are disadvantaged in both economic and societal terms as a result of their status and the prevailing sociocultural norms. The literacy rate (defined as the percentage of persons aged 15 years old and over who can read and write) is 33% for women and 52% for men. The percentage of women aged 20–24 years old who were married before the age of 18 years old is 39%. Senegal has a population growth rate of about 2.5% per year and a total fertility rate of 4.6 children born per woman.27Most women who are cut in Senegal undergo excision (type II according to the WHO classification). This involves the partial or total removal of the clitoris and the labia minora. About 12% of women stated that they had been subjected to infibulation .3It is against this background that the Committee on the Elimination of All Forms of Discrimination against Women issued its General Recommendation on Female Circumcision , which calls on states to take appropriate and effective measures with a view to eradicating the practice and requests them to provide information about measures being taken to eliminate FGM in their reports to the Committee.29The Demographic and Health Survey (DHS), funded by the US Agency for International Development (USAID), is a well-established source of reliable population-level data with a substantial focus on health. The objectives, organization, sample design, and questionnaires used in the DHS surveys are described elsewhere.30a priori approval by the institution's human research committee. Ethical approval was granted by the Ethics Committee of the National Statistical Office of Senegal.The 2010–2011 Senegal Demographic Health Survey and Multiple Cluster Survey (SDHS-MICS) is a nationally representative cross-sectional survey (multistage stratified random sampling of households) of women of reproductive age (15–49 years old). The resulting sample was representative of the underlying populations of the different regions of Senegal. It was carried out between October of 2010 and April of 2011. Nationally representative samples of 15,688 women between 15 and 49 years old in all selected households and 4,929 men between 15 and 59 years old in one-third of selected households were interviewed. Response rates were over 93% for individual women and over 87% at the household level, and informed consent was obtained from participants. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in Data collected were representative at the national level, the urban/rural level, and the level of each administrative region when tested using a number of sociodemographic and household indicators. There were few participants with missing data for FGM and other covariates; thus, data analysis on FGM was based on 14,228 women with a complete set of data.30The 2010–2011 SDHS-MICS collected an optional additional series of questions about FGM. The history of the development of FGM questionnaire is discussed elsewhere.32Experts generally assume that women respond truthfully when asked about their own experience. If bias exists in some of the responses, it has not been documented. It is hypothetically possible that some women may not admit to having undergone FGM in countries where the practice has been forbidden, but no solid evidence of this has been found.The module on FGM included questions on whether the woman herself had undergone FGM and if she had daughters, whether they had also undergone the practice  or whethWe use the binary outcome whether a woman or dependent daughter has undergone FGM, and for the daughters' analysis, the unit of analysis was circumcised daughters from any women because of interpretability reasons, because with the binary outcome, one can estimate the likelihood of FGM in a given region of Senegal, while accounting for a number of potential covariates.The main exposure variable investigated was the respondent's geographic location   in addityi = 1 if the woman/daughter was circumcised and yi = 0 if the woman/daughter was not circumcised. The standard measure of effect was the odds ratio (OR) and 95% confidence interval (95% CI).To account for geographic variation in the prevalence of FGM at the regional level in Senegal, we used a logistic regression model to investigate the geographic distribution of FGM across the 14 regions while accounting for individual-level risk factors. The response variable was defined as 2 and Mann–Whitney U tests as appropriate. Adjusted marginal ORs of FGM risk across regions were obtained from standard logistic regression models, with Diourbel used as the reference category because of its lowest crude FGM prevalence . The statistical significance of associations between potential risk factors and the prevalence of FGM was explored with χevalence .N = 14,228) and in N = 14,228). The bivariate results show that, overall, 5,689  of women had undergone FGM; 1,340 (9.4%) women reported that they had daughters who had undergone FGM, and 3,330 (23.4%) women reported that they intended the practice of FGM continue. Overall, mean age of participants was 27.9 (0.09) years, and for their partners, the mean age was 43.5 (0.17) years. The percentage of participants with no education was high (57.9%), and it was 75.4% among their partners; 49.3% of participants were living in an urban area, 95.4% were Muslim, 16.5% were in the poorest quintile of the wealth index, and 38.7% were from the Wolof ethnic group. Prevalence values of FGM among respondent women and daughters were 28.1% and 6.2%, respectively, with variation across provinces and ethnic groups ranging from 0.7% in Diourbel to 92.0% in Kedougou and from 2% among the Wolof to 89.6% among the Mandingue ethnic group for respondent women. For daughters, the prevalence of FGM varies from 0.3% in Thies to 26.9% in Sedhiou and from 0.2% among the Serer/Wolof to 22.1% among the Mandingue ethnic group.Baseline characteristics of the study population are displayed in On average, circumcised women were older than their non-circumcised counterparts and their partners, more likely to have a lower education and have non-educated partners, more likely to be living in rural areas, and more likely to be Muslim. In addition, circumcised women were more likely to be in the poorest quintile of the wealth index, from the Mandingue ethnic group, and living in Kedougou . For theSpecifically, women from the Mandingue ethnic group  and the Soninke ethnic group  followed by the Diola  and Poular/Fulani ethnic groups  from rural settings  were consistently associated with higher odds of being circumcised. Also, daughters from the Poular/Fulani ethnic group  from the rural settings  were consistently associated with higher odds of being circumcised than their counterparts of the Madingue and Soninke ethnic groups. The associations of women and partner education, wealth index, and religion with FGM risk were not statistically significant. Moreover, there were linear associations between women's age and FGM status: the risk of undergoing FGM increased with age. In other words, older women from the age group 36–49 years  and age group 26–35 years  were more likely to be circumcised compared with their counterparts in the younger age group less than 25 years old. Also, daughters from older women  were more likely to be circumcised compared with daughters from younger women (age group less than 25 years old) .With regard to FGM status, in the regression analyses, there was a striking variation in FGM risk across regions for both women and their daughters, with the highest risk being in Kedougou region  followed by Tambacounda , Sedhiou , and Kolda  and the lowest risk being in Louga  and Diourbel for women respondents. For daughters, the highest risk was in Sedhiou region , Kolda , and Tambacounda  and the lowest risk was in Kaolack region  and Thies .The above results for covariate-adjusted province variation of FGM status show a clear pattern of regions with higher risk of FGM . These geographic patterns confirm the observed and model findings shown in Even after multiple adjustments of the urban environment and other risk factors, findings for both women and daughters confirm the fact FGM is lower in the largest urban province Dakar.This combined epidemiological and legal study offers a unique opportunity to examine the geographic variation of the FGM prevalence and the effectiveness of the law in Senegal. We used the most recent data from the 2010–2011 SDHS-MICS, a large nationwide sample of women and their children across the 14 regions of Senegal. Then, we considered the effectiveness of the legal responses to the issue of FGM prevalence in that country.The overall prevalence of FGM in Senegal was 28.1% using the most recent survey, the 2010–2011 SDHS-MICS. However, according to the DHS conducted in 2005, 28% of women aged between 15 and 49 years old in Senegal have been subjected to FGM. Comparing the previous survey with the recent survey, it indicates a zero change in prevalence in the 5 years separating the surveys. However, there were large geographic variations within the country by region. For instance, Kolda region changed from a prevalence of 94% in 2005 to a prevalence of 86%, an 8% decrease during the 5-year period. There were also other regions with similar decreases in percentages, such as Tambacounda. However, the prevalence of FGM was still high, even after Senegal signed on to the Maputo Protocol in 2006. According to the 2010 DHS data, in urban areas, the prevalence was 35.6%, and rural residents reported a prevalence of 43.1%.In this study, we investigated social, demographic, and economic factors associated with FGM in Senegal. In summary, living in a particular region in the south of the country , living in a rural area, coming from a particular ethnicity , or being a Muslim were all associated with a higher likelihood of undergoing FGM for women and their daughters. Age of the respondent, education, and household socioeconomic status were no longer associated with the likelihood of FGM after multiple adjustments of other factors.Returning to the relationship between women's own experience of FGM and that of their daughters, we found that the difference between the percentage of younger and older women whose daughters had undergone FGM was much greater than the difference between the percentages of respondents who had undergone FGM themselves. This could represent an important change in cultural norms with decreased use of FGM, whereby younger women are less willing to have their daughters undergo FGM. This offers possible hope that the practice may be reducing over time. However, this finding could also represent a cohort effect—younger women have younger children who are not yet at risk. We found a large difference in Senegal in the risk of FGM between regions and ethnicity, with some regions and ethnic groups having a higher risk of FGM. It is worth investigating these findings further, because spatial variation and ethnicity may be indicative of an association of place of residence with FGM practice as a proxy for social norms.One response to the prevalence of FGM has been to enact anti-FGM legislation. In this respect, numerous provisions exist to combat the practice of FGM. These provisions consist of international human rights standards, which Senegal has incorporated into its domestic system as well as the Senegalese 1999 anti-FGM law. The commitment to international human right standards was shown through the ratification of important treaties, such as the Convention on the Elimination of All Forms of Discrimination against Women (CEDAW), the UN Convention on the Rights of the Child (CRC), the African Charter on the Rights and Welfare of the Child, and the Maputo Protocol (to the African Charter on Human and Peoples' Rights) on the Rights of Women in Africa.At the domestic level, the Senegalese Government adopted Article 299 of the Penal Code, which imposes a maximum penalty of 5 years imprisonment for performing FGM. Subsequently, the Ministry of Family Affairs produced and adopted Action Plan 2000–2005, according to which FGM is to be eradicated in Senegal by 2015. The main objectives were to improve networking and coordination among actors involved in efforts to combat the practice, explaining the legal framework to them and integrating the issue into formal and non-formal education. An evaluation of the Action Plan conducted in 2008 notes that, of 5,000 or so villages previously practicing FGM, a total of 3,300 had forsworn the practice by 2008 in public declarations. There are, however, still areas in which the practice is still strongly defended. It is also important to ensure the sustainability of what has been achieved. The Second National Action Plan 2010–2015, which was adopted in February of 2010, is to step-up action against FGM. The objective remains the complete eradication of the practice by 2015.34Returning now to 1999 Senegalese Law no. 99–5, it should be stressed that FGM was legally called a violation of human rights, and such a law superseded social norms and the relevant provisions of the criminal code. It made carrying out FGM on a child or woman against the law and carried a maximum penalty of 5 years and/or a fine. A spokesperson for the human rights group The African Assembly for the Defense of Human Rights (RADDHO) pointed out that, although adopting the law was an important step forward, only its enforcement would ensure that women derive the most benefit from it. One way in which enforcement is achieved is through prosecution and deterrence.However, despite this law and indeed, human right standards, FGM cases have rarely been brought before a court of law. Only a few notable exceptions exist. For example, since the law went into effect, only a limited number of arrests were made. In January 1999 the law has seen only two arrests but no convictions. In July of 1999, the public prosecutor in Tambacounda ordered the arrest of the grandmother and mother of a 5-year-old girl after a complaint filed by the girl's father alleged that the two women had ordered FGM performed on his daughter. The practitioner was also charged. After emotional public outcry in the region, however, the cases were not pursued, and no convictions resulted. The press has suggested that the passage of the law has driven the practice underground.Moreover, FGM is accepted as common as male excision, which leaves disability in many cases. Also, prosecuting authorities are the products of their communities and cultures and may not feel it a matter of public interest to expend resources to prosecute a practice that had stood the test of time and been handed down from generation to generation. Successful attempts to enforce the law depend on gathering evidence to make a positive prosecution case against the perpetrator of FGM. However, obtaining such evidence can prove exceedingly difficult. Additionally, as stated before, there is some reluctance for prosecuting officials to take on the case where the public interest test is not satisfied in enforcing the law. Such evidence might come from several potential sources. One is from health professionals who may have come into contact with these children, and the law enforcement officials look to them to blow the whistle on those suspected of having committed FGM. Another source is the victims themselves, who may have suffered as a result of the practice. The difficulty with the first source of evidence is that health professionals might be breaking their duty of confidentiality to patients. The duty to disclose information would, in that situation, conflict with the duty of confidentiality. It might be suggested that FGM is a criminal practice after the 1999 law, and therefore, confidentiality should be waived to give way to the legal duty to disclose.Likewise, some may consider the failure to disclose as amounting to conspiracy to a crime. However, that argument is tenuous, because it would be nonsensical to call someone an accomplice when the crime was committed without their knowledge or participation. Moreover, before any charge can be brought against those who fail to report, evidence of their knowledge of FGM commission may prove difficult to establish. It is also questionable how the police can possibly collect such evidence when health professionals refuse to record FGM information or do not feel that they ought to ask the FGM question for fear of discriminating or being prejudiced against other people's culture.35Apart from the paucity of prosecution cases, the 1999 law has only a limited extraterritorial effect, consistent with the French tradition on which Senegal law is based. Such law does not clearly state what happens to cases where believers in FGM cross Senegalese borders to have their daughters mutilated. In other words, the current uncertainty in Senegalese law can be illustrated as follows. A woman living in the southern regions of Senegal  can easily cross the border into Guinea and have her daughter or herself mutilated and return safely back to Senegal. There is nothing that anyone who attempts to prosecute the perpetrator in Guinea or the person who sought his/her assistance can do when FGM is not illegal in Guinea.The 2007 legislative reforms incorporate traditional international crimes  into the Senegalese Criminal Code . The extraterritorial jurisdiction has so far been tested over the Hissene Habre saga.36In principle, the notion that the state should apply justice only to offenses committed within its territorial borders can be qualified by principles, such as passive personality, where the Senegalese court would look at the nationality of the FGM victim as the basis for taking jurisdiction.1Although the principle of passive personality applies in relation to FGM, that alone would not necessarily lead to a meaningful prosecution. This is because the issue will arise as to how to bring the perpetrator leaving abroad into Senegalese jurisdiction. Some jurisdictions have controversially resorted to kidnapping as one possible approach to such a move . Other jurisdictions are unlikely to use this method .One viable approach is to have recourse to extradition laws as stated in Senegalese law nos. 71–77 of December 28, 1971. However, Article 5 of this law suggests that extradition will be allowed only where the person is of Senegalese nationality and the offense has been committed on Senegalese soil .38Another way could be to ensure that an anti-FGM treaty is signed between Senegal and its immediate neighbors, such as the Gambia, Guinea, and Mauritania, or harmonize anti-FGM legislation at regional or African levels.Another limitation of the current law in Senegal is that it seeks to provide legal redress for those females who have already suffered FGM and does not offer sufficient protection to females yet to be mutilated. As stated above on the point of extraterritoriality of the 1999 anti-FGM law, there is little the law would do to save Senegalese women and girls from undergoing FGM in neighboring Mauritania, Guinea, or the Gambia.As with the laws in many countries in the region, the Senegalese anti-FGM law is more effective in terms of facilitating prosecutions of those who violate the law rather than protecting women and girls who have yet to undergo FGM from the practice. There are some efforts from the government on how to prevent FGM and provide protection for those who have not yet been cut. For policy strategies to prevent FGM, it is, instead, multilateral agencies, such as UNICEF, in conjunction with the WHO, German Federal Ministry for Economic Cooperation and Development, and NGOs, such as the United States-based Population Reference Bureau (PRB), that have played a crucial role in advocating the end of FGM in the region. This is also true for countries such as Senegal, where NGOs,2Despite the shortcomings of the legislation identified above , it must be noted that the 1999 law and human right norms present many advantages. The first is that no national group or NGO would have been engaged in the eradication campaign unless it believed that their actions were legally justified under the Senegal law. Also, the law stands as a formal framework, which confers on public officials the power to ensure legal protection of women. Although the law is not always enforced, its existence may send deterrent signals to the perpetrators who might fear criminal prosecution. In this respect, the adoption of the 1999 law is regarded as critical to effect change of social attitudes toward FGM as a social norm.What Senegal has achieved so far suggests that FGM can be significantly reduced in the regions identified in this paper. However, the law can only contribute to efforts to stamp out the practice if there are sufficient resources to accelerate the campaigns and secure a social contract between campaigners and targeted populations per se had been completed .The FGM activities that were part of the FANKANTA program aimed above all to raise the level of acceptance of the legal ban on FGM with the help of education and sensitization. In view of the difficult political situation in the Casamance, it aimed to ensure that the local population did not see the ban as a central government meddling in their affairs but something that is well-founded and rational. Thanks to this approach, FANKATA found many supporters and advocates among not only local NGOs and action groups but also, religious and social leaders who were influential within their communities. In cooperation with the project, they developed various educational materials in local languages which were used widely within the scope of numerous special events. They also made education activities possible after the project This involvement of multifarious stakeholders suggests that the solution to banning FGM cannot simply be strict legal enforcement. The Senegal model can be regarded as the best exemplar for the rest of the world for dealing with FGM. The model seeks to educate and protect women by providing communities, whose members are likely to be subject to FGM, with information and knowledge about their commitment to social change. In other words, whereas in most cases, the persons convicted under the law are liable for fines and imprisonment, enforcement of the law is not satisfactory, and many believe this poor enforcement is the result of low fines, short duration of imprisonment, and sympathy of law enforcement agents because of the cultural nature of FGM. Involvement of all persons in the implementation process is equally necessary. When the practice is abandoned, communities effectively enforce new legislation and should give effect to policy strategies.Although there is scant literature on the available policy strategies in Senegal, multilateral agencies, such as UNICEF and the WHO, have played a crucial role in advocating the end of FGM. These efforts have not yielded the desired effects, but the Community Empowerment Program in Senegal has been effective in preventing the practice. However, other obstacles remain, which lead to the conclusion that FGM cannot be completely rooted out like any crime that can be eliminated within society. These obstacles must, however, be addressed and include resistance to legal change by the traditional healers, passivity of some public officials, lack of sufficient resources at the state level to sensitize the population, and the lack of knowledge of the law banning FGM. One way to overcome lack of knowledge is to translate the law into local vernaculars and involve young men and women in the campaigns. Such campaigns have to also involve the police in their preventative rather than protective role.


Technological advances on the development of mobile devices, medical sensors, and wireless communication systems support a new generation of unobtrusive, portable, and ubiquitous health monitoring systems for continuous patient assessment and more personalized health care. There exist a growing number of mobile apps in the health domain; however, little contribution has been specifically provided, so far, to operate this kind of apps with wearable physiological sensors. The PhysioDroid, presented in this paper, provides a personalized means to remotely monitor and evaluate users' conditions. The PhysioDroid system provides ubiquitous and continuous vital signs analysis, such as electrocardiogram, heart rate, respiration rate, skin temperature, and body motion, intended to help empower patients and improve clinical understanding. The PhysioDroid is composed of a wearable monitoring device and an Android app providing gathering, storage, and processing features for the physiological sensor data. The versatility of the developed app allows its use for both average users and specialists, and the reduced cost of the PhysioDroid puts it at the reach of most people. Two exemplary use cases for health assessment and sports training are presented to illustrate the capabilities of the PhysioDroid. Next technical steps include generalization to other mobile platforms and health monitoring devices. Healthcare is a pending matter that challenges worldwide . The sevDuring the last years, several concepts have emerged as part of the new healthcare era. Medicine 2.0, Health 2.0/3.0, ePatient, and eDoctor, among other more established terms such as eHealth, telehealth, or telemedicine, are widely disseminated examples of these concepts. Most of the ideas behind these novel domains are devoted to increase patients' self-management, procure preventative care, and enhance health professional expertise. Particularly fundamental to this renovated healthcare paradigm is to make patients more participatory of their care process. To that end, patients should be equipped, empowered, enabled, engaged, emancipated, equals, and experts , social Although these innovative tools are truly interesting to promote a more personalized and independent healthcare, a crucial aspect that may not be approached through web technologies is corporeal monitoring. Body monitoring deepens into the patients' physiology, biological conditions, and behavioral aspects, which are utterly necessary to have a precise understanding of their status and particular necessities. According to the traditional health care model, patients' monitoring is normally relegated to sporadic doctor visits or institutionalization, which goes against the principles of proactivity, independence, accessibility, and cost-effectiveness. Oppositely, embracing these principles arises mobile Health . mHealth is an emerging and rapidly developing field that builds on a wide range of mobile technologies such as smartphones, tablets, and portable health devices to support community and clinical health data retrieval, delivery of healthcare information, or direct provision of care. Most interestingly, mHealth covers technological solutions for the monitoring of patients' behavior and vital signs. The potential of mHealth stems from the capacity of making technology portable or even wearable . AccordiFrom a technological perspective, one of the main limitations of up-to-date portable health monitoring devices are processing and storage capabilities. Monitoring devices normally consist of a set of sensors that measure physiological magnitudes and convert them into machine readable information. Although some of these devices include dedicated resources to process the information, these are very sparse and limited. Conversely, mobile devices are the perfect means to collect the data retrieved from health monitoring devices, as well as to provide local processing capabilities or even grant access to cloud functionalities  . ThroughIn this work, we present the PhysioDroid system, which combines both commercial wearable health devices and mobile devices to provide continuous and personalized patient physiological monitoring. An application that runs on the Android platform is implemented to enable the collection, sharing, and exchange of physiological data registered through the ubiquitous wireless health monitor. Other features such as health data visualization, storage, and alerts on conditions are further available from this. Firstly introduced in , the PhyThe rest of the paper is organized as follows. Looking at the market for state-of-the-art mobile health care sensors, an estimated number of 16 million devices will be sold by the year 2016, as predicted by ABI Research . These d Irythm Zio Patch [ fitbit [ Zeo Sleep Monitor [ Smartheart [ ViSiMobile [ AVIVO MPM PiiX [ Equivital LifeMonitor [ Zephyr Bioharness [ RS TechMedic DynaVision [Examples of specific purpose commercial health monitoring devices are theio Patch , a long-[ fitbit , for int Monitor , which iartheart , the firSiMobile , which mMPM PiiX , which ieMonitor , that cooharness , a garmenaVision , which iThe use of mobile medical applications has increased over and over during the last years. Apple's iOS platform has been demonstrated to be much more mature in this field; however, its use is tailored to a reduced and expensive catalog of devices. As an alternative, Android provides its users with a wider variety of systems of different prices and vendors at the reach of a broader audience , 30. Thi Medscape, Epocrates, or Eponyms are popular examples of this category, particularly intended to provide comprehensive and updated information for medical procedures, disease monographs, drug references, or practice guidelines [ Calculate by QxMD, which provides them with medical calculators and decision support tools that apply to General Practice, Internal Medicine, Cardiology, Surgery, Obstetrics, or Neurology, among others. Electronic reference manuals are also close at hand, as is the case of Monthly Prescribing Reference (MPR), an app that incorporates prescribing notes and drug records to facilitate clinical practice and promote the access to the latest advances in treatments [ DoctorMole, which offers a first diagnosis of the malignancy of a given mole. To do so, the app makes use of the smartphone's built-in camera to take a picture from the affected area and superimposes the diagnosis directly on the picture through augmented reality. Another application that takes advantage of the camera to diagnose is uCheck. uCheck analyzes the color of the chemical strips dipped in a sample of urine. This is subsequently compared to a color-coded map and within a few seconds, a full report containing levels of glucose, bilirubin, proteins, ketones, or leukocytes is available to the user. Normally, the information is presented in an easy to understand format, which applies to both medical and general users interests. This type of tools could be of worth to identify potential diseases and track the evolution of detected illnesses. In turn, this may translate into more precise and proactive monitoring than usual quarterly/annual medical examinations.The vast majority of medical apps have informative and academic purposes, which make them specially recommended to professionals and students.idelines . Other aeatments . Health  Instant Heart Rate or Cardiograph, which use the smartphone's camera to get an accurate heart rhythm reading from the user fingertip. Mainly intended for entertainment purposes, iStethoscope also turns the mobile phone into a stethoscope, allowing the users to listen to their heartbeats and visualize the heart waveform on the screen. One of the major advantages of these apps, with respect to others, is the fact of not requiring additional devices to the own smartphone. However, they demonstrate inaccurate as well as cumbersome for continuous monitoring. Moreover, there exists almost no regulation for these apps, thus, making their public embracement and use difficult, despite the high interest shown by physicians and trainees [ iBGStar, an electronic blood glucose meter for diabetes management, or iSpO2, which measures the oxygen saturation level in the blood and heart rate, let us envision a promising future for mobile and ubiquitous health care.Although there is a relevant number of medical apps that apply to diverse health domains, there are very few that support physiological monitoring. Examples of these scarce apps aretrainees , 34. ThePhysioDroid is an advanced ubiquitous system for remote and continuous monitoring of people's physiological and behavioral status. The PhysioDroid system builds on the combination of wearable health sensors, capable of measuring physiological and behavioral data, and mobile devices, in charge of gathering and processing the collected information. The system is particularly conceived to empower users in their daily living, as well as to make them conscious and participatory of their healthcare and well-being, through the access to a simplified description of their health status. PhysioDroid also provides track and alerts on conditions, as well as mechanisms to trigger emergency procedures at the point of need. Besides, the PhysioDroid system does not only apply to individual users, but it is devised to leverage health data collected from multiple users. This is seen to be a key accelerator of medical and social knowledge, helping carers to provide more efficient medical diagnoses, treatments and proactive policies.a wearable monitoring device that records different types of physiological data on a subject and transmits them wirelessly;a mobile device, for example, smartphone, which runs an app that acts as collector of the data delivered by the vital sensor, support system for medical diagnosis and health alerts, interface for user data inspection and gateway to forward the data to a remote storage for further analysis;a remote persistent storage system to store data from multiple users, particularly devised to support advanced health services and analytics.The PhysioDroid system consists of :a wearabThe monitoring of the user's vital signs is performed through the Equivital EQ01 system see . The EQ0The data measured through the EQ01 is further transmitted to a mobile device . In particular, Android devices have been here considered. Several advantages of the Android operating system with respect to its competitors were conclusive during the platform selection. These include the greatest growing mobile market, opensource framework, highest performance stability and security, and continuous updates and upgrades of the application programming interface (API), among others. Different mobile devices have been tested during development and validation of the system, including Samsung, HTC, LG, or Sony devices for a representative selection of the various Android API available versions (“Gingerbread” API 2.3 and newer). The average battery lasting time for most of the evaluated mobile devices, during full operation of the PhysioDroid system, is above ten hours. In the following, the PhysioDroid app is described.The process to get started on the app is depicted in By pushing the button “Monitoring,” the user starts the monitoring procedure and gets access to some of its main functionalities. First, the app triggers the process of binding both mobile device and EQ01. To that end, the user is asked to allow the Bluetooth connection. As soon as both mobile device and EQ01 are bound, the application starts collecting the data delivered by the wireless monitoring device. The EQ01 raw data are encoded into the PhysioDroid proprietary format to be used by other application functionalities. These application functionalities principally enable data processing and real-time visualization on the mobile device. expert view provides real-time representation of physiological data waveforms. This is particularly suited for clinical specialists that may require a precise description of the recorded information. Amongst others, the ECG, acceleration, and respiration waveforms may be displayed, as well as the skin temperature. A simpler presentation of the health data is provided for the regular users. The user view includes averaged values  and visual indicators that inform about the status of the monitored vital data . The phone number to whom the calls should be addressed could be also set through the “Configuration” menu. The emergency call is directed to the “112” by default, in order to reach emergency services. Given the costs of triggering a false alarm, and although the EQ01 sensor holds various medical certifications that supports its reliability, specific situations that may lead to an erroneous alert have been especially considered. This refers, for example, to the case when the user removes the vital band before ending the monitoring process or the communication between mobile and wearable devices is lost.For the motion data interpretation, a stick that imitates the identified posture or exercise is particularly used. At the bottom of the screen the user also gets information about the EQ01 battery status, apnea occurrence, vital signs, and irregular heart beat events. All these events come from the data provided by the EQ01.The user may display some of the stored data through the “Database” menu see . Neverth HowTo are neatly described in the manuals that can be access through the “Help” menu.Apart from the functionalities already explained for the “Configuration” menu, here the user may also change other application settings such as data uploading interfaces (WIFI/3G) or user profile updates. All functionalities and the cache, drawing, login, monitoring, upload, storage, and add-ons.The PhysioDroid app consists of seven packages named according to the functionality they provide: cache package prototypes classes that implement a cache memory based on a buffer. This allows the application to perform on-the-fly data processing without requiring local permanent storage . In fact, the use of a persistent storage is observed to slow down significantly the processing of the data or at worst prevent it.The monitoring package, which further supports the Bluetooth connections between the vital monitor and the mobile device. These connections are established through the Bluetooth radio frequency communication protocol  and the, which  storage package manages local persistence processes. The storage functionalities build on SQLite [Then SQLite , which i upload package controls remote storage functionalities. The transmission to the remote storage is implemented using a HTTP POST request method, which encloses in the message's body the SSL-encrypted representation of the data.The drawing package. This package implements some of the native functions provided by the Android API.Graphs and general data presentation are implemented through the login package. Here again, Android native functionalities are used to implement authentication and authorization mechanisms. Finally, the add-ons package contains classes that are not essentially needed for the application core functionalities but provide features to make the user experience more pleasant .User login and registration are handled within theThe implemented software is built on Android API levels 9 to 15 and makes use of the best practices recommended by Google in order to improve user experience, reduce power consumption, and optimize performance. The software modularity also allows developers to easily include new functionalities for signal acquisition, data storage, data analysis, and data transmission as well as other add-ons whether required. In fact, the PhysioDroid app has not been defined as a closed application but as a primary tool that may be specifically configured to approach different medical and health-related problems.The third component of PhysioDroid is the remote persistent storage system. Physiological data collected by the wearable monitoring device may be transmitted through the mobile app to a remote storage component. The app can be operated without making use of this remote component; however, in this case the spectrum of value-added services would be more limited.Remotely-stored health data could be accessed by doctors in order to control the patients' vital information or by any other authorized third party, for example, a clinician. Moreover, the collected data could be further processed to infer some knowledge about the users' physiological conditions, or even to determine behavioral patterns of a certain demographic group, for example, elderly. upload package and data is transmitted both via the WIFI or the 3G network, as described in The current implementation of PhysioDroid uses a remote server to provide the storage capabilities. An Apache application server and a MySQL database enable the persistent storage and allow the secure communication with the mobile device. The connection from the PhysioDroid app to the server is established in theIn case thousands of users made use of PhysioDroid, the server would run into scalability issues. This problem would get even worse if PhysioDroid became one of top Android Apps in Google Play and gets millions of installs. One of the main issues relates to the fact of having thousands of users accessing the server simultaneously. A second important matter refers to the storage of huge amounts of data, generated by a large number of users. Finally, the bigger the data sets are, the higher the computational processing costs are.Cloud computing  and big  Open-Source, Web-Based, Framework for Integrating Applications with Social Media Services and Personal Cloudlets (OPENi)  for the cloud storage of collected physiological data and their management.We are working at the moment on a new version of PhysioDroid, which uses theOPENi offers the Cloudlet platform to store users data on the cloud. The OPENi Cloudlet platform provides application users, like PhysioDroid users, with a single location to store and control their personal data. The Cloudlet builds on the cloud database MongoDB and empowers application users to remain in control of their data. The control mechanisms are inherently secure and trustworthy, assuring the users data are not disclosed without their consent. Each PhysioDroid user will have their own Cloudlet to store their data. The Cloudlet functionalities will give the PhysioDroid users the maximum control of their data and over third party access to their data.The PhysioDroid will use the Cloudlet API in order to upload the collected physiological data to the user's Cloudlet. The OPENi Encryption functionality, which is based on AES and one-time-keys, will allow on-the-fly encryption of the data collected by the PhysioDriod application preserving its confidentiality when uploading it from the mobile device to the user Cloudlet.Not only will the PhysioDroid data be securely transmitted and stored into the user Cloudlet, but its secure and trustworthy access will be also granted by the OPENi Privacy and Security Framework. The OPENi permission visualization functionality will allow the PhysioDroid user to set up the data access rights via an intuitive graphical user interface, thus, defining who can access their data. These permissions and the authorization and authentication OPENi functionalities will ensure that the user physiological data is not disclosed to any malicious applications or users. Only the authorized parties, for example, the doctor, the clinician, or the family member, will be able to access the PhysioDroid data available in the users Cloudlet.Last but not least, OPENi will allow the easy development of new applications that use the PhysioDroid data stored in the users Cloudlet and any combination of independent cloud-based services made available through the OPENi API Platform, as well as the development of processing and reasoning functionalities on the PhysioDroid data available on the Cloudlet.Two practical use cases for both average users and specialists in health and sports domains are described in the following.One of the key features of the PhysioDroid system is the ability of presenting and detecting risk conditions. Some vital sign measures are easy to interpret, as they reach critical or extreme values . However, the interpretation of these very data in a more ordinary situation varies from patient to patient. For example, heart rate measurements differ depending on personal factors such as gender, age, weight, or height. The differences may be even higher for patients that suffer from illnesses or health conditions. Medical experts are capable of benefiting from all this information to correctly interpret the patient's vital signs. This medical knowledge could be easily incorporated by the specialist into the PhysioDroid system. The PhysioDroid app has been defined to allow specialists to customize the interval of interest  for each measured physiological sign, thus, adapting the visual representation and alarms to them. Taking advantage of this characteristic, a possible application could be referred to the persistent evaluation of the user's cardiac rhythm to detect abnormal situations and further trigger proactive policies. Once detected, and depending on the magnitude of the abnormality, the patient could be directed to follow specific guidelines provided by the doctor. Should it be required, an automatic emergency call/message may inform the closest clinical center.In a clinical or emergency setting, the medical expert may also benefit from the use of the PhysioDroid system to accelerate the diagnostic. Patients often need to wait for some time before the device to run, for example, an ECG test or a respiration check, is available. The cost of these devices determines that they are normally shared among various specialists. The PhysioDroid system brings here a readily available alternative for a practical vital sign monitoring. Thus, for example, when the patient arrives to the clinical center the doctor may connect the PhysioDroid app to the wearable monitoring device to rapidly check the patient vital signs. Moreover, the monitoring may also be continuously performed in the ambulance on the way to the hospital or clinical center.The PhysioDroid system is not just limited to the medical field but well-being, well-working, or other health-related domains. Here, an example for its use in sports is presented. Particularly, the idea is to assess whether the user reaches the target or training heart rate (THR) during the exercising. This has been shown to coincide with the phase when heart and lungs receive the most benefit from a workout. The approach basically consists of analyzing the heart rate while the user performs diverse intensity activities e.g., . HR rang × age), ), Lund ( × age), ; HRmax ( × age), ) or Gula × age), ) among o × age), , therebyThe previous use case is not only devised for the amateur user but for athletes and their coaches. Athletes may be continuously monitored during their exercises while the coach analyzes the measured information. This data could be of worth to improve training routines or avoid injuries normally caused from an inadequate warm up or cool down procedure.In this paper, a portable physiological and behavioral monitoring system devised for people health and wellbeing empowerment is presented. The system consists of a wearable monitoring sensor, a mobile device, and an optional remote persistent storage unit. The wearable monitoring device records diverse vital signs and transmits them to the mobile device on which a specifically developed Android app runs. The app acts as gateway supporting physiological data gathering and local storage, as well as data uploading to the remote storage for further processing. The application also allows the users to visually inspect the vital signs information collected through the wearable health sensor. This information is presented according to the users' level of expertise. Simple alerts and emergency calls are also features included as part of the app. Although the application has been here defined for the Equivital EQ01 monitor, it has been implemented in a way that little effort is required to make it compatible with any type of Bluetooth interfaced health monitor. Finally, a couple of use cases for the PhysioDroid system has also been suggested as part of this work.Next steps aim at incorporating sophisticated data analysis and decision support techniques that may lead to a more profound description of the users' status and their evolution, key information for a customized, and personalized health care. As much as the number of users of the PhysioDroid system increases, more powerful resources should be also considered. The use of mainstream cloud solutions such as the ones provided by the OPENi platform is within the scope of current and future work. The authors also aim to shortly grant full and free access to the app through the Google Play store. Moreover, the source code will be also provided under GPL license so the app may be adapted to the particular requirements of the target problem.


Clinical audits have emerged as a potential tool to summarize the clinical performance of healthcare over a specified period of time. However, the effectiveness of audit and feedback has shown inconsistent results and the impact of audit and feedback on clinical performance has not been evaluated for COPD exacerbations. In the present study, we analyzed the results of two consecutive nationwide clinical audits performed in Spain to evaluate both the in-hospital clinical care provided and the feedback strategy.The present study is an analysis of two clinical audits performed in Spain that evaluated the clinical care provided to COPD patients who were admitted to the hospital for a COPD exacerbation. The first audit was performed from November–December 2008. The feedback strategy consisted of personalized reports for each participant center, the presentation and discussion of the results at regional, national and international meetings and the creation of health-care quality standards for COPD. The second audit was part of a European study during January and February 2011. The impact of the feedback strategy was evaluated in term of clinical care provided and in-hospital survival.∶3,493 and audit 2∶4,650). The initially provided clinical care was reasonably acceptable even though there was considerable variability. Several diagnostic and therapeutic procedures improved in the second audit. Although the differences were significant, the degree of improvement was small to moderate. We found no impact on in-hospital mortality.A total of 94 centers participated in the two audits, recruiting 8,143 admissions (audit 1The present study describes COPD hospital care in Spanish hospitals and evaluates the impact of peer-benchmarked, individually written and group-oral feedback strategy on the clinical outcomes for treating COPD exacerbations. It describes small to moderate improvements in the clinical care provided to COPD patients with no impact on in-hospital mortality. The existence of a gap between the healthcare that patients actually receive and the guidelines for that healthcare is now well acknowledged In this context, feedback from the audited information constitutes a key step to improve clinical practice Chronic obstructive pulmonary disease (COPD) is a major and growing health problem In recent years, Spain had used an auditing process for COPD, named AUDIPOC, which has resulted in the completion of two major clinical audits in the country The present study is an analysis of two clinical audits performed in Spain that evaluated the clinical care provided to COPD patients who were admitted to the hospital for a COPD exacerbation. Both audits had a similar methodology that has been extensively reported in previous publications The first audit was conducted from November–December 2008, and 129 hospitals participated, recruiting 5,178 patients. The second audit was part of a European study in which 432 centers from 13 countries recruited 18,016 patients. In Spain, 94 hospitals participated and recruited a total of 5,271 cases during January–February 2011. For the purpose of the present study, we selected the centers that participated in both audits. Ninety-four centers were included in this analysis. Altogether, a total of 8,143 cases were included in both audits.The recorded variables have been reported and included information on the patient characteristics , disease characteristics , resources available  and clinical practice . Adherence to the clinical practice guidelines was analyzed following the GOLD recommendations for exacerbation management, which were available at the time of each audit. An adequate use of mechanical ventilation or antibiotics was considered to be present when a patient with such prescriptions correctly received them or when a patient who did not have such prescriptions did not receive them accordingly.After the first audit, feedback was planned in three different ways. First, a specific report was created for each participant center. In this report, the value of each recorded variable was presented for that center and benchmarked against the regional and national values. Second, the results of the audit were presented in the Spanish Society of Pneumology and Thoracic Surgery (SEPAR) annual congress and in the European Respiratory Society (ERS) annual meeting, and all investigators were invited to attend. Additionally, several smaller local meetings were planned during the next two years following the first audit to communicate the results. Notably, investigators were encouraged to organize meetings at the regional level to discuss the audit results, and several meetings were organized. Third, after the first audit, the SEPAR organized a working committee to create COPD healthcare quality standards, which were made available to all respiratory physicians In Spain, both audits were approved by the institutional review board of Hospital Universitario Virgen del Rocío  and confirmed by each participating hospital t-test  or chi-squared test . Kaplan-Meier curves were constructed that evaluated in-hospital survival using the log-rank test to compare the in-hospital global mortality in both audits. The alpha error was set at 0.05.The statistical computations were performed with the Statistical Package for Social Sciences  version 18.0. Variables were characterized by the mean and standard deviation or the absolute and relative frequencies of their categories. For describing the centers, we calculated the inter-regional range (IRR), which indicates the region with the highest or lowest mean value for a particular variable. Inferential studies comparing both audits were analyzed with the unpaired Student’s Ninety-four Spanish hospitals participated in both clinical audits. The main characteristics of the participant hospitals are summarized in 1) was 3,273, including 2,874 patients without spirometry and 399 patients with some spirometric information but no FEV1. Altogether, the availability of the FEV1 significantly improved in the second audit. The majority of these patients were considered to have severe or very severe disease. More than 40% of the patients had not been previously admitted, and this percentage increased significantly in the second audit. Although there were some statistical differences, the clinical presentation according to the three Anthonisen criteria was not clinically different between the audits.A total of 8,143 admissions were analyzed from the two audits . The characteristics of the patients are summarized in The diagnostic procedures improved by the second audit . The proThe therapeutic interventions before admission, during hospitalization and at discharge are summarized in The 10 recommendations evaluated according to the GOLD guidelines are summarized in The survival curves for both audits are shown in The present study describes the state of COPD hospital care in Spanish hospitals and evaluates the impact of a feedback strategy on clinical care. After two consecutive audits, with feedback performed in between audits, we have observed some improvements in the clinical care provided to COPD patients. However, the majority of these improvements were small or moderate and did not impact the in-hospital mortality. This finding suggests that performing a clinical audit and providing the participant centers with the results according to our feedback strategy increased awareness and improved some aspects of COPD exacerbations, although there was no clear benefit on the outcomes.2, potentially leading to an incorrect assessment Clinical audits have gained traction in healthcare systems as a way of obtaining information on the clinical care being provided. This information is of interest both for people funding healthcare, who want to ensure that the care they purchase is of the highest possible standard, and for patients who hope to receive safe and effective healthcare. However, despite evidence from many studies on audit and feedback, there is still limited information on how to use these data. A recent systematic review assessed the effectiveness of audit and feedback and reported an inconsistent picture; some evaluations obtained positive results, whereas others did not Feedback can be delivered in different ways, and audit and feedback can be used as components of a multifaceted strategy to improve the quality of healthcare. In our study, we provided oral and written information at the individual level and oral information at the group level. Additionally, healthcare quality standards for COPD were constructed according to the experience with the first AUDIPOC audit Some limitations must be considered when interpreting our results. Within each region, the participating hospitals volunteered. Therefore, although all regions were sampled, there was no attempt at representative sampling. As a consequence, the hospitals involved in the study were different in organizational terms and there was a certain degree of variability concerning the available resources . HoweverIn summary, our study evaluated the impact of a peer-benchmarked, individually written and group-oral feedback strategy on the clinical outcomes for treating COPD exacerbations. The results of our study suggest that performing a clinical audit and providing the participant centers with the results according to our feedback strategy increased awareness and improved some aspects of COPD exacerbation treatment. Accordingly, other feedback strategies may yield different results. Although we did not observe a clear benefit in the clinical outcomes, several aspects of the diagnostic and therapeutic clinical care provided to the COPD patients admitted to hospitals seemed to improve, which, in turn, may reduce the gap between the healthcare that patients receive and the guidelines for that care.Table S1Percentual distribution of the cases included in both audits according to the region within the country.(DOCX)Click here for additional data file.File S1Membership of the AUDIPOC and the European COPD Audit studies.(DOCX)Click here for additional data file.


Drosophila melanogaster has been adopted as one of the most-used model systems since it was first introduced by Thomas Morgan for the study of heredity in the early 20th century. Its experimental tractability and similarity of its biological pathways to those of humans have placed the model at the forefront of research into human development and disease. With the ongoing accumulation of genetic tools and assays, the fly community has at its fingertips the resources to generate diverse Drosophila disease models for the study of genes and pathways involved in a wide range of disorders. In recent years, the fly has also been used successfully for drug screening. In this Editorial, we introduce a Special Collection of reviews, interviews and original research articles that highlight some of the many ways that Drosophila has made, and continues to make, an impact on basic biological insights and translational science. Drosophila Collection: This Editorial introduces a new Special Collection, ‘Spotlight on Drosophila: Translational Impact’, providing a summary of its contents so far and highlighting the impact of Drosophila as a model for human diseases. Identifying functions for each of the 20,000-25,000 estimated human genes, and determining which of these genes play a role in disease, is one of the greatest challenges in medicine today. Although the advances in genome sequencing over the past decade have meant that DNA variants linked to disease can now be rapidly and accurately identified, understanding whether a particular variant is causal and, if it is, how it perturbs cellular function and overall organismal physiology remains a daunting problem. The major obstacles to determining causality and understanding underlying pathogenic mechanisms are: (1) in the majority of cases the cellular function of a specific gene is unknown, meaning that we lack hypotheses to link the disease to a physiological process; (2) genetic diseases are commonly the products of mutations in multiple genes in combination with lifestyle and environmental factors; and (3) organisms are complex integrated systems within which there is extensive cell- and tissue-level communication; thus, understanding the basis of human syndromes requires a systems biology approach.Drosophila genome, completed in 2000, and recent further annotation by the modENCODE consortium reveal striking conservation between fly and human genes, underscoring the utility of Drosophila for studying fundamental processes relevant to human health. Indeed, Drosophila orthologs have been identified for approximately two-thirds of all human disease genes, and all major signal transduction pathways are conserved between flies and humans  collection, ‘Spotlight on Drosophila tools and assays that can be utilized to generate fly models of human diseases and study disease-associated genes. In their ‘At a Glance’ poster article, they highlight how, despite the morphological differences between some fly and human organs, the extensive toolbox available for Drosophila research can provide unique insights into mechanisms of diseases affecting the central nervous system, heart, liver and kidney  that affect the aging process have been elucidated in the fly. Because aging is an organismal process, studies in Drosophila allow dissection of both tissue-intrinsic and -extrinsic factors, as discussed in another earlier review, written by Fabio Demontis and colleagues, on the mechanisms of skeletal muscle aging and the relevance to sarcopenia , the Drosophila ortholog of human neuropathy target esterase (NTE), impairs neuronal function . The protein encoded by the human homolog of sra, known as Down's syndrome critical region 1 (DSCR1) protein, is a calcineurin inhibitor whose levels are elevated in the brains of individuals with AD  to provide insight into circadian behavioral defects and the role of iron in this AD model . They showed that removal of the fly ortholog of human oneurons . Althougin vivo platform to evaluate potential therapeutic compounds, the authors also reported the efficacy of a known anti-DM1 drug, pentamidine, to effect partial rescue of the heart phenotypes  to assess heart function in their newly generated fly model of myotonic dystrophy type 1 (DM1) cardiac dysfunction. Mimicking what is observed in humans with DM1, these flies show reduced survival, increased arrhythmia, altered systolic and diastolic function and reduced contractility. Providing proof-of-concept that the model could be used as an enotypes .Drosophila models allow elucidation of the biological pathways and environmental factors that influence the clinical presentation of the disease, providing a wealth of information for translational efforts in compound and small-molecule screening.In recent years, the world of fly models for human disease has exploded. We anticipate continued growth in this area as advances in genomics lead to a greater need to understand the impact of polymorphisms in genes, as well as other influences on disease, including environmental triggers. Drosophila research, a theme that is discussed by Gerry Rubin in his interview with DMM, coming up soon. The sharing of reagents is a fundamental backbone of these interactions, as are the advances in technological approaches to manipulate gene function in the animal in ways that allow detailed study and exquisite understanding of pathways and the impact of their disruption. These features are among those that have allowed Drosophila studies to take a prominent position in providing insight into human biology and disease. We hope you will enjoy the Collection, which will be added to over the coming months, with all articles being collated on this dedicated page: http://dmm.biologists.org/collection/drosophila-disease-model.This Collection also highlights the creativity and innovation of the fly community in generating important and appropriate models for a range of human biological complexities. We also underscore the collaborative and interactive spirit of the fly community as a whole to advance We dedicate this Collection to Marcos Vidal, who sadly passed away in January, 2016. An obituary written by Ross Cagan and Eyal Gottlieb is also published in this issue .


Neurotoxicity associated with chemotherapy continues to be of great concern to both advanced practitioners in oncology and the patients they care for. Chemotherapy-induced peripheral neuropathy (CIPN) is considered the dose-limiting toxicity for oxaliplatin, an agent commonly used to treat colorectal cancer ., 2014. One of the issues that plague oncology clinical trials is determining exactly when new treatments tested are ready for implementation into practice. While randomized clinical trials are considered the gold standard for answering research questions, the results of several similar trials can have divergent recommendations or conclusions that inhibit the translation of research into oncology practice. In the case of calcium and magnesium for the prevention of oxaliplatin-induced peripheral neuropathy, a recent study by Study Design and SamplingOne of the first considerations is the design of the study to be conducted. The 2004 study by Prospective studies are designed to follow subjects over time, and usually have fewer potential sources of bias and confounding variables than retrospective studies. The CONcePT study referenced in the The sample size and criteria for study entry are certainly factors that can impact study results. For example, in the study by Ishibashi, Okada, Miyazaki, Sano, and Ishida (2010), the study consisted of only 33 patients enrolled over a 1-year time frame where the participants had differing entry criteria. The patients entered into this study had both unresectable metastatic disease and had undergone resection for metastases, with differing modified FOLFOX6 protocol lengths, and thus, potentially different neuropathic outcomes of Ca/Mg treatment based upon the small sample size, differing study entry criteria, and lastly, the premature closing of the trial. Similarly, in a study by Measures of the OutcomeAn additional consideration in prior trials of Ca/Mg is how the outcome—in this case, CIPN—was measured. The selection of a standard instrument provides a means of comparing the same outcomes of different trials based on using the same measurement tool. For the two major studies (N08CB and N04C7) that tested Ca/Mg for the prevention of CIPN, the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) was used as the primary neuropathy measure. A letter to the editor  discussing the two disparate trial results found the absolute benefit of neurotoxicity reduction to be only between 1% and 16%.While the CTCAE provides a standard measure, the manner in which it is used poses additional issues in research. The criteria for the CTCAE were established as cut points to determine treatment toxicity, not as a measure of the symptom experience. There are no standardized instructions or training manual for how to apply or interpret this scale, thus the method for applying this grading scale varies widely, and the interpretation of the meaning of the scale gradations has been inconsistent, potentially affecting study results .On the other hand, there is a decided lack of consensus among experts in the field concerning which instrument or combination of instruments should be used to measure CIPN as a study endpoint, with consideration of both objective and subjective aspects of the CIPN experience. A recent clinical practice guideline for the prevention and management of CIPN from the American Society of Clinical Oncology identified the need for valid and reliable measures of CIPN that assess the extent and severity of CIPN. Such measures should focus on patient-reported outcomes (PROs) as opposed to clinician assessment ., 2014. In addition, the timing of the measure of CIPN could potentially produce conflicting clinical trial results. For example, in oxaliplatin-induced CIPN, the patient may experience a phenomenon known as "coasting," where neuropathic symptoms actually worsen 2 to 6 months posttherapy, or may go on to partially or completely resolve in 40% to 80% of patients within 6 to 8 months of treatment . So, depending upon when the measure is taken in the course of a clinical trial, different results can be obtained.Power, Data Analysis, and Missing DataStatistical power in a clinical trial refers to the ability to detect a difference in an outcome made by a treatment, when a difference truly exists. There are several reasons power can affect study results in the trials conducted to ascertain if Ca/Mg infusions can indeed prevent oxaliplatin-induced CIPN. Having excessively small sample sizes, or very unequal sample sizes between the treatment and control groups, can affect study results through the loss of statistical power to be able to detect differences between groups. The study by In all clinical trials, the issue of missing data becomes an important consideration that can result in the loss of statistical power and bias study results. The percentage and pattern of missing data are also important for the researcher and study statistician to consider. Missing data can take the form of a missing question or missing one or more items on a multilevel instrument or measure . In the Loprinzi study (2014), the missing data are duly reported, as were the statistical considerations for imputation of missing data in the final analysis. When the pattern of missing data is reviewed, it appears that there is a very small (.03–.06) amount of missing data for the baseline sensory score and patients with only one cycle of sensory data. However, data regarding FOLFOX dose reduction and discontinuation by treatment arm denote missing data treatment discontinuance in all three treatment arms that ranges from 12% to 14%. While this is not a primary or secondary study outcome of this trial, this example of missing data illustrates the point that if missing data for the primary aim exceed 10%, the conclusions drawn in the final analysis may be suspect .In summary, the potential for study design, study sample characteristics, study outcome and measurement, as well as considerations of statistical power and analysis, along with missing data can all influence the outcomes of a clinical trial, and thus result in different findings for the same treatment received.