We present the first case of multiple fixed drug eruption caused by tranexamic acid, which was confirmed by the LTT. This case was difficult to diagnose because the drug‐induced aseptic meningitis by loxoprofen was occurred simultaneously. We present the first case of multiple fixed drug eruption caused by tranexamic acid, which was confirmed by the LTT. This case was difficult to diagnose because the drug‐induced aseptic meningitis by loxoprofen was occurred simultaneously. It is widely used to treat various diseases, such as leukemia, hypermenorrhea, and hemophilia, and for prevention of blood loss during surgery or acute trauma. Besides its hemostatic effect, tranexamic acid is also applied in mucocutaneous diseases such as tonsillitis, angioedema, stomatitis, and urticaria.A 42‐year‐old Japanese woman was admitted to the intensive care unit of our hospital with fever, moderate disorientation, and multiple, well‐circumscribed, round, pigmented patches with surrounding erythema on her precordia, neck, and back, which had appeared 2 days prior to presentation Figure  after amLTT is a minimally invasive procedure and is the first‐line diagnostic procedure when drug eruption is suspected. In this case, although LTT was performed 5 days after the discontinuation of prednisolone, it would have been better to perform LTT at least 4 weeks after treatment with prednisolone,Altogether, we should be aware that tranexamic acid, although generally a safe and frequently used drug, is associated with potential life‐threatening drug eruptions. Furthermore, detailed history taking of drug use and symptoms of collagen disease is useful for diagnosis in young women.No conflict of interest.KK: conceived and designed the case report and wrote the manuscript. SK and MI: contributed to patient management. HS: conceived and designed the case report and edited manuscript. All authors have read and approved the final draft of the manuscript.


Research suggests that collaboratively delivered maternity care can positively impact health outcomes. However, women’s perspectives on models of care involving interprofessional collaboration between midwives and health visitors are not well understood. Accounts of women’s maternity care experiences are key to improving maternity services. This study considered women’s views and experiences of maternity care as collaboratively provided by midwives and health visitors in England.n = 12) were recruited from two Children’s Centres in London, England. Data were analysed using thematic analysis.A qualitative focus group study with an exercise exploring women’s ideal maternity care pathway was conducted. Three focus groups were conducted in London, England between June and August 2017 with women who had had a child within 18 months prior to the study. The participants  contains supplementary material, which is available to authorized users. Interprofessional collaboration is widely promoted across health services, including maternal and child health services, both in the UK , 2 and iIn the UK, midwives and health visitors  are key maternity care providers. These groups share overlapping professional remits both antenatally and postnatally and are encouraged to work together . SpecifiPrevious research suggests that collaborative maternity care models can have a positive impact on health outcomes , includiWomen’s involvement in the exploration of interprofessional collaboration care models in maternity is limited e.g. , 14), de, de14]),empirical level concerns the directly observable, perceived and experienced. For example, a woman observes a midwife and a health visitor communicating about her care. Midwives’ and health visitors’ professional competencies as applied to care provision represent the actual level; these influence the empirical, and are not always observable  just went through loads of forms and just circled stuff, you know, that I had to remember and then that was it really and then she went, but yeah, it was, it was a bit of a waste of time, really. […] There wasn’t much point to the visit.FG 1, P2Some women reported having less positive experiences from both healthcare professionals, such as pressure to breastfeed with limited support on how to achieve this. Women observed a lack of engagement from health visitors, particularly when going through routine questions:So I met my health visitor, contacted me when I was pregnant and met me […] and we just had an introduction […]. And I thought it was quite helpful actually, because it was quite nice that we’ve already got to know her then, and then she said that she would be my health visitor and be the person who’ll come and see us once the baby got home and she did.FG2, P10Although the majority of the participants reported not having any contact with their health visitors antenatally, those that did shared that this contact was positive, individualised and supportive:[…] if they could introduce themselves to you before you have the baby, but …P1: Yes, I definitely agree that to have the session that I had at home, to have had that prior to birth would have been much more helpful, because it [New Birth Visit] was literally leaflet after leaflet after leaflet, and then I keep meaning to go through it and you know, it takes a while to get round, […] some downtime so even prior, just before the birth, I would have found it more beneficial, just information overload I think at a really quite manic time.P3: FG 1Moreover, women expressed a desire to meet health visitors in pregnancy to establish rapport, process the information that is given to them, and ask questions about areas of care that they are concerned about :Mine were definitely completely fragmented, because on the days that […], but perhaps that was to do with the miscommunication initially with the addresses, but I would get a call from the health visitor on the day the midwife was coming, saying she was coming and I’d have to say no, I’ve already seen the midwife today, so there was definitely no communication between the teams in my experience.FG 1, P3Regarding midwife-health visitor communication, women reported that this appeared to take place largely via their Red Book“No, no, but the midwives did check if the health visitor was coming, so yeah, so I think there was some connection, but yeah that’s it really” .Although women reported limited communication between midwives and health visitors taking place, they noticed that midwives had an awareness of health visitors being responsible for seeing women at home postnatally: …they [midwives and health visitors] all came to my house on the same day, after they got back they must have talked and I asked them one question about what kind […] oil to put on the baby because she was quite bad and they couldn’t agree. So they then had a disagreement about what the midwife was recommend this and the health visitor would recommend this, and they kind of knew that they would give different recommendations but, so they were talking amongst themselves and then I was like, oh I’ll just ask someone else.FG 3, P10In addition, women in this study reported valuing continuity of care, and of carer. Women shared experiences of seeing various health professionals throughout their pregnancy and after the birth, reflecting a lack of continuity of carer. This was associated with variations in the level and quality of care that the women receive as well as conflicting advice:However, participants acknowledged that whilst it would be ideal to have a single healthcare professional providing maternity care  this might not be feasible.This theme represents maternity care areas where midwife-health visitor collaboration could be beneficial. Participants focussed on information that they received from midwives and health visitors, and the co-ordination of their care.Even if they [midwives and health visitors] did a group session within the area, so you, it’s a chance to meet other mums going through the same thing before giving birth.P2: […]Yeah, that’s true because things like what immunisations they need could be said.P4: Yeah. And that gives a chance for mums to share any concerns and stuff at the same time and they’re all at the same stage of their pregnancy, so that’s nice.P2: FG1Women expressed concerns regarding the inconsistent information they received and suggested that centralised records accessible to midwives and health visitors could be useful. All participants agreed it was important for midwives and health visitors to be aware of their health status and relevant medical information, to counter unnecessarily narrating their needs repeatedly. This aligns with women’s suggestions on how maternity care should be co-ordinated; in particular, through midwife-health visitor led antenatal group classes, and joint midwife-health visitor appointments. They considered group classes apt for learning about pregnancy and parenting from midwives and health visitors, along with other parents-to-be:[…] for me it would have been nice to meet them during their [midwives’] session and have them deliver something for 20 min or maybe on their role, what they do, da, da, da, da, that might be quite nice.FG 2, P5Participants acknowledged that there could be greater clarity around the health visitor’s role in order to maximise women’s engagement with them. This was especially important for women who immigrated to the UK. Women expressed interest in learning about what health visitors can offer, and midwives could help to facilitate this:“So maybe it would be helpful if they have a last midwife appointment, the health visitor would be there then to do a handover” . In addition, participants identified Children’s Centres as potentially useful venues for meeting midwives and health visitors, along with other parents and/or parents-to-be, to do group activities and seek support and/or expert advice:Yes, actually being introduced to the children’s centre, I think lots of mums don’t actually get automatically told about children’s centres and playgroups and things like that, and actually it can be a real life saver in those first few weeks.FG 1, P1Women suggested that joint appointments/visits could enable transfer of care particularly in the postnatal period: Drawing from the women’s accounts and visual data  should be shared by healthcare professionals; midwives and health visitors having good knowledge of women’s history demonstrates connectedness between them. Participants were confident that the healthcare professionals involved in their care would share only pertinent information about women/families relevant to their welfare. At the same time, some women recognised that this could be more challenging for women who might present with vulnerabilities. Reflecting on personal experiences, however, the majority were comfortable with midwives and health visitors sharing information about them:[…] I do, personally, I’m happy with that information being shared between health visitor and midwife, I think it’s quite helpful and […] if the health visitor knows that you’ve had a C section, you’ve had a particularly traumatic birth, then they can be a bit more sensitive, I think that’s quite useful.FG 1, P1 […] if there could be something, like I said tongue tie it is in their system, I know it’s categorising and listing again, but if we make it a bit more focussed and individualised rather than give you general knowledge, then perhaps that is something that midwives and health visitors could easily share.P9:FG 3Women were enthusiastic about centralised files that healthcare professionals could access in order to share accurate information with each other, and provide women with adequate, individualised support and advice:One participant (FG 1) had experience of meeting various healthcare professionals who had shared access to her information, which she appreciated.Participants’ key recommendation for postpartum care was increased support from midwives and health visitors. The groups had a variety of suggestions including having the opportunity for informal discussions with healthcare professionals (e.g. drop-ins), midwives and health visitors ensuring appropriate referrals, and providing adequate breastfeeding and mental health support:I think what could be quite useful is if there was groups in general, maybe led by midwives or health visitors, during pregnancy, and afterwards for mums to just go to, so not just for breastfeeding, but say, you know you’re not feeling well afterwards.P7: YeahP6: […]Like a support group almost.P5: FG2Extended midwife and health visitor involvement was important for making women feel cared for and supported, with their specific needs addressed.This study explored women’s experiences of midwife-health visitor collaboration, as well as their ideal maternity care pathway. The main findings are: 1) women’s experiences of maternity care as delivered by midwives and health visitors are varied, 2) women perceived the communication between midwives and health visitors as limited, fragmented, and associated with conflicting advice, and 3) collaboration throughout the maternity pathway could be beneficial particularly in relation to information-giving and care co-ordination. Each of these will be discussed sequentially.empirical level given the diversity in women’s reported experiences [First, concerning midwife-health visitor collaboration, the findings showed that women’s experiences were a mixture of positive and negative ones, supporting previous research , 31. Foreriences –21.Second, women reported observing service fragmentation, evidenced by scant communication between midwives and health visitors. This reflects findings from the National Maternity Review, where women emphasised that good communication and information sharing amongst health professionals is essential . HoweverHealthy Child Programme [Finally, women contributed strategies for improving current maternity care provisions, aligned with the National Maternity Review  and Publrogramme  recommenrogramme . Thus, crogramme  do not mrogramme , which wHealthy Child Programme [actual level), as well as their views on the kind of care that healthcare professionals ought to provide . Despite these differences which the participants were aware of, they still had shared experiences and needs, suggesting that these layers only provide a partial understanding of the complex nature of reality [The participants also made recommendations for improving mental health and breastfeeding support. Both are core requirements of delivering the rogramme . Redshawrogramme  researchrogramme . It was rogramme . One pla reality , 21.Finally, women suggested that their care pathway could be made clearer to them. This is in line with previous research, where women have stressed the value of being better informed about what they could expect from perinatal care such as the frequency of appointments and the purpose of these . GeneralA key strength of this study lies in the manner in which women’s views were elicited – through semi-structured interview questions, and women-led, open group discussion to visualise their ideal maternity care pathway . This foHowever, the participants were a self-selected sample, and evidently proactive about their maternity care (e.g. accessing Children’s centres that they advocated for). Additionally, there were pre-existing relationships between a few of the participants (i.e. some were known to each other) which could have influenced how they responded to the questions. However, all the women appeared comfortable in the group setting, and still openly discussed their experiences with the rest of the group.and health visitors. In addition, women’s care pathways need to be made clear to them at the outset, including information about the health professionals who may be involved in their care, and these professionals’ roles. In terms of midwife-health visitor interprofessional collaboration, the participants showed an awareness of the issues previously raised by these healthcare professionals [The present study contributes to the body of knowledge by validating past research , 36, andssionals , 37–39 sssionals , 35, ultConsiderations for future research include exploring specific service changes for improving maternity care pathways such as the feasibility of group-based antenatal classes jointly provided by midwives and health visitors, and evaluating the impact of midwife-health visitor communication on health  and service outcomes . Maternity care models and guidance developed should include health visitor input if services are to achieve midwife-health visitor collaboration throughout the care pathway. In addition, future research should include other stakeholders such as policymakers and service commissioners to obtain a better understanding of how midwifery and health visiting services could be redesigned to support collaborative working.This study explored women’s views and experiences of collaboratively provided maternity care by midwives and health visitors. Women reported limited midwife-health visitor collaboration; however, they acknowledged the potential value of collaborative working between these groups. Reflecting upon their experiences of care, women were able to identify the issues that they perceived could benefit from collaborative working, such as the provision of inconsistent or inaccurate advice, as well as fragmentation between services. Moreover, the participants offered potential solutions to these, such as the provision of group-based midwife-health visitor antenatal appointments. Women also highlighted positive experiences of the care that they received, such as having helpful midwives and health visitors. Women’s recommended strategies regarding how midwife-health visitor interprofessional collaborative practice could be improved demonstrate the necessity of their input in service development efforts.Additional file 1:Focus group topic guide. This document outlines the topic guide used in the focus groups with women. (DOCX 105 kb)


SPIEGEL ONLINE and Tagesanzeiger, we developed a web interactive that predicts users’ regional backgrounds from within German-speaking Europe. More than 1.9M people have participated in the interactive, more than 770K users have provided metadata. Said metadata allowed us to capture regional variation in language as of today, which we can compare to historical survey data–enabling us to track the evolution of German in Europe over the past 40 years. We report on regional levelling of lexical variants, a process which appears to be particularly prevalent in the northern parts of German-speaking Europe. We further found an effect of (former) national and regional borders on language use. This innovative paradigm allows us to collect sociolinguistic data of an unprecedented scale–at the same time it presents significant challenges, both of which–benefits and challenges–will be discussed in this contribution.Research on regional linguistic variation typically involves data collection in the field. This process itself can take up several months if not years. In the present study we demonstrate how we can use web interactives in collaboration with media outlets for a fast gathering of regional, sociolinguistic data. In collaboration with  Brötchen, people in Baden-Württemberg call it Weck(er)le, in Bavaria and most of Austria Semme(r)l, and in German-speaking Switzerland one typically hears Mütschli or Brötli.German is one of the world’s major languages and is spoken in many regions across Europe and other parts of the world ,2. With Wortatlas der deutschen Umgangssprachen (WDU) [WDU. In about one third of the localities, he and his collaborators were able to interview their informants so that in these cases, it was actually the interviewer, not the interviewees who completed the questionnaire. The questionnaire used a mainly onomasiological approach: the informants were asked to provide the local expression for a certain concept, e.g. the local word for ‘the boy’, for ‘to chat’, or for ‘wallet’. The questionnaire also included images, for example a clock showing the time ‘8:15’, a ‘carrot’, or items in which the informants were asked to translate short phrases or choose between a short list of variants. Unlike traditional dialect surveys, Eichhoff focused on participants from the younger and middle generation in urban areas, and the participants were asked not about their own language use, but to report variants they believed are typically in use in the respective locality. In the case of Germany and Austria he thus targeted more regional, supralocal varieties, whereas in the case of German-speaking Switzerland, he elicited dialects. He surveyed, for example, the regional variants of the Standard German word der Junge (‘the boy’). He retrieved the following regional distribution: in the north of Germany, Junge was reported most dominantly, while Bub, Bu(e)(b) or Bua(b) were particularly prevalent in central Germany, Switzerland, and Austria. Knabe was reported in northern Bavaria and Baden-Württemberg and Bersch (/Bursch) in the Austrian state of Styria  , i.e. ‘W. One AdA survey from 2006 was directed at perceptual data [WDU localities. This first survey attracted 1,763 participants, and it was followed by new surveys at regular intervals. Over the years, the number of participants snowballed so that in the tenth survey over 20,000 people provided data. The AdA is still ongoing and is now in its 12th survey round.The second survey of central importance to the current study is the nguage’, ,13) by Eual data . InitialWDU, the data of which was mainly collected in the 1970s –i.e. c. 40–50 years ago. This is plausible because (a) the lexicon is typically more prone to change compared to phonetic / phonological domains [WDU specifically asked for variants of a form of language which is spoken everyday–thus more likely (but not necessarily) non-standard–and which is regionally-colored, i.e. a form of language which is less stable and more in flux than traditional local dialects on the one end or standard varieties on the other end [It is reasonable to assume that the distribution of lexical variants in space has changed since the time of the  domains –17 and  from the first two volumes of the WDU, published in 1977 and 1978, to eleven equivalent maps from an online survey conducted in 2002 –thus studying language change across a time span of c. 25–30 years. The online survey, a pilot study for the subsequent AdA, provided data from roughly 1,500 respondents across Germany, Austria, German-speaking Switzerland and northern Italy. [used to be the political border between West and East Germany, even thirteen years after the effective fall of the Iron Curtain. On a side note: the WDU maps based on data from the 1970s displayed only first signs of the divergence process. German-speaking Switzerland and to some extent also Austria often maintain their own variants, with isoglosses typically following along the border to Germany. (iii) Thirdly, in two other instances , formerly southern variants  had spread to the northern parts of Germany. This is all the more striking as the general trend in other linguistic domains, notably in the phonetic-phonological domain, is that northern German forms have spread to southern Germany; [sein ‘to be’ and haben ‘to have’ in analytical forms of the perfect tense of the position verb sitzen ‘to sit’).The hypothesis that the regional distribution of these variants has changed over the past decades was tested by  using a Germany;  claimed WDU and the AdA. After 24 such questions, the web interactive tells the individual participant, depending on which variants they indicated, where they are from within German-speaking Europe. The user can then evaluate the quiz result, provide metadata on age and gender, and submit this data. This enables us to collect regional language data on a large scale, which we can subsequently use to compare to historical data, in this case Eichhoff’s data, thus enabling the study of linguistic change (for more details see section 2 Methods). The web interactive that collected the data which the present study is based on was developed by Adrian Leemann, Marie-José Kolly, Timo Grossenbacher, Marc Brupbacher, Daniel Wanitsch, and colleagues from the online edition of the news magazine SPIEGEL ONLINE and the Zurich-based newspaper Tagesanzeiger [In the present contribution we follow suit with the line of research conducted by –albeit wanzeiger .Going into the study, we have the following prediction:WDU data from the 1970s to contemporary data we crowdsourced in 2015) and analyses of apparent-time change . If the older generation speakers in our apparent analyses show less change when compared to WDU than the younger generation does, we can be fairly certain, that actual language change has taken place. We suspect that both analyses will point in a very similar direction, as crowdsourcing methodology has been shown to indicate very similar diffusion patterns, similar to those found in more traditional paradigms [We expect substantial lexical change to have occurred since the 1970s, the time Eichhoff’s survey was conducted. We will examine this by performing analyses of real-time change  breakfast that people have at their workplace’–i.e. Frühstückspause, Pause, Frühstück, Brotzeit, Jause, or Vesper. This user interface (UI) is shown in The process of collecting the data for the current study is based on a quiz we developed with anzeiger . Analogoanzeiger , we deveTo trigger the user’s linguistic intuition, we asked them to click on the word that they would typically use if they spoke to friends at their location. Once the user had completed the quiz, the web interactive prompted them to indicate metadata on age and gender. Finally, the web interface showed the result of the quiz: a heatmap and the top five localities as pins on a map. The ‘hotter’ (i.e. the redder) the area, the more likely it is that the user speaks like someone from that region–the ‘colder’ (i.e. the bluer), the less likely it is that they are from that region. Once the result has been presented, we then asked users to ‘validate’ this prediction. We asked them to rate the result on a scale from one (very inaccurate) to seven (very accurate). Further, we asked the users to click the point on the map where they believe they, i.e. the people from this locality with the pin, spoke most like they do. Once the user has evaluated the result, they click on ‘submit’. This geotagged data is sent to our servers along with the 24 variants the users selected and metadata on their age and gender.http://www.kek.zh.ch/internet/gesundheitsdirektion/kek/de/home.html) and the accompanying federal laws on experimentation on humans in Switzerland (http://www.admin.ch/opc/de/classified-compilation/20061313/index.html). We therefore did not seek further ethical approval from cantonal or federal institutional bodies. This new, crowdsourced data can then be compared to the maps provided by Eichhoff, which allows us to track change in language over time.None of these pieces of information individually or in combination allow for identification of users in the database. Users always had the opportunity to opt out of providing us with their metadata on age, gender, regional variants, and place of origin. This procedure of collecting anonymous user data conforms to the regulations of the Zurich cantonal ethics committee . After see also ’s Harvar in 2013 . The Swiof weeks .When comparing the data from the web interactive with Eichhoff’s data, it has to be remembered that Eichhoff used paper questionnaires and asked one to two informants per locality on their notion of the local word or expression for a certain concept. To account for local variation, the informants could provide more than one variant, but if they did so they were requested to highlight the more frequent of the two (or more) variants. In contrast, the web interactive asked for the user’s own language use and allowed for one variant per variable only. The different methods of data elicitation may put a certain caveat on the comparability of the data sets. However, both methods aimed primarily at the representation of language use at particular localities. In Eichhoff’s data, this was achieved by the informants assuming the role of experts of the local colloquial language, whereas the web interactive collected data per locality to arrive at one (two or three) variant(s) which are inter-individually used at this locality.AdA, rather than WDU because we wanted to ensure that prediction accuracy was relatively high–which may have been problematic had we used historical data, such as WDU, for the prediction. To develop the prediction, we needed a set of maps (i.e. variables) that allowed for a geographical partitioning of German-speaking Europe. We chose variables with different geographical distributions so that very small areas could be distinguished from each other on the basis of unique answer combinations. The variables (and variants) were selected from AdA: fuffzehn, fuffzeh, fünfzehn/füfzäh, and fuchzehn. The vast majority of variables in the quiz are lexical in nature (21/24), only two were phonetic variables, and only one (3rd p. pl. haben wir) can be categorized as morphological. An overlay of these 24 maps revealed a fine-grained regional partitioning of German-speaking Europe.The phonetic variable ‘Pronunciation of ‘15”, for instance, featured four variants in AdA localities  and identifies the locality with the most hits. As a result, the user is presented with the top five from a total of 487 ies . The quiz garnered widespread participation, particularly so in the first days following its release on 25 April 2015. Until today, more than 1.91 million users participated, of which 46% were females, 54% were males. The largest segments of participants come from the age bracket 25–34, with a share of 33.5% of all participants. This is roughly the age bracket which Eichhoff aimed at in the survey for In WDU on the left, and localities that were crowdsourced in our contemporary data (right)–the latter shows counts of localities in the current data that were aggregated for each locality in WDU cf. While Eichhoff sent questionnaires to residents in 402 localities across German-speaking Europe, our web interactive sampled users from more than 22,000 localities. WDU. The Thiessen polygons often comprise urban regions, such as around Vienna, Berlin or Zurich. For most localities our data features 100–1000 participants. More urban regions and regions with major city hubs typically feature between 1000 and >5000 participants. As an example, cities like Zurich, Berlin, or Vienna along with their urban regions show the following areal (as represented by the respective polygon) and user distributions: Zurich : 6,659, Berlin (890km^2): 22,711, and Vienna (460km^2): 11,758.Our users clicked on 22,828 unique localities (see 2.1), which we retrieved via Google reverse geocoding API. WDU. The other ten variables were not comparable as they were not elicited in WDU but only in AdA. These 14 variables include: ‘(second) breakfast that people have at their workplace’, ‘non-professional soccer playing’, ‘pancakes’, ‘breadman’, ‘beef patty’, ‘chatting’, ‘slippers’, ‘10:45’, ‘slingshot’, ‘hiccups’, ‘wallet’, ‘heel end’, ‘pencil case’, and ‘mashed potatoes’. This comparison allows us to perform analyses of language change in real and apparent time [WDU volumes were published, we performed analyses of real-time change between 23 and 44 years. For us to perform the comparison, the original 14 WDU maps–printed on paper–were scanned and georeferenced, using standard GIS software, and manually converted into vector format. All digitized maps are available as shapefiles from a GitHub repository [For the present study, we compared 14 variables from our contemporary data 2015) to those found in 15 to thopository .WDU maps is aggravated by the different spatial granularity of the two datasets, i.e. 22,828 localities vs. 402 WDU localities. The comparison results in a measure of degree of change between the historical and the current data. The degree of change is computed for each of the 402 WDU localities and for each variable individually. The methodology for computing the degree of change for one WDU locality is sketched in The comparison of the current data, collected through the web application, with the historical WDU locality in question (black dot with red outline), the area which is closest to the respective locality–relative to the neighboring WDU localities–is identified, using voronoi tessellation (grey dashed line), i.e. without creating overlaps or gaps between the localities. Voronoi polygons for all WDU localities are shown in For each N localities from the web app (grey dots) are drawn at random, with localities closer to the WDU locality in question having a higher probability to be selected. These are called selected localities (red dots). This step of selecting N places is explained in further detail below.Within this area, WDU locality in question (black dot with red outline). Step 3 is not covered in The linguistic information aggregated over all selected localities (red dots) is compared to the single linguistic information available for the N Web App places results in a frequency of use for each variant, for each linguistic variable. This frequency distribution enables the computation of the degree of change measure. If the variant used at the WDU locality in question is not used at any of the N selected places from the web app, change for the respective variable is 100%. Accordingly, if all N selected places use the same variant as used at the WDU locality in question, change is 0%. Degree of change is thus identical to the conditional probability of observing a variant at the WDU locality in question, given the distribution in the selected, and proximate, web app localities. In the infrequent case where WDU indicates two variants in use for one locality, both historical variants are compared to the contemporary data; yet our maps then only show the change that was smaller. The same methodology as described above is used to compute degree of change for different age groups (see section 3.2), the only difference being that prior to the first step, the web app data is filtered, such that only information from the respective age group is retained and used in the computation.The aggregated information from the selected N is chosen to be 100, if 100 or more places are available for comparison. The rationale for considering ‘only’ 100 randomly selected, nearby localities is twofold. One, subsampling leads to manageable computing times. Two–and probably more importantly–subsampling warrants that the unbalanced distribution of web app localities . Hence, this threshold value of N ≥ 20 localities only comes into effect for the computations of degree of change for different age groups (cf. section 3.2), which requires additional stratification of the input data and thus leads to smaller sample sizes. Note that we can only draw comparisons to the original WDU localities, which, unfortunately, do not include datapoints in East Belgium, Luxembourg, and Liechtenstein (cf. Introduction). The data underlying this study can be retrieved from here: https://osf.io/49tcj/.A few more details concerning step (2): the number of selected web app localities Following up on the prediction stated in section 1, we show findings of the current study in three domains: (i) change in real-time–i.e. comparing our contemporary data to the historical data provided in  and (ii)WDU. The maps can be read as follows: the left-hand map shows the contemporary and historical distribution of variants. Contemporary data is aggregated into 1000 hexagons. We only show the mode, i.e. the most frequent response for each hexagon. The more dominant the variant, the more intense the color of the hexagon. On top of these hexagons we placed the localities from Eichhoff, i.e. the historical data–shown as dots. If the dots are small and, consequently, show the same color as the hexagons in the backdrop, no change has taken place. If the dots are large and show a different color, a change has taken place. The larger the dot, the less we find this historical variant in this locality in the contemporary data. Orange outlines indicate different types of missing data. Orange outlines with black filling represent localities for which there were no responses in the WDU. Orange outlines with grey filling highlight rare and particular variants which were not included in the study. Orange outlines with white filling means that users or WDU participants did not have a word for the object in question. On the right hand-side we show a map illustrating the degree of change (for computation thereof see section 2.6). Using Thiessen polygons, we demonstrate where and to what degree change has taken place–comparing contemporary data to historical data–light grey means <20% of the nearby selected localities in the web app exhibit a different dominant variant from [WDU. Red indicates that there are not enough responses (i.e. <20) for that polygon; blue is used for polygons for which the historic Atlas used another variant that we did not query in the quiz; and green is used for polygons where participants from the historic Atlas did not have a word for the item in question. In all these cases–red, blue, and green–we cannot calculate a comparison score.ant from ; black (bäbbeln (green on the left panel)–typical for the region of Saxony–or pöhlen (pink) in Westphalia appear to have lost ground due to the more generic bolzen (light brown)–a trend which is also observable on the corresponding AdA map from 2006/2007 . A comparability of WDU and AdA is clearly possible, since AdA has adopted the basic concept of WDU, i.e. collecting data at a given locality by asking informants not about their personal language use but the language use which is ‘typical’ for the everyday language at the locality. See The trend we observe for the variable ‘non-professional soccer playing’ is one of regional levelling–i.e. the reduction of variants, particularly marked, minority variants, because already widespread forms are becoming even more dominant ,33. Regikicken (dark purple) is still the most dominant form, and in German-speaking Switzerland, tschutten (red) and schutten (dark brown)–derived from English ‘to shoot’, cf. [WDU respondents reported to not have a variant for the object in question and (b) WDU used a variant that was not used in our quiz.The opposite, i.e. little or hardly any change in lexical variants, is evident for much of the southern regions of German-speaking Europe, in particular German-speaking Switzerland, but also in the eastern part of Austria. In the latter case, ot’, cf. –are stilWe find somewhat similar patterns of levelling and change when looking at the regional variants for ‘slippers’, see slippers. As can be seen in the two maps shown here, substantial change appears to have occurred over the past 40 years. In the west of Germany, for example, the now dominant form Pantoffeln (pink) appears to have gained ground at the expense of Schluppen / Schluffen (light green). Similar patterns of supralocal forms emerging are found in Bavaria, where our current data shows predominantly Pantoffeln (pink)–while the historic data also showed a more regional variant including Hausschuhe (grey) and Schlapfen (dark green). In short–forms which had already been dominant have become even more widespread and have pushed aside more small-scale variants. The right-hand map in Finken , Patschen (light brown) in Vorarlberg, Tyrol, Salzburg and Styria and Schlapfen in Upper Austria, Lower Austria and Vienna (dark green). This stability in the south is already evident when looking at 2009/2010 data from the AdA for this variable .WDU specifically asked for a yeasty breadman with raisins which may not correspond to the traditional preparation in some regions.The changes we observe for ‘breadman’ are shown in WDU (white circles with orange outlines), today we find a substantial proportion of Lebkuchenmann (light brown) and Pfefferkuchenmann (pink) in these regions . Here, again, the different traditions of preparing the breadman may be taken into account (Lebkuchenmann and Pfefferkuchenmann are made from gingerbread). In the southwest of Germany (north of Basel), however, we observe some trends of levelling: near Lake Constance we find that regionalized variants such as Klausenmann (dark purple) have become less known by the users in our contemporary data, as shown by the larger dots in that region–indicating that this variant is receding and being replaced by ‘word unknown’. The right-hand map in While for much of the eastern part of Germany this pastry used to be unknown in In the three exemplary variables introduced so far, it became evident that substantial regional levelling occurred for a number of variants. It further emerged that this regional levelling is particularly prevalent in the center and the north of Germany. In German-speaking Switzerland, on the other hand, little change has taken place, as seen for example in ‘breadman’. In this section, we explore further how regions differ in terms of degree of change that has taken place: we illustrate this by examining the variants for ‘(second) breakfast that people have at their workplace’ and ‘pencil case’. One variable that shows how regions differ in degrees of change is ‘(second) breakfast that people have at their workplace’, see WDU, north of the river Main–an isogloss which German dialectologists refer to as Speyerer Line, separating Upper German in the south from Central German north of it [(zweites) Frühstück  (i.e. ‘second breakfast’). Today, however, virtually all of these localities have changed to Frühstückspause / Pause / Kaffeepause today (light brown). There are some exceptions in Rhineland-Palatinate and Saarland, where Vesper (grey) used to be dominant, which is now being pushed aside by Frühstückspause / Pause / Kaffeepause. For the rest of German-speaking Europe, however, very little has changed: Vesper, the typical variant of Baden-Württemberg, the Bavarian Brotzeit (pink), the Swiss Znüni (dark green) and the Austrian Jause (purple) have remained largely unaffected by this change. On the right-hand side map in WDU.According to th of it ,35–speakThe map for ‘pencil case’ shows similarly interesting patterns in terms how regions differ with regard to where change has taken place the most:(Schul)-Etui (purple) appear to be pushed aside by more widespread variants such as Federmappe (light green). Similarly, Federtasche (brown) is losing ground in Thüringen at the cost of Federmappe. In Lower Austria, Federpennal (dark yellow) appears to be gaining ground at the cost of the more localized Federschachtel . In Saxony, Schiefermappe and Schieferkästl were in use back at the time of the WDU, which we did not query. Similarly, for South Tyrol, Griffelschachtel was in use, which we also did not query -Etui (purple) and the central and southwestern German variant Mäppchen/Mäpple (turquois) are virtually unaffected by the change–as reflected in the bright grey polygons on the right-hand map in AdA map from 2006/2007  to our current data.WDU from the 1970s to the results of a pilot study for the AdA [Sonnabend (‘Saturday’) used to be distributed in the entire north and eastern parts of Germany. Some 25 years later, in the west this variant was largely replaced by Samstag, whereas Sonnabend was still the dominant variant in the east and so developed into one of the lexical shibboleths of the east of Germany. Similarly, the isogloss between Viertel vor sechs and Dreiviertel sechs (‘5:45’) had shifted eastwards so that it then corresponded to said political border .As mentioned in section 1,  compared the AdA , with daWDU and our contemporary data. Pfannkuchen  has gained ground at the expense of Eierkuchen (grey) ). At the same time, the variant Plinse  has lost ground in Saxony and it appears to have been pushed back to its central area of distribution in the far-eastern bilingual Sorbian-German regions. As a consequence, both developments have resulted in a consolidation of Eierkuchen as the dominant east German variant.Similar real-time changes are observable in the results of a comparison of WDU map  elicited ‘6:15’). The regional distributions have not changed considerably over the past 40 years. However, we can observe a shift of the isogloss which runs across the northern and central parts of Germany and which separates the areas with Viertel nach zehn  and Viertel elf (turquois)–with the northwestern variant Viertel nach zehn gaining ground and pushing aside Viertel elf  from AdA 2009/2010 already shows how viertel nach zehn is gaining ground in these regions).Viertel nach zehn and Viertel elf areas, where substantial change appears to have occurred. A look at the corresponding map from the AdA, which features the political borders, reveals that a divergence has taken place right along the border between the former FRG and the former GDR by way of an ‘exchange’ of variants.These patterns of change are again reflected in the right-hand panel in Schlucken (light yellowish grey) has been largely abandoned in favor of the more supraregional (and indeed standard) variant Schluckauf (dark yellow) ). The panel on the right reveals the extent of the change. Most of the polygons in the eastern part of Germany are dark grey or even black, indicating substantial change.Not in all cases, however, East German variants have been maintained. The most dramatic changes become apparent in the east of Germany when looking at the map for ‘hiccups’, cf. Kloß (light purple) and its diminutive variant Klößchen (ibid.) seems to have been largely abandoned in favor of Klops (light blue). In Saxony and also in Mecklenburg-Western Pomerania, Beefsteak (green) has lost ground in favor of Klops or of Bulette (bright blue) ). Again, the right-hand panel shows that most of the changes, to be recognized by the dark coloring of the hexagons, are concentrated in the east of Germany. Strikingly, these leveling processes are limited to the territory of the eastern German states. In the end, we are still dealing with variants that can be considered genuine east German shibboleths, i.e. Klops and Bulette.Similarly, most changes on the map for ‘beef patty ’, cf. We can now aggregate these degrees of change across the 14 variables, cf. Main line. This line, following for the most part the course of the river Main, has been identified as the most notable isogloss for lexis of colloquial German; it divides the northern and southern regions of German-speaking Europe considerably further south of the famous Benrath line, which in German dialectology serves as the traditional isogloss between Low German dialects in the north and High German dialects in the south [he south ,36,37. SWDU vs. contemporary data). One way to test the validity of this real-time paradigm is to perform analyses in apparent-time–where, in our contemporary dataset, the degrees of change of different age groups are compared amongst each other [WDU, while the younger users demonstrate more change. For this purpose, we subset the data set into users <25 years of age  and >60 years of age , i.e. with c. 35 years, i.e. one generation, between the cohorts. Overall, we found the younger cohorts to demonstrate more change compared to WDU than the older cohorts. By way of example, Section 3.1 provided a real-time analysis of language change, where the distribution of variants are compared at different moments in time , >60 a median of .37 (SD = .30). The t-test was significant .In this study we examined lexical variation in everyday language using web interactives as a new methodology of data collection. Going into the study we predicted that we would find substantial lexical change since the 1970s. In what follows, we want to explore potential reasons for this change in greater detail: 4.1.1 discusses reasons for levelling and 4.1.2. explores the role of political borders in the process of change. Finally, we discuss methodological limitations (4.2) and potential ways of validating this new paradigm of data collection (4.3).Pantoffeln, a both colloquial and standard variant for ‘slippers’ which is spreading and gaining ground at the expense of Schluppen / Schluffen and Schlapfen, which are all considered to be less standard than Pantoffeln. This phenomenon, typical of language change in progress, is often referred to as levelling. There are different reasons for regional levelling and for supralocal norms to emerge. In this context, a principle of frugality may play a role, where speakers move away from linguistic diversity as a means of being more frugal and at the same time wanting to become supralocally understood [In sections 3.1.1 and 3.1.2, we reported that variants with geographically broader usage are becoming more dominant at the cost of more localized, regional variants. As an example, this is the case for derstood . This prderstood :Social mobility may lead to levelling as a result of an orientation towards standard varieties . This, hGeographical mobility is known to be a significant driver of language change ,43. It mSchluffen and Schluppen . Another example is the spread of the variant Bulette for ‘beef patty’ from the Berlin area to large parts of east of Germany, pushing aside more localized variants such as Beefsteak, (Fleisch-/Gehacktes-) Kloß/Klößchen and (Brat-) Klops (cf. Pause (‘break’) and its relatively transparent compounds Frühstückspause  and Kaffeepause (‘coffee break’), have become the dominant variants, whereas in most other areas, regionally salient variants , some of which are also quite opaque , have remained relatively stable. There are also instances, however, where regional, relatively localized non-dominant variants have actually spread: Weck(en)mann (in the northwest of Germany) and Krampus (in the east of Austria) are extending into regions where previously respondents did not have a word for this variant. It has been observed elsewhere that the spread of regional lexical variants, in particular, can be attributed to the fact that they have become indices of regional identity and thus helped to “enregister” regional varieties, thus–to use the terminology of traditional sociolinguistics–turning from being associated with covert prestige to overt prestige [The effect of these two sometimes conflicting processes can be seen on the map for ‘slippers’ cf.  above. Ward, cf. ) by Pantlops cf. . The mapprestige . While m(Schul-) Etui) and Austria  seem to have been consolidated. Whereas Federpennal can be regarded as an Austriacism, (Schul-) Etui is not a ‘pure’ Helvetism, as it is also used in northwestern regions of Germany. South Tyrol, however, has seen considerable change. Here, Federschachtel has spread and has become the dominant variant. Again, it is not an exclusive variant of this region, as it is also used in some parts of Austria. Similarly, the maps for ‘slippers’, ‘beef patty’ and ‘(second) breakfast that people have at their workplace’ show a substantial degree of variation and change in Germany, and, in contrast, a spread and consolidation of variants within the national borders of German-speaking Switzerland, Austria, Liechtenstein and German-speaking Italy. Here, these variants have become dominant but not necessarily specific for the respective country or region berl, South Tyrol: Fleischkrapfen/-krapferl; ‘(second) breakfast that people have at their workplace’: Switzerland Znüni, Austria: Jause). In some cases, a clear process of divergence along national borders has taken place. Certain variants which were attested in the WDU as being used in border regions of neighboring countries have virtually disappeared, e.g. the southwestern German variant Fleischküchle from Switzerland, the Austrian Fleischla(i)ber(l) (both ‘beef patty’) from South Tyrol, or Austrian Geldbörse(rl)  from Bavaria. In some cases, processes of consolidation can be explained with the conventionalization of lexemes in administrative contexts, such as Schul- (Etui), Federpennal or Federschachtel having become the ‘official’ word for ‘pencil case’ at school, or Probe (in the canton of Bern–as opposed to Prüfung/Prüefig in the rest of German-speaking Switzerland) and Schulaufgabe (in the German state of Bavaria–as opposed to Klassenarbeit in most other German counties) as the specific term for ‘school exam’.What was also striking for a number of variables was the effect of national borders and political borders within nations on language use. Whereas the variants for ‘pencil case’ have seen considerable change within Germany, the formerly dominant variants in Switzerland . The maps for ‘pancake’, ‘10:15’ and ‘beef patty’ demonstrate, firstly, a consolidation of  western and  eastern German variants, and secondly, a divergence of such variants along the former Iron Curtain in Germany: Pfannkuchen vs. Eierkuchen, Viertel nach zehn vs. Viertel elf, and Frikadelle vs. (Brat-/Fleisch-) Klops or Bulette. The latter variants may have been regarded as ‘national variants’ towards the end of the GDR; over the twenty-eight years after the fall of the Iron Curtain, some of them have essentially become regional markers of East-German identity.The most striking processes of divergence, however, seem to have taken place at a Finally, we want to reflect the methods chosen. This section will be structured in three subsections: (i) we explore the benefits of this new paradigm of collecting data, we (ii) point to some of the limitations of this paradigm of data collection, and finally, (iii) we discuss a way of validating the method selected.This new method of data collection for the purposes of studying language variation and change brings with it a number of key benefits: (a) a collection and analysis of datasets of unprecedented scale; (b) wide engagement with the public, thereby creating broad, public impact; and, (c) more generally, pushing methodological boundaries using technological advancements that interface with a traditional field such as dialectology.As for (a), studies in dialectology typically examine speakers that have been carefully selected. Often, this speaker selection is time-consuming and ultimately results in a limited pool of participants. Collecting language data through web interactives sidesteps this problem–as the potential participant pool is virtually unlimited . Which leads to (b): the web interactive allows researchers to reach millions of users. Such large-scale dissemination strategies are becoming more important in times of Research Excellence Framework (REF) and, most recently, Knowledge Exchange Framework –as outlLinguistics Vanguard [SPIEGEL ONLINE has roughly 20M unique users per month, Tagesanzeiger has roughly 1.3M unique users per month. This combination of gamification and collaboration with a strong media partner has–to our knowledge–not been done before. This collaboration brings up the question of how science and data-driven journalism are distinguished and what opportunities and pitfalls such a collaboration entail. [While these endeavors obviously had a wide reach as well, to the best of our knowledge none of them had such a wide impact as our quiz for German-speaking Europe. It was successful because, for one, we applied the concept of gamification, i.e. users engage with a system and, in return, they get a reward–which in our case was the prediction of their regional origin. Gamification for use in linguistics is not new. In 2015,  showed tVanguard  is devot entail.  defines There are number of limitations to the data collection method applied in this study. The greatest problem (and at the same time the greatest strength) of the current paradigm is that anybody could (and still can) participate in the survey. There is no control over who participates in the web interactive. Consequently, this means that we do not know whether the users go through the quiz trollingly or sincerely and whether or not they fill in the metadata on gender, age, and evaluation of the result felicitously. Moreover, users may go through the quiz multiple times–although  suggeststhink they use. Here we have to trust the users’ linguistic intuitions. [Further noise is added to the dataset on a number of different levels: (a) We do not know if our speakers are first, second, or third language German speakers. Obviously, this may have a large effect on the nature of the data collected. (b) We have some users who are very mobile, geographically and socially, and we have users who exhibit opposite patterns. (c) Further, to evaluate the quiz result (see section 2.1), users placed a pin on a map. The precision of where this pin is placed exactly strongly depends on the zoom level the users selected–with a higher zoom level enabling a much more precise placement. (d) Furthermore, it is reasonable to assume that speakers–for nostalgic reasons–tend to respond rather ‘hypercorrectly’ and click variants which, for instance, they fondly remember from their childhood . AdA’s survey round no. 4 question 2 from 2004/05, with c. 7.000 responses) result of ‘(second) breakfast that people have at their workplace’ (left) obtained through controlled elicitation and the same variable as collected through our web interactive (right).Given the plethora of methodological caveats mentioned in 4.2.2, the question of legitimacy of the current paradigm of data collection emerges. Are the findings and interpretations legitimate, given all the factors contributing to noise in the data presented in 4.2.2? Can we still make out the actual signal from the noise? One way to validate this is to explore, for example, whether Elspaß & Möller’s survey, AdA (2003ff.) did: users in German-speaking Switzerland reported Znüni, in much of Austria both surveys collected Jause, Baden-Württemberg shows Vesper, Bavaria Brotzeit, and north of the river Main, both surveys predominantly report Frühstückspause. What is interesting here, though, is that in the AdA data (left hand-side (zweites) Frühstück–the same variant that was dominant in Eichhoff’s WDU–is still being used  sporadically, whereas in our data, this has virtually disappeared from the map and change in this variant appears to have been concluded today; in AdA, this change appears to have been still ongoing. Given the very high degree of overlap in this and other variable(s)–in spite of the two different approaches to elicit data on regional variation–we argue that using web-interactives as a way of linguistic data collection can be very powerful and useful in the study of language variation and change.Judging by the regional patterns evident in This study set out to (a) determine the usefulness of a new crowdsourcing methodology for sociolinguistic research and to (b) examine linguistic change in German-speaking Europe with said methodology. This study has found substantial regional levelling particularly in the center and the north of Germany and has shown the effect of national and regional borders on lexical change. The scope of this study is limited in a number of ways, as addressed in 4.2.2. In spite of its limitations, the findings contribute to our understanding of regional variation and linguistic change in present-day German-speaking Europe; moreover, they underline the importance of updating surveys on colloquial speech periodically , as this has proven a highly dynamic area of our language. We presented an innovative methodology on how large data sets on regional variation can be collected. A natural progression of this work will be to apply this paradigm on other languages.


Increasing evidence is demonstrating that a patient’s unique genetic profile can be used to detect the disease’s onset, prevent its progression, and optimize its treatment. This led to the increased global efforts to implement personalized medicine (PM) and pharmacogenomics (PG) in clinical practice. Here we investigated the perceptions of students from different universities in Bosnia and Herzegovina (BH) towards PG/PM as well as related ethical, legal, and social implications (ELSI). This descriptive, cross-sectional study is based on the survey of 559 students from the Faculties of Medicine, Pharmacy, Health Studies, Genetics, and Bioengineering and other study programs.p = 0.003). Students with this opinion are also more willing to continue their postgraduate education in the PM . Furthermore, 45% of students are aware of different ethical aspects of genetic testing, with most of them (46%) being concerned about the patient’s privacy.Our results showed that 50% of students heard about personal genome testing companies and 69% consider having a genetic test done. A majority of students (57%) agreed that PM represents a promising healthcare model, and 40% of students agreed that their study program is well designed for understanding PG/PM. This latter opinion seems to be particularly influenced by the field of study  contains supplementary material, which is available to authorized users. ImporPrevious studies have shown that many physicians and pharmacists have positive attitudes towards the clinical application(s) of PG/PM , 15. HowThere are also many additional challenges that have to be addressed in order to facilitate its broader clinical implementation –21. For It is also important to mention here an issue which is often overlooked and that is of the fairness (or lack thereof) related to how the benefits of pharmacogenetic research, such as an increasing number of genomic advances relevant to disease prevention, diagnosis, and treatment  togetherMore than a decade ago, the International Society of Pharmacogenomics proposed recommendations regarding PG education standards to the medical, pharmacy, and health schools globally . ConsequThis is the first study of students’ perception of pharmacogenomics in Bosnia and Herzegovina (BH). Although there are a few pharmacogenetic studies that have been performed in BH –50, an iThis descriptive, cross-sectional study was done using online and hard copy questionnaires  demographic and professional characteristics of the participants, (ii) participants’ diseases and treatment, (iii) awareness and attitudes towards genetic testing and personalized medicine approach, and (iv) challenges towards genetic tests, PG, and its clinical application. Key definitions of genetic testing, personalized medicine, and pharmacogenomic/pharmacogenetic test were provided to the participants in the instruction section of the survey. All survey questions were consistent across all participating faculties. The survey included yes/no/I do not know (not sure) questions. In addition, the survey asked for levels of agreement with various statements using a Likert scale  and also offered multiple choice questions. Before being sent to students for the study, this questionnaire was reviewed by three experts from various backgrounds . Along with the survey, an introductory cover page was attached describing the purpose and objectives of the study and inviting the students to participate in the study. Participants were assured their identity and all data are confidential. Participation was voluntary, and the study was approved by the Ethical Committee of the International University of Sarajevo.All categorical variables including participants’ demographics, professional information, and answers to questions regarding the perceptions about PG and PM were expressed as frequencies and percentages. Descriptive analysis was performed by using chi-square test and ANOVA for categorical variables. In addition, the binary logistic regression was performed in order to assess association between question of interest and hypothetically related covariates, while adjusting for age, gender, and level of education. In model I, we present this association prior to adjustment; in model II, we analyzed this association adjusted for age and gender, while model III additionally included an adjustment for the level of education. Odds ratio (OR) and corresponding 95% confidence intervals (CI) were computed, using a significance level of 5% for all statistical tests. Statistical analysis was performed by using IBM Statistical Package for Social Sciences (IBM SPSS®23).N = 559, 10% response rate), including students from the Faculty of Pharmacy (N = 183), students from the Faculty of Medicine (N = 158), students from the Faculty of Health Studies (N = 64), students from the Genetics and Bioengineering (N = 66), and 88 students from other non-HS- and non-MLS-related study programs  (N = 88). The majority of participants were female (71%) and undergraduate students , while 12% (N = 60) were attending Master and 3% (N = 13) PhD programs, with age ranging from 19 to 26 years old (86%).Table Participants’ responses to almost all survey questions regarding their awareness and attitudes towards genetic testing, pharmacogenomics, personalized medicine, and corresponding ELSI are shown in the tables, with selected ones that are further elaborated in the discussion. As shown in Table p = 0.010 and p = 0.025, respectively). A significantly lower number of these students agreed that PM represents the new and promising healthcare model as compared to the pharmacy and genetics students  (Table p = 0.001). In addition, students who are ready to make necessary changes in their lifestyle to reduce disease risk would also consider having a genetic test done to know their genetic tendency to develop a disease . Our results also indicated that students’ response on how much money they would be willing to spend to examine the effectiveness of a specific drug by using PG test was associated with their family monthly income , regardless of the field of their study . This association does not seem to be affected by age, gender, and/or levels of education.Our results of logistic regression analysis, performed to determine which independent variables were the strongest predictors of the specific students’ responses, demonstrated belief that genes influence health in moderate to complete extent. Students with this belief would consider having a genetic test done to find out which illnesses they might develop in the future .Results presented in Table p = 0.01). They also believe that in their future practice they should be able to identify patients that could benefit from genetic testing  as well as to be able to answer patients’ questions regarding PG and PM .Our findings presented in Table p = 0.011) as well as influences students’ wish to continue their postgraduate education in the area of personalized medicine. As compared to other respondents, it appears that the highest number of GBE students would like to continue their postgraduate education in this field . Furthermore, our results suggest that students who believe that their study program is well designed to provide them with an adequate understanding of PG are also more willing to continue their postgraduate education in the area of personalized medicine . Similarly, it appears that these students also believe that PG should be an important part of their study curriculum , and this opinion is particularly affected by the level of education .As shown in Table p = 0.011), consider having genetic test done (p < 0.05), and agree that PM represents a new and promising healthcare model (p < 0.001), as compared to their colleagues from the Faculty of Pharmacy in Tuzla whose curriculum seems to cover PG education only as a few topics built into other coursework. In addition, the higher number of pharmacy students from Sarajevo agree that PG should be an important part of their study curriculum (p < 0.001). All surveyed pharmacy students from the University of Tuzla disagree that PG should be an important part of their study curriculum as opposed to only 6% of pharmacy students from the University of Sarajevo who believe that PG is not essential for their education.Furthermore, as shown in Table p < 0.01, Table p < 0.01). Other ethical issues, such as incidental findings, racial issues, and stigma, were selected by 9%, 5%, and 4% of students, respectively. Our results revealed that 44% of students are worried about the possibility that PG test results may be passed to the unauthorized persons, and this opinion was shared similarly across different faculties (no significant difference). When asked which of the healthcare professionals should have an access to their PG information, 75% of students believe that a physician, 50% of students selected a genetic counselor, while 35% of them believe that a pharmacist should have this information. Furthermore, approximately one third of the respondents believe that they would be disadvantaged at work or job seeking in a case of unfavorable results of genetic test. Our analysis of questions related to the social issues showed that about half of participating students would not feel “helpless” or “pessimistic” (49%) nor they would feel “different” or “inadequate” (50%) in case of the unfavorable test results. Students’ answers regarding all above ELSI were similar across all participating disciplines (no significant difference). Our results presented in Table p = 0.004). A similar finding was demonstrated upon adjustment to students’ age, gender, and level of education .Our results showed that about 45% of all students participating in our survey are aware of different ethical aspects of genetic testing, ranging from 27% of students at the Faculty of Health Studies to 54% of pharmacy students . Our results showed that health and molecular life science students are generally aware of PG, and the level of awareness about personal genome testing companies appears to be similar between medicine and pharmacy students. However, students from the Faculty of Health Studies (FHS) seem to be less aware of these companies and less interested to employ PM as the novel healthcare model as compared to pharmacy, medicine, or genetics students. Although the respondents from the other non-health- and molecular life science-related studies are also generally aware of genes influence on their health, our results suggest that the level of their awareness about personal genome testing companies is significantly lower than that of their peers from medicine, pharmacy, and genetics.http://frmf.untz.ba/web/bs/integrisani-i-i-ii-ciklus/), pharmacy students from the University of Sarajevo think that their curriculum is well designed to understand PG and PM. The Faculty of Pharmacy in Sarajevo implemented changes in their curriculum in 2012. Based on our knowledge and information available at the Faculty’s website , so far in BH only this Faculty included an elective course Pharmacogenomics and Personalized Therapy in the biomedical study course. In addition, pharmacy students from Sarajevo have a lot of subject education built into their other coursework. This is may be the reason why student pharmacists from Sarajevo had more positive attitude and future plans towards PG, while the majority of the pharmacy students from Tuzla disagree that PG should be an important part of their study curriculum.Importantly, here we also demonstrated that about 40% of pharmacy students believe that PG should be an important part of their study curriculum and more than 60% of these students would like to continue their postgraduate education in the field of personalized medicine. This is in line with the recent study, which showed that the majority of students from the eight pharmacy schools in California were aware of pharmacogenomics, agreed that PG is important for the future pharmacist, and would be interested in a residency, fellowship, and/or career specializing PG . HoweverStudents of the Genetics and Bioengineering program at the International University of Sarajevo have special PG topics included in the syllabus of several undergraduate and graduate courses, including courses Pharmaceutical Biotechnology and Omics Technologies. Interestingly, more than 70% of GBE students agree that PG should be an important part of their study curriculum and more than half of them would like to continue their postgraduate education in the field of personalized medicine. Furthermore, as expected, in contrast to students from HS and MLS studies, half of students from other non-related study programs are not interested to continue their education in the field of pharmacogenomics and personalized medicine. Thus, in line with previous studies , 51, ourIt is expected that PG will continue to evolve over time and become one of the most relevant aspects of patient care. For this reason, it is of key importance to increase the number of professional practitioners in this new and expanding area of PG and to modify the current curricula to increase students’ knowledge and interests. The survey performed in the UK in 2008 found that typically 2–8 h of PG teaching were included in the pharmacology curricula of UK medical schools . PreviouAs our results indicate, BH students are interested to continue their education in PG. They would like to learn more about pharmacogenomics, its clinical examples and benefits, as well as about ELSI and future developments in this field. Students consider performing genetic tests in their future practice to optimize therapy for their patients as well as answering patients’ questions regarding PG and personalized medicine. Interestingly, our results suggest that the field of study significantly influences students’ wish to continue their education in this area. This is in line with the previous studies which indicated that healthcare students believe that PG is important for patient care , 40 and Students participating in our survey have shown to be aware of different ethical aspects of genetic testing. Interestingly, our results demonstrated that the majority of students appear to be concerned about the patient’s privacy and data confidentiality, followed by other ethical issues, such as autonomy, trust, beneficence relating to incidental findings, racial issues, and stigma. The majority of participants in our survey believe that the physician, pharmacist, and genetic counselor should have an access to their PG information. If genetic information is inappropriately disclosed, individuals may suffer from embarrassment, stigma, and discrimination, and these issues are recently considered as the key aspects of respecting confidentiality . This isOur results suggest that students from non-HS- and non-MLS-related faculties, including architecture, psychology, industrial, mechanical, electrical engineering, and others, are also generally aware of genes influence on their own health as well as about benefits of PM-based healthcare model. About half of these students agree that personalized medicine represents a new and promising healthcare model, and the majority of them would consider having a genetic test done to find out what illnesses they might develop in the future. However, their awareness of personal genome testing companies is lower as well as their readiness to contact a personal genome testing company and order a PG test, as compared to their peers from medicine, pharmacy, and genetics. Furthermore, these students from non-HS- and non-MLS-related faculties appear to be less aware regarding the potential ethical implications of PG testing, as compared to the students from medicine and pharmacy. These findings may indicate the significance of educating the public about genomics and its relevant bioethical implications. As recently suggested by Dressler et al. , roundtaInterestingly, our findings revealed that almost half of all respondents are worried about the possibility that PG test results may be passed to the unauthorized persons, and this opinion was shared similarly across different study programs. Students who are worried about the possibility that PG test may reveal that they have additional risk factors for other diseases would also feel “different” and “inadequate” in case of the unfavorable test results. Otherwise, about half of respondents would not feel “helpless” or “pessimistic,” nor they would not feel “different” or “inadequate.” This is in line with the previous study, which indicated that every individual would respond in a different way to the genetic test results, and it is considered essential for patients to have a proper counseling to help them understand the meaning and significance of the test results related to their own health , 61. ThiAn important strength of our study was that we recruited a variety of health science students across the nation within three different settings , genetics students, and students from other non-molecular life and non-health science programs. Another key aspect of our study was that, for the first time in BH, we have investigated students’ perceptions regarding their knowledge, skills, and attitudes towards pharmacogenomics and personalized medicine as well as their ethical, legal, and social implications. In addition, we compared opinions and attitudes of students who were exposed vs. students who were non-exposed to the PG course that further strengthens our results. Although our survey explored students’ interest in learning more about PG, we did not investigate which teaching tools students would favor in order to determine the most effective way to educate students in PG. Another limitation is that the survey which we designed assessed perceived (or self-reported) understanding and skills in pharmacogenomics and personalized medicine, with the limited possibility to evaluate actual students’ knowledge and capabilities. Lastly, survey tools that employ Likert scale are prone to central tendency bias due to selection of neutral answers. However, the potential impact of this type of bias on our results is probably small due to low percentage of neutral answers in the majority of our questions. Notwithstanding these limitations, our study will offer an important reference point for future comparative studies between different regions and countries as well as between different disciplines.Here we investigated for the first time students’ perceptions about pharmacogenomics and personalized medicine across the nation and various study programs that was, based on our knowledge, never studied before in Bosnia and Herzegovina. Our results show that most of the students participating in our survey, other than pharmacy students from Sarajevo, believe that they do not have well-designed curricula for understanding and practicing PG. The large number of students enrolled in molecular life and health sciences clearly expressed their wish to be more educated in this field. This implies the need for the development of study programs in the area of PG in order to equip future providers with the knowledge, skills, and attitude required to practice personalized medicine. This could also further highlight the need for increased genetic literacy education throughout high school levels throughout Europe and beyond. In order to accomplish this important goal, it would be pertinent to enhance collaboration between universities, healthcare institution, and governing bodies to incorporate more training and continued education topics related to pharmacogenomics and genetic testing. There could also be a potential here for increasing the number of interdisciplinary events or training between different disciplines, such as those highlighted in this study, both for students and for educators and researchers in order to discuss various forms of curriculum development. Thus, expanding the pharmacogenomic path of biomedical education represents an essential step for ensuring the widespread clinical implementation of personalized medicine.Additional file 1:The survey questionnaire—the file describes the questionnaire that was employed in this study. (PDF 295 kb)Additional file 2:p values calculated with chi-square test between each faculty, based on the first question from Table Students’ awareness about pharmacogenomics—the table represents Additional file 3:p values calculated with chi-square test between each faculty, based on the fourth question from Table Levels of students’ awareness about genetic tests and pharmacogenomics—the table represents Additional file 4:p values calculated with chi-square test between each faculty, based on the first question from Table Students’ opinion regarding the study curriculum and their future plans in pharmacogenomics—the table represents Additional file 5:p values calculated with chi-square test between each faculty, based on the third question from Table Students’ opinion regarding the study curriculum and their future plans in pharmacogenomics—the table represents Additional file 6:p values calculated with chi-square test between each faculty, based on the first question from Table Students’ awareness and opinion regarding the ethical, legal, and social issues—the table represents


The aim of this study was to investigate whether non-reassuring foetal status (NRFS) affected an infant’s temperament, or if the temperament formed prenatally resulted in an excessive heart rate reaction that was diagnosed as NRFS. We examined the correlation between NRFS and difficulty in holding a baby, and the amount of crying in the one month after birth, which was considered an indicator of the newborn’s temperament. We divided the cases with NRFS into positive NRFS and false positive NRFS. NRFS was associated with bad mood, frequent crying for a long duration, and intense crying. After adjustment for other covariates, NRFS was associated with bad mood , and intense crying . In the multi-variable model, positive and false positive NRFS were not clearly associated with neonatal irritability. When stratified by parity, NRFS and false positive NRFS were likely to be positively associated with neonatal irritability in parous women. The clear association between NRFS and intense crying was observed in parous women , but not in nulliparae  (p for effect modification <0.01). Similarly, increased odds of intense crying associated with false positive NRFS were only found in parous women  (p for effect modification = 0.03). There was no association observed between positive NRFS and irritability; therefore, NRFS has no effect on an infant’s temperament. It has also been reported that changes in the temperament of babies with diseases related to neuropsychiatric development can be seen in the neonatal and infant stages3. However, there are almost no reports on the association between foetal distress and infant temperament. Irritability is an important element of temperament. It can negatively affect parent-child relationships, which in turn can lead to child abuse. Furthermore, it affects the interactions between the mother and child as well as the child’s mental health.Foetal distress during labour is a risk factor for developmental disorders, including autism4.To the best of our knowledge, only one study has investigated the relationship between postnatal irritability and changes in foetal heart rate during labour that was used to diagnose foetal distress. The study reported a correlation between reduced heart rate during labour and the proportion of crying as an indication of irritability up to day 5 after birth. However, it is unknown whether this reaction was due to hypoxia or acidaemia during labour, or it was simply caused by the predisposition of the neonate6. If we presume that an infant’s temperament is already formed before birth, then their heart rate reactivity to the stress of labour may also differ.Regarding the possibility that an infant’s personality is already formed in infancy, there are reports that heart rate reactivity in infancy is related to postnatal temperamental reactivity, and the characteristics of an infant’s behaviour represent the individual differences in reactivity during infancy9. However, the cause of NRFS false positives is unknown11. Furthermore, the term ‘foetal distress’, an inaccurate and non-specific term, does not reflect the reality; therefore, this term is now being replaced with the term non-reassuring foetal status (NRFS)12. In this article, examples that were previously described as foetal distress are called NRFS.Either way, in clinical practice in obstetrics and gynaecology, the well-being of the foetus is evaluated by monitoring the foetal heart rate. When abnormalities in foetal heart rate are observed, which are usually a result of hypoxia and/or acidaemia, the well-being of the foetus cannot be ascertained. However, even if there is an abnormality of the foetal heart rate, and a diagnosis of non-reassuring foetal status (NRFS) is made, normal umbilical cord arterial blood pH and Apgar scores are noted after birth. Therefore, NRFS false positives are thought to be associated with an increase in the number of Caesarean deliveries14. We believe that foetuses with these features and false positive NRFS had an overreaction to labour stress. Given that the amount of crying is said to be related to the behavioural characteristics of the newborn16, and the difficulty in holding a baby is said to be related to developmental characteristics17, we examined the correlation between NRFS and the difficulty in holding a baby and the amount of crying in the one month after birth that was considered the temperament of the newborn.Cases with foetal heart rate abnormalities that satisfied the criteria of an umbilical cord arterial blood pH ≥ 7.2 and an Apgar score ≥7 at 5 minutes were classified as NRFS false positiveThe aim of this study was to ascertain if NRFS affected an infant’s temperament, or if the temperament formed prenatally generated an excessive heart rate reaction diagnosed as NRFS.19.The Japan Environment and Children’s Study (JECS), an on-going large-scale birth cohort study, enrolled women as early in pregnancy as possible. The protocol of JECS is described elsewhere along with a discussion on its population representativenessThe JECS protocol was approved by the Japan Ministry of the Environment’s Institutional Review Board on Epidemiological Studies, and the Ethics Committees of all participating institutions. JECS protocol was conducted in accordance with the Helsinki Declaration and other nationally valid regulations, and written informed consent was obtained from each participant.Between 2011–2014, a total of 103,099 pregnancies from fifteen Regional Centres located throughout Japan  were identified. Of the 103,099 pregnancies, only 97,454 unique mothers were included. Of these, we further excluded 27,129 women due to the following reasons : multiple pregnancies (n = 949); miscarriages or stillbirths or no delivery records ; preterm (<37 weeks of gestation) or post-term (>41 weeks) deliveries ; missing information on maternal age at delivery, umbilical cord blood pH, or Apgar scores at five minutes ; and no responses to the three irritability questions in the maternal questionnaire at one month after delivery . The remaining 70,325 participants were included in our final analyses.20. In Japan, when abnormalities in foetal heart rate are observed, obstetricians diagnose the cases using intrapartum management guidelines based on the foetal heart rate pattern classification20. That is, the combination of the various components of the FHR patterns serves to estimate the degree of risk for the foetus, which is then classified into five levels. The five level categories are the same as those used in countries such as the United States21. Those with high risk levels of 3–5 are diagnosed with NRFS. However, in the cohort data, there was no information on the five levels, and only information on the presence or absence of NRFS was available. Of all the infants with NRFS, infants with an umbilical cord blood pH <7.2 and an Apgar score of <7 at 5 minutes after birth were categorised as having positive NRFS, and infants with an umbilical cord arterial blood pH ≥7.2 and an Apgar score ≥7 at 5 minutes were categorised as having false positive NRFS.In the present study, we defined NRFS as that diagnosed by an obstetrician, which was obtained from the medical record transcriptions at birthA self-administered questionnaire was distributed to mothers who visited for a health check-up at one month after delivery by research coordinators or via mail. The questionnaire included three questions about a baby’s irritability. The first question was “When you hold your baby, how often do you feel difficulty to hold your baby due to his/her fretting, crying or throwing his/her head back?” with options of “often”, “sometimes”, “seldom”, and “none”, and those who answered “often” were categorised as ‘bad’ mood. The second question was “How often and long does your baby cry?” with options of “quite often and long”, “sometimes and shortly”, and “seldom and hardly”, and those who answered as “quite often and long” were categorised as ‘frequent crying for a long duration’. The third question was “Does your baby cry very hard sometimes no matter what you do to stop him/her?” with options of “yes” and “no”, and those who answered as “yes” were categorised as ‘intense crying’.22. Postpartum depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) included in the questionnaire at one month after delivery23. According to previous studies, participants with a score of 9 or more were categorised as having depressive symptoms24.Maternal characteristics, including maternal age at delivery, smoking habits, alcohol consumption, educational background, household income, parity, and infertility treatment, were collected via self-administered questionnaires and/or medical record during the pregnancy. Also, delivery and birth record transcripts were obtained to gather information about the gestational age at delivery, type of delivery, infant sex, and birth weight. In this study, small for gestational age (SGA) was defined as birth weight <10th percentile of birth weight standards by gestational age, sex, and parity for Japanese neonatesMultilevel logistic regression analyses were used to explore the association between NRFS and neonatal irritability, considering that mothers were nested in each Regional Centres, and to estimate the odds ratios (ORs) of neonatal irritability and 95% confidence intervals (CIs), without NRFS as a reference. We initially adjusted for maternal age at delivery, and then further adjusted for educational background , household income , smoking habits , alcohol consumption , gestational age at birth , SGA , infant sex , parity , infertility treatment , type of delivery , and postpartum depressive symptoms .When the frequencies of NRFS were affected by certain background factors , we performed stratified analyses. Effect modification of the association between NRFS and neonatal irritability according to such factors was evaluated by a likelihood ratio test. This study used the dataset jecs-ag-20160424, which was released in June 2016, and revised in October 2016. Stata version 14  was used for all analyses.The mean maternal age at delivery was 31.2  years in this study population. The baseline characteristics in those with or without NRFS are shown in Table Table When we stratified by parity, NRFS and false positive NRFS were likely to be positively associated with neonatal irritability in parous women Table . The cleAlthough all cases of NRFS were associated with a bad mood, and intense crying, cases of positive and false positive NRFS were not clearly associated with infant irritability. However, the clear association between false positive NRFS and intense crying was observed in parous women. Therefore, the events during labour did not affect the irritability of the newborns, and, thus, the irritability had formed prenatally.28, while others have stated that it affects the temperament of neonates29. Furthermore, recently there have been reports on the link between the autonomic nervous system reactivity and temperament; people with small fluctuations in their heart rate during the resting phase have excessive circulation reactions–the smaller the fluctuation, the less able they are to control their emotions, and their emotional reactions are greater–and they are less able to withstand significant stress32.Some reports have stated that the intrauterine environment affects an infant’s mental development35. Despite NRFS resulting in emergency Caesarean section deliveries in foetuses with cardiac malformations, many of them do not have acidosis36. Foetal heart rate patterns are mainly produced by the autonomic nervous system and the cardiovascular centre in the brain stem11. We believe that the false positive NRFS may be caused by several factors that can affect these systems in the absence of hypoxia and/or acidaemia.Factors such as congenital malformations, infections, and cigarette smoking have been linked to false positive NRFS; furthermore, there are reports of a high rate of false positive NRFS even when the foetus’ well-being has been maintained39. We previously clarified that air pollution exposure during early pregnancy, which results in systemic inflammation, is related to false positive NRFS40. The intrauterine environment affects the foetus, and it may affect the irritability of the newborn; therefore, so we presume that false positive NRFS also incorporate factors related to the infant’s temperament.Recently there has been an increasing number of reports about the effect of maternal inflammation and immune activity on the neuropsychiatric development of a childOne of the limitations of this study was that the cohort data had no information on the NRFS 5-grade classification; only data on the presence or absence of NRFS after diagnosis by an obstetrician was available. Thus, we could not perform analyses for the FHR pattern risk level in this study. However, since obstetricians diagnosed the patients using intrapartum management guidelines based on the foetal heart rate pattern classification, at least the diagnosis of NRFS can be considered accurate. We expect that analyses based on the FHR pattern risk levels will be conducted in the future.43. An association was found between false positive NRFS and intense crying only in multipara women. With the first child, the mother has little childrearing experience, she is unable to make a comparison, which may have suppressed the distribution spread. Either way, there was no correlation seen between positive NRFS and irritability. Therefore, we believe that NRFS has no effect on an infant’s temperament.In addition, another limitation of this study is that the information was collected from the mothers via a questionnaire. The infants were not directly examined, which could possibly result in a bias. However, the strength of this study is in its large sample size. Therefore, we believe that a certain trend can be detected; namely, the differences in experiences of the mothers depending on the birth order of the child may have affected the outcome. Therefore, we conducted our investigation after classifying the mothers based on paritySupplementary figure & table