Two important challenges in the analysis of molecular biology information are data (multi-omic information) integration and the detection of patterns across large scale molecular networks and sequences. They are are actually coupled beause the integration of omic information may provide better means to detect multi-omic patterns that could reveal multi-scale or emerging properties at the phenotype levels.coli metabolic response to treatments at the whole network level. Our algorithm, MORA (Multi-omic relations adjacency) is able to detect patterns which may represent metabolic network motifs at pathway and supra pathway levels which could hint at some functional role. We provide a description and insights on the algorithm by testing it on a large database of responses to antibiotics. Along with the algorithm MORA, a novel model for the analysis of oscillating multi-omics has been proposed. Interestingly, the resulting analysis suggests that some motifs reveal recurring oscillating or position variation patterns on multi-omics metabolic networks. Our framework, implemented in R, provides effective and friendly means to design intervention scenarios on real data. By analysing how multi-omics data build up multi-scale phenotypes, the software allows to compare and test metabolic models, design new pathways or redesign existing metabolic pathways and validate in silico metabolic models using nearby species.Here we address the problem of integrating various types of molecular information  to analyse the E.coli multi-omic metabolic networks contain position dependent and recurring patterns which could provide clues of long range correlations in the bacterial genome.The integration of multi-omic data reveals that E.The online version of this article (10.1186/s12859-018-2175-5) contains supplementary material, which is available to authorized users. As it is shown in Fig. 1c(1)(2)g4,g5,g6 could be on the same strand or on both. As said previously, the gene reciprocal positions on the double strand are merged and represented on a line sequence. Thus, when the gene order changes in one of the two strands, then the multi-omic pattern ) changes the arrangement of its values. Indeed, in Fig. 1c(1) and (2) the fragment of the pattern changes because of the swap of g5 and g6.In an integrated multi-omic space, as that in Fig. 1rocesses . As showdata-structure relations could involve more than one omic layer. For example, the proteomic and the metabolomic layers can be represented as a protein-centric network of reactions G where the node-set V contains proteins and the edge-set E represents the enzymatic reactions. In the protein-centric network representation, as illustrated in Fig. 1b(1), the reversible reactions are depicted as a double arrow link (⇔) and the irreversible reactions are represented as single arrow links (←or→) ). A high score is assigned when the multi-omics ej and ej+1 are directly connected on the pathway (green dotted lines) or with the shortest path (magenta dotted lines), otherwise a score of 0 is assigned. The multi-omic reciprocal adjacency is computed for all the adjacent couples c. The median value of the MORA weights is a summary index of the reciprocal influences between multi-omics and underlines the interplay among them on the MLS. Note that in multi-omic sequence the propagation of influences of an element becomes gradually weaker as the distance from its neighbouring elements increases: the propagation of influences is limited to the metabolic network average path length (APL) , decreasing its influence gradually and in an inversely proportional way with respect to the path length. If sequences and pathways do not present reciprocal influences (RI=0), the oscillating multi-omics lose their significance with respect to the pathways and vice-versa. In these cases, MLS interactions do not present a real biological meaning.MORA is a search algorithm that weights the multi-omics with respect to their positions on the MLS. Its purpose is to assign a high score to the multi-omics that have two properties at the same time: they are adjacent on the sequence and strictly connected on the pathway. The algorithm assigns a score equal to zero to the multi-omics that are adjacent on the sequence but unconnected to the pathway. In Fig. movi, which is the pattern of the i-th MLS, Gi, which is its pathway and APL. Let us define δ=2 as the distance on the sequence from ej to ej+1,∀j∈ . δ is fixed to 2 and identifies the adjacency of positions j and j+1 on the pattern  is associated with a couple of nodes in the pathway with the same index for simplicity: . Then, the algorithm will search in Gi the shortest paths with the end nodes nodefrom=pj and nodeto=pj+1. Also, we define ψ∈  as the path distance between pj and pj+1. For example, in Fig. MORA algorithm takes as input the following parameters: infl as an array of all zeros with the same length of movi. When the algorithm finds the shortest paths on Gi from nodefrom to nodeto, it takes the positions z of the path nodes on the movi and in correspondence of these positions he gives a weight to the vector element inflz . The weights are computed with the following formula: y -th shortest path found. These weights are summed up in the vector infl as follows: infl[z]=infl[z]+w. If there are c couples with δ=2 and ψ=2 then a perfect adjacency on movi and a direct edge on Gi are present, and then w=1. The weight w becomes progressively smaller if the distance ψ between the end nodes increases. The maximum distance between the end nodes is limited by the upper bound that is properly ⌈APL⌉. The supplementary Section S6-Figure 4 ), in snaked networks  and on complete networks (not shown).We define the array of weights MORA is given as yardstick for validating and deciding if the measures that are taken in next Sections for oscillating multi-omic patterns and pathways are comparable and at what level of reliability.https://github.com/lodeguns/MORA.Algorithm 1 presents a schematic description of the MORA methodology. The code is available at N=2). A multi-omic pattern presents an alternation if the two adjacent ej and ej+1 in the pattern sequence are subtracted and ∣ej−ej+1∣=1. If the result of the subtraction is 0 then ej and ej+1 are equal and there is not an alternation a1).In this work, the multi-omics are discretized in a binary field as described in the previous “l is defined as the length of mov and div=l−1 is the number of divisors between the ej. For each pattern, the relative multi-omic pattern score a.s  from the maximal absolute score . Thus, we have a powerful instrument to investigate how much the oscillations observed in movobs are found to be distant from the ideal  oscillations movid. The distance d in Eq. The maximal absolute score is proved to exist and it is unique for each pattern sequence with a specific length ). Instead, they show an anti-dyadic property if they have oscillating multi-omics (couples of red-blue nodes). Following the model of Park and Barabási, it is possible to compute the expected value of an anti-dyadic effect on the couples of nodes that present an alternation. Let n1 be the number of pathway nodes with multi-omic values equal to 1, and n0 be the number of pathway nodes with multi-omic value equal to 0. In this way, the total number of nodes in the pathway is N=n1+n0. The number of links between nodes that show the anti-dyadic property are described by the variables m10 and m01. The number of links between nodes that do not show an alternation (dyadic property) are represented by the variables m11 and m00. Therefore, the total number of edges for a pathway is M=m10+m01+m11+m00. Note that the maximal possible number of edges in a directed network is equal to N(N−1). The network density δ .The proposed methodology with regard to performances could be comparable with well-known mining methodologies of sequence patterns  and dyad, etc …) , 52. Oscfeatures . We suggnt works . Once thcoli. The lack of methodologies for multi-omics integration decreases the chance to detect emerging motifs and patterns across sequences, networks or pathways. The current need of analytics to compare and test metabolic models, the accurate design of a new pathway or the redesign of an existing metabolic pathway or the experimental validation of an in silico metabolic model using a nearby species require the information of how multi-omics data build up multi-scale phenotypes. The high level comparison is based on novel algorithms which take the low level approach at pathway level framework and generate multi-scale multi-omic metabolic networks. The goal is to find relations between oscillating multi-omic patterns on sequences and oscillating motifs on metabolic networks. Recurring oscillating multi-omic patterns are discovered to be related to multi-omic metabolic network motifs. This last novel feature can be related to the highly conserved gene order and to the highly specificity of enzymatic reactions and their network topology. The discovered motifs can be not only useful in the study of bacterial phenotypic responses but also in applications of metabolic engineering and optimizations. Then, this work can contribute to the study and to the creation of new interesting metabolic circuits based on binary multi-omic network motifs and their recurring patterns. Our framework is implemented in a software written in R which provides effective and friendly means to design intervention scenarios in the perspective of the synthetic biology.In this paper a multi-omic integration based methodology is introduced to analyse bacterial oscillating multi-omics on sequence patterns and network motifs. The subject of our analysis is E.Additional file 1This file describes all the technical details and procedures used for the multi-omic data-integration. In addition, some Sections show some math proofs for what is concerning the oscillating multi-omics, a toy example for the multi-omic relational adjacencies and some concrete examples of pathway and patterns. (PDF 767 kb)Additional file 2It is a PDF document which contains 66 measures of dyadic/anti-dyadic effects, oscillation similarity scores, and reciprocal influences computed with MORA. Data are reported in standard conditions and considering the average effect of 69 treatments. (PDF 108 kb)


Primary reasons for drinking were not associated with alcohol intake for former flushers. Never flushers had significantly higher AUDIT scores when drinking for pleasure , stress/depression , or boredom  than peer pressure. Our results suggest that former and never flushers consume higher amounts of alcohol on average than never flushers. For current flushers, drinking for pleasure or stress/depression may increase alcohol intake, while for never flushers, drinking for pleasure, stress/depression, as well as boredom may have the same effect.Alcohol consumption among individuals who experience a flushing response  can result in serious health problems. However, studies on reasons for drinking among flushers, especially in the college context, are limited. Thus, this study investigated the association between primary reason for drinking and alcohol use among a nationally representative sample of current, former, and never flushing college students. The aim was to measure whether college students with current or former experience of facial flushing have different primary reasons for drinking compared to students with no experience of facial flushing. We surveyed and analyzed the data of 4590 students in a nationally representative sample of 82 colleges in South Korea. Multiple regression analysis was used to identify the association between primary reason for drinking and alcohol intake. Alcohol intake was measured using the Alcohol Use Disorders Identification Test (AUDIT). Among 1537 current (33.5%), 152 former (3.3%), and 2901 (63.2%) never flushers, mean AUDIT scores were 7.715 ± 5.434, 11.039 ± 6.405, and 10.465 ± 5.779, respectively. Current flushers had significantly higher AUDIT scores when drinking for pleasure (β = 2.696,  Alcohol consumption among college students contributes to an average of approximately 1825 deaths , 97,000 sexual assaults, and 600,000 injuries in the United States each year [Consequently, a large body of research has identified reasons for drinking and alcohol intake among college students. Such reasons include motives to maintain or increase positive affective states , social However, few studies have compared reason for drinking and alcohol intake according to flushing status. This is alarming as flushing upon alcohol intake is a common health concern among East Asians. Brooks and colleagues found that approximately 36% of Korean, Chinese, and Japanese individuals experience facial flushing  while TaFlushing occurs among individuals who inherit a deficiency in the acetaldehyde-breaking enzyme, aldehyde dehydrogenase 2 (ALDH2) . Upon coFortunately, because of the unpleasant and noticeable consequences of drinking alcohol for flushers, flushers consume less alcohol than non-flushers. In many studies, it has been noted that flushers consume lower amounts of alcohol than non-flushers with respect to drinking frequency, binge drinking, and number of drinks per drinking session . A 2006 Subsequently, primary reasons for drinking are likely to differ among flushers and non-flushers. In a 1997 study of Japanese college students, it was found that while non-flushers are likely to enjoy consuming alcohol at home, with intimate friends, or at club parties, whereas flushers are more likely to consume alcohol when pressured to drink, especially by non-flushers, at social events .Given the limited literature on reasons for drinking and alcohol intake among current, former, and never flushing college students, our study asks two questions. Firstly, do the same primary reasons for drinking and alcohol use apply to flushers and non-flushers? Secondly, how do the primary reasons for drinking and alcohol use differ among current flushers and former flushers? We hypothesize that different primary reasons for drinking and alcohol use will apply to flushers and non-flushers due to the unpleasant and noticeable consequences of drinking for flushers. According to previous studies, flushers are more likely to drink because of social pressures than enjoyment, whereas non-flushers have a range of reasons for drinking including positive, social, and emotional . We alsoThe present study examines the association between primary reasons for drinking and alcohol intake among current, former, and never flushing students in a nationally representative sample of college students in South Korea. It also investigates the factors that strengthen and weaken this association.In the 2017 national statistics published by the Korean Educational Development Institute on college students, we found that 1,951,940 students  are enrolled in 356 colleges  in South Korea. From these colleges, we excluded 23 that had fewer than 500 administered students or were located in the remote island of Jeju. Of the remaining 333 colleges, we randomly selected 85 colleges for our survey analyses. During the recruitment process, three four-year colleges declined to participate in our survey for religious reasons, decreasing the total number of colleges in our investigation to 82 . From these colleges, we stratified a proportionately representative sample of undergraduate students to match national statistics  see .Data were collected via face-to-face surveys with interviewers randomly selecting students passing by each campus’s department buildings. Data collectors were instructed to survey around 60 students from each campus; three males and three females from 10 different majors. Teams of collectors were trained for consistency by Gallup and researchers of our investigation; each question of the questionnaire was required to be administered orally in a face-to-face manner, at an enclosed space like a café or lecture room.In total, 5000 students completed our survey instrument. The response rate was 68.7%, with the total number of approached participants being 7278. A financial incentive of 10,000 Korean Won  was given to each participant upon completion of the 14-page survey instrument. For the purpose of this investigation, we excluded 211 students who reported never consuming a sip of alcohol in their entire lives, 199 students who reported not consuming a single drink in the last 12 months, and 43 students who reported only consuming alcohol during special traditional Korean events.The survey instrument asked students a number of questions about their drinking behavior, health, and thoughts on campus-alcohol policy. Whenever possible, the instrument included alcohol-related questions that had been previously given in other international, national or large-scale epidemiological studies including the Harvard College Alcohol Study, the Korea National Health and Nutrition Examination Survey (KNHANES), and the Korea Youth Risk Behavior Web-Based Survey (KYRBS).Following the standards of the Korea Centers for Disease Control & Prevention, a standard drink was defined as the amount of alcohol contained in one standard drinking glass of alcohol , equivalent to: 1 shot of soju, 1 glass of bottled beer, 2/3 of a canned beer, 1/2 glass of draft beer, 1/2 bowl of makgeolli (rice wine), 1/2 glass of wine, 1 glass of whiskey, 1 shot of cheongju (refined rice wine), 1 shot of herbal liquor, 1 shot of fruit wine, or a 3/5 glass of mixed liquor (soju+beer).All subjects gave their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by Yonsei University Health System’s Institutional Review Board (Y-2017-0084).In this study, alcohol use was measured through the Alcohol Use Disorders Identification Test (AUDIT) scale and selected as the outcome variable. The AUDIT questionnaire was given in its original format, consisting of ten questions related to frequency of drinking, number of drinks per session, frequency of heavy drinking, impaired control following drinking, morning-after drinking, and feelings of guilt upon drinking, frequency of blackouts, alcohol-related injuries, and family concern over drinking. While total scores can range from 0 to 40, the World Health Organization states that a score of 0–7 indicates low-risk of alcohol-related problems and harm, 8–15 moderate risk, 16–19 high-risk, and 20 or more almost certainly representative of alcohol dependence . As a scPrimary reason for drinking was measured via individual answers to the question, “In the last 12 months, what was your primary reason for drinking alcohol?” Respondents were required to select one primary reason for their drinking in the last 12 months, ranging from the following options: “peer pressure,” “pleasure,” “stress/depression,” “boredom,” and “other”. “Other” responses included the following: “force of habit,” “birthday,” “anniversary,” “to sleep.”Flushing was measured through the questionnaire created by Yokoyama and Omori, which asks the following questions to determine past and present ALDH2 heterozygotes: (1) Do you have a tendency to develop facial flushing immediately after drinking a glass (about 180 mL) of beer? (2) Did you have the tendency in the first one or two years after you started drinking? Individuals who replied “yes” to question 1 were determined current flushers; individuals who replied “yes” to the second question were determined former flushers, and individuals who replied “no” to both questions were determined never flushers. This questionnaire was rated to have a high sensitivity rate of 90.1% and specificity rate of 88.0%  in classA series of three regression analyses were conducted for our investigation. First, frequencies and mean AUDIT scores were calculated for subjects according to sex, year level, major, grade point average (GPA), allowance, living status, smoking, underage drinking experience, and number of sororities/clubs through analyses of variance. To examine the association between primary reason for drinking and alcohol use, multiple regression analysis were performed, after controlling for the following confounders: sex, year level, major, GPA, allowance, living status, smoking, underage drinking experience, and number of sororities/clubs. Lastly, an examination of primary reasons for drinking by flushing status, by gender was conducted for our subgroup analyses. Multiple regression analyses were used to test this interaction, while controlling for year level, major, grade point average (GPA), allowance, living status, smoking, underage drinking experience, and number of sororities/clubs. The calculated p-values in this study were considered significant if lower than 0.05. All analyses were performed using SAS software, version 9.4 .p < 0.0001) or stress/depression . Having a grade point average below 3.0 , having higher amounts of allowance or spending money , living alone/flatting , having underage drinking experience , and being in two or more sororities  were also associated with higher AUDIT scores.p = 0.028), being in the highest allowance quartile , and having underage drinking experience  were associated with increased AUDIT scores.No primary reasons for drinking were associated with higher AUDIT scores for former flushers. However, having a grade point average below 3.0 , stress/depression , or boredom  than peer pressure. Having a grade point average below 3.0 , having higher amounts of allowance , living status , and having underage drinking experience  were associated with higher AUDIT score. Such statistically significant trends were not found in the logistic regression analysis investigating the association between various factors and a one-unit increase in the AUDIT  and females had higher AUDIT scores when drinking for pleasure . Among former flushers, both males  and females  had higher AUDIT scores when drinking due to boredom, however, this association was not statistically significant. Among never flushers, both males  and females  had higher AUDIT scores when drinking due to pleasure.In our investigation, former flushers had the highest average alcohol consumption score among current, former, and never flushing individuals. With continued drinking, current flushers can have diminishing symptoms over time and become former flushers; alcohol flushing diminishes in intensity due to the development of tolerance to acetaldehydemia by higher-risk persons with a long or heavy drinking history . HoweverOne possible explanation for the emergence of former flushers is that individuals who flush often attempt to overcome the social embarrassment of flushing by continuing to drink . HoweverAccording to a study of Asian-Americans and Pacific Islanders, pleasure is not a reaction that is usually associated with reason for drinking among flushers. Because of the unpleasant flushing reaction, individuals with the flushing reaction are likely to consume less or no alcohol, and have reduced risk for alcoholism . On the However, in our study, it was found that female flushers drink more for pleasure than peer pressure. The difference may be cultural; from 2005 to 2015, there has been a 10% increase in the monthly drinking rate of South Korean women between the ages of 19 and 29 . The difThe associations between primary reasons for drinking and alcohol intake among current and never flushing college students were the main findings of our study. While both groups had greater alcohol intake if primary reasons for drinking included pleasure or stress/depression, drinking due to boredom was only associated with increased alcohol intake among never flushers. As drug-makers have associated flushing with displeasure and incorporated acetaldehyde dehydrogenase inhibition to develop effective treatments for alcoholics, more research must be done regarding this finding ,35.Furthermore, among current flushers, males had higher AUDIT scores when drinking due to stress/depression while females had higher AUDIT scores when drinking for pleasure. Among never flushers, both males and females had higher AUDIT scores when drinking for pleasure. In previous studies, popular reasons for drinking among college students include pleasure and social reasons; however, stress was only a primary reason for drinking among 2.1% of college students .This study has several limitations that should be considered when interpreting results. First, our study is cross-sectional in design; thus, caution should be exercised in interpreting causality between primary reason for alcohol consumption and alcohol intake. Furthermore, the Yokoyama and Omori questionnaire for determining ALDH2 deficiency are limited in reliability and validity relative to clinical evaluations of these symptoms by a healthcare professional. A more reliable method of evaluating the ALDH2 genotype would be combined use of the self-reported facial flushing questionnaire and an ethanol patch test, as used by Ishibashi and colleagues . Also, gSecond, there are not enough previous studies with regard to a nationally representative sample of Koreans when it comes to measuring flushing and its effect on drinking behavior/related problems. It is difficult to see whether the values we calculated are similar to that of the statistics found in previous studies for Koreans, especially for the college students’ age group.Third, various biases may have emerged from our sampling and surveying methods; because college students in South Korea drink large amounts of alcohol relative to adults, different patterns are likely to emerge in an adult sample. Likewise, a small number of Christian colleges that were originally in our sample declined our request for participation because of their principles regarding abstaining from drinking and thus, had to be replaced with non-Christian colleges. Because of the face-to-face method that we employed for accuracy of obtaining responses to complicated questions, there may have been response biases, relative to social desirability. The majority of questions in our survey instrument required students to think about their drinking behaviors in the last 12 months or so, which likely resulted in recall bias. Finally, although we included numerous lifestyle covariates as potential confounders, the limited nature and number of questions in our instrument made it difficult in other confounding variables, relative to health, socio-demographics, gene-environment, and lifestyle, to be measured and controlled.Lastly, our survey measure only questioned the “primary reason” for drinking among students in the last 12 months. However, over a 12 month period, drinkers are likely to drink for a variety of primary reasons and this should be considered when interpreting our results.Despite these limitations, our study also has several strengths. Few studies have measured ALDH2 deficiency for a nationally representative sample in South Korea or taken an epidemiological approach to see the association between primary reasons for drinking and alcohol intake among current, former, and never flushing college students.Our study has found certain risk-groups in the college sample including former flushers, who primary drink due to peer pressure and/or social embarrassment, male flushers who consume alcohol due to stress/depression, female flushers who consume alcohol due to pleasure, and never flushers who primarily consume alcohol due to pleasure, stress/depression, and boredom. However, more research is required to understand why female flushers consume alcohol due to pleasure despite the disagreeable side effects of drinking in a college context. More research must also be conducted on the primary reasons for drinking among former flushers as they are in the greatest danger of developing detrimental health effects among current, former, and never flushers. Researchers, educators, and policy-makers are encouraged to further investigate, and target such students when creating campus alcohol initiatives and education programs to alleviate these problems.


There is no common consensus on how to define the reference population for determination of high‐sensitivity cardiac troponin (hs‐cTn) upper reference limit (URL). This study aimed to establish 99th percentile URLs of hs‐cTnT under both 2018 AACC/IFCC criteria and improved selection criteria for further judging whether two URLs are different.Applying the stratified cluster sampling protocol, this study took 1848 apparently healthy subjects in communities of Shenyang China as the screening objects. We first followed 2018 AACC/IFCC criteria using surrogate biomarker for diabetes, myocardial dysfunction, renal dysfunction, and electrocardiogram. Then, we followed improved selection criteria to exclude hypertension, overweight and obesity, and dyslipidemia by physical examination and laboratory screening. Accordingly, 99th percentile URLs of hs‐cTnT were established.If the 2018 AACC/IFCC criteria were applied, 99th percentile URLs  of hs‐cTnT male, female, and total were 19 (17‐20) ng/L, 16 (15‐17) ng/L, and 18 (16‐19) ng/L, respectively. If added a single supplementary selection criteria, 99th percentile URLs of hs‐cTnT total reduced to 16 ng/L, 17 ng/L, and 16 ng/L, respectively. If the improved selection criteria were applied, 99th percentile URLs  of hs‐cTnT male, female, and total were 18 (14‐24) ng/L, 13 (11‐16) ng/L, and 16 (13‐17) ng/L, respectively. The 99th percentile URLs of hs‐cTnT male were higher than those of female in every age group.Improved selection criteria through questionnaire survey, physical examination, and laboratory screening to further exclude hypertension, overweight and obesity, and dyslipidemia can avoid overestimation of the 99th percentile URL of hs‐cTnT. The CLSI document Reference Intervals in the Clinical Laboratory EP28‐A3c)c3 recommThe chief objective of screening was to exclude cardiovascular disease and related disease, especially the ones which might influence hs‐cTn values. There was still a possibility that 2018 AACC/IFCC criteria, through questionnaires, surrogate biomarkers, and imaging, might omit these important cardiovascular risk factors,To summarize, the objective of our study was to establish 99th percentile URLs of hs‐cTnT (Roche Diagnostics) under both 2018 AACC/IFCC criteria and improved selection criteria through questionnaire survey, physical examination, and laboratory screening to further exclude hypertension, overweight and obesity, and dyslipidemia in a Chinese population, further judging whether two 99th percentile URLs of hs‐cTnT established are different.22.12 was used to represent surrogate biomarker for renal dysfunction. Aminoterminal pro–B‐type natriuretic peptide (NT‐proBNP) ≥ 125 ng/L (<75 years) or 450 ng/L (≥75 years) was used to represent surrogate biomarker for myocardial dysfunction. Electrocardiogram was used to exclude ventricular hypertrophy, atrial hypertrophy, WPW syndrome, MI, atrial fibrillation, atrial flutter, supraventricular tachycardia, ventricular tachycardia, premature beat, and atrioventricular block. According to this procedure after exclusion outliers, 1639 individuals were enrolled in our study under 2018 AACC/IFCC criteria. Furthermore, we applied stricter exclusion criteria (such as hypertension (systolic blood pressure (SBP) ≥ 140 mm Hg and/or diastolic blood pressure (DBP) ≥ 90 mm Hg), dyslipidemia (with history of dyslipidemia or TC ≥ 6.2 mmol/L or TG ≥ 2.3 mmol/L or LDL‐C ≥ 4.1 mmol/L or HDL‐C < 1.0 mmol/L),2)This study was approved by the ethics committee of the First Hospital of China Medical University. All individuals signed informed consent before the study. From January to July in 2014, applying the stratified cluster sampling protocol, this study took 1848 apparently healthy subjects through questionnaire , heart failure, arrhythmia, hypertension, stroke , diabetes) in communities of Shenyang China as the screening objects. Blood donation, blood transfusion, pregnancy, and individuals younger than 18 years of age were excluded. Fasting blood glucose (FBG) ≥ 7.0 mmol/L was used to represent surrogate biomarker for diabetes. Estimated glomerular filtration rate (eGFR) ≤ 60/mL/min/1.73 m2.2g for 10 minutes within 2 hours after collection, and serum was analyzed within 2 hours after separation.All subjects maintained normal working and dietary habits 1 week before blood collection, avoided strenuous exercise and physical labor, avoided heavy drinking, prohibited drinking 1 day before blood collection, and avoided overeating at night and high‐fat and high‐protein diet; fasting time was 8 hours to 14 hours after dinner , and water consumption was not more than 200 mL before blood collection. Smoking and vigorous exercise are prohibited for one hour. Blood samples were collected from the elbow vein and allocated to 5 mL SST tube with gel . All blood samples were centrifuged with 1200 We measured concentrations of FBG, TG, TC, HDL‐C, LDL‐C, and creatinine (Cr) by using Roche Modular automatic biochemical analyzer (Roche Diagnostics). We measured concentrations of NT‐proBNP and hs‐cTnT on a Cobas E170 Analyzer (Roche Diagnostics).2.3The statistical analysis of this study was performed using SPSS 22.0. The Mann‐Whitney test was used for comparison between two subgroups. Outliers were identified in the total population and in male and female separately using the methods of Dixon33.1Characteristics of the study population are presented in Table 3.2The 99th percentile URLs of hs‐cTnT under different selection procedures are presented in Table 3.3P = .004 in ≥60 years old and P < .001 in other age groups). The 99th percentile URLs of hs‐cTnT male were higher than those of female in every age group. The 99th percentile URLs of hs‐cTnT increased with age in both genders except for 18‐29 years old and 30‐ to 39‐year‐old men. The difference in the 99th percentile URLs of hs‐cTnT between women aged 50‐59 and over 60 was very small (18 ng/L vs 19 ng/L).Distribution of hs‐cTnT values by age and gender under improved selection criteria is presented in Table 3.42 vs BMI ≥ 25 kg/m2) but without dyslipidemia exclusion. The Dutch study followed 2018 AACC/IFCC criteria but without supplementary selection criteria. The 99th percentile URLs of hs‐cTnT varied between races under different selection criteria. The 99th percentile URL of hs‐cTnT male was higher than that of female, and the 99th percentile URL of hs‐cTnT elderly persons was higher than that of younger persons in the Italian study.Table 4Being a single‐center study, our research programs are more representative such as stratified cluster sampling protocol but not volunteers nor blood donors, which avoided selection bias. The Han nationality accounted for around 90% of the individuals enrolled in our study under two selection criteria, which accorded with the composition of the Chinese population in the sixth nationwide population census. The ethnic distribution and urban‐rural distribution under two selection criteria were basically the same, indicating that it was not the result of selective bias. Our improved selection criteria can be used by other researches.To the best of our knowledge, we conducted the first study to determine 99th percentile URLs of hs‐cTnT under both 2018 AACC/IFCC criteria and improved selection criteria through questionnaire survey, physical examination, and laboratory screening to further exclude hypertension, overweight and obesity, and dyslipidemia, which was proven in our study that the latter criteria avoided overestimation of the former. Compared with other two studies for 99th percentile URLs of hs‐cTnT among different races under 2018 AACC/IFCC criteria,Gender is an important factor affecting the 99th percentile URLs; therefore, when using hs‐cTn, gender‐specific 99th percentile URLs are recommended.The physiological difference between genders was one thing but whether or to what extent it would affect clinical management and improve outcomes still needs further studies. There were two studies using gender‐specific URLs of hs‐cTnT (15.5 ng/L for men and 9 ng/L for women), but reclassification has little effect on diagnosis and prognosis. Mueller‐Hennessen et alConsidering no guidelines recommended age‐specific 99th percentile URLs till now,Till now, there were no strong data to prove that the 99th percentile URL of hs‐cTnT by ethnicity should be established. These same or different conclusions whether caused by race or by comorbidities need further discussion. Gaggin et alThis study has several limitations. Firstly, participants of male were 345 (37.0%) and participants more than 60 years old were less than other age group. But we still included more than 300 individuals of each gender, which met the requirements of 2018 AACC/IFCC criteria.In conclusion, compared with 2018 AACC/IFCC criteria, improved selection criteria through questionnaire survey, physical examination, and laboratory screening to further exclude hypertension, overweight and obesity, and dyslipidemia can avoid overestimation of the 99th percentile URL of hs‐cTnT. As to what extent it would affect clinical management and improve outcomes still needs further investigation.There are no conflicts of interest.


Background: Responding to high levels of alcohol-related harm among students, a New Zealand university deployed a security and liaison service, strengthened the Student Code of Conduct, increased its input on the operation of alcohol outlets near campus, and banned alcohol advertising on campus. We estimated the change in the prevalence of alcohol consumption patterns among students at the university compared with other universities. Methods: We conducted a controlled before-and-after study with surveys in residential colleges at the target university in 2004 and 2014, and in random samples of students at the target university and three control universities in 2005 and 2013. The primary outcome was the prevalence of recent intoxication, while we analysed drinking per se and drinking in selected locations to investigate mechanisms of change. Results: The 7-day prevalence of intoxication decreased from 45% in 2004 to 33% in 2014  among students living in residential colleges, and from 40% in 2005 to 26% in 2013  in the wider student body of the intervention university. The intervention effect estimate, representing the change at the intervention university adjusted for change at other universities , was consistent with a benefit of intervention but was not statistically significant (p = 0.17). Conclusion: In this period of alcohol policy reform, drinking to intoxication decreased substantially in the targeted student population. Policy reforms and coincidental environmental changes may each have contributed to these reductions. University students in Australasia, North America, and Europe have a high prevalence of hazardous drinking ,2,3,4. AMany students suffer acute harm from the intoxicating effects of their own and others’ drinking ,15,16,17Code of Student Conduct [Campus Watch, a security and liaison programme designed to enforce the code and support students and other residents of North Dunedin [The University of Otago is one of eight universities in New Zealand (population 4.7 million). Located in Dunedin , and the majority of Otago students live in residential colleges and shared houses surrounding the campus in North Dunedin . Between Conduct  enabled  Dunedin . In 2009 Dunedin .Residential colleges tightened their alcohol policies in this period , and theCampus Watch found that drinking decreased between 2005 and 2009 among Otago students compared with students at other New Zealand (NZ) universities [The broad view within the university administration is that hazardous drinking and disorderly behaviour have decreased because of these changes . An evalersities .In this study, we examined changes in the prevalence of drinking, recent intoxication, and drinking at various locations among Otago students between 2004/2005 and 2013/2014, encompassing the period in which the aforementioned policies were introduced. This builds on our previous research  by incluNZ’s Multi-Region Ethics Committee (MEC/05/01/013) and the University of Otago Human Ethics Committee  approved the survey protocols.http://ipru3.otago.ac.nz/demo/halls2004/). We employed many of the same questions in a web survey of the same colleges, plus two new colleges, in April–May 2014 . The questions relied upon for the comparison reported were worded identically in the pre- and post-study surveys.We conducted a web survey of University of Otago students living in 12 Dunedin residential colleges, in April–May 2004, halfway between the beginning of the academic year and first semester exams  inviting them to participate by clicking on a personalised hyperlink sent to their university e-mail account. We sent up to one reminder letter and three reminder e-mails to residents who had not responded.The sampling frame was the list of residents held by the university. We sent personalised letters to all residents (2004: http://ipru3.otago.ac.nz/demo/) at participating NZ universities. The data collection procedures are described in detail elsewhere [We conducted web surveys of randomly selected full-time intramural students aged 17–24 years, in April–May of 2005 and 2013 . We classified drinkers as respondents who reported alcohol consumption during any of these periods.We asked participants who had consumed alcohol in the previous calendar year to complete the Alcohol Use Disorders Identification Test (AUDIT)  in relatIntoxication and locations of drinking in the previous seven days. We asked respondents who reported drinking in the previous seven days (7-day drinkers) to complete a retrospective 7-day record for each of four location types  in which they had consumed alcohol, indicating the number of standard drinks (10 g ethanol) and the duration of drinking in hours. We used this information to estimate a blood alcohol concentration (EBAC) for each drinking occasion [occasion  and desiWe used Stata/SE 13.1  , adjustin = 3262) were 56% and 3% respectively.Of the 2497 Otago students living in the Dunedin residential colleges in 2004, 64% completed the questionnaire. A further 3% submitted responses meeting the minimum data requirement. These figures for 2014 (n = 1228) was 61%. The combined response fractions at the other universities were 66% (n = 2152) in 2005 and 42% (n = 3301) in 2013.Four universities  participated in both the 2005 and the 2013 TSHS. Of the 854 Otago students invited to participate in 2005, 73% completed the questionnaire or submitted responses meeting the minimum data requirement. The response fraction in 2013 . Seven-day drinkers consumed less per drinking occasion in 2014  than in 2004 , the difference attenuating slightly after adjustment for changes in respondent demographic characteristics between the surveys .p = 0.04) but not after adjustment for changes in respondent demographic characteristics between the surveys . Unadjusted  and adjusted  estimates among 7-day drinkers only were both non-significant.The 7-day prevalence of intoxication decreased between 2005 and 2013 at Otago and at the other universities combined , and theThe proportion of 7-day drinkers who had consumed alcohol at on-license premises in the preceding week fell substantially from 2004 to 2014 . The preThere were significant decreases between 2005 and 2013 in the proportion of 7-day drinkers at Otago who had consumed alcohol at private residences and on-license premises in the previous week . There wA decrease between surveys in the proportion of 7-day drinkers at the other universities who consumed alcohol at private residences and on-license premises in the previous week was significant . There wTo investigate bias from selective non-responses, we adopted an approach previously employed to investigate non-response bias in survey data . We estiWe then estimated differences in the proportion of respondents drinking to intoxication in 2004 versus 2014, based on the assumption that the true 7-day prevalence of intoxication among non-respondents was 20%, 33%, 50%, or 100% higher than among respondents. The result was differences in estimates from 2004 to 2014 by up to 1.5%.Our findings suggest that while the proportion of drinkers in the Otago student population did not change in the decade between the surveys, a smaller proportion of drinkers consumed alcohol or became intoxicated in the preceding 7 days. This was true even after adjusting for differences in the pre-university drinking profiles of the populations between surveys. Intoxication was also less prevalent over time among university students overall in NZ. The reduction (of around a third) was large among Otago students, but not significantly larger than it was among students at other universities. Dunedin college residents drank less per occasion in 2014 than in 2004, mainly driven by substantially decreased drinking in pubs and bars, which was only slightly offset by drinking more in their residential colleges.In 2014, a smaller proportion of residential college students had consumed alcohol hazardously in the previous calendar year . This may reflect the greater proportion of 16–17-year-olds in residential colleges in 2014. While NZ law does not prohibit the consumption of alcohol at any age, people under 18 years of age cannot purchase it legally, a restriction that research suggests is effective in reducing alcohol-related harm . AccordiThe strengths of the study include the equivalent timing of the surveys within the academic calendar, and the use of identical questions and survey methods, facilitating valid comparisons over time and between residents and wider student populations. The sensitivity analyses on RCAS-based estimates suggested that the differences in response fractions are unlikely to have substantially biased estimates of change.The sampling design used in the TSHS meant a similar sensitivity analysis on these estimates was infeasible. Previous studies suggest the prevalence of drinking is underestimated to a greater extent when response rates are lower ,39. AccoThis and other factors may have contributed to our non-significant finding when comparing change in the prevalence of 7-day intoxication at Otago with change at the other universities. In addition to limitations of statistical power, our measure of 7-day intoxication may not have been sensitive enough to detect a modest change in drinking behaviour, for example, going from having 10 drinks in an evening to having two or three fewer drinks, or to spreading the consumption over a longer period, but without reducing their mean estimated BAC to below our threshold for classifying them as intoxicated.We did not attempt to formally determine whether institutional policies or programmes were introduced at the other universities that could impact on student drinking. Such developments, if effective, would have biased our findings towards the null, potentially masking any effects of the Otago interventions.While the TSHS allowed for directly comparable control sites , the RCAS included residential colleges at Otago only, limiting inferences about the Otago interventions on alcohol consumption in the colleges. It should be noted, however, that the decrease in drinking to intoxication among residents is consistent with the direction of change in the wider Otago student population, albeit of lesser magnitude. The large proportion of first year students living in the residential colleges may have different perceptions and expectations about alcohol use in the university environment than students in the wider population, many of whom are more senior. Those in their first year may be more motivated to drink to intoxication and this could be reinforced by the social aspect of college living.During the study period, local government alcohol policies focused on the Central Business District rather than North Dunedin . LegislaIt is unlikely that the relative reduction in 7-day drinking and intoxication among Otago students, including those living in residential colleges, merely reflects a national trend or local government interventions. Without a randomised design, we cannot safely infer that they are due, even in part, to the strategies implemented by the university. The marked decrease in drinking at on-license premises makes the pub closures in North Dunedin a strong candidate explanation for the estimated reductions, given that drinking episodes in pubs are more likely to result in intoxication, particularly among men, than drinking in other locations .Pub closures, perhaps combined with the blood alcohol limit reduction for driving, may have influenced the number of drinks Otago students consumed per occasion and where they drank. NZ research shows that the proximity of on-licensed premises to university students’ homes is associated with their drinking and related problems . The redCampus Watch may be reinforcing this by deterring students from drinking in public places around the campus.Only a small proportion of Otago students appear to have substituted drinking in pubs with drinking at other locations. There was, however, an increase in the proportion of college residents drinking in private homes in the preceding 7 days. How much these 2014 students drank at private homes compared to what their 2004 predecessors were drinking in pubs is unknown. We found that the amount consumed per occasion by residents was lower in 2014, although the overall amount consumed within residential colleges increased slightly. Focus group research conducted in this population in the early 2000s suggests that residents were drinking at their college before going to a pub . ResidenOverall, there has been a shift among Otago students to drinking less than weekly and across fewer types of locations, with a large shift away from drinking in pubs. This coincided with a large reduction in the prevalence of intoxication among Otago students, consistent with what we know from previous research. Drinking in pubs, residential colleges, and private residences facilitates heavy drinking and intoxication among NZ university students relative to ‘other’ locations ,45. As fCode of Student Conduct), introducing a policy with highly visible symbolic value (the advertising ban) and implementing a well-resourced prevention programme (Campus Watch), the university began attracting fewer hazardous drinkers. It seems likely that the actions of the university along with the reduction in pubs surrounding campus has helped to reduce hazardous drinking in the Otago student population.The confluence of findings from surveys conducted over a decade, involving students at four NZ universities, and 12 residential colleges in North Dunedin, suggests that with concerted effort, it is possible to change a drinking culture. The university’s involvement in objecting to license renewals may have created a tipping point for businesses that had survived by breaching server laws. By issuing a clear statement of institutional values (through the


Experimental studies indicate that oxygen transport is altered, and we have previously reported a drop in hematocrit and extensive downregulation of genes involved in blood oxygen transport capacity after decompression from professional saturation diving. Here we investigate the initial period of hematological adjustment back to normobaric air after professional saturation diving. Erythropoietin (EPO) and hemoglobin (Hb) were measured in blood from 13 divers at two time-points after saturation assignments lasting up to 4 weeks; first immediately after decompression and again 24 h later. Pre-dive levels defined baselines. The ppO2 varied from 40 kPa in the saturation chambers during storage, 50 to 80 kPa during bell excursions, and gradually reduced to 21 kPa during decompression to surface pressure. EPO was similar to baseline immediately after saturation diving (P = 0.4), and markedly increased within the next 24 h . Hb levels remained slightly reduced at both time-points . The results imply that the hematological acclimatization back to normobaric air was ongoing, but not completed, during the first 24 h after professional saturation diving.Saturation divers are exposed to elevated partial pressure of oxygen (ppO Therefore, we decided to investigate the changes in hemoglobin (Hb) and erythropoietin (EPO) during the initial 24 h after decompression from a long commercial saturation dive, to see the divers’ readjustment when they move from a hyperoxic hyperbaric helium-oxygen (heliox) atmosphere to normobaric air. We hypothesized that the levels of Hb and EPO should be decreased immediately post-surfacing and start to increase during the first 24-h post-saturation with some delay for Hb increase after EPO increase.Saturation diving is considered a safe method for human subsea interventions for extended periods of time. Commercial saturation divers live onboard dive support vessels in chambers compressed to a certain storage depth. They use pressurized diving bells to take them to the seabed/work location maximum 13 msw shallower or deeper than their storage depth; where they conduct different tasks from construction to maintenance. Several experimental studies into physiological acclimatization and possible harmful effects of saturation diving reported reduction in the production of reticulocytes, erythrocytes, serum erythropoietin, and hemoglobin; and cases of anemia . HoweverThis study was organized from Norway, and performed on occupational saturation divers during work assignments in the United Kingdom, with TechnipFMC as a Diving Contractor. The study protocol was approved by the local Regional Committee for Medical and Health Research Ethics (REK), approval reference number 2015/351; and by TechnipFMC’s Diving and Health services in Norway and United Kingdom divisions. The data and sample collections were conducted according to the Declaration of Helsinki principles for ethical human experimentation. All participants gave informed, written consent before inclusion into the study, and held valid health certificates for working as saturation divers on the United Kingdom Continental Shelf. The study group consisted of males who were cleared for diving by the Diving Contractor’s hyperbaric nurse after the mandatory pre-dive medical examination. All were non-smokers, and without infections at the time of their pre-dive examination.2 of 40 kPa. Each bell run lasts for up to 8 h with <6 h in-water per bell run. During bell diving, the ppO2 was maintained between 50 and 80 kPa. Between the third and fourth hour of in-water dive time, the divers had to return to the diving bell for a 20-min restitution break for rehydration. The work tasks conducted on the seabed included, but were not limited to, pipelines tie-ins, handling of rigging and equipment and installation of flexible jumpers and umbilical. During decompression, a ppO2 of 50 kPa was kept up to 12.7 msw; then the ppO2 was gradually decreased while the oxygen content in the heliox was kept between 21 and 23% until surfacing. The ascent rate was 1.5 msw/h until arriving to 15 msw; from thence to surface, the ascent rate was 0.6 msw/h. The decompression was stopped for 5 h after every 19 h of ascent, for the divers to stabilize.The diving operations took place during September to November 2016 off the northeastern coast of Scotland, and were conducted according to the Diving Contractor’s procedures. The divers’ storage depths varied between 80 and 90 meters of seawater (msw), depending on the work location. A saturation period included compression, bottom time with bell runs, and decompression. During compression, the chamber was pressurized at 1 msw/min with 20 min stop at 10 msw for chamber leak checks before proceeding to the storage depth at which the divers were held. At storage depth, the divers had a 1 h stabilization period before bell runs commenced. Throughout the period at storage depth, the living chamber’s heliox atmosphere kept a ppOn = 5 stayed 27 days and 6 h and n = 4 stayed 27 days and 21 h. The total duration of saturation depended on the operations; with a maximum of 28 days as per the Diving Contractor’s requirements. After surfacing, the divers stayed on the vessel for at least 12 h for “bends watch.” They were instructed to rest and avoid physical exertion during the first 24 h.Four divers stayed in saturation for 25 days (d) and 15 h, ® Z Serum Sep Clot Activator 5 ml gel tubes , prior to saturation during the pre-dive medical examinations; at the end of decompression during the post-dive medical examinations, always within 2 h before or after saturation diving. The final sample was collected 24 h after the end of the decompression. Sampling was conducted between 08:00 and 24:00 h, depending on the time of day when the divers emerged from the chamber.Blood samples were collected by standard antecubital venipuncture; in VACUETTEHb was measured immediately after blood collection. A capillary pipette was used to transfer a 10 μl drop of blood from the tube and deposit it into the well of a disposable test strip attached to a portable Mission Plus Hb apparatus . The same apparatus was used for all measurements. Control strips were used regularly to check analytic performance. The manufacturer indicated that the apparatus’s accuracy was ±0.4 g/dl for Hb. All Hb values were within the reported normal range for healthy males (14–18 g/dl) . The witWithin 30 min of sampling, the blood tubes were centrifuged in an EBA 270 centrifuge  at 4,000 RPM  for 10 min at room temperature to separate the serum. The serum was stored frozen at -20°C onboard the vessel before being transported in cooling cubes  at 4°C to NTNU, where it was kept frozen at -80°C until analysis. Transportation from the vessel to the analytic facility took 12–18 h.EPO measurements were made as a single-batch run on a Siemens DPC IMMULITE 2000 Immunoassay System  in the IEC 17025-accredited laboratory at the St Olav’s University Hospital, Department of Clinical Chemistry, Trondheim, Norway. The laboratory reported analytical variation of 8.6%. With one exception, (EPO 37.7 IU/l), all EPO values were within the normal range, 4.3–29.0 IU/l, reported by the laboratory.post hoc test was performed. Paired t-tests were conducted for group-wise comparison of data 0 h post-dive to 24 h post-dive. All statistical tests were done using a standard computer package, GraphPad Prism version 7.00 . P-values < 0.05 were considered significant.Prior to the analyses, the data were assessed for normality using the Shapiro-Wilk test. Hb data was normally distributed, whereas the EPO data became so after log transformation. Grubbs’ test was used to examine the data for outliers: none where identified. Percentages changes relative to pre-saturation diving values were calculated for each parameter at 0 and 24 h post-saturation diving. A repeated measures ANOVA with a Dunnet’s Table 1 for a summary of the study participants’ demographics, diving history, body-mass index (BMI) and resting heart rate pre- and post-saturation diving.The dives were completed in accordance with the Diving Contractor’s saturation diving procedures, without adverse events. Out of 20 divers originally enrolled in the study, seven were excluded as they left the vessel shortly after surfacing, before the 24 h post-dive blood samples could be obtained. One diver had a bacterial infection on his face during decompression; he was given antibiotics but not excluded from the study. See Figure 1. Pre-saturation diving values were used as a baseline for each diver to avoid the intra-subject variance. Hb fell during the dive, and continued to do so during the initial 24 h after saturation diving. Immediately after decompression, Hb was reduced by 4% relative to the pre-dive values (P = 0.01); and 24 h post-dive the Hb was reduced by 8% (P < 0.0001).Hb and EPO data are shown in P = 0.4). However, during the 24 h post-dive, there was a marked increase in which EPO levels almost doubled . Between 0 and 24 h post-saturation dive, there was a decrease in Hb levels (P = 0.02) and an increase in EPO (P < 0.001).EPO was unchanged immediately after decompression relative to the pre-dive values (In this study, Hb levels were reduced after decompression from commercial saturation diving, and remained below their pre-dive levels 24 h later. The observed reduction of Hb immediately after decompression is in agreement with findings in a recent report . Whereas2 of 40 kPa, which is close to twice the ppO2 in normal air (2. EPO is up-regulated when a reduction is sensed in the breathing gas oxygen content; which occurs after the divers emerge from the hyperbaric chamber and readjust to life in ambient air (The EPO levels in this study were unchanged immediately post-saturation diving, but markedly increased during the next 24 h. During the long saturation period, the divers acclimatize to a ppOrmal air . EPO dowrmal air , workingient air . Moving ient air ; and latient air . The priient air . Bindingient air . Under sient air . But wheient air .2 for 14 days. Before the experiment, EPO was 11.6 ± 3.1 IU/l. This decreased by the 14th day of saturation to 4.2 ± 1.6 IU/l, and at the end of the experiment, EPO was 4.5 ± 1.7 IU/l. At this point, one of the divers displayed mild signs of anemia. The authors discussed that the prolonged hyperoxia might have caused a clinically relevant anemia if the exposure was prolonged. In the present study’s setup, despite the higher ppO2 and longer exposure times, the results show a different trend. EPO levels trended toward a decrease at the end of the decompression before increasing, but still – with one exception – they remained within the normal range. To our knowledge, a transient increase in EPO is not associated with disease risk in healthy individuals. Also, even though total duration of the diver’s stays in saturation differed, this did not affect the outcome.In a previous experiment , six divHematological variables may be subject to circadian and other temporal variations. Studies of circadian variation in EPO have come to different conclusions  and it wBlood Hb was reduced immediately after decompression from commercial saturation diving, compatible with acclimatization to the hyperbaric hyperoxia the divers experienced during saturation. A marked increase of EPO levels 24 h after decompression suggested re-acclimatization back to breathing normobaric air, advocating for a physiologically compensated effect of the dive procedure.FK, IE, and CB designed the study. ØL obtained the necessary consents. FK managed the blood and data sampling. CB conducted the statistical analysis. FK initiated the manuscript and all the co-authors contributed to the analysis, writing and approval of the final manuscript.FK and ØL were employed by TechnipFMC in Norway. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer NN and handling Editor declared their shared affiliation at the time of the review.


Advance directive (AD) completion can improve transitions between hospitals and skilled nursing facilities (SNF’s). One CMS Innovations Demonstration Project, The Missouri Quality Initiative (MOQI), focused on improving advance directive documentation and use in sixteen SNF’s. An analysis was conducted of data collected from annual chart inventories occurring over four years. Using a logistic mixed model, results indicated statistical significance (p<0.001) for increased AD documentation. Greatest gains occurred at project mid-point. The relationship between having an advance directive and occurrence of transfer to a hospital was tested on a sample of 1563 residents with length of stays more than 30 days. Residents who did not have an advance directive were more likely to be transferred. A logistic regression was conducted and the results were statistically significant (p<0.02). The MOQI model and initiatives will be explained followed by a discussion of research methodology, data collection, and analyses. Practice implications will be discussed.


Near-infrared fluorescence probes (NIFPs) have been widely used in immunoassay, bio-imaging and medical diagnosis. We review the basic principles of near-infrared fluorescence and near-infrared detection technology, and summarize structures, properties and characteristics of NIFPs , quantum dots and rare earth compounds). We next analyze applications of NIFPs in immunoassays, and prospect the application potential of lateral flow assay (LFA) in rapid detection of pathogens. At present, our team intends to establish a new platform that has highly sensitive NIFPs combined with portable and simple immunochromatographic test strips (ICTSs) for rapid detection of food-borne viruses. This will provide technical support for rapid detection on the port. Near-infrared fluorescent probes have a characteristic molecular structure with a highly conjugated polyene system. This exhibits a long emission wavelength over 650 nm up to 900 nm ,2. In thNear-infrared fluorescent dyes are classified into the following categories, including cyanines, xanthenes fluorescent dyes, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPYs), phthalocyanines, porphyrin derivates and other related fluorescent dyes  that combines near-infrared fluorescence probes (NIFPs) with immunoassay. Near-infrared fluorescent probes have small background interference and strong tissue penetration. NIFPs have attracted more and more attention in recent years . When the heteronuclear core structure is the same, the longer the hemi-chain, the worse the photostability. That is very important for the design of near-infrared cyanine dyes with good light stability. Cyanine dye-labeled biological samples mainly have non-covalent, covalent forms of electrostatic/hydrophobic interactions and bioconjugates with some biomolecules through reactive groups for labeling nucleic acids, proteins, immunoassays, and bio-imaging . Among tThere is less literature on the direct detection of non-covalently labeled proteins with near-infrared cyanine dyes. It has been reported that direct measurement of protein by fluorescence detection may result in higher sensitivity than hemimethine cyanine absorption spectrophotometry  as show. In the + in living cell. Lee et al. further improved and derivatized it by DOFLA (diversity-oriented fluorescence library approach) [At present, many cyanines ave been commercialized. For examples, Hirayama and his colleagues have combined a NIR cyanine dye with a sulfur-rich receptor . This mopproach) . They obpproach) . Aggregapproach) . Since ipproach) . This copproach) . The welpproach) .In order to effectively increase the fluorescence intensity of dyes to determine trace target analytes, researchers continue to explore efficient signal amplification strategies. For example, a large amount of fluorescent dye is wrapped in nanoparticles to form a near-infrared nanoparticle probe with higher fluorescence intensity. This has been widely confirmed to effectively improve the detection signal intensity while improving the chemical and photostability of the labeled molecule . FurtherTetrapyrrole group-containing dyes such as porphyrins and phthalocyanines are very important class of NIFPs. Scholars have applied porphyrin probes to the structure, properties and functions of biological macromolecules such as DNA and proteins . Small pChen et al. used tetraamine aluminum phthalocyanine as the red region fluorescent substrate to establish a fluorescence analysis method for the determination of peroxidase and hydrogen peroxide . Some reXanthene fluorescent dyes mainly include two classical fluorescent dyes, fluorescein and rhodamine. Naphthalene ring fluorescein is in the near infrared spectral region. Some near-infrared rhodamine fluorescent dyes such as Rhodamine 800 (IX) and Texas Red (X) are used in bioanalysis . RhodamiA small Stokes’ displacement may result in back scattering from biological samples and self-quenching. Gong and colleagues had expend a p-conjugated system of xanthene to develop an efficient NIR fluorophore . The flu−11 mol/L, the detection limit of aromatic acid in plasma is 7.33 × 10−11 mol/L [Both thiazine dyes and oxazine dyes contain amino groups which can be used for labeling. Currently, these dyes are mainly Nile Blue (XI), Nile Red, Methylene Blue (XII) and Oxazine 750. Nile Blue (XI) derivative is used for HPLC-LIF analysis of carboxylic acid, the detection limit can reach 3.98 × 1011 mol/L . The thi−1·cm−1), a high fluorescence quantum yield. Its fluorescence is not sensitive to the polarity of the solvent, pH, narrow fluorescence peaks, long fluorescence lifetime and good light stability. A styryl group was introduced at the 3 position of the dye precursor, and two phenyl groups (XV) were introduced at the 1st and 3rd positions to synthesize two long-wavelength fluorescent dyes having a wavelength exceeding 600 nm [The boron difluoride-dipyrromethane (BODIPY) fluorescent dye has a high molar absorptivity  known as semiconductor nano-microcrystals, have been widely used in bioanalysis and medical diagnostics recently as a new class of fluorescent probes due to their excellent optical properties . The fluHowever, biocompatibility remains to be further explored because of its potential toxicity to living tissue. In order to solve the potential acute and chronic toxicity of NIR quantum dots, a less toxic coating is often considered in the design of QDs ,56. Curr3+, Er3+, Yb3+ and Tm3+ in the near-infrared region have been widely developed in recent years [3+ ions with the sensitizer phenylenevinylene dicarboxylate (PVDC) in a small volume [Complexes of rare earth elements (lanthanides) containing Ndnt years ,63,64,65nt years . Due to nt years . In ordel volume . This stl volume ,70.3+ and Tb3+. Its Stoke’s displacement is large and the fluorescence lifetime can reach milliseconds, so it is widely used in biotechnology and time-resolved fluorescence detection technology. The main emission peak of Tb3+ is around 550 nm, while the main emission peak of Eu3+ is around 620 nm. Rare earth complex fluorescent probes are sensitive to external environmental pH and coexisting ions such as alkali metal ions and halogen ions. Therefore, they are often used in chemical and biological sensors. The detection limit of lecithin was determined by direct fluorescence spectrophotometry with Eu3+-tetracycline complex to reach 3.9 × 10−8 mol·L−1, and it was successfully used for the determination of lecithin in serum samples [3+- oxytetracycline complex for detection of adenosine triphosphate can reach 2.67 × 10−9 mol·L−1 [3+ is also used for sensitive detection of nucleic acids. In the system of Eu3+-benzoylacetone-hexadecy lammonium bromide, the presence of nucleic acid enhances fluorescence, so this system is used to detect the sperm DNA of black carp. The detection limits of calf thymus DNA and yeast RNA were 0.33, 0.21 and 0.99 ng·mL−1 respectively [3+ complex is also synthesized and used for staining and labeling of the nucleus and exhibits highly selective labeling of the nucleus.The rare earth complex luminescent probe mainly comprises a complex fluorescent probe of Eu samples . This co mol·L−1 . The comectively . Rare eaectively . A Eu3+ As a new type of carbon material, single-walled carbon nanotubes (SWCNTs) have great potential for application in the biomedical field due to their special nanostructures and excellent optical, mechanical, electrical and magnetic properties . More anDue to its high quantum yield, small background interference, and good light stability, SWCNTs have been widely used in recent years as ideal NIFPs for in vivo and in vitro bio-imaging, and immunoassays for important diagnostic and therapeutic marker molecules ,78.In 2016, Chen et al. developed a multiple lateral flow immunoassay based on NIR by combining near-infrared labeling with broad-spectrum-specific monoclonal antibody/receptor as a detection complex. The method could simultaneously detect four antibiotic families in milk such as β-lactams, tetracyclines, quinolones and sulfonamides within 20 min .Compared with a few NIR immunoassays for antibiotic tests, this method is more widely used in immunoassays of important marker molecules in diagnostics. So far, NIFPs have been successfully developed for immunotiter plates, fiber-optic immunosensors, and capillary blotting, capillary electrophoresis immunoassays and immunochromatographic assays ,81,82. ALegionella pneumophila [In the early 1990s, NIFPs were first applied in immunoassays. Researchers achieved quantitative determination of human immunoglobulin by adding an excess of NIR-labeled antibody and subsequent fluorescence detection in an antigen-coated polyethylene microtiter plate . Daneshvumophila . The detWeissleder et al. used a biological conjugate of active protease-near-infrared cyanine to detect cancer. Many cancers overexpress some small peptide receptors (Receptors), such as Somatostain  Folate rBrucella sp., which can achieve a Brucella sp. antibody in serum of sick sheep (0.005–0.11 mg/mL) quantitative analysis [−1 boric acid and 1% CHAPS PH 8.5. It was used for normal human and patient saliva sample determination. MeCy5-OSu(VII) is a newly synthesized cyanine dye near-infrared fluorescent labeling reagent. With biopolyamine as the analysis object, a new method for capillary biophoresis/laser induced fluorescence detection of biopolyamines was established. The linear range is 10–200 nmol·L−1, the detection limit is 0.8–3.0 nmol·L−1. This method has been used for the determination of biopolyamines in red blood cells of normal human and bladder cancer patients.In addition, Silva et al. developed an optical immunosensor based on the near-infrared dye Cy5 for the determination of disease infection in sheep analysis . AccordiIn recent years, novel NIFPs other than organic fluorescent dyes have also been introduced into near-infrared fluorescent immunoassay systems. For example, Deng et al. prepared a novel core/shell NIF nanoparticle by encapsulating the inexpensive near-infrared fluorescent dye methylene blue in a hydrophobic silica gel shell . The imm3+ and Tb3+ were covalently labeled for double labeling. Xu et al successfully detected the simultaneous detection of hepatitis B virus surface antigen and e antigen. In addition, the lanthanide ion-coated nanoparticles prepared in this study are highly stable and can be stored for up to two years [The lanthanide ion represented by lanthanum can emit fluorescence under specific excitation light, and has been developed into a novel fluorescent labeling probe for ICTSs in recent years. Because of its unique emission half-life longer than other fluorescent probes and background materials, lanthanides have been well developed as powerful labeling probes for time-resolved immunofluorometric assays. By delaying the measurement time, after all short-lived background fluorescence and excitation photons are completely decayed and then measuring the fluorescence signal of the lanthanide ions, the background interference can be effectively reduced or even eliminated, thereby improving the detection sensitivity by at least two orders of magnitude. According to Xia et al. and Zhang et al., the detection limits of ICTSs labeled with ruthenium nanoparticles are up to 100-fold relative to colloidal gold-labeled chromatographic strips and ELISA ,95. In awo years .One of the early pathological markers of Alzheimer’s disease (AD) is the deposition of amyloid-beta (Aβ) plaques in the brain. Optical imaging and particularly NIRF imaging has become a safe, low-cost, real-time and widely available technique that provides an attractive method for in vivo detection of Aβ plaques in many different imaging techniques. In 2015, Tong et al. briefly outlined the latest developments in NIRF Aβ probes and their applications in vitro and in vivo .Researchers synthesized a specific COX-2 probe celecoxib-MPA probe (CMP), based on celecoxib and a water-soluble near-infrared dye dye ICG-Der-02 (MPA) for monitoring COX-2. The results suggested that the probe CMP, with favorable hydrophilic property, good biocompatibility, long-term observation, excellent targeting ability and optical imaging capability, and it could serve as a promising probe for real-time monitoring of COX-2 in inflammation and tumor .Despite their high sensitivity, NIFPs in immunoassays are still lacking in simplicity, so its user friendliness needs further improvement. To overcome this shortcoming, Swanson and D Andrea developed quantitative immunochromatographic test strips (ICTSs) based on NIFPs for single and multiple-synchronous detection of interleukin-6 and C-reactive protein. In 2013, Swanson developed a quantitative ICTSs based on a near-infrared fluorescent probe. The NIR dye was coupled to the selected antibody and integrated into the LFA. The test strip can detect single and multiple simultaneous detection of interleukin-6 and C-reactive protein . The higAlthough current in vitro and in vivo bio-imaging is still the main application field of NIFPs, its application in immunoassays has not stopped over many years since Boyer first researched it in 1992 . With coLegionella pneumophila (LP) antigen [Mycobacterium tuberculosis by targeting the multi-antibody of LAM coated on the surface of the nanomagnetic beads [In 2013, Cheng et al. extracted the anti-pulmonary Legionella LP antigen to prepare immunofluorescent LP antibody kit, and explored application value of near-infrared fluorescence detection of  antigen . It was ic beads . They usic beads .Foodborne pathogens are one of the most important threat factors for food poisoning incidents worldwide. However, traditional microbial culture-based assays are time-consuming and labor-intensive, failing to provide timely data to effectively reduce the incidence of foodborne illness. Therefore, whether it is from the control of product quality by food companies, or the government’s effective supervision of food safety, so as to protect public health, we urgently need a faster and independent method for detecting food-borne pathogenic microorganisms. Although current colloidal gold-based LFA are still the gold standard for rapid detection of pathogens, the labeling technique is still limited by its low sensitivity and inability to accurately quantify defects. Fluorescent probes are methods that use optical properties of fluorescent molecules to study some of the physical, chemical, and physical properties of a particular environmental material at the molecular level. It has high sensitivity and wide dynamic response range, so it is widely used in biological macromolecules. In the near-infrared region, biomolecules have weak self-fluorescence and small background interference, and high sensitivity is obtained in this region. Therefore, the research of NIFPs has become a research hotspot in recent years, showing great potential in biological analysis.Salmonella, Vibrio parahaemolyticus, Vibrio cholerae and Listeria monocytogenes by near-infrared immunoassay .Salmonella, Vibrio parahaemolyticus, Vibrio cholerae and Listeria monocytogenes by near-infrared immunoassay (as shown in Vibrio Parahemolyticus monoclonal antibody, test line marks rat anti-Vibrio Parahemolyticus polyclonal antibody, and control line marks Goat anti-mouse IgG polyclonal antibody. The emission wavelength of low noise excitation fluorescence dye is 650–1000nm. A kind of fluorescent molecules DyLight800 which excitation and emission wavelength are 777 and 790 nm is used. The control lines and test lines are arranged in parallel, and the line spacing between test lines and control lines is 0.5 cm.In recent years, our team has developed a method for detecting pathogens including Our team is working on foodborne viruses such as rotavirus, norovirus and hepatitis A virus, and we could develop near-infrared ICTSs using NIFPs-labeled antibodies to detect these foodborne viruses. Our team intends to establish a new platform which has a highly sensitive near infrared probe combined with portable and simple ICTSs for rapid detection of food borne viruses. This will provide technical support for a rapid detection on the port.


Heidelberger Interprofessionelle Ausbildungsstation – HIPSTA) was implemented at the University Hospital Heidelberg, Germany. On HIPSTA future physicians and nurses take care of the patients self responsibly and in close interprofessional collaboration, supervised by facilitators of both professions. Although there are positive experiences with IPTWs internationally, little is known about the impact of IPTW on the acquisition of interprofessional competencies. For future interprofessional training and implementation of IPTWs evaluation of interprofessional learning and collaborative practice on Germany’s first IPTW is of high relevance.To meet the patients’ needs and to provide adequate health care, students need to be prepared for interprofessional collaborative practice during their undergraduate education. On interprofessional training wards (IPTW) undergraduates of various health care professions potentially develop a mutual understanding and improve their interprofessional competencies in clinical practice. To enhance collaboration of 6th-year medical students and nursing trainees in the third year of their vocational training an IPTW  and undergraduate participants and staff participants on a comparable ‘conventional’ ward without special interprofessional training (comparison group) immediately pre and post HIPSTA and, as follow-up, after three to six months , using three questionnaires, namely the University of the West of England Interprofessional Questionnaire (UWE-IP), the Interprofessional Socialization and Valuing Scale (ISVS) and the Assessment of Interprofessional Team Collaboration Scale (AITCS). Qualitative data is gathered in form of interviews and focus groups based on semi structured guidelines, video recordings of handovers and overt non-participant observations of daily rounds. Quantitative data will be analysed in a longitudinal comparison, presented descriptively and tested with an analysis of variance. Qualitative data will be analysed deductively and inductively.The results of the evaluation will give insight in undergraduates’, staff’s and facilitators’ experiences and their self-perception of competency development. In addition the results will help identify benefits, challenges and areas for modification when implementing and establishing similar interprofessional training wards. Despite the importance of interprofessional collaborative practice (IPCP) in clinical practice in order to maintain high quality patient care , undergrFor improvement of educational strategies to develop interprofessional competencies these need to be identified and described. Within the past eight years a number of frameworks have been developed which describe interprofessional core competencies –6. All fHeidelberger Interprofessionelle Ausbildungsstation” (HIPSTA) was implemented in the Department of General, Visceral and Transplantation Surgery of the University Hospital Heidelberg, being the first of its kind in Germany [In order to enable interprofessional learning and collaborative practice within the undergraduate education of the health professions nursing and medicine, in spring 2017 an interprofessional training ward (IPTW) named “Positive outcomes of interprofessional training wards regarding clarification of the own and the others’ professional role as well as the understanding and appreciation of teamwork have mainly been described in Scandinavian countries, where placements on interprofessional training wards have been an integral part of the curricula across the health care programmes for over 20 years –24. HencHow do interprofessional competencies of undergraduates on HIPSTA (intervention group) develop compared to undergraduates on a ‘conventional’ surgical ward (comparison group)?What influence does HIPSTA have on staff working on the surrounding surgical ward HIPSTA is integrated in (intervention group) compared to colleagues on a ‘conventional’ surgical ward, who are not affected by HIPSTA (comparison group)?What influence does HIPSTA have on the interprofessional competencies of the facilitators?What influence does HIPSTA have on the self-perception of the facilitators concerning their teaching competencies?Which basic conditions do facilitators and students (intervention group) describe as beneficial or impeding for an interprofessional education setting?What kinds of competency gain can be observed during the daily interprofessional rounds and handovers?A prospective mixed methods evaluation is being conducted to systematically gather and assesses initial experiences with the IPTW with self-assessment surveys and observational assessment.Aim of this study is to assess the development of interprofessional competencies of the undergraduates and staff on HIPSTA (intervention group) compared to undergraduates and staff on the comparison ward (comparison group) based on quantitative and qualitative self-assessment surveys and observational assessment.On HIPSTA, a two-room section within a surgical ward at the Department of General, Visceral and Transplantation Surgery of the University Hospital Heidelberg, Germany, four undergraduate medical interns and four nursing trainees (undergraduate participants) are responsible for patient treatment and care, supervised by nursing and medical facilitators. On the comparison ward at the same department ‘conventional’ patient care is delivered by medical and nursing staff and undergraduates without special interprofessional training.To answer research questions 1–3 a prospective quantitative approach with questionnaires will be conducted on HIPSTA (intervention group) and on the ‘conventional’ surgical ward (comparison group). To get an in-depth insight in competency development, beneficial or impeding factors and experiences in general (questions 1–6) interviews and focus groups will be performed with undergraduate participants and facilitators on HIPSTA and with staff participants on the surrounding ward (intervention group), and hand-over video documentations and structured ward round observations will be performed on HIPSTA.During their four weeks placement on HIPSTA the nursing and medical undergraduates are responsible for pre- and post-surgical inpatient treatment of six patients in two rooms on a visceral-surgical ward, in shift work (early and late shift). They all participate in an introduction day immediately before placement, where they can get to know each other and learn about some relevant aspects of the daily practice on HIPSTA. During the placement they work self responsibly and in close interprofessional collaboration, supervised by two facilitators, one of each profession (nurse / physician). Undergraduate participants work in a tandem , each tandem being responsible for three patients. Alongside their profession specific daily routine, they conduct daily rounds and handovers and plan, deliver and reflect on patient treatment together in an interprofessional team. The facilitators supervise their actions mainly passively and only interfere if necessary. They support the undergraduates by encouraging them to autonomous and collaborative decision making and problem solving, as well as by giving them feedback and facilitating reflective processes.Primary outcome are interprofessional teamwork and collaboration, interprofessional learning and interprofessional interaction as measured with the University of West of England Interprofessional Questionnaire (UWE-IP) . Within All undergraduate participants and staff participants placed or employed on HIPSTA or its surrounding ward (intervention group), or on the comparison ward (comparison group) are included in the study and questioned to participate. To answer the research questions three different participant samples were identified and divided into three levels. Undergraduate participants on HIPSTA and the comparison ward are assigned to level one, staff working on the surrounding ward HIPSTA is integrated in and on the comparison ward is assigned to level two and the facilitators on HIPSTA are assigned to level three. All participants of the study have to be at least 18 years old.For the medical undergraduates the placement on HIPSTA is part of their surgical four months placement during their practical year, after their study programme and before taking their final exams . In Germany nursing training at present is predominantly not an academic programme. In most cases it is a hospital based 3 year vocational training programme in contrast to medical school programmes which are all university based . Nurse uWithin 15 months 12 consecutive cohorts comprising four medical and four nursing undergraduate participants at a time will be placed on HIPSTA for four weeks. In terms of the pragmatic approach of the study all of the undergraduates employed on HIPSTA and all undergraduates on the comparable ward are integrated in data collection following an exploratory design. By that a sufficient sample size for longitudinal analysis of all three points in time can be achieved, as a high drop-out rate is expected. Hence, an estimated number of about 96 undergraduate participants will be recruited (level 1) within the phase of one year (April 2017 – June 2018). Accordingly, all affected staff members working on the ward HIPSTA is integrated in, and all colleagues working on the comparable ward, as well as all facilitators employed on HIPSTA are recruited within the time of data collection (April 2017 – June 2018). The number of colleagues and facilitators that can be recruited for the study can roughly be projected at 30 to 60 participants, depending on the number of employees working on the wards at the points in time of the survey (levels 2 and 3).Within a mixed methods design quantitative and qualitative data is collected. Staff and facilitators working on HIPSTA and staff working on the comparison ward are informed about the study before the first cohort’s placement on HIPSTA and their consent to participate is obtained. Undergraduates are informed about the study by the researchers during the introduction day and their consent to participate is obtained before starting their placement on HIPSTA or on the comparison ward. Besides being informed verbally, staff, facilitators and undergraduates receive an information sheet, which clarifies how their data is used and gives them the contact information on the principle investigator. Since May 2018, in an updated version according to the General Data Protection Regulation, the contact information of the data protection officers of the faculty and of the state is provided. They are informed that their participation in the study is voluntary and that they can withdraw their consent to participate any time. After being informed they can give their consent to participate by signing a consent form.Quantitative data is collected at different points in time for undergraduate participants (level 1), staff participants (level 2) and facilitators (level 3), with a questionnaire consisting of the validated German version of the University of Western England Interprofessional Questionnaire (UWE-IP) , the GerThree scales of the UWE-IP, each consisting of nine items, are applied: The “Communication and Teamwork Scale” uses a four-point Likert-scale with ratings from 1 = strongly disagree to 4 = strongly agree. Both the “Interprofessional Learning Scale” and the “Interprofessional Interaction Scale” use a five-point Likert scale with ratings from 1 = strongly disagree to 5 = strongly agree. Scale scores are calculated by summing items, achieving scores from nine to 36 (communication and teamwork), and nine to 45 for the other two scales.At this point in time, based on my participation in interprofessional education activities and/or clinical practice …,. Items can be scored on a seven-point Likert scale with ratings from 1 = not at all to 7 = to a very great extend and a further “0= not applicable” option. Items are summed achieving scores from 0 to 147. The AITCS consists of 37 items, each with the introduction When we are working as a team …,. Items are scored on a five-point Likert scale with ratings from 1 = never to 5 = always, including a response option “no answer”. The AITCS consists of three subscales, namely “partnership” (19 items), “cooperation” (11 items) and “coordination” (7 items).The ISVS comprises 21 items, each item beginning with All three questionnaires are administered to the undergraduate participants and the staff participants  directly before the beginning of HIPSTA, at the end and as follow-up. Hence, all undergraduate participants of each cohort fill out the questionnaires at the beginning of their introduction day (T0), four weeks later, at the last day of their placement T1) and three months after their placement T2) . Scale scores will be calculated, and differences between time points will be analysed for each of the questionnaires  individually  in a longitudinal comparison and tested with an analysis of variance (ANOVA). Data is analysed with focus on longitudinal and intergroup comparisons concerning cohort, profession and gender, as well as comparisons with the undergraduate and staff participants on the comparable ward without special interprofessional training (comparison group). Qualitative data will be analysed within qualitative content analysis deductively and inductively using the computer-assisted data analysis program MAXQDA in order to generate categories for hypothesizing . InductiA placement on an interprofessional training ward does not only address interprofessional competencies on a theoretical level but contributes to prepare undergraduate health professionals in a real-life clinical setting for future interprofessional collaborative practice in order to improve patient care. The four weeks placement on HIPSTA facilitates undergraduate health professionals’ competency and professional identity development, for example due to responsibility for the patients’ well-being, decision making processes with health care team members and patients, and thus clarification of the various roles in the team. The amount of responsibility undergraduate participants have on HIPSTA is unusual in undergraduate education for medical and nursing training in Germany , 30. FurThe placement of the first cohort of undergraduates started on the 10th of April, 2017. At present, questionnaires have been collected from 112 undergraduate participants and 52 staff participants. 5 focus groups with 36 undergraduate participants and 4 focus groups with 9 facilitators, as well as individual interviews with 31 undergraduates and 9 facilitators have been conducted. To date 30 ward rounds and 14 handovers have been observed.