Female genital mutilation/cutting (FGM/C) is a clear violation of women’s rights and can have adverse and irreversible health effects as well. Worldwide, more than 200 million women and girls have undergone FGM/C. Utility value of FGM/C has not been estimated yet, so we designed this study to extract the health utility value of FGM/C for the first time in the world.In a cross-sectional study in Iran, 125 girls and women who underwent FGM/C procedure were examined by the trained midwives in order to determine its type. In addition, a questionnaire was completed for identifying the socio-demographic factors and extracting the health utility of these individuals. Health utility was measured using Time Trade-off method and also to determine the effects of the socio-demographic factors on the health utility a two-limit censored regression model was applied.The mean and median of the health utility of women with FGM/C were 0.971 (SE: 0.003) and 0.968 (IQR: 1–0.95), respectively. Number of non-traders was 58 (46.4%) who reported perfect health utility. However, the mean of health utility among traders was 0.946 (SE: 0.002). Only type 1 (Clitoridectomy) and type 2 (Excision) FGM/C were seen in this study. Women with Type 1 FGM/C had significantly lower health utility value  than their type 2 counterparts . Moreover, women in the age group of 31–45 years , single , divorced , employed , and with supplementary insurance  had significantly lower health utility than their counterparts.FGM/C affects physical and psychological well-being of these individuals, resulting in a lack of personal and marital satisfaction, which ultimately leads to a 3% reduction in their health related quality of life. Therefore, preventing from this practice is very important and should be considered by health system policy makers more than before. Female Genital Mutilation/Cutting (FGM/C), which is considered as a global concern, is defined by World Health Organization (WHO) as “all procedures that involve the partial or total removal of external genitalia or another injury to the female genital organs for non-medical reasons” . The praThe highest prevalence of FGM/C is seen in African countries such as Somalia 98%), Guinea 96%), Djibouti (93%), and Egypt (91%) . It may %, Djibou%, GuineaResearchers have divided the causes behind practicing FGM/C into five groups: psychosexual, sociological and cultural, hygienic and aesthetic, religious, and socio-economic . Some stThis cross-sectional and multicenter study was conducted in 2018 in Kermanshah province, west of Iran. One hundred twenty-five females aged over 16 who had experienced the FGM/C participated in the study after giving their written consent. The samples were selected by non-random consecutive sampling method from the girls or women referred to the midwifery offices for examination. Next, they were examined by trained midwives, and a questionnaire was completed for them. An obstetrician examined these women for having FGM/C and identified its type.Type 1 FGM/C (Clitoridectomy) means removing part or all of the clitoris; type 2 (Excision) is defined as removing part or all of the clitoris and the labia minora, with or without removal of the labia majora; type 3 (infibulation) is narrowing of the vaginal opening by creating a seal, formed by cutting and repositioning the labia; and type 4 (other harmful procedures) means any injury to the female genitals, including pricking, piercing, cutting, scraping or burning the area. The females who did not have any illness, disorder, and psychological disability, except FGM/C entered the study.Time trade-off (TTO) approach has been used to measure the health-related utility of FGM/C. In this approach, the researcher asked the participants: how many years in the current health state (X) you would be willing to lose in order to regain full health. The number of these years changes to the degree that the individual has to subjectively stay indifferent between their health state in remaining future years (Y) and perfect health state in a shorter period of time and sees their value both the same. The amount (x/y) is presented as disutility and the result of formula 1- (x/y) indicates the health utility of each individual. In all cases, in the first question, the value of x was considered four years. If the interviewees agree/disagree, this amount could be increased/decreased, and it continued until reaching the indifference point. Life expectancy at birth for Iranian women was considered 79 years.The best and the worst health state of the individual measured by TTO method equals zero and one, respectively. It gets zero if the individual is not willing to lose any years of their life, and it gets one if the individual is willing to lose all their remaining years of life to fix the FGM/C problem.After determining the type of FGM/C, questions about socio-demographic factors were asked from the participants by the midwife. These questions included determining the age , marital status , education , employment status , standardized monthly household expenses (monthly household expenditure is divided by its household dimension), and having basic and supplementary health insurance.The two-limit Tobit linear regression model was used in order to determine the effects of socio-demographic factors on the level of health utility among women with FG/CM. In this model, given that the dependent variable is assumed to have a normal distribution; therefore, we considered the logarithmic value of health utility as a dependent variable and factors of age (years of life); type of FGM/C (1: type 2 and 0: type 1); marital status (1: married and 0: non-married); education (number of years of education); occupation (1: employed and 0: non-employed); and standardized monthly household expenditure (average monthly spending per person) as independent variables. To determine the predictive variables in this model, some univariate logistic regressions were performed for all socio-economics factors. Only parameters were selected that had a statistically significant association with the dependent variable at 0.05 error level. Pearson test for scale variables and Spearman test for categorical variables were used to identify the autocorrelation problem.The distribution of studied women among socio-demographic groups is represented by number and percentage. For each of these socio-demographic sub-groups, the amount of measured utility has been reported with mean, standard error, median, and interquartile range.p-value < 0.05. All statistical analyzes were performed using STATA version 13 .Due to the non-normal distribution of the utility values, Kruskal Wallis (for groups with more than two subgroups) and Mann-Whitney (for groups with two subgroups) were used to measure the significant difference between the mean values for subgroups of each socio-demographic group. The exchange rate used for conversion is 1 USD = 120,000 Iranian Rials. The significance level was set at a The Research Deputy of Kurdistan University of Medical Sciences approved this study. Before the study, all participants gave written informed consent to participate in the study. The researchers adhered to the tenets of the Declaration of Helsinki in the implementation of all stages of the study.A total of 125 women and girls who had a history of FGM/C participated in this study. The mean age of these participants was 35.74 years (ranged 19–55). The participants included 10 (8%) single women, 17 (13.6%) divorced / widowed, and the rest were married. The distribution of first and second type of FGM/C among the participants was 104 (83.2%) and 21 (16.8%), respectively  with a median of 0.968 (IQR: 1–0.95). In other words, they lost about 3% of their Health-Related Quality of Life (HRQoL) due to FGM/C, on average.Generally, the results of the regression model and univariate analysis were highly consistent, except for the education level. These findings confirm that the value of FGM/C disutility is positively and significantly associated with age, income level, having a job, and not having a husband. Univariate analysis indicates a statistically significant association between FGM/C disutility and education years, but this relationship is not confirmed by multivariate analysis. Of course, these results need to be interpreted with caution, which are discussed below.The utility value, which subjectively represents the sum of the effects of FGM/C on women’s health, was statistically significantly lower for single  and divorced women  compared to married women . In other words, single and divorced women experienced more reduction in their HRQoL than married women. This finding is confirmed in both univariate and multivariate analysis models. One possible explanation for this finding is that FGM/C practice delayed marriage for the circumcised single women, as the mean age of them was significantly higher than their married counterparts (38.2 vs. 33.8 years). Besides, it could conceivably be hypothesized that FGM/C, due to its psychosexual problems , is a crThis negative effect may vary in different countries and cultures, as in countries such as Nigeria, Somalia, and Sudan, girls who have performed FGM/C have a higher chance of finding a partner and having a timely marriage , 18. WhiAnother important result of this study was that women in the 31–45 age group statistically significantly reported a lower HRQoL  than others. The reason could explain this finding is that middle-aged women are more likely to have experienced the adverse effects of the FGM/C than their younger counterparts, and they also have higher expectations of the quality of their sexual relations than their adult peers. However, further analysis of the data showed that the middle-aged group had the highest divorce rate than others, accounting for 69% of all divorces. This result could support the theory, as mentioned earlier, that FGM/C could be a risk factor for divorce. This finding is in line with the results of other studies –24.Unexpectedly findings showed that employed subjects reported less health utility than unemployed women and housewives . It is difficult to explain this result, but with more analysis, we find that the average years of education in this group were significantly higher than in other groups so that all 16 members of this group had a university degree. Therefore, the difference in their level of disutility may be more due to their level of education, not their employment status. To study the association between employment factor and HRQoL of women with FGM, a larger sample size that enables us to control factors such as age, marital status, and degree of education are required, and this study is not able to give an accurate answer in this regard.In this study, only FGM/C types 1 and 2 have been seen, and due to the very low prevalence of other more severe types of the practice, we have not found them . AlthougFifty-eight participants of the study (46.4%) were not willing to lose any time to regain their usual genital condition, and they reported a full health utility. These are referred to as non-traders. All of them were married, and more than 81% of them were housewives. These people, on average, had a larger household size with a monthly household expenditure below the average. Therefore, it can be concluded that non-traders were less influenced by the effects of FGM/C, and were able to live their lives following the community conditions and their expectations, so they did not complain about it. The mean health utility for traders was 0.946 (95% CI: 0.943–0.950). In other words, women, who have been hurt in their personal and family life due to FGM/C, lose 5.4% of their HRQoL.We know that the effects of FGM/C, which violates women’s rights, are not limited to their health and HRQoL, but their individual and social lives. According to the findings, if we consider only the HRQoL effects, FGM/C can be compared with diseases such as non-severe hypoglycemic, mild primary dysmenorrhea, skin neoplasm, myopia, and otitis media associated with pain. On average, these all result in a 3% loss of HRQoL in individuals. Subgroups such as single or middle-aged women with FGM/C, who are affected by this procedure more than others, have disutility almost equal to mild gastroenteritis. Of course, since the FGM/C procedure is mainly performed during the childbirth or childhood, it has life-time effects and imposes more disease burden than the diseases as mentioned earlier (Table The burden of FGM/C is unnecessary and avoidable, provided that governments take indigenous and effective initiatives and measures to prevent the FGM/C procedure. To develop domestic protocols, the main reasons for performing FGM/C should be extracted in each community and should be considered as a basis for identifying prevention strategies.Numerous studies have shown that the social factors that determine the performance of FGM/C vary from country to another, which requires different policies to control this practice. Snow et al. introduced ethnicity, age, religion, and education as the most critical social predictors of FGM/C in Nigeria , which hOf course, all prevention programs require intersectoral collaboration and should include activities such as health education to parents, passing national laws, standing against some meaningless social norms and traditional beliefs, encouragement of mothers and girls to educate, and getting help from religious missionaries , 39. NowThe strength of the current study was to examine FGM/C victims by trained midwives to determine the degree of FGM/C. However, the results of the present study should be interpreted in light of its limitations. First, we did not include types 3 and 4 of FGM/C; therefore, our results can only be generalized to women with types 1 and 2. Given the fact that the more severe types of this disorder impose more long-term adverse effects on the individuals and create more family and personal problems for them, it may also generate greater health disutility. Therefore, it is highly recommended that the disutility of FGM/C types 3 and 4 should be extracted in other studies. Second, the value of health disutility of FGM/C seems to be very much influenced by the culture of the community, so if the restrictions imposed by FGM/C prevent women from meeting their personal and social expectations, it can raise women’s dissatisfaction and create more disutility. Therefore, the results of this study are not necessarily the same in different societies and communities.Iranian women undergoing FGM/C types 1 and 2 lose an average of 3% of their HRQoL due to their health problems. Of course, this figure for non-traders and traders is estimated as zero and 5.5%, respectively. Therefore, the epidemiological burden of FGM/C is very considerable, and it is recommended that the countries involved in this social and health challenge develop prevention protocols for FGM/C and stick at them seriously.


Only two individuals yielded values >87Sr/86Sr = 0.711. This suggests that most of these individuals had local origins but some had cultural affinities beyond present-day Denmark. Our results raise new questions concerning our understanding of the social and cultural dynamics behind the urbanization of Scandinavia.Individual geographic mobility is a key social dynamic of early Viking-Age urbanization in Scandinavia. We present the first comprehensive geographic mobility study of Scandinavia’s earliest emporium, Ribe, which emerged around AD 700 in the North Sea region of Denmark. This article presents the results of strontium isotope analyses of 21 individuals buried at Ribe, combined with an in-depth study of the varied cultural affinities reflected by the burial practices. In order to investigate geographic mobility in early life/childhood, we sampled multiple teeth and/or petrous bone of individuals, which yielded a total of 43 strontium isotope analyses. Most individuals yielded strontium isotope values that fell within a relatively narrow range, between  Throand Åhus –14. HoweRibe was the earliest major emporium in Scandinavia, dating to around AD 700, when a trading center with far-reaching contacts emerged on the northern bank of the River Ribe  Fig 1)..Fig 1). th and 9th centuries. The main settlement area consisted of narrow, rectangular building plots, represented here by the plot boundaries. Some have been documented archaeologically (red lines), others reconstructed (light grey lines). The plots were placed in two rows on either side of a street running in a NW-SE direction. A main road (thick grey line) connected the site to inland areas. The surface of the burial ground to the east has been estimated to cover c. 8–9 ha. Graphics: Morten Søvsø and the Graphics Department, Moesgård Museum. Background map retrieved from Natural Earth. Free vector and raster map data @ naturalearthdata.com. Reproduced under the copyright terms of use of Natural Earth.Ribe is located near the coast of Southwest Jutland, in present-day Denmark, facing the Wadden Sea. The map presents a reconstruction of the site in the early Viking Age and of the natural topography: dry areas are depicted in grey shades, and have elevations between 2 and 6 meters above sea-level, whereas wet areas, with elevations under 2 meters above sea-level, are depicted in green. A number of excavations on the north side of the River Ribe have allowed a reconstruction of Ribe’s townscape in the 8th to the late 10th centuries, but at one point or another, all these sites hosted a large, permanent population. Their success implies that some people moved there, and stayed. Furthermore, they acted as nodal points in a long-distance exchange network [Addressing the question of cultural affinity and geographical origin is of paramount importance for understanding social dynamics in the early Scandinavian towns. The emergence of these more or less permanent coastal settlements, whose economy focused on trade and crafts, is considered one of the most important societal changes in the essentially agrarian and pastoral communities of Northern Europe in the late Iron Age/early Middle Ages –21. Alth network , and vis network –8. The hIn the context of Scandinavia’s early towns, questions of origin have often been treated based on burial remains. From an archaeological perspective, burial practices, defined by a number of criteria—such as the treatment of the body, grave markers, and the objects found with the remains of the dead—have been used to discuss cultural affinity, which in some cases may be related to specific regions. This approach, which has been widely used and debated for decades in early medieval archaeology e.g. , 27, hasBesides interpretative challenges, such interdisciplinary studies use a different vocabulary to convey the notion of geographic origin. Within the field of isotopic studies, this notion is typically referred to in terms of “local” and “non-local”. The word, in this context, refers to locality, which may be of considerably variable extent, rather than to a small region defined by its relation to a specific place. In artefact-, burial-, and settlement studies, archaeologists may associate cultural traits to a place or type of places and to regions, which scale may vary, depending on the research question, area of study, and time period involved. In the case of the Scandinavian emporia, it may signify a few kilometers’ range, sometimes designated as the “local” area, or Scandinavia as a whole, for example in contrast to the rest of Europe e.g. , 10. Theth–10th centuries, where the abundant artefactual material leaves no doubt as to its special functions: trade -local, regional, and long-distance- and specialized manufacture of crafted goods. Remains of houses also indicate a resident population [th-11th centuries) have been found in the immediate vicinity, but their extent and character are less clear. On the south side of the River Ribe, a Christian cemetery, founded c. 860, was excavated in 2008–2009 and 2011–2012 [Since its archaeological discovery in the 1970s, Ribe’s emporium has occupied a special place in the study of early medieval urbanism and in Viking-Age archaeology in particular , 30, 31.pulation . Traces 011–2012 .During the early Viking Age, Ribe’s trade network grew to encompass Norway and the Baltic Sea area, and eventually, to form distant links to the Mediterranean and the Middle East , 35. How14C dates, artefact chronology, and stratigraphy, the site has been dated to the 8th century and early 9th century, with a small cluster of graves in the southern part of the site dated to the 9th and 10th centuries [The earliest documented cemetery in Ribe is located to the east of the emporium, on the north side of the River Ribe. Graves have been found in this area on several occasions, and there have been two main excavation campaigns, in 1988–1989 and 2014–2016. To date, exactly 100 archaeological features have been interpreted as belonging to the burial ground, including a number of grave markings (ring ditches), animal offerings, and animal burials ; Fig 2. enturies . This di100 archaeological features excavated on the north side of the Ribe River have been interpreted as belonging to Ribe’s earliest cemetery. The table presents a general overview of the data divided by main burial types. The number of burials with preserved bone material submitted to osteological analysis is indicated for each burial type, as well as the number of human individuals identified by osteological analysis. These figures do not include the cases where the outline of the body was recorded as a darker coloration of the sediments at the bottom of the grave pit, although these do represent human individuals as well. The Ribe graves were generally poorly equipped in terms of grave goods. The number of burials containing objects is indicated for each burial type.The human and skeletal remains from Ribe’s earliest burial ground are publicly deposited and accessible by others in a permanent repository at the Museum of Southwest Jutland, Ribe, Denmark, on record under site numbers 43M70, ASR 8, ASR 937, ASR 1000, ASR 1030, SJM 129, and SJM 348. According to Danish law, the Museum of Southwest Jutland has full ownership and responsibility of the archaeological remains and granted all necessary permits for the studies described in this paper, following all relevant regulations.All in all, human and animal skeletal remains were preserved in 71 of the 100 certain and probable burial features documented at the cemetery. All were submitted to osteological analyses, which were conducted by Susanne Østergaard, Department of Conservation and Natural Science, Moesgård Museum . Owing tUnburnt human and animal remains from 27 burial features were examined, as well as burnt human and animal remains from 44 burial features. The analysis identified 67 human individuals, 57 of which from single graves and 6 from double graves. The remaining 4 human individuals identified were associated to disturbed contexts, which does not allow deciding on whether they belonged to single or double graves. The heterogeneity of the material means that different analytical methods were applied for sex and age estimation.For sex estimation, sex-specific traits of the cranium and the os coxae, as well as the skeleton’s general morphology, were assessed, when possible –42. OwinAge estimation was conducted based on knowledge of skeletal development from birth to senescence, including dental eruption/wear, timing of bone fusion, signs of ageing in articulations, especially between vertebrae and the iliofemoral joint . As not Besides being at the crossroads of long-distance exchange routes, Ribe is also located in a complex cultural landscape. On the one hand, its position in Jutland and north of the Danevirke, the historical border of the Danish kingdom, positions Ribe in a Southern Scandinavian cultural sphere; on the other hand, it is located in a marginal position in present-day Denmark, looking towards the Wadden Sea, and in relatively close proximity to other cultural groups, in Frisia and Saxony, and to the North Sea region as a whole. On several levels, the cultural landscape of Southwest Jutland seems to have shared many similarities with that of the Northern and Eastern Frisian regions , 45. BurThis diversity is evident in the highly varied treatment of the dead, starting with the various modes of treatment of the corpse, such as inhumation and cremation . In the Various burial practices were carried out at Ribe’s earliest cemetery, the most common consisting of cremated human, animal, and artefactual remains retrieved from the pyre and deposited indiscriminately in a shallow pit , and of simple inhumations in oblong pits . Photos: Aarhus University/Museum of Southwest Jutland.When taking all the foregoing factors into account, the degree of variation in burial practices is striking, especially for the early phase of the cemetery, where inhumation graves were mostly oriented W–E or S–N; most did not involve any container, but there are several examples of coffins or logboats. The dead could be placed in a supine position, especially for W–E graves, whereas they were mostly laid in a crouched position in S–N graves. Inhumation graves rarely contained any deposited objects or animals, apart from a few instances of dress fittings, ornaments, coins, and single horse teeth. Cremation graves may be divided into three main types: one where the pyre remains were deposited in a small pit, one where the cremated human remains were carefully retrieved from the pyre and redeposited in an urn, and one where pyre remains seem to have been left as small deposits on the surface. Both pottery of regional type and Frankish imports could be used as urns. For both deposits in pits and in urns, the human remains were often mixed with the cremated remains of animals and various objects, such as small personal implements, tools, riding equipment, jewelry, and so on. Animals include various domestic mammals, various species of birds, and even fish in one case. Animals sometimes also received their own burials, as shown by one horse inhumation with harness and saddle, and one dog inhumation.Theoretically, these variations may result from differences of treatment due to the social status, age at death, and/or gender of the individuals. However, variations in the degree of expenditure involved in the burial process  cannot be considered to be reliable indicators of social status in this context, as each burial sub-type comprises a small number of relatively more lavish cases. Also, children, adults, and elderly are all represented among the different burial types, including male and female individuals, when sex could be provisionally estimated. Therefore, multiple cultural affinities should be considered the most likely explanation for the observed diversity, rather than age at death and gender identity.th century [th century, probably as a result of the Christian influence brought by the Frankish expansion [th century [Although some burial practices at Ribe’s earliest cemetery are also documented at other sites in the immediate area, several have their best parallels outside this zone . Cremati century , but als century . Cremati century ; 74–76,  century . They ar century . In both century : 260–262 century , with ve century . Artefac century .naturalearthdata.com. Reproduced under the copyright terms of use of Natural Earth.The burial customs at Ribe’s earliest cemetery present discrete regional distributions beyond Ribe’s immediate area, and differ from the pattern otherwise known from the rest of Jutland in this period. The map shows the regional distribution of some of the most characteristic types: cremation deposit on the surface and/or in pit (blue); cremation deposit in urn (red); inhumation, oriented W-E and S-N (purple); horse and dog, as special deposit or animal burial (black polyline). Besides Ribe, all these types are only represented in the northern Elbe-Weser region and along the Eastern Frisian coast. Ribe is indicated by a black star. Graphics: Sarah Croix, drawing based on data published in [th century, possibly because they consisted mostly of cremations deposited on the surface of the ground. This applies to the rest of the Jutland peninsula and Funen [th century in the Frisian and Saxon regions. It should also be emphasized that, on many levels, the burial practices documented in Southwest Jutland are very similar to those of the Northern Frisian coast [The abovementioned results should be viewed with caution, owing to current limitations in the available comparative data set. Burial practices in Southwest Jutland are well-documented for the Roman and Early Germanic Iron Age, but from c. 550, burials almost disappear from the archaeological record until the 9an coast : 298–300As previous debates have shown, the interpretation of burial practices as indicators of cultural affinity is far from straightforward. Mortuary rituals have been shown to provide a context for negotiating identities and social relations, as well as for an idealized representation of the dead e.g. , 57. The88Sr, 87Sr, 86Sr and 84Sr), and the ratio of 87Sr/86Sr is used as a geological tracing system for provenance [87Sr/86Sr ratio is dependent on the age of the rock and its composition. Strontium enters the body through food and water, and is absorbed by human tissue (e.g. bone and teeth), where it replaces calcium [Strontium isotope analyses provide a means of examining human geographic mobility and the provenance of archaeological human remains at the individual level , 60–62. ovenance . The 87S calcium , 29. In To investigate the geographical provenance of individuals by applying the strontium isotope system, the baseline or isoscape ranges of the isotopic composition of local bioavailable strontium must be known. Most of Denmark (with the exception of the island of Bornholm) consists of a pre-Quaternary geological basement composed primarily of Tertiary and Cretaceous sediments. These are overlaid by glaciogenic sediments deposited during the Ice Ages. Ribe is located west of the Maximum glacial advance line (~22.000 B.P.), which delineates the maximum expansion of the ice cover in Jutland during the last Ice Age -the Weichsel Ice Age. West of this line, the landscape is characterized by Weichselian outwash plains and Saalian glacial deposits, which form shallow hills rich in coarse sand and clay soil, and between them are meltwater valleys with fine sand. Detrital carbonates (with relatively high strontium concentrations) also occur in sediments of the West Jutland glaciogenic province, in some areas constituting up to ~50% of the clastic components in moraine sediments .Several studies conducted during the last decade aimed to shed light on the question of which type of proxy  is suitable for establishing baselines that may be used as reference maps for provenance studies e.g. , 66. Des87Sr/86Sr ~0.7081 to 0.7111 [e.g. In the last decade, several baseline studies have been conducted in Denmark, which aim to establish the bioavailable strontium isotope range of this region. Although some studies aim to provide a general overview based on surface water  and faun111 e.g. , 70–72. 111 e.g. . These r111 e.g. . TherefoIt is important to state that the strontium isotope system can identify geographic mobility only in cases where the bioavailable strontium possesses distinctive source-area ranges. In the present study, the cultural affinities of Ribe’s community may be understood as reaching beyond Southwest Jutland, to the coastal regions of the Wadden Sea, including the Frisian coast of Northern Germany and the Netherlands. These areas have strontium isotope baselines that partially overlap those of present-day Denmark, making it impossible to distinguish geographic mobility between these regions based solely on the strontium isotope system , 74–77.In order to identify provenance and possible geographic mobility through childhood, we collected multiple samples from each individual e.g. . We cond3 (Seastar) and 30% H2O2 (Seastar). The samples typically decomposed within 15 minutes, after which the solutions were dried on a hotplate at 80°C. Samples were taken up in a few drops of 3 M HNO3 and loaded on disposable extraction columns with a 0.2 ml stem volume. The columns were charged with 200 μl intensively pre-cleaned mesh 50–100 SrSpec™ (TrisKem Int.) resin. The elution recipe essentially followed that used by Horowitz et al. [Tooth enamel and petrous bone samples (a few mg) were taken with a Dremel tool (diamond burrs) after surface pre-cleaning with a diamond sanding bit to remove potential contamination or/and dentine. The samples were dissolved in a 1:1 mixture of 30% HNOz et al. , scaled 2O5–H3PO4–HF activator solution, and directly loaded onto previously outgassed 99.98% single rhenium filaments. Samples were measured at 1,200–1,300°C in dynamic multi-collection mode on a VG Sector 54 IT mass spectrometer equipped with eight faraday detectors . Five-nanogram loads of the NBS 987 Sr standard gave 87Sr/86Sr = 0.710236±0.000010 . The correction for inter-laboratory bias of the strontium isotope ratios of the samples studied here, for example to 87Sr/86Sr value for NBS 987 of 0.710248 [Samples were dissolved in 2.5 μl of a Ta0.710248 , was not87Sr/86Sr = 0.709404 to 0.715708, and are presented in 87Sr/86Sr = 0.708759. This value falls within the previous baseline range that seems to characterize present-day Denmark. Multiple sampling of individuals was possible in 11 of the 21 cases. The strontium isotope results reveal that most of the individuals yield strontium isotope values that fall in a relatively narrow range, between 87Sr/86Sr = 0.7094 to 0.711. Only two individuals yielded values > 87Sr/86Sr = 0.711. This suggests that most of these individuals were of “local” origin. However, as mentioned above, there are other areas outside present-day Denmark with similar or partially overlapping strontium isotope baseline ranges. For example, at present it seems impossible to distinguish between individuals from Southwest Jutland and from the Frisian coast. Based on the strontium isotope values from our dataset, only the two individuals, with values above 87Sr/86Sr = 0.711, suggest non-local origins. The two non-local individuals are KF 998 (SJM 129 G1/A14 x1) and KF 1004 (ASR 8 G10/A129 x196), with values that range from 87Sr/86Sr ~0.713 (KF 998) to 87Sr/86Sr ~0.716 (KF 1004).The strontium isotope analyses for the 21 individuals investigated here yielded a range from th to 14th centuries). They reported two individuals  with strontium isotope differences of >0.0010. The authors wrote that “Significantly, for both of these individuals, the later-developing tooth (one M2 and one M3) has a local ratio while their early-developing tooth has a non-local ratio, suggesting these individuals came to the American Bottom during later childhood or adolescence. Differences of this magnitude are less easily attributed to local post-weaning dietary changes alone and, we suggest, reflect movement between areas with distinctly different 87Sr/86Sr signatures during the period of tooth formation” [87Sr/86Sr ~0.713 in the first molar to 87Sr/86Sr ~0.715 in the second and third molars. Whereas there can be different explanations to why we observe this large difference, we suggest that this individual may have moved during childhood, from an area with strontium isotope values of 87Sr/86Sr ~0.713 to an area with more radiogenic values. Alternatively, the area in which this individual lived may have been characterized by a broad baseline range that included both values. If one assumes that relocation took place, it seems to have happened early in childhood, as we can see from the difference between M1 and M2. M1 normally starts to mineralize in utero, and finishes doing so at c. 3 years of age, whereas M2 mineralizes later (from c. 2 to c. 8 years of age) [The multiple sampling strategy seems in this case to provide additional information on the two non-local individuals. Earlier studies have suggested that significant differences in the strontium isotope ratios (in the order of around the fourth and third digit) between paired teeth of the same individual might indicate movement . In theirmation” . In our  of age) ; hence, Of the 19 individuals with local signatures, 9 were also analyzed using the multiple sampling strategy. Although in some cases the strontium isotope ratios of individuals in the “local” group differ relative to one another, most of the 9 individuals for which multiple sampling was possible seems to have relatively similar strontium isotope values during early life. This may be interpreted in several ways. One possible scenario is that these individuals did not change their area of residence during childhood, as the values are consistent throughout the period of growth. Alternatively, if they did move, they did so between areas with similar strontium isotope baseline ranges, and therefore the strontium isotope composition in their tissues did not change significantly.th century onwards, Ribe’s trade networks included Nordic areas such as Norway and the Baltic Sea, and more distant regions, such as the Mediterranean and the Middle East [Ribe’s emporium is located at the crossroads of the North Sea and the Scandinavian spheres, and plays a key role in the study of early medieval urbanism. From the 8dle East , 35, witdle East , 37. Thedle East , 83–88.From the methodological point of view, the correlation among the four individuals  for which we conducted strontium isotope analyses of both M1 and pars petrosa indicates that there is a strong correspondence between these two types of tissue. Other recent studies also reinforce the validity of petrous bone as an alternative sample tissue to of M1 , 90.th-early 9th century, it was performed mostly in the Frankish areas to the south, and increasingly in Frisia and Saxony [One of the two individuals who we interpret as being of non-local origin, KF 998 (SJM 129 G1/A14), is an inhumation, oriented W–E with the head to the W, the body in a supine position, with no objects deposited along their side . The burd Saxony .The other non-local individual, KF 1004 (ASR 8 G10/A129) is also an inhumation; however, it differs in that the deceased was oriented S–N with the head to the S . The bodConsidering the currently available baseline knowledge of northern and central Europe, combined with the archaeological context, it seems that the non-local KF998 individual may have originated in the Rhine area of central and southern Germany e.g. , 84, 88,Regardless of the difficulty of pinpointing possible areas of origin of these individuals, some similarities emerge. Both individuals were sub-adults, inhumed during phase I of the cemetery, and both show similar radiogenic values in their second molars, which may indicate that they spent parts of their childhoods in similar geographical areas. However, there are also significant differences in the way they were treated after death, suggesting that even if they lived in similar regions at some points in their childhoods, the people who buried them had rather different ideas about how this should be done.th/early 9th-century graves and presumed 10th-century graves. However, in several cases, the burial treatments have close archaeological parallels outside the region of Ribe. The grave of individual KF 994, whose cremated remains were placed in an urn together with horse-harness fittings, in the first half of the 8th century, may be compared to finds in the local area  [th century, inside a pitcher imported from the region of Mayen near Koblenz [th–early 9th centuries, but which is better documented in the Elbe region during this period [In the following section we discuss some interesting features of the group of individuals  whose strontium isotope ratios fall within the local baseline range of present-day Denmark. Our data set does not suggest any obvious differences with respect to the various phases of the cemetery, that is, between 8. Darum) . The sam Koblenz . At thisAlthough possible geographic mobility cannot be excluded, because the strontium isotope baseline ranges of the abovementioned areas partially overlap e.g. , in thesThe relatively small variation among the strontium isotope values between most of the local individuals, also in the cases that multiple sampling was possible, does not indicate a community visibly characterized by geographic mobility between childhood and adulthood. A single adult individual, KF985, possibly a female, shows some differences between the strontium isotope composition of her M1, M2 and M3, which may indicate that during childhood, she moved among areas that have strontium isotope baseline ranges that fall within the local baseline range for present-day Denmark. The manner of her burial, a simple inhumation grave without a coffin or deposited objects, oriented SW–NE, dated to phase II of the cemetery, is not diagnostic of any regional cultural affinity in Northwest Europe in this period. Although one of the non-local individuals was also tentatively identified as female, based on the artefacts deposited alongside them in the grave, the data set is too small, and the sex estimation too uncertain to interpret female individuals as particularly geographically mobile. However, the cases of sub-adult geographic mobility identified here are thought-provoking, as they suggest that the (adult) agents who are commonly assumed to have traveled along the routes of the exchange networks were at times accompanied by young individuals.87Sr/86Sr = 0.70892, 0.709102, and 0.709013, which were interpreted as local [Ribe’s results are difficult to contextualize in the light of the current state of research, as to this date there is only a limited number of published studies of urban mobility in an early Viking-Age context based on the results of strontium isotope analyses. The emporium Ribe is typically compared to sites such as Birka, Hedeby, Kaupang, and Reric / Gross Strömkendorf, where large cemeteries contemporary with the trading sites have been excavated. In Birka, 42 human samples have been analyzed so far applying the strontium isotope methodology, revealing both local and non-local individuals . Howeveras local . SigtunaAlthough mortuary practices are often interpreted to be indicators of the  affinities of the person buried—based on burial practices, grave goods, and their association to specific regions—the geographic origin of individuals may be investigated through geobiochemical analyses, such as strontium isotope analyses. Today, a combination of both approaches is widely used in archaeological investigations.Netherlands to Denmark) and the northern part of the river Elbe region (Germany). These areas have strontium isotope baselines that partially overlap those of Jutland (Denmark), thus limiting the possibility of identifying geographic mobility of individuals who traveled between them, when using this approach. Hence, based on the combination of the contextual archaeology and strontium isotope results, we cannot exclude the possibility that some of Ribe’s “local” individuals originated from other regions with strontium isotope baselines that overlap that of present-day Denmark. Only two of 21 individuals had strontium isotope values that did not fall within the local baseline range, and therefore are regarded as originating from an area other than, and possibly distant from, Ribe. Both these individuals were sub-adults, and were inhumed in the oldest phase of the cemetery while the emporium was flourishing in the 8th and 9th centuries.In the context of maritime trade networks in early medieval Northwestern Europe, the flow of materials and things suggests the existence of connecting communities from various regions. Although human geographic mobility is considered to be a prerequisite for these exchanges, the social dynamics characterizing the emporia through which these networks were articulated, and the extent to which they hosted mobile and/or more permanently settled communities still needs further scrutiny. The results of our analysis of the burial remains from Ribe’s earliest cemetery reveal that most of the sampled individuals have strontium isotope values that fall within the previously characterized baseline range of present-day Denmark, including Southwest Jutland, where Ribe is located. On the other hand, the diversity of burial practices reflects cultural affinities that may be connected to communities outside present-day Denmark, for example, with the Frisian coast (stretching all the way from the Viewed in light of our current knowledge of Viking-Age Ribe, our results seem somewhat surprising. Although the material culture unearthed in the dwellings and workshops of the emporium suggests the presence of, or at least contact with, individuals belonging to communities from local, regional, and distant areas, our study has not revealed geographic mobility from distant regions on a large scale. The apparent scarcity of “long-distance” travelers, originating from regions outside present-day Denmark and the lower North Sea region, may be because the number of individuals analyzed here represents only a fraction of Ribe’s Viking-Age community. Our results do not exclude the possibility that more non-locals settled and died in Ribe. Similarly, our approach does not provide final conclusions on the geographic mobility of the adult actors in trade. “Local” individuals may have travelled extensively during adulthood, both in areas with similar strontium isotope baseline ranges as present-day Denmark, and in other areas, without it appearing in our data. Our current results suggest that, if Ribe’s emporium did attract a permanent relocation of individuals who were not born there, it may have done so for individuals originating in communities in the Wadden Sea and Elbe regions, which show a high degree of cultural integration with Southwest Jutland. Further research may contribute to enlightening us about the role of regional actors, beyond the local area, in Ribe’s social networks, and thus, in the early stages of the urbanization of Scandinavia.


Kawasaki disease (KD) is a form of systemic vasculitis that occurs in children under the age of 5 years old. Due to prolonged fever and elevated inflammatory markers that are found in both KD and sepsis, the treatment approach differs for each. We enrolled a total of 420 children (227 KD and 193 sepsis) in this study. Logistic regression and a nomogram model were used to analyze the laboratory markers. We randomly selected 247 children as the training modeling group and 173 as the validation group. After completing a logistic regression analysis, white blood cell (WBC), anemia, procalcitonin (PCT), C-reactive protein (CRP), albumin, and alanine transaminase (ALT) demonstrated a significant difference in differentiating KD from sepsis. The patients were scored according to the nomogram, and patients with scores greater than 175 were placed in the high-risk KD group. The area under the curve of the receiver operating characteristic curve (ROC curve) of the modeling group was 0.873, sensitivity was 0.893, and specificity was 0.746, and the ROC curve in the validation group was 0.831, sensitivity was 0.709, and specificity was 0.795. A novel nomogram prediction model may help clinicians differentiate KD from sepsis with high accuracy. Early and timely diagnosis, as well as effective treatment, can help reduce coronary artery lesions (CAL) and improve intravenous immunoglobulin (IVIG) treatment response4. However, both the etiology and pathogenesis of KD remain unclear. Incomplete KD and Kawasaki disease shock syndrome (KDSS) are at a high risk of delayed diagnosis and heart complications. In clinical practice, incomplete KD and KDSS are often misdiagnosed as sepsis or septic shock initially, thus increasing the difficulty in making a KD diagnosis, as well as CAL complications6.Kawasaki disease (KD), also known as cutaneous mucosal lymph node syndrome, is an acute, self-limiting vasculitis that is common in children under the age of 5 years old, with coronary aneurysms occurring in about 25% of untreated cases. KD has also become the main cause of acquired heart disease in children7. The main manifestations and laboratory findings of sepsis include fever, elevated white blood cell count (WBC), C-reactive protein (CRP), and procalcitonin (PCT), which are also the manifestations found in KD8. Although the early clinical manifestations and laboratory results of sepsis are similar to KD, their clinical treatments differ substantially. Patients with sepsis need timely and appropriate antimicrobial treatment to control and remove the source of infection9. In contrast, antibiotics are unnecessary and ineffective for KD patients, while IVIG infusion with follow-up cardiac ultrasonography are the main treatment methods for KD2.The differential diagnosis of KD and sepsis in the early stage of onset is challenging. Sepsis is a systemic inflammatory response syndrome caused by infection, which is also an important cause of septic shock and multiple organ dysfunction syndromes (MODS)Both KD and sepsis are characterized by fever and elevated inflammatory markers in the acute stage, but the treatments are very different. However, from information evident in previous literature reviews, no relevant or single indicator can differentiate KD from sepsis. Therefore, we conducted a retrospective analysis of patients' medical records to set up a single or multiple index equation for clinicians in early KD evaluation to prevent cardiac injury.We enrolled a total of 420 children (mean age: 24.4 ± 18.4 months) in this study, including 254 males (60.5%), 166 females (39.5%), 227 KD patients (54.0%), and 193 sepsis patients (46.0%). According to univariate analysis, we observed no statistically significant differences regarding gender, age, and body weight, as shown in Table Of those patients, 247 (60%) cases were in the modeling group, including 133 cases of KD (53.8%) and 114 cases of sepsis, and 173 (40%) cases were in the validation group, including 94 cases of KD (54.3%) and 79 cases of sepsis. We conducted multivariate logistic regression analysis for the modeling group. Logistic regression analysis was carried out using the statistically significant factors in the univariate analysis as independent variables.The p-value of the Hosmer and Lemeshow test in this model was 0.32. After the multiple logistic regression analysis of the cut-off values, we found WBC, hemoglobin, PCT, CRP, ALB, and ALT to be the independent risk factors of KD  analysis, the nomogram demonstrated good discrimination ability, with an area under the ROC curve of 0.873  in the modeling group and 0.831  in the validation group. The sensitivity and specificity were 0.893 and 0.746, respectively, in the modeling group and 0.709 and 0.795, respectively, in the validation group. Calibration curves of the nomogram for the two groups are shown in Figs. We evaluated performance of the nomogram using discrimination and calibrationKD is currently diagnosed primarily according to clinical manifestations, but no specific laboratory method is available for diagnosis. Furthermore, the diagnosis of incomplete KD is also difficult and increases delayed diagnosis. Although the clinical manifestations and laboratory findings of KD and sepsis differ, some overlap has still been noted. In particular, incomplete KD and KDSS make differentiating the diagnosis from sepsis difficult in clinical practice. The purpose of this study is to compare laboratory findings in KD and sepsis to provide specific characteristics that can help clinicians detect KD earlier.11, indicating that the decrease of albumin may be related to the increase of vascular permeability. Said increase in vascular permeability may be caused by the increased movement of albumin from the blood vessels to the interspaces mediated by hormones, innervations, or cytokines 12. Kuo et al. reported that the lower the albumin level, the higher the rate of CAL formation in KD13.In this study, compared to the sepsis group, the KD group showed a significant decrease in albumin. Children with KD are often associated with hypoalbuminemia, a pathogenesis that has many explanations. Previous research has reported that the albumin level of KD was significantly lower than that of the febrile control group14. In one retrospective study, hemoglobin level was found to be the most important indicator for distinguishing KD from the febrile control group15. Furthermore, Lin et al. found that hemoglobin is a useful clinical indicator to distinguish KDSS from toxic shock syndrome (TSS)4. Recently, Kuo et al. reported that inflammation-induced down-regulation of hepcidin is associated with anemia in KDSS patients16. In our study, the hemoglobin level of the KD patients was significantly lower than that of the sepsis patients. From previous literature reviews, no sepsis-related anemia has yet been reported. Moreover, anemia is a good indicator for distinguishing KD from sepsis and other infectious diseases.Anemia is one of the most common clinical features of KD and is considered to be a marker of the acute phase and disease outcome19. Elevated ALT is also one of the biochemical indicators for predicting IVIG resistance in KD and assisting in incomplete KD diagnosis20. In our study, the ALT in KD children was significantly higher than that in the sepsis patients and was found to be the most important laboratory indicator (with the highest score of 100) in this novel nomogram model.Previous studies have reported that elevated alanine aminotransferase (ALT) is an important laboratory finding for KD, as well as that abnormal liver function including ALT accounts for 37% of total KD children. The elevation of ALT in most children was only slightly elevated, less than twice that of the normal threshold21, and it has been reported that a high CRP level is one of the important laboratory indicators for predicting IVIG resistance in KD22. However, CRP, PCT, and other inflammatory indicators are also significantly increased in sepsis patients and have been proposed as potential markers for diagnosing neonatal sepsis23. Studies have shown that PCT is significantly higher in KD children than in viral infections and other autoimmune diseases24. In our study, the levels of WBC, CRP, and PCT in KD patients were increased but lower than the levels of sepsis patients, indicating that the immune-pathogenesis of KD lies somewhere between sepsis and viral infection. Antibiotics are vital for treating sepsis but may not be as important in the treatment of KD.Several studies have shown that WBC, CRP, and PCT increased in KD childrenAccording to the literature review, this report is the first to identify KD and sepsis by using ordinary laboratory indicators. Based on clinical laboratory results, we constructed a novel nomogram model with five laboratory markers  for predicting KD and sepsis, which will help clinicians treat KD and sepsis patients more precisely. Furthermore, the timely recognition and treatment of KD can reduce coronary artery damage or progression to KDSS. However, the results of this study still need to be clarified through more cases and from more areas.25 reported that among the total of 1,065 KD patients, 26 cases admitted to the ICU were identified during a 10-year study period. Shock  was the most common reason for KD patients to be admitted to the ICU, and ICU KD patients were more likely to receive antibiotics (but not for every KD patient), albumin infusion, and steroids, as well as to require a second dose of IVIG therapy. Kanegaye et al.26 reported that patients with KDSS may be resistant to immunoglobulin therapy and require additional anti-inflammatory treatment. In this article, antibiotics were not among the treatment suggestion for KDSS. Altogether, if patients presented with fever and hemodynamic failure with two or three signs suggesting KD, both IVIG and antibiotics were administered in case of KD with uncertain infections, or only IVIG when infections were excluded.Kuo et al.This is the first study to use a nomogram to develop a novel prediction model that shows that WBC, anemia, PCT, CRP, albumin, and ALT may help clinicians differentiate KD from sepsis with high accuracy.27. Incomplete or atypical KD (N = 47) diagnosis was made in patients with a history of fever lasting more than 5 days but fewer than four of the five major KD clinical diagnostic criteria, with echocardiography showing evidence of coronary artery changes28. We compared KD ) with sepsis but not septic shock. Our hospital only had a few cases of KDSS (fewer than 10 cases) during the study period of our recent publication29. Sepsis is defined according to the “2016 Surviving Sepsis Campaign”30.A retrospective analysis was conducted on the medical records of patients who were admitted to the maternal and child health hospital of the Baoan District in Shenzhen, China from 2017 to 2019. All the children were younger than 18 years of age. KD diagnoses were made according to the American Heart Association (AHA) criteria and showed at least four of the following five clinical manifestations: bulbous conjunctival congestion, lips or oral cavity changes, hand and foot symptoms, skin manifestations, and cervical lymph node enlargement31.The laboratory data of the patients enrolled in this study, including complete blood count/differential count (CBC/DC), C-reactive protein (CRP), aspartate aminotransferase (AST), alanine transaminase (ALT), albumin, procalcitonin (PCT), sodium, and erythrocyte sedimentation rate (ESR), were all collected prior to IVIG treatment in KD patients and before antibiotics were administered to the sepsis patients during admission. The anemia criteria were defined by age according to the World Health Organization (WHO)32. Furthermore, the validation group was used to verify the scoring results of the nomogram, draw the ROC curve, and calculate the area under the curve. The highest point of the Youden index was used to calculate the sensitivity and specificity of the verification group. The calibration of the models can be assessed using calibration plots, which can predict probabilities against the actual observed risk10. SPSS 13.0 statistical software was used for the analysis, and the nomogram was drawn based on the R software .The data in this study were analyzed with mean ± standard deviation (x ± s) used for measurement data and n and percentage used for enumeration data. We compared the normal distribution data using independent sample t-test or single factor analysis of variance. We adopted rank sum test to compare non-normal distribution data. The Chi-square test was used for counter measurement. A p-value less than 0.05 was considered statistically significant. Multivariate logistic regression was applied to analyze the influencing factors of KD and sepsis. Some continuous data were converted into classified data , according to the cutoff value when the area of the ROC curve is the maximum value. In part, according to the reference range of the normal values, the upper-limit levels as the cutoff point were converted into classified data . We developed the nomogram model using the result of the multivariate logistics regression model to show the odds ratio and β-factor of each predictor. We adopted Hosmer and Lemeshow to test whether the logistic prediction equation was suitable. The performance of the nomogram was evaluated as reported by Harrell et al.This study was conducted in accordance with the Declaration of Helsinki. The Institutional Review Board of Baoan Maternal and Child Health Hospital, Shenzhen, China approved the study (IRB No. LLSCHY2019-07-01-02).This retrospective data analysis was approved by the Institutional Review Board of Baoan Maternal and Child Health Hospital (IRB No. LLSCHY2019-07-01-02). The need of informed consent in this study was waived.


Recent data suggest that robotic platform has become the most accessible minimal invasive surgery even for surgeons without previous training in laparoscopy. Laparoscopic partial nephrectomy (LPN) is a well-stablished procedure, however, with high level of complexity and long learning curve that limit its use.To describe safety, efficiency and learning curve of a single surgeon without previous experience in LPN to reach “TRIFECTA” at robot-assisted partial nephrectomy (RAPN).This is a retrospective study, with prospective data collection of 101 patients submitted to RAPN by a single surgeon. In order to analyze the learning curve, sample was chronologically divided in two phases: first phase: P1: 50 first patients, second phase: P2: 51 subsequent patients. TRIFECTA was defined as: ischemia time lower than 25 minutes, negative surgical margin and absence of severe complications (Clavien >2).2 vs. P2=29kg/m2; p=0.03). Rate of bleeding, surgical time, presence of positive margin and peri-operatory surgical complications were similar in both phases. TRIFECTA was higher in P2 in relation to P1  and median time of hot ischemia was significantly lower at P2 . At multivariate analysis independent factors related to TRIFECTA included: chronological phase  and tumor size .Mean age of patients was 54 years (SD=11.85), median tumor size was 32mm (SD=17) and surgery was performed with zero ischemia time in 33.6% of patients (29.8% at P1 and 40.9% at P2). Demographic data of patients were similar between both groups, except tumor size  and body mass index (BMI)  since the beginning. Experience improvement was related to treatment of larger tumors, higher proportion of patients with zero ischemia and higher rate of TRIFECTA. Gold standard treatment of localized renal carcinoma is surgery, with oncologic and functional benefits very well stablished and validated , 2. NephMinimally invasive techniques have been more used in order to benefit patients with lower time of recovery, less pain and lower rate of complications related to surgical wound .Many surgeons with basic training in laparoscopy are able to perform an ablative surgery such as radical nephrectomy with safety and good results. However, partial nephrectomy is a procedure with high complexity where it is mandatory to remove the tumor and to reconstruct renal parenchyma with hemostasis in a very short time interval. It is necessary the presence of a high trained team . The conTransition from LPN to RAPN has been well studied . HoweverTo describe the safety, efficiency and learning curve of a single surgeon without previous experience in LPN of the first 100 cases treated by robot-assisted partial nephrectomy (RAPN).Primary objective: to evaluate complication rate, time of hot ischemia (THI) and TRIFECTA rate.Secondary objectives: to evaluate tumor size, complexity (nephrometry), surgical time, bleeding and rate of transfusion.This is a retrospective study of data collected prospectively with a single arm of patients submitted to robot-assisted partial nephrectomy from January 2009 to June 2016, in a private hospital in Brazil by a single surgeon (GCL) without previous training in video-laparoscopy. The study was approved by the institutional ethics committee (76547917.5.0000.0071).The data of the present study are presented in a descriptive form. In order to analyze the learning curve patients were divided chronologically in two groups, that were compared in all aspects. Sample was chronologically divided in two phases .The procedure was standardized and performed according to previous study . InitialReconstruction of renal parenchyma was performed with two layers  with continuous suture . Early de-clamping (following medullary suture) was routinely performed after patient # 72.Abdominal computer tomography was reanalyzed by two urologists  and the nodules were classified according to nephrometry R.E.N.A.L. score , and werDuring the pre-operatory period, the following information were obtained: age, sex, body mass index (BMI), race, laterality, comorbidities, ASA (physicil status of the American Society of Anesthesiologists), renal function and tumor size. The tumors were classified as endophytic when more than 50% of its volume was located inside the renal parenchyma.During surgery, the following data were collected: time of use of robot, bleeding (mL), complications, time of hot ischemia (THI), need of clamping, early de-clamping.Following surgery, it was collected data related to serum hemoglobin (Hb), hematocrit (Ht), renal function and complications.Complications were recorded and classified according to Clavien-Dindo system, and the need of conversion to open surgery was classified as an adverse event .Renal function of patients were evaluated by serum creatinine and creatinine clearance, calculated by the Cockroft-Gault formula. Evolution  was evaluated by an analysis in three moments: before surgery, recent post-operatory period (one to three months after surgery) and the last data during follow-up. Reduction of renal function was considered when creatinine clearance was lower than 80% of initial.Surgical success (TRIFECTA) was defined, according to Gill et al., as: ischemia time lower than 25 minutes, negative surgical margin and absence of severe complications (Clavien>2) . If the All statistical analysis were performed using the SPSS software for Windows version 20.0 . Significance level was <0.05.Numeric variables were expressed as median and standard deviation. Non-parametric numeric variables were submitted to Mann-Whitney U test. In order to evaluate renal function in the three moments (related samples) it was used the Friedman paired test. For categorical variables, it was used the Chi-square test or exact of Fisher, depending on the quantity of positive at outcome . Multivariate analysis with binary logistic regression was performed to evaluate the factors related to TRIFECTA.2 vs. P2:29 kg/m2; p=0.003) (Median age of patients was 54 years (SD=11.85); median tumor size was 32mm (SD=17). Demographic characteristics of patients were similar between both phases except for the tumor size  and body mass index (BMI) (P 1:26.6 kg/mp=0.003) .Tumor complexity was similar between groups. However, in a sensitive analysis according to complexity level, it was observed that at P1 there was a higher proportion of patients with low complexity  and a lower proportion of high complexity ; 79.1% at P1 were endophytic  and 93.2% at P2 (p=0.056) .In a paired analysis of both phases it was not observed any difference of creatinine clearance before and after surgery  and the proportion of surgery with zero ischemia was proportionally lower at P1 .Bleeding, surgical time, presence of positive margin and peri-operatory complications were similar in both phases .Clavien 1 and 2 complications occurred in 16% of Phase 1 patients and in 7.8% of Phase 2 patients (p=0.506). Only one patient presented a severe complication at P1 (Clavien 3 or 4). This patient presented hematoma at the renal site that was treated with percutaneous drainage. One patient at P1 needed conversion to open surgery due to difficulty to expose the nodule (it was located at the posterior region of the upper pole of right kidney). Two patients showed positive margins . These patients are been followed, and showed no recurrence for 20 months. At P2 it was not observed any patient with severe complication or positive margin .Treatment success (TRIFECTA) was significantly higher at P2 in relation to P1  .In the multivariate analysis, the independent factors related to TRIFECTA included: phase and tumor size . Other aThis study shows the experience and evolution of a surgeon without previous experience in video-laparoscopy surgery, during the 100 first cases of RAPN. Since the beginning, the results were satisfactory, with significant improvement of TRIFECTA rate at the second phase (after 50 cases), especially due to the reduction of ischemia time. With experience gain, larger tumors were operated and the no-clamping technique was more used.The steep learning curve, of the transition from open partial nephrectomy to laparoscopy has become one of the most limiting factor for the use of minimally invasive techniques for this procedure, used only in a few centers with a big number of surgeries and specialized team. Robotic platform is proving to be an important tool to change paradigms, mainly in urologic surgery and has made minimally invasive surgery more available, even for surgeons without previous experience in video-laparoscopy , 10. ThiWith the advances of minimally invasive surgery, it is possible to reduce the hospitalization time and costs, not only of the surgery itself but the social costs, as described by the series of Chang et al. they demonstrated a medium withdrawal time of 35 days from work, from 7 to 92 days, with a medium salary loss of US$ 10.152 in the United States .In the last years, a great number of institutions acquired the robotic platform, even in developing countries. Radical prostatectomy is the main surgery in most programs, and high volume surgeons, used to conventional surgery, are using it more frequently. The transition from radical prostatectomy to robot-assisted was widely studied and the data showed that it is not necessary previous experience with laparoscopic radical prostatectomy .Ghani et al. reported an expressive increase of the use of robotic platform instead of laparoscopic surgery in partial nephrectomy in the US. It was also suggested that it is possible to move from open surgery to robot-assisted without learning video-laparoscopy  and the The promising results of our study since the first patients may be explained by the adoption of a structured program with PROCTOR to follow the procedures until consolidation of learning of surgeons, allowing for a safe and efficient transition from conventional technique to robot-assisted.Many surgeons, especially those from developing countries, have limited training in laparoscopy and use open conventional surgery routinely, particularly in more complex cases. With the dissemination of the robotic platform and wider availability, more and more surgeons without previous training in laparoscopy are been trained to use the robotic platform .The rate of conversion to open surgery, complications and positive margins are closely related to the experience of the surgeon. Similar to our study, Khalifeh et al. also reported conversion from open surgery at first phase, with absence of any type of complications, positive margins and ischemia time longer than 25 minutes, for partial nephrectomy . SimilarHot ischemia time has already been widely studied and it was stablished that the lower the time the better the functional preservation . HoweverIn our series, at P2 there was an important change of ischemia results, that certainly was reflected in the TRIFECTA results. This occurred mainly due to change of approach and more frequent use of no-clamping technique and early de-clamping, that certainly was the main factor related to the increase of TRIFECTA at Phase 2. Different from others authors, we observed a significant reduction of the ischemia time due to a wider use of the no-clamping technique and not due to lower time of suture : more imAt P2 we observed a higher rate of bleeding and this may also be justified by the increased use of the no-clamping technique. However, this difference had no clinical significance and did not alter the rate of transfusion.Rate of complications at literature varied from 8% to 22% , 21 and In relation to oncological results, we observed positive margins in two patients, exclusively at P1. According to good practices of oncologic surgery, it is essential to assure negative margins. Otherwise, at literature it was not possible to demonstrate an increased risk of local recurrence or progression to metastatic disease in patients submitted to partial nephrectomy with positive margins . Recent Differently of other series, such as Carneiro et al., that demonstrated a significant increase of renal complexity and size of tumor, as well as endophytic cases in later groups , in our At Gill et al. series, evaluation of progression of renal function in three different moments in the same patient showed in the last patients submitted to laparoscopic partial nephrectomies a lowering of medium glomerular filtration rate (GFR) of 11% . In our Similar to the study of Khalifeh et al., TRIFECTA rate above 60% was reached in special after the first 50 patients, similar to other studies, that reported a short and safe learning curve , 26. We At multivariate analysis, the independent factors of TRIFECTA included the experience of the surgeon and the size of the tumor. Therefore, we suggest that in the beginning of the learning curve tumors with lower volume and lower nephrometry must be selected, although in the last aspect in our series that fact was not observed.It is important to highlight that this study has some limitations. This is a small series with a short follow-up period compared to some already published in big centers of developed countries.This study demonstrated that the transition from open nephrectomy to robot-assisted without learning laparoscopic nephrectomy is safe, with satisfactory functional and oncologic results since the beginning (TRIFECTA). Increased experience lead to a higher proportion of patients operated with zero ischemia and TRIFECTA.


Self-organization of locomotion characterizes the feature of automatically spontaneous gait generation without preprogrammed limb movement coordination. To study this feature in quadruped locomotion, we propose here a new open-source, small-sized reconfigurable quadruped robot, called Lilibot, with multiple sensory feedback and its physical simulation. Lilibot was designed as a friendly quadrupedal platform with unique characteristics, including light weight, easy handling, modular components, and multiple real-time sensory feedback. Its modular components can be flexibly reconfigured to obtain features, such as different leg orientations for testing the effectiveness and generalization of self-organized locomotion control. Its multiple sensory feedback  can support vestibular reflexes and compliant control mechanisms for body posture stabilization and compliant behavior, respectively. To evaluate the performance of Lilibot, we implemented our developed adaptive neural controller on it. The experimental results demonstrated that Lilibot can autonomously and rapidly exhibit adaptive and versatile behaviors, including spontaneous self-organized locomotion  under different leg orientations, body posture stabilization on a tiltable plane, and leg compliance for unexpected external load compensation. To this end, we successfully developed an open-source, friendly, small-sized, and lightweight quadruped robot with reconfigurable legs and multiple sensory feedback that can serve as a generic quadrupedal platform for research and education in the fields of locomotion, vestibular reflex-based, and compliant control. The motor behaviors of animals are characterized by numerous features , such as the MIT Cheetah  self-organized locomotion under flexibly reconfigurable leg orientations; (2) vestibular reflexes for stabilizing the body posture on a tiltable plane; and (3) compliant behaviors regarding an external load. Details on Lilibot and its adaptive neural control are provided in section 2. The performance examination of Lilibot is presented in section 3. Finally, section 4 provides a discussion of the experimental results and conclusion.In this section, we briefly introduce the main approaches and processes of Lilibot design, of which the basic restrictions are the small size, in detail, light weight, robust, and compactness but rich sensory feedback. To meet these requirements, selection and sizing of high-end small servo motors with comparative torque density were firstly considered. Secondly, according to the motor dimensions  to study quadrupedal locomotion, various leg orientations (joint/leg configurations) have appeared in certain impressive robots . τi is the current feedback of the servo motor at the knee joint, while ki and bi are the slope and intercept of the linear function gi, respectively. flimit is the threshold of the indirect GRF, and v is the joint velocity. A measured GRF (obtained from the custom-designed force plate platform for legged robots) is used as a baseline for tuning the model parameters. One can observe a positive correlation between the keen joint current signal and the GRF signal. The signals show high activation (>0.0) when the leg is in a stance phase and low activation (around 0.0) when it is in a swing phase. An experiment for tuning the parameters of the model can be seen in where Although Lilibot exhibited a small size and compact space, the onboard PC (NUC7 from Intel Inc.) can simultaneously acquire 61 sensory feedback signals see  at a freTo test the performance of Lilibot as a friendly quadrupedal platform, particularly for studying adaptive and versatile behaviors, including vestibular reflexes and leg compliance, it is necessary to implement control. For this purpose, by exploring bio-inspired approaches with sensorimotor loop   in the adaptive neural controller were conducted separately first for clearly demonstrating the functionality of the different features of Lilibot. Subsequently, a combination of the vestibular reflex and compliant controls was executed to evaluate their integrated functions. Therefore, the experiments consisted of: (1) self-organized locomotion under different leg orientations, driven by the decoupled CPGs control, (2) leg compliance to compensate for an unexpected external load, driven by the compliant control, (3) body stabilization on a tiltable plane, driven by the vestibular reflex control, and (4) body stabilization and payload compensation on a tiltable plane, driven by the combination of the vestibular reflex and compliant controls.http://www.manoonpong.com/Lilibot/video1.mp4).Four experiments were performed to test whether Lilibot could exhibit self-organized locomotion driven by the decoupled CPGs control under the four leg orientation types  and mg is the weight of the robot. The energy is estimated from: E = IVt, where I and V are the electric current and voltage, respectively. They can be acquired from the joint current and voltage sensors. t is the time the robot uses when it walks a distance d. The average specific resistances of Lilibot under the four leg configurations  are ~3.57±0.12, 3.32±0.43, 5.16±0.32, and 3.82±0.30, respectively. A low ϵ corresponds to high energy-efficient walking. Thus, the results indicate that the all-elbow and all-knee configurations have relative high energy efficiency and the outward-pointing configuration exhibits the lowest energy efficiency. The details of the experiment can be seen in where http://www.manoonpong.com/Lilibot/video2.mp4).Compliance is an important function that allows a robot to effectively deal with unexpected load or large perturbation. In this experiment, we demonstrated that Lilibot could deal with an unexpected load  based on the presented compliant control . To cleahttp://www.manoonpong.com/Lilibot/video3.mp4).To test the effectiveness of the IMU sensor of Lilibot for body stabilization, an experiment was conducted using the presented vestibular reflexes on Lilibot because the vestibular reflex control can stabilize the robot according to the inclination feedback measured by the IMU. Firstly, Lilibot, with vestibular reflexes, was placed on a tiltable plane see . The expA combination among the self-organized locomotion, vestibular reflexes and leg compliance plays a crucial role for adaptive locomotion on natural terrains  vestibular reflexes with leg compliance and (2) vestibular reflexes without leg compliance. In both experiments, Lilibot was placed on a tiltable plane under a roof . The roof acts as a payload (>1.0 kg) if the supported tiltable plane is inclined upward  where Lilibot hits the roof. Note that a case with only leg compliance was not used because Lilibot without vestibular reflexes cannot keep balance on the plane if it is tilted or inclined. The experimental results are shown in http://www.manoonpong.com/Lilibot/video4.mp4).It can be seen that the behaviors of the robot under the two controls were different when it negotiated the payload while standing on the slope. Without leg compliance, Lilibot rigidly resisted the payload; thereby, the knee joints of its front legs drew a substantial amount of current . In thisIn this work, we developed a small size, light weight quadruped robot (Lilibot) with flexible configurations and multiple sensory feedback. Lilibot can act as a friendly open-source platform for research and education in the field of locomotion. The features of small size and light weight provide Lilibot with several apparent advantages, such as an easily modular design, and simple yet practical structure. It can be handled with ease to conduct joint control and locomotion generation owing to its appropriate (1) actuator torque , (2) size , and (3) weight (2.5 kg) for operation. Moreover, it has a considerable endurance capability, which allows it to handle a payload of ~1.25 kg (50% of its weight) with walking, for up to 30 min. This enables Lilibot to carry extra exteroceptive sensors . In addition to the real robot, the compatible Lilibot simulation see  allows tThe experimental results show that Lilibot, with its controller, can exhibit three basic functions, including autonomous gait generation under different reconfigurable leg orientations , compliaFirstly, self-organization of locomotion, in this study, is considered as an ability of a legged system  that can form a gait in a self-organized manner, in which its inherent physical properties play a crucial role for interlimb coordination via sensory feedback .In the experiments of the self-organized locomotion shown in , we usedConsequently, the self-organization of Lilibot in different leg orientations demonstrates the effectiveness of the robot structure design, the GRF model (see Equations 1–4), and the proprioceptive feedback of joints. It also confirms that Lilibot can easily be used to study the functionality of the limb morphology. However, the flexibly reconfigurable legs are currently organized by a rigid trunk, which cannot be used to study the functionality of the spine dynamics for self-organized locomotion generation. Thus, in the future, we plan to integrate actuated joints in the trunk to connect the front and rear legs, which will imitate a compliant spine with active stiffness.Secondly, the vestibular reflexes, which are the fundamental biological principle of legged locomotion, have been demonstrated in many quadruped robots for adapting body posture to maintain balance when facing, e.g., an inclination (slope)  and uneven terrain locomotion . This advantage was demonstrated by using decoupled CPGs to control Lilibot under its four leg orientation types in the experiments. Moreover, inspired by a hexapod robot (Mathias et al., All datasets generated for this study are included in the article/TS developed the entire robotic system, performed the experiments, analyzed the data, and drafted the manuscript. XX led the development of compliant control and reviewed the manuscript. ZD provided the general direction of the project and reviewed the manuscript. PM led the development of adaptive neural control, helped with data analysis, drafted the manuscript, and supervised the whole project. All authors contributed to the conception and design of the work, approved the final version of the manuscript, and agree to be accountable for all aspects of the work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Menopause is associated with the increased risk of metabolic syndrome (MetS) and cardiovascular (CV) disease. Most studies have focused the postmenopausal women and the relationships among estrogen, androgen, and Mets risk. The main aim of the study was to investigate the Mets risk in perimenopausal women and whether the variation of FSH is associated with metabolic factors.  A single-center cross-sectional retrospective analysis including 154 premenopausal women and 124 perimenopausal women was performed. p = 0.023). The prevalence of central obesity and NAFLD also increased in the perimenopausal group than in the premenopausal group. We grouped the population by FSH tertiles; compared with women in the lowest tertile, women in the highest tertile had higher age, WC, serum TC, LDL-C, AST, ALT, and creatine levels. The prevalence of hypertriglyceridemia, raised BP and Mets also increased in the highest tertile group. Further, we subdivided the perimenopausal women according to FSH tertiles. Compared with perimenopausal women in the lowest tertile, the prevalence of raised BP significantly increased in the highest tertile.  The prevalence of Mets in the perimenopausal group was much higher than the premenopausal group (49.19% vs. 35.71%,  The risk of Mets increased in perimenopausal females than in premenopausal women. And a higher FSH level was associated with higher WC, TG, BPs, and the risk of Mets in perimenopausal women. Elevated FSH level appears to be a risk factor of MetS biomarkers in perimenopausal women. Menopause, characterized by decreased serum estrogen level and increased follicle-stimulating hormone (FSH) level, is a normal part of a woman's life cycle, which has been associated with increased risk of metabolic syndrome (MetS), atherosclerosis, and cardiovascular (CV) disease , 2. It wNumerous studies have focused on the relationship between estrogen and metabolic factors, such as lipid, glucose, and obesity –9. BesidPerimenopause is the transition period from the reproductive to the nonreproductive stage of life, with important changes in their hormone, including FSH and estrogen . Women mIn this study, we performed a retrospective study to examine the risk of Mets and the association between FSH and components of MetS among Chinese perimenopausal women. To the best of our knowledge, the current analyses are a part of the few studies focusing on the relationship between FSH and metabolic factors in perimenopausal women.The cross-sectional study included females aged ≥40 years who participated in an epidemiological investigation performed in Ningyang County in the Shandong Province of China in 2014. All the participants had lived in their current residence for at least 5 years. All participants were instructed to complete a self-reported questionnaire, including detailed questions regarding the menopausal status, provided an overnight fasting blood sample, and underwent a medical examination. Written informed consent was obtained from each participant prior to data collection. This study was approved by the ethics committee of Shandong Provincial Hospital and the procedures were conducted in accordance with the Declaration of Helsinki.The inclusion criterium was females aged ≥40 years with natural menstrual states. The exclusion criteria were as follows: (1) undergone hormone replacement therapy during the three months prior to the examination; (2) presence of complications or conditions that affect the menopausal status or lipid metabolism, such as ureterectomy, bilateral ovariectomy, premature ovarian failure, history of irregular menstruation during premenopause, pregnancy, lactation, psychiatric illness, acute cardiovascular or cerebrovascular disease, chronic respiratory disease, malignant tumors, or renal dysfunctions; (3) use of medications that affect the natural state of menopause or lipid metabolism, including estrogen, progesterone, androgen, glucocorticoids, statins, fibrates, thyroid hormones, antithyroid drugs or thiazide diuretics, over the preceding three months; (4) subjects with incomplete data.As a result, 154 premenopausal and 124 perimenopausal female subjects were eligible for inclusion in our study.The metabolic syndrome was defined according to the Adult Treatment Panel (ATP) III guidelines by the presence of three or more of the five following criteria , 18: (1)The determination of the menopausal status was based on the responses to questions regarding menstrual irregularity and amenorrhea in the self-reported questionnaire. Perimenopause was defined as the presence of menses within the past 3 months with a decrease in cycle predictability in the year preceding examination or 3–11 months of amenorrhea.For the premenopausal participants, venipuncture was scheduled on days 2–5 of a spontaneous menstrual cycle to evaluate sex hormone levels. For the perimenopausal participants, fasting serum samples were randomly obtained . Blood sTrained investigators obtained information on age, sex, and other essential data from the standardized questionnaire . Height t-test or the Mann–Whitney U-test . Differences among multiple groups were compared using one-way analysis of variance (followed by a multiple comparison test for subgroups using Least Significant Difference or Dunnett's T3 tests). All statistical tests were two-tailed, and statistical significance was defined as p < 0.05.All statistical analyses were performed using SPSS software . The continuous variables data are presented as mean ± standard deviation, mean ± standard error, or median . Differences between the two groups were compared using the Student's p < 0.001), and the serum FSH and LH levels were elevated significantly while the serum estrogen levels were similar between the two groups. At the same time, the serum progesterone levels were decreased in perimenopausal females.The study population was divided into two groups according to the menstrual status: the perimenopausal group and the premenopausal group. The characteristics of the study population are shown in p = 0.006). The serum TC, LDL-C, TG levels, and the liver enzyme (ALT and AST) and serum UA levels were much higher in perimenopausal females than in premenopause subjects. In addition, the blood pressure (SBP and DBP) levels, HDL-C levels, creatine levels, and thyroid function  had no significant difference between the two groups.The body weight and BMI had no difference between the two groups, while the waist circumference was much higher in the perimenopausal group than the premenopausal group .As shown in p = 0.012).Further, we also observed the difference of different metabolic components between the two groups. Only the prevalence of central obesity increased in the perimenopausal group, while the prevalence of hypertriglyceridemia, raised FPG, hypertension, and low HDL had no difference between the two groups. Nonalcoholic fatty liver disease (NAFLD) often cooccurred with one or more MetS-associated phenotypes and they shared common pathogenic mechanisms . We founThe serum FSH levels increased while the serum estrogen levels had no significant change in the perimenopausal group, so we grouped the population by FSH tertiles. The tertile ranges of FSH in the population were <8.55 (Q1), 8.55∼19.11 (Q2), >19.11 IU/L (Q3). As shown in We also observed the prevalence of MetS biomarkers. Overall, compared with women in the lowest tertile (Q1), the prevalence of hypertriglyceridemia, raised BP, and Mets increased in the highest tertile (Q3) group. However, the prevalence of raised FPG and low HDL had no difference .p value was close to the significance (p = 0.090). However, the prevalence of central obesity raised TG and FPG, and low HDL had no difference (n = 40), and thus the statistic power might not be enough to detect a moderate effect.Further, we subdivided the perimenopausal women into three groups according to FSH tertiles  and examined the association of FSH with risks of MetS biomarkers in perimenopausal women. Compared with women in the lowest tertile (Q1), the prevalence of raised BP significantly increased in the highest tertile (Q3). The risk of Mets was higher in Q3 than in Q1, and the fference . We notiIn this study, we found that the risk of Mets increased in perimenopausal females than in premenopausal women. A higher FSH level was associated with higher WC, TG, BPs, and the risk of Mets in perimenopausal women.Midlife women have a high risk of Mets, which was reported that they had a one-in-three chance of developing MetS that predisposes them to T2DM and CVD , 23. MidA hallmark of the menopausal transition is the dramatic reduction in estradiol levels, and with this reduction, there is a progressive shift toward androgen dominance in the hormonal milieu , 27. Mosαi/Ca2+/CREB pathway [Central obesity was the most frequent component of Mets for midlife women . In our  pathway . Moreove pathway . A previ pathway . These rSome studies also reported the associations between FSH and other Mets components in postmenopausal women. SBP and DBP increased by 6.11 and 3.54 mmHg after menopause, respectively . One stuOur study also has some limitations. The main limitation was the small samples. We only enrolled 154 premenopausal women and 124 perimenopausal women. Some phenomenon may be masked by the small samples. Second, this was a retrospective study that cannot establish causal relationships. A large-scale, randomized, prospective study would be a better study design to investigate the relationship between FSH and MetS, as well as MetS biomarkers. Third, we used a self-reported questionnaire to determine menopausal status but did not have the Anti-Müllerian hormone (AMH), which is a reliable indicator of ovarian reserve and menopausal status . Fourth,In conclusion, the risk of Mets increased in perimenopausal females. A higher FSH level appears to be a risk factor of MetS biomarkers in perimenopausal women. However, further clinical and mechanistic studies are needed to explore the effect of FSH on metabolism disturbance.