Respiration rate (RR) is a proficient indicator to measure the health status of cattle. The common method of measurement is to count the number of respiratory cycles each minute based on flank movements. However, there is no consistent method of execution. In previous studies, various methods have been described, including counting flank movements for 15 s, 30 s or 60 s as well as stopping the time for 5 or 10 breaths. We assume that the accuracy of the aforementioned methods differs. Therefore, we compared their precision with an RR sensor, which was used as the reference method in this study. Five scientists from the fields of agricultural science and veterinary medicine quantified the flank movement according to each of the five methods mentioned above. The results showed that with an average RR of 30 breaths per minute (bpm), all methods showed a high correlation to the values of the RR sensor. However, counting breaths for 60 s had the highest level of conformity with the RR sensor (Lin`s concordance correlation coefficient: 0.96) regardless of the level of RR. With rising RR, the inaccuracy increased significantly for the other four investigated methods, especially when counting 5 and 10 breaths. Therefore, we would recommend that counting for 60 s should be used as the standard method for future studies due to its high precision regardless of the level of RR. Respiration rate (RR) is an important parameter to evaluate the health status of cattle since it is an indicator of stress and painful processes  regarding their agreement with respect to the measured RR of an RR sensor, recently developed in our working group  and gestation stage (4–80 days) were filmed consistently at a 45-degree angle from behind. The dairy cows were housed in a free-stall barn, equipped with 53 lying cubicles (straw-lime mixture) and were part of an existing herd of 55 cows on the first day and 54 cows on the second day. The animals were able to move freely in the barn during the experiment so as not to restrict their natural behavior. Water and a total mixed ration were freely available. Seven to nine video sequences were taken of each cow during the lying and standing periods , with and without ruminating and while dozing . In addition, each cow was equipped with a respiration rate (RR) sensor attached to a halter  over one minute each in an experimental barn in Groß Kreutz (Germany) over 2 days in January 2018. In the experiment, six healthy cows differing in age, lactation stage  in random order using a smartphone stopwatch app. By means of an LED lamp that lights up briefly at the beginning and end of the recorded minute, the period to be studied was dependably defined. The LED lamps were fixed on the halter of the cows and were synchronized with a marker in the RR sensor recordings  and reliability (differences between observers). The number of cases “n” was obtained from the 46 studied videos and multiplied by five (number of observers). First, we determined the mean absolute deviation of the studied methods compared to the RR of the sensor and investigated whether there were differences depending on the level of RR. For this, we used JMP . To assess the agreement between the five different methods and the RR sensor, Lin's concordance correlation coefficient (CCC) Akoglu  was calcThe results substantiate that counting respiration rate (RR) for 60 s has the lowest mean absolute deviation and therefore the highest level of agreement with the values measured by the RR sensor regardless of the level of RR. Counting for 60 s differed from the RR sensor by an average of 1.8 breaths with a standard deviation of 2.02. The second highest level of agreement can be attributed to counting breaths for 30 s, followed by stopping for 10 breaths  had no influence on the detectability of the RR, and the mean absolute deviation from the RR sensor was approximately the same for both positions.Regarding the CCC, all methods achieved a CCC > 0.8 Table . HoweverConcerning the reliability, the five observers differed only slightly when comparing the CCC of the different methods Table . All fivOverall, the hypothesis that longer observation times result in a more accurate RR measurement was confirmed. Therefore, we would generally recommend using counting for 60 s as the standard method in future studies because it is the most accurate method regardless of the level of RR. An exception are very restless animals, where a longer observation period would distort the results due to cow movements and make counting flank movement more difficult, for example, in calves (Lowe et al. Although the average RR in cattle is between 24 and 36 bpm (Rosenberger Nevertheless, when counting 5 and 10 breaths, it is necessary to consider the reaction time in counting the last breath and stopping the stopwatch of the person evaluating the video. Even with rigorously trained researchers, human physical limitations will inevitably influence the study results. Furthermore, when extrapolating up to one minute, the number of breaths must be rounded down as well as up to obtain whole breaths.In fact, when counting by time, different initial conditions must be considered; when counting for 15 s and then rounding up to one minute by multiplying by 4, logically from the outset, only every fourth value can be obtained as an end result, and when counting for 30 s, only every second value can be obtained. Therefore, we conclude that the counting of breaths for 60 s is the most valid method.


Clear aligner treatment has become popular over recent years. It is necessary to identify methods by which we could avoid the bowing effect in extractions with clear aligner. The present study was to identify the appropriate method to design torque movement involving the upper anterior teeth of extraction cases, in order to maintain or improve the axis and torque of the upper anterior teeth with a clear aligner during movement and closure of the extraction space.As the height of the power ridge increased, the rotation angle of the upper central incisor in the sagittal direction decreased gradually and the location of the rotation center changed significantly; the rotation center moved in the apical direction and then changed to the crown side. The highest von-Mises stress of the upper central incisor root, periodontal ligaments, and alveolar bone, showed little change as the power ridge height increased. When the axial inclination of the upper central incisor was normal (U1-SN = 105°), the tendency of movement for the upper central incisor approached translation with a power ridge height of 0.7 mm (corresponding distorted angle: 5.8415). When the axial inclination of the upper central incisor was oversized (U1-SN = 110°), the axial inclination of the upper central incisor reduced to normal following completion of the anterior segment retraction with a power ridge of 0.4 mm (corresponding distorted angle: 3.4265).. Variation sensitivity of the rotation center should be considered carefully due to biological problems when designing translation of the upper anterior teeth with normal axial inclination.Analysis indicates that pure palatal tipping movement of the upper anterior teeth is generated without torque control, thus resulting in the bowing effect. The required torque control of the upper anterior teeth with oversize axial inclination is weaker than that of the upper anterior teeth with normal axial inclination because limited torque loss is expected for oversize axial inclination teeth Clear aligner treatment has become popular over recent years because it is both comfortable and aesthetically acceptable. On the one hand, this form of treatment involves a series of orthodontic operations covering all of the teeth and the keratinized gingiva without obvious damage to the periodontal tissues . On the Using a mathematical model derived from the computer-aided design (CAD) discretization of solids in three dimensions, finite element analysis (FEA) can estimate the stresses generated within different tissues, such as alveolar bone, the PDL, and teeth, and can also determine the loading and displacement patterns of all structures . Recent The aim of this paper was to use FEA to identify an appropriate technique to design torque movement when the upper anterior teeth were retracted in order to maintain or improve the axis and torque of the upper anterior teeth when undergoing movement caused by closure of the extraction space. Our overall goal is to provide direction for the use of clear aligners in the clinic.Cone beam computed tomography (CBCT) data  were acquired from a healthy volunteer with well-aligned dentition and normal axial inclination of the upper anterior teeth. As shown in Fig. All structures were assumed as linear elastic isotropic and homogeneous materials. Their mechanical properties were obtained from previous studies , 11 and Two protocols were established according to the axial inclination of the upper central incisor   and were then loaded back on the corresponding tooth in the reverse direction [For both two protocols, a displacement of 0.25 mm in the distal direction was preset for the maxillary anterior teeth to simulate one stage of anterior teeth retraction in the clinical setting. Different power ridge heights 0–1 mm) were used as a carrier to mimic torque control in the clinical setting. The upper central incisor was the main observation object of this study; therefore, the power ridge was set on the surface of the upper central incisor. The location and dimension of the power ridge are shown in Fig.  mm were When the axial inclination was normal (105°), a group with a power ridge of 0 mm in height was taken as the control group, and power ridges of different heights (0–1 mm) were added on the basis of the control group until the rotation angle of the upper central incisor was close to 0° in the sagittal plane and the corresponding mechanics could favor translation. When the axial inclination was oversized (110°), the group with a power ridge of 0 mm in height was taken as the control group and power ridges of different heights (0–1 mm) were added on the basis of the control group until the oversize axial inclination of the upper central incisor to the Sella-Nasion (SN) plane reduced to normal after the completion of anterior retraction. That is, the rotation angle of the upper central incisor was limited to 5° in the sagittal direction. Assuming that the number of orthodontic steps was 60, the rotation angle of the upper central incisor in the sagittal direction was limited to 0.08333° per step.In this study, we used an FE model to simulate retraction of the upper anterior teeth. The group with a power ridge of 0 mm in height was taken as the control group. When the axial inclination of the upper central incisor was 105°, the rotation center of the upper central incisor was located approximately between the middle and apical thirds of the root Fig. a and theNext, power ridges of different heights were added on the basis of the control group to simulate torque control (moment adding). Figure The rotation angle gradually decreased as the height of the power ridge was increased when the axial inclination of the upper central incisor was 105° Fig. ; when thWhen the axial inclination of the upper central incisor was 110°, the changing trends for the rotation angles with different power ridge heights were similar to those with an axial inclination of 105° Fig. . We consWhen the axial inclination was 105°, when compared with the control group, the highest von-Mises stress value of the PDL and alveolar bone showed very little change as the height of the power ridge increased. Furthermore, compared with the control group, although the highest von-Mises stress value of the upper central incisor root showed an upward trend as the height of the power ridge was increased, they were the same order of magnitude Fig. . When thFEA is a widely used and effective method to explore the biomechanical principles on orthodontic studies. Most FEA studies relate to the initial stress distribution and displacement pattern within different structures, including teeth and periodontal tissue , 14, 15.Previous studies determined that tipping movement is the most predictable movements with clear aligner, but there still remains somewhat difficult to achieve a comparable amount of root control –19. ElkhPertinent studies suggested that the force couple generated at the cervical and incisal regions of the aligners is not large enough to generate an adequate counter moment because of limitations in material properties , 20. ThiIn essence, the presence of a power ridge in the tooth neck made the aligner undergo further distortion, thus generating an angle between the inner face of the aligner and the tooth surface, thereby favoring a counter moment Fig. . From meAnother issue addressed in our study was the variation sensitivity of the CRot. The relative position between the center of resistance (CR) and CRot reflected the type of tooth movement. The CR is equal to the center of mass, which is not influenced by the M/F ratio. The method of finding CR of teeth has been explored by relevant studies in recent years. In a previous study, CR was determined by a second force that resulted in bodily tooth movement . A subseFEA represents one of the best ways to analyze force systems delivered by clear aligners. This study provided valuable information for the design of torque movement for upper anterior teeth with clear aligners in extraction cases. However, our findings must be clinically validated to support plastic aligners with solid evidence. One of the limitations of the present study was that FEA could not take the biological events into consideration, such as root length, root morphology, aligner material property, and so on. Another limitation was that the current FE model lied in the difficulty associated with simulating the large displacements on the tooth as a result of the long-term application of orthodontic forces. That was, FEA ignored the events of resorption–apposition present in variable time frames. What’s more, in the clinical scenario, an air gap between an aligner and a dentition is filled with saliva, causing friction between the aligner and the dentition. However, the friction was not designed in this model. Considering the limitations above, there was necessity of relevant clinical practice. Additionally, this study did not consider the unintended intrusion of the anterior teeth caused by distortion of the appliance. This was another side effect of extraction and needed to be considered carefully in further research.In this study, a pure palatal tipping movement of the anterior teeth is generated without torque control, thus resulting in the bowing effect. The required torque control for anterior teeth with oversize axial inclination is weaker than that of anterior teeth with normal axial inclination; this is because oversize axial inclination teeth need a limited loss of torque. Finally, the variation sensitivity of the CRot should be considered carefully in the clinical setting when designing translation of the upper anterior teeth with normal axial inclination. These conclusions provide direction for the use of clear aligners in the clinic.


Consultation data from emergency general practitioners known as SOS Médecins and emergency departments (ED) from OSCOUR® network to the French syndromic surveillance system SurSaUD® (Surveillance sanitaire des urgences et décès). These data are aggregated and monitored on a daily basis through groupings of one or more medical symptoms or diagnoses (“syndromic groups” (SG)).The objective of this study was to evaluate, revise and enrich the composition of SGs through a consensus of experts who contributed or have experience in syndromic surveillance.Three rounds of a Delphi survey were organised, involving 15 volunteers from SOS Médecins and 64 ED physicians in the OSCOUR® network as well as 8 international epidemiologists. Thirty-four SOS Médecins and 40 OSCOUR® SGs covering major medical specialities were put to the experts, along with their diagnostic codes and their surveillance objectives. In each round, the experts could retain or reject the codes according to the surveillance objective. The panel could also put forward new diagnostic codes in the 1st round, included in subsequent rounds. Consensus was reached for a code if 80% of participants had chosen to keep it, or less than 20% to reject it.A total of 12 SOS Médecins doctors (80%), 30 ED doctors (47%) and 4 international experts (50%) participated in the three rounds. All of the SGs presented to the panel included 102 initial diagnostic codes and 73 additional codes for SOS Médecins, 272 initial diagnostic codes and 204 additional codes for OSCOUR®. At the end of the 3 rounds, 14 SOS Médecins (40%) and 11 OSCOUR® (28%) SGs achieved a consensus to maintain all of their diagnostic codes. Among these, indicators of winter seasonal surveillance (bronchiolitis and gastroenteritis) were included.This study involved a panel of national experts with international representation and a good level of involvement throughout the survey. In the absence of a standard definition, the Delphi method has been shown to be useful in defining and validating syndromic surveillance indicators.The online version contains supplementary material available at 10.1186/s12889-022-14157-x. The ability of the system to detect an epidemic or a public health threat earlier is highly dependent on the upstream definition of indicators as well as on the choice of sensitivity or specificity criteria to group patients according to coherent diagnostic groups  for SOS Médecins and 11.4  for OSCOUR®.For the first round questionnaire, the participant was asked to give their opinion on the composition of each SG. The proposed medical diagnostic codes could be selected or not, depending on their relevance to meet the set surveillance objective. This selection was to be based on their clinical expertise, regardless of the software tools available at their own facility. In the first round only, the respondent could suggest codes to be added to the SG for it to meet the surveillance objective in the best possible manner. To help them put forward other codes, SOS Médecins participants received a copy of the specific thesaurus and the ED doctors received an Internet link to the ICD-10 thesaurus . FoFor the second and third questionnaires, the results of the previous rounds were displayed as a bar chart. Each bar represented the number of times a given code was ticked relative to the total number of participants (expressed as a percentage) , 100% in the 2nd and 3rd rounds  and 63% (n = 5) in the first round, 86% (n = 36) and 80% (n = 4) in the second round, 83% (n = 30) and 100% (n = 4) in the third round  and 4 international experts out of 8 (50%) responded to the three rounds of the survey with a participation rate of 66% , 27 ED doctors (64%) and 1 international participant (20%) said they were aware of the SurSaUD® syndromic surveillance system. Eleven out of 12 (92%) SOS Médecins and 33 out of 42 (79%) OSCOUR® respondents reported they had more than 10 years’ medical professional experience. International participants in the OSCOUR® survey were all experts in syndromic surveillance.For the SOS Médecins network, participants came from 11 of the 13 French regions, with 1 to 2 respondents for each. For the Oscour® network, they came from 9 of the 13 French regions with 1 to 9 per region.Thirty-four SGs (including 24 with a sensitive objective and 10 with a specific objective) for SOS Médecins and 40 SGs (31 with a sensitive objective and 09 with a specific objective) for OSCOUR® were submitted during the various rounds. Some of them were only present in one of the 2 surveys, while 25 were common to the OSCOUR® and SOS Médecins surveys  and 11 OSCOUR® (28%) SGs reached consensus for all their codes (inclusion or exclusion). Their surveillance objective, their composition and the results produced in Delphi can be found in Additional file By broadening the scope to the group of SGs that reached a consensus for 75 to 99% of their codes, 17 SOS Médecins (+ 3) and 27 OSCOUR® (+ 16) SGs were found, bringing SGs with at least 3/4 of their codes retained, including 9 SGs common to both networks, to 50 and 68%, respectively. In addition to monitoring indicators for winter epidemics, SGs used for summer surveillance , as well as injuries, abdominal pain, headache/migraine, and burns/corrosion, were also identified among the joint SGs . This approach probably had a positive impact on maintaining the participation rate over the course of the survey. In addition, the OSCOUR® survey was interrupted during the summer holidays , as some areas are impacted by an increase in their tourism-related activity, leaving only a little time to respond to this type of survey for the ED physicians involved. Extending the duration of the survey had negative impacts, such as the higher number of reminders for SOS Médecins only. This may also have led to a memory bias of the participants, even if it was partially made up for by use of the bar chart corresponding to the response selected in the previous round.Although syndromic surveillance has existed for several years and is widely used , 17, theTo our knowledge, this is the first time that the Delphi method is used to work on the definition and composition of SGs. In existing publications, the method often used is that of a group consensus reached after a discussion meeting , 8. UsinFinally, this approach also measured a consensus percentage, which was a more objective decision-making aid for the codes to be maintained or not in each SG.The SGs for which consensus on codes was reached as early as the first round had a specific surveillance objective.In syndromic surveillance, sensitivity is used to detect the highest number of patients likely to be in the early stage of a disease that is not yet characterized (with presentation of little specific signs) while specificity is used to refine investigations if a large number of cases with similar symptoms are identified . In studThe diagnostic codes for SGs used for winter surveillance  were all kept from the 1st round. The specific objective and the small number of codes they comprised probably facilitated consensus among the experts. Used every season for many years, they are used in region-based, multi-source surveillance, which is widely communicated, with weekly reports published and meetings held with data provider partners, during which they were regularly reworked. This visibility can also help healthcare professionals see how seasonal surveillance can make sense, as it is carried out in the aim of contributing to the organisation and adaptation of the care offer, directly benefiting clinicians in their daily activity. These hypotheses could also explain the results for hyperthermia/heat stroke or insect bite SGs, traditionally used in summer surveillance, even if both SGs have poorer consensus, especially the latter, or for trauma and abdominal pain SGs, which correspond to the diagnoses found most frequently in the lead among the top 10 reasons for recourse to emergency medicine.There is difficulty in reaching consensus for SGs with a sensitive objective that more often incorporates symptoms . Among them, some codes of impaired general condition SG (OSCOUR®) were rejected while others did’nt reach consensus. This SG reflects a clinical picture that can have variable aetiologies and come with several pathologies, which means that it may be perceived differently from one clinician to another. This example showed that the surveillance objectives were not always sufficiently explicit or the responses of experts in line with the expectations of epidemiologists. Thus, the participants’ responses focused on supporting the end of life or the condition of the elderly, whereas, for epidemiologists in charge of health surveillance, this SG aimed to measure the sudden deterioration in a patient’s condition (with or without clearly identified aetiology).Another example is lower respiratory infection SG for which most of the codes did not reach consensus. However, this SG relates to several issues, particularly in the surveillance of winter respiratory diseases .SGs with a sensitive objective are composed of a multitude of diagnostic codes that can be a barrier to reaching a consensus. In addition, as not all codes and subcodes were displayed, this certainly influenced participants’ choice and could partly explain the lack of consensus for some codes. It is not certain that all participants saw the tool tip displayed on rolling over certain codes with the mouse, thus meaning they only read part of the subcodes in the selection in response to the set surveillance objectives.There was little discrepancy between the responses of international experts and those of the ED specialists. Despite the lack of a reference definition, these results suggest that the development of indicators coincides between countries and thus allows for the comparison of observations between international systems, which is a strong point in the case of international threats.More generally, the outputs highlighted two limits of using the complete ICD10 classification  to code medical diagnosis in ED. First, this classification contains symptoms which should not be used for coding medical diagnosis . This syIn France, a similar process was launched to revised the format for collecting ED data. Particularly, a new format for ED data proposed three major evolutions: for coding medical diagnosis, a list of 1500 ICD10 codes were defined, instead of the entire ICD10 classification. Symptoms codes are removed from this list. A thesaurus were also proposed for coding chief complaint . Finally an additional information would be collected to indicate circumstance of the ED visit. This new format is still on discussion and may be implemented soon.Even if the survey made it possible to add diagnostic codes initially absent and proposed by the experts to SGs, other diagnostic codes were not selected and the differences should therefore be discussed with the expert group.The epidemiological impact of the results of this survey on the composition of SGs should be analysed by comparing the temporal dynamics of the former and the new composition for each SG. It would also be relevant to assess the performance of SGs by calculating their sensitivity and specificity with regard to the diagnoses actually mentioned in the patient records, however, such studies at national level are burdensome and expensive and can only be considered over a small scope, be it geographic or in terms of the SG selected.The definition of SGs is a key element of syndromic surveillance. It must be evaluated on a regular basis and is subject to change depending on surveillance requirements and to be consistent with the set objectives. The Delphi method, by consultation with experts, may be used to validate the contents of SGs with regard to the objectives and systems concerned. The results of this survey are applicable to any other syndromic surveillance system using emergency medicine data, at national or local levels, depending on the organization of surveillance system. The planification of the survey have to be done upstream and take into account many factors like: the availability of experts along the process, the period of the year , the tool to be used , the human resources dedicated to the survey, extra time for unexpected events.However, for SGs with several diagnostic codes that did not reach a consensus at the end of the three rounds, discussions with the experts will be necessary to fully understand the reasons for lack of consensus, the determinants of the various choices. Effectively understanding this will prove useful when compiling the next SGs and more broadly for the organization of a new Delphi survey.Additional file 1. Screenshot of the OSCOUR® survey questionnaire for Injury SG in the 2nd round. This figure shows the display of the questionnaire for the syndromic group “injury” in the 2nd round of the Delphi OSCOUR® survey. On this screenshot, we have at the top the remind of surveillance objective. On the graph, each bar represents one diagnostic code, the proportion of consensus is represented on the abcissa axis. The blue color on the bar indicates to the participant the code he chose while the grey color indicates the codes he did not choose. Below the graph are listed the ICD-10 codes of syndromic group “injury”, the participants were invited to indicate again relevant diagnostic codes according to the surveillance objective. By rolling over T79 with the mouse, they could view included subcodes in the dark blue box.Additional file 2. a. Number of participants contacted and having answered the Delphi SOS Médecins survey. The first column indicates the different rounds of the Delphi SOS Médecins survey. The next 3 columns indicate results for the different groups of the survey. The last column shows the total for all the three groups. The 3 first lines give the number of people per group to whom the questionnaire was sent for each round. The last 3 rows show the number of people who responded to the questionnaire and the participation rate in percentage (number of persons who completed the questionnaire by the number of persons contacted) in each group, for each round. b. Number of participants contacted and having answered the Delphi OSCOUR® survey. The first column indicates the different rounds of the Delphi OSCOUR® survey. The next 3 columns indicate results for the different groups of the survey. The last column shows the total for all the three groups. The three first line give the number of people per group to whom the questionnaire was sent for each round. The last 3 rows show the number of people who responded to the questionnaire and the participation rate in percentage (number of persons who completed the questionnaire by the number of persons contacted) in each group, for each round.Additional file 3. a. Diagnostic codes by syndromic groups (SG) (n = 14) and their proportion of consensus in the 3 rounds of the Delphi SOS Médecins survey. The first column indicates the syndromic group, the 2nd column the surveillance objective and the 3rd the label of diagnostic codes. Proportions of consensus are indicated in column 4th to 6th. And the last column indicates if the diagnosis was kept or no in the syndromic group. b. Diagnostic codes by syndromic groups (SG) (n = 11) and their proportion of consensus in the 3 rounds of the Delphi OSCOUR® survey. The first column indicates the syndromic group, the 2nd column the surveillance objective and the 3rd the label of diagnostic codes. Proportions of consensus are indicated in column 4th to 6th. The last two columns indicate if the diagnosis was kept or no in the syndromic group and the number of subcodes.


Sudden cardiac death (SCD) in young people is due to genetic cardiac causes in the majority of cases. In UK all cases have an autopsy and results are given to the family. We now have  a national pathway with detailed programme to establish that all members of the family  are screened by cardiologists in inherited cardiac centres . Also genetic testing of material taken at autopsy will be carried out in all cases which will be a valuable addition to the pathological and clinical findings. All this will aid the family in coming to terms with the tragic death and provide genotype phenotype correlation within the family to prevent future deaths. Sudden unexpected death (SUD) is defined as natural unexpected death in witnessed cases as an acute event with time to death being < 1 h and in unwitnessed cases as person last seen alive < 24 h before being found dead –5.Retention of cardiac tissue with storage and location of the retained tissue.Consent to be obtained from the family to retain the tissueThe appropriate tissue to be taken for genetic testing, the pathway for the genetic testing and who should pay for this.Who would arrange cardiological screening of the families?There are many difficulties facing the pathologist in such cases in view of the genetic implications and prevention of further deaths within families, as we have published on previously . There aFollowing this meeting, a UK charity funded by bereaved families called Cardiac Risk in the Young (CRY) established with me a nationally available free service for prospective reporting on the cardiac pathology of SCD. This work enables us to process hearts referred from coroners and pathologists from throughout the UK and we have built up over 7000 cases in this database, with the majority of cases due to SADS and CM Fig. . Since 2In the 21st century, the National Health Service (NHS) England sees its role as harnessing the power of genomic technology and science to improve the health of the population. In 2019, an NHS document on genomics and prevention resulted in the implementation of genetic medical service alliances in 2021 to deliver a single national testing directory covering use of all technologies from single genes to whole-genome sequencing. Most importantly from our point of view, it established a national genomic testing directory for rare and inherited cardiac diseases including aortopathies, vasculopathies, cardiac channelopathies and cardiomyopathies . This leWith NHS England and charities including the British Heart Foundation (BHF) and CRY, I have worked on a pilot study to establish a multidisciplinary team of coroners, coroner officers, pathologists, cardiologists, geneticists and genetic scientists in each of the seven pilot sites. A coordinator has been appointed in each region to direct the pathway from the pathologist, to coroner, coroner officer, retention of tissue, taking of genetic sample, through to the family and referral to inherited cardiac conditions services within each genomic region. Genetic testing will be undertaken within the genetic hubs once the family has been seen by a specialist cardiologist and the cardiac phenotype has been established by the pathologist at autopsy. The logistics of tissue retention and sample handling for genetic testing will be supervised by the regional coordinator and will be appropriately funded.The pilot study highlights the need for specialist cardiac pathology centres, as a study we undertook highlighted the need for this expertise . This isThe autopsy rate for SUD in Europe varies widely, with an average of 43% and genetic testing in 48%, which leaves a large gap . This pi


To find out the comprehensive principles of synthetic jet control effects on airfoil stall characteristics, fundamental contrastive wind-tunnel tests were conducted systematically. By using six-component balance, Particle Image Velocimetry (PIV) technology and boundary layer probe, the measurements of model aerodynamic forces, the whole velocity field over airfoil and velocity profiles in the boundary layer were conducted, respectively. Based upon the experimentally parametric analyses of synthetic jet control on airfoil, it is concluded that the incline angle of synthetic jet has an important impact on both the flow in boundary layer and aerodynamic forces of airfoil. A tangential jet inject energy and accelerate the velocity of flow in inner boundary layer thus has a better control effects on delay stall of airfoil when the momentum coefficient of jet is relatively large, and the normal jet helps to enlarge the thickness of boundary layer which is proved to have better control effects on flow separation control and improving the aerodynamic characteristics of airfoil when the momentum coefficient of a jet is relatively small. Flow separation induced by the leading-edge vortex over the airfoil under high angle of attack may lead to the loss of the lift, the divergence of drag and pitching moment, and further decrease the aerodynamic performance of rotor and induce vibration of blade. Therefore, the delay even suppression of airfoil flow separation and stall is one the focus of helicopter aerodynamic. As an emerging method, active flow control (AFC) for airfoil flow separation and stall has been developed rapidly, among which, synthetic jets can transfer momentum to the surrounded flow and enhance the mixing of the boundary laryer without net mass injection across the flow boundary, thus, compared with the injected jet, it is more suitable for the flow control of airfoil2.The pitch of retreating blade of rotor is commonly larger than that of advancing blade, especially at high forward speed and large maneuvering flight status of helicopter, as a result,flow separation is easy to occur on retreating blade of rotor at these flight states3, and then the flow charateristics of synthetic jet were experimentally and numerically investigated5. Glezer et al. pointed out that the interaction domain between a synthetic jet and a cross flow induce an “apparent” modification of the flow boundary and alter the local pressure and vorticity distributions, and these attributes may be exploited to modify or control the evolution of wall-bounded and free-shear flows on scales that are one to two orders of magnitude larger than the characteristic length scale of the jets themselves6. Manikandan et al. further carride out the PIV tests on interactions betweent the sythetic jet and the cross flow7, the results indicated that the interaction caused by the synthetic jet was limited to the viscous sublayer and log layer and never reached beyond 60% of the boundary-layer thickness from the surface to interact with or transport energy from the mean flow. Besides, the time evolution of the synthetic jet was founded to be completely different between still air and crossflow, which suggested that any performance prediction, such as momentum added to the boundary layer or the penetration of the jet in terms of boundary-layer thickness based on still air conditions may not be applicable in crossflow conditions at all.Synthetic jet actuator (SJA) was firstly developed by Smith and Glezer in 19948. The experimental resulsts illustrated that when the highest velocity was achieved did not mean the highest momentum was generated, and the added momentum might be idealer for flow control than the maximum velocity of synthetic jet. Therefore, geometry effects of jet orifice might have a pronounced influence on the flow field structures and, as a result, alter the effectiveness of the flow control. After that, Buren et al. conducted PIV experiment on investigaions of flow structures associated with a finite-span synthetic jet9. The results show that synthetic jet would result in a boundary layer less susceptible to separation in an adverse pressure gradient flow, and the wall-normal, transverse jet induced the most flow unsteadiness near the orifice, and the unsteadiness decreased with an increase in skew angle and a decrease in pitch angle. Additonally, Buren et al. investigated the influences of orifice aspect ratios on interactions of synthetic jet and zero-pressure gradient laminar boundary layer10, it was founded that a decrease in aspect ratio resulted in a reduction in the distance between the edgewise vortex structures and the reduction in aspect ratio reduced the virtual blockage of the jet. Furthermore, Buren’s results suggeted that the spacing and interaction of multiple actuators should be taken into because the unsteady and steady features of the flow were characterized three-dimensionally. Chiatto et al. conducted tests on control of continuous water spray by employing synthetic jet11, the experimental results showed that the synthetic jet could energize the region downstream of the impact and producing higher droplet velocity, and the effect tended to reduce as the injection pressure of water spray increases.In 2014, Buren et al. measured the three-dimensional flow structures of a finite-span synthetic jet by employing the PIV technique12. Under such a background, active flow control (AFC) for suppressing airfoil stall has been attached much importance and developed rapidly. So far, the novel periodic excitation method by using synthetic jet is demonstrated to be one of the most promising AFC methods on controlling stall characteristics of an airfoil17.The investigations on flow structures of synthetic jet in still and cross flow showed that the interaction of a synthetic jet with an external cross flow can displace the local streamlines and induce an apparent or virtual change in the shape of the surface, thus, the synthetic jet had potential utility for flow control applications, specifically control of the performance of aerodynamic surfaces through fluidic modification of their apparent aerodynamic shape18, and the numerical results showed that synthetic jet could enhance the aerodynamic characteristics of airfoil under stall. Seifert et al. conducted test for synthetic jet control on NACA0015 airfoil19, which partly verified the conclusion of Hassan, and the results indicated that a jet placed just upstream of the separation location was effective on controlling the flow separation of an airfoil. In 2003, Lee et al. experimentally investigated the control effects of synthetic jet on controlling the adverse pressure gradient and boundary layer separation20. The results showed that when the synthetic jet actuator was excited by the unstable frequency of boundary layer flow, the modulation control effects of synthetic jet on boundary layer flow was significantly enhanced. Dandois et al. performed numerical simulations on flow separation control by synthetic jet over a smooth ramp21, and the influences of frequency were studied. The results showed that the separation length is reduced by half for a low excitation frequency F+ = 0.5 of synthetic jet, however, the effect of the high frequency forcing at F+ = 4 is a significant increase of the separation length, which indicated the importance of excitation frequency. Sahni et al. carried out experimental and numerical investigations on the interaction of a finite-span synthetic jet with a crossflow over a finite wing at a chord-based Reynolds number Rec = 105 and 0° angle of attack22. The reslusts show that the larger the blowing ratio (jet velocity to freestream velocity) was, larger spanwise structures and wavelength were obtained, which could help to enhance the control effect of synthetic jet.Hassan et al. carried out preliminary researches for synthetic jet control of airfoil by employing RANS method with B-L turbulance model26. There were some consensuses regarding the parametric analyses of jet parameters, such as the influences from jet momentum coefficient, location of jet and excitation frequency. In the investigations of the implications of synthetic jet location, a general good agreement was concluded that the jet adjacent to the separation position enabled the jet vortex penetrate into large separated flow state more efficiency27, and thus it reduced the substantial size of the separation vortex and delay the stall of an airfoil29. Further, as another influential parameter, the momentum coefficient of the synthetic jet was demonstrated to be proportional to the growth of aerodynamic characteristics of an airfoil in the previous studies32, and the control effects tended to be stabilized with momentum coefficient exceeding a critical value33.Overall, a variety of numerical and experimental investigations had already been carried out to explore the mechanisms of a synthetic jet on improving the maximum lift of airfoil as well as the stall angle37, whereas the comparison made by Monir et al. showed that an approximately 45° angle of a synthetic jet is the optimal one of NACA23012 airfoil in large angle of attack (AoA)38. Moreover, the numerical analyses by He et al. reported that the control effects of a synthetic jet were not sensitive to the jet angle39.Though some mechanisms of control effects of synthetic jet on airfoil stall were revealed and recognized in current stage, there are some different conclusion on the control efffecs for incline angles of synthetic jet on delaying the stall of an airfoil. Several investigations indicated that a nearly tangent jet state, with the jet angle less than 30°, could enhance the aerodynamic performance of an airfoil more significantlyIn this paper, to investigate the control effects of incline angle of synthetic jet and other parameters in mechanism, a series of wind-tunnel tests were conducted for parametric verifications of NACA0021 airfoil stall characteristics, including the measurement of velocity profile in boundary layer. In the studies the jet momentum coefficient, the jet angle and the jet location are incorporated thoroughly. In consideration of the inconsistent influences of the jet angle in actual tests, detailed investigations were carried out in a variety of freestream conditions and electrical excitation voltages to investigate the inconsistencies.c = 0.2 m and a span size La = 0.36 m. Because the cover plate of SJA is a flat surface, so the installation of the SJA changes the local geometry and curvature of original NACA0021 airfoil, Considering this imperfection, the SJA is installed at 0.15c and 0.4c respectively where the curvatures of the airfoil are relatively small. Though the test might obtian different data from that of a real NACA0021 airfoil, the experiment with and without SJA control are both based on the same model with the SJA installed, so the experiment could show the control effects of the SJA on flow separation and stall of airfoil.Considering the size of the synthetic jet actuators (SJA) and the installation of the actuator arrays in the wing (airfoil) model, the NACA0021 airfoil is used for the test model with a chord size 40, with maximu wind speed 25 m/s and the turbulence intensity of the wind tunnel is about 1.2% measured by the hot wire anemometer with the model in the test section. The measurements are performed at chord-based Reynolds number Rec ≈ 0.7 × 105 ~ 3.5 × 105 (freestream velocity V∞ = 5 ~ 25 m/s). The AoA of the airfoil is adjusted within a range of − 9° < α < 28° through a computer-controlled actuator. The wing (airfoil) model is mounted on a shrouded six-component force and moment balance system fixed on the tunnel test position. Two elliptical endplates are used and installed at both the ends of the wing model to avoid the influences of three-dimensional flow along the spanwise of wing model, as shown in Fig. The tests are conducted in the 0.75 m diameter working section closed-return wind tunnel of Nanjing University of Aeronautics and Astronauticsjet = 20 mm and h = 1.5 mm respectively, and the spacing of the two orifices on the same cover plate is D = 40 mm. The jet angle  is varied by changing the cover plate with different incline angle of orifice.The SJA is designed by the 1-inch full range speaker unit with the size being 43 mm × 35 mm × 16 mm, the resistance 4 Ω, impedance 8Ω, and the rated power 5 W. There are two slots arranged in the wing model at 0.15c and 0.4c respectively, and two cover plates (360 mm × 35 mm) are used to cover the slots. On each cover plate, the synthetic jet array is intalled with 6 actuators along the spanwise direction connected in parallel, as shown in the following figure. There are 6 orifices just on the actuators, and the length and width of the orifice are LVjet) increases with a larger excitation voltage (Ujet), and there is a peak mean velocity when the excitation frequency (fjet) is about 200 Hz (which is adopted in the whole test). Therefore, the excitation frequency of each SJA is fixed 200 Hz (F+ = fjetc/V∞ = 1.6 ~ 8) to ensure relative large jet mean velocity, and the jet velocity and momentum coefficient with different excitation voltage and freestream velocity are illustrated in Table Figure The wing model, balance and support system are show in the Fig. The aerodynamic forces and moment are measured by the six-component balance system as shown in Fig. The velocity field over the airfoil is measured by PIV technology. The PIV system contains double pulse laser sources, optical element, CCD camera, synchronizing device, Insight 3G processing software and traditional solid particles devices etc. In order to improve the accuracy of the CCD camera for capturing the information of the local flowfield over airfoil, three valid zones of PIV measurement are distributed to comprehensively cover the suction surface of airfoil. The Insight 3G operating software for Windows is used to control the work of the entire PIV system. Firstly, a high-speed image acquisition card is used to capture the particle image of the flowfield from the CCD camera, and then the particle image is analyzed and processed by the cross-correlation algorithm to obtain the velocity vector of the whole flowfield. The main parameters of PIV system are given in Table Furthermore, the velocity profiles of boundary layer are evaluated by the boundary layer probe as shown in Fig. α = − 21° under freestream velocity being 20 m/s. The 0.15c SJA is turned on at an angle of θjet = 90°. As shown, the stall vortex begins to form at the leading edge and its sequential convection along airfoil surface induced a large flow separation, resulting in a large-scale recirculation region near the trailing edge position containing zone II and zone III. The large flow separation finally causes a loss of lift, which threatens the efficiency of the airfoil. With the control of leading-edge synthetic jet, the mixing between the internal layer and the external layer of the boundary layer is heightened, and the energy of the entire boundary layer is strengthened consequently. Above effects enabled the effective inhibition of the leading-edge vortex and further makes the separation point move downstream along the airfoil, thus it could reduce the large flow separation region significantly which is illustrated in the figure.The control effects of synthetic jets on preventing flow separations over airfoil are investigated at first, and Fig. c and 0.4c are measured by boundary layer probe.The effects of synthetic jet on separation flow are caused by its interaction on boundary layer, so in order to investigate the control mechanism of synthetic jet on boundary layer in post stall condition, the velocity profiles in boundary layer at 0.2c is larger than at 0.2c. Though synthetic jet with 90° angle might not inject energy to the boundary layer directly, it could enhance the mixture of flow in and out of boundary layer, and enlarge the thickness of boundary layer and further make the flow hard to separate from the surface of airfoil.Figure c and 0.4c are demonstrated to be large recirculation zone, especially apparent at 0.4c. Once jet control is turned on, flow separation is well suppressed, and the separated flow reattaches to the surface of the airfoil, and the effects of jet angle are similar to the case of airfoil with 20° angle of attack. Besides, comparing to the jet with 60° and 90° incline angle, the jet with 30° angle incline to the airfoil surface has a better control effect on control the separation flow of inner boundary. It is because that the nearly tangential jet could inject energy to the boundary layer directly, which could suppress the flow separation due to the adverse pressure gradient.Figure c and 0.4c on suction surface of airfoil with AoA = 20° when freestream velocity is 20 m/s and 25 m/s respectively. The control effects of synthetic jet are similar to the condition when freestream velocity is 15 m/s. In order to investigate the relation between flow characteristics in boundary layer and aerodynamic force of airfoil, the relevant lift, lift-to-drag ratio and pitching moment coefficients are presented in Fig. Figures ∞ = 20 m/s and V∞ = 25 m/s) and varied jet parameters (θjet and Cμ). As shown in the figure, at all the freestream velocity, A1 has better control effects than A2 on increasing the maximum lift coefficient and delaying stall AoA of airfoil when the two SJAS have the same jet angles and momentum coefficients. The reason is that stall of airfoil is induced by the large flow separation near the leading edge, and A1 is closer to the separation point, so the synthetic jet could inject momentum to the boundary layer and enhance the mixing of the shear layer more directly. Moreover, when the magnitude of inflow was relatively large, the SJA2 with a 60° or 90° jet angle might lead to the decrease of stall AoA.The investigation on control effects of SJA with different locations are carried out in this part. Figure The disagreements about the influences of jet angle on synthetic jet controls exist for many years, it is necessary to find out the reasons or promote further relevant investigation by means of experimental technologies. In this part, a series of freestream conditions (10 ~ 25 m/s) are considered to carry out the experimentally parametric analyses. Figure 36. As the freestream velocity increases , the control effects on increasing the lift coefficients and the stall angles of airfoil decrease. The reason might be that the decrease in jet momentum coefficient suppress the energization from synthetic jet, and thus the control effects are less impacted by the jet angle . The phenomenon is also similar to the numerical results of He38.As shown in the figure, when the freestream velocity is lower than 15 m/s, the control effects is demonstrated to be wakened as the value of jet angle increases, which is in accordance with Hassan’s results9. As shown in Fig. 9, which could delay the flow separation.Overall, for the freestream with relatively larger velocities, the control mechanisms of SJA from the jet angle are a little different from the cases under smaller freestream velocities. The interactions induced by synthetic jet to the flowfield over airfoil are mainly due to the mixing effects when the momentum coefficient of a jet becomes much smaller, and a jet with a larger inclined angle  could penetrat the farthest into the freestream thus enhance the mixing effects between inner layer and outer boundary layers, which has been proved by BurenThe experimental results indicate that the influences of the jet angle on the stall control of airfoil by synthetic jet are very complicated, and only considering a single jet angle could not obtain the best control effects for all freestream and excitation states, and such effects are highly dependent on the jet momentum coefficient. Better control effects could be achieved by setting jet to a smaller angle when the momentum coefficient is large enough. The difference is, when the jet momentum coefficient is small to a reference extent, a larger jet angle is required to improve the control effects on delaying the stall of airfoil.The mean velocity is an important parameter for synthetic jet. To investigate its influences on airfoil stall and flow separation, four excitation voltages  are conducted to explore the effects of velocity of synthetic jet on enhancing the aerodynamic characteristics of a stalled airfoil.Figure As another parameter affects the momentum coefficient of synthetic jet, the control effects of synthetic jet with different freestream velocity are investigated, and the comparisons about airfoil lift coefficients versus AoA are conducted at different freestream velocity.Figure The comparison about results also reveal the mechanisms of synthetic jet control about the jet angle. As shown in the plots, the control effects in smaller incline angle are more effective with respect to various freestream conditions, indicating that the control effects in nearly tangent jet would be significantly impacted by the jet momentum. Unlike the small incline angle cases, a normal jet configuration could control the aerodynamic characteristics of airfoil with less implication of the freestream velocity (jet momentum).To expound the control effects of synthetic jet on delaying the stall of airfoil more visually, Fig. The control effects of synthetic jets on the stall characteristics of airfoil could be effectively evaluated in both micro and macro ways through the measurements of aerodynamic forces, the transient flowfield using PIV technology and the velocity profiles of boundary layer.The tangential jet inject energy and accelerate the velocity of flow in inner boundary layer, which helps to suppress the flow separation and delay airfoil stall. The normal jet enhances the mixing of flows in inner and outer boundary layer, which helps to enlarge the thickness of boundary layer and reduce the drag coefficient of airfoil when the momentum coefficient of synthetic jet is relatively small.Arranging the SJA near separation point over airfoil could suppress the flow separation more effectively. Overall, a jet with larger momentum coefficient has better control effects on improving the lift coefficient of an airfoil and also increasing the stall angle.In view of the previous disagreements about the control effects of the jet angle, the present investigations indicate that the control effects of jet angle are sensitive to the freestream conditions and the jet momentum coefficient. When the momentum coefficient of a jet is relatively larger (the jet velocity is as large as the freestream velocity), small jet angle tends to have better control effects on delaying the stall and improving the lift coefficient of an airfoil. When jet coefficient become relatively small, larger jet angle state is demonstrated to be more expectant to obtain optimal control.In this paper, the experimental investigations regarding the control effects of synthetic jets on the lift and stall angle of airfoil have been done, the tests contain the measurements of flowfield over suction surface of airfoil, the velocity profiles in the boundary layer and the overall aerodynamic forces of the model. Based on the comprehensive parametric analyses, the disagreements of synthetic jet control mechanisms among different references are partly explained by working out the coupling effects of the jet parameters. The most specific conclusions are shown as following:


Selenium is important for human health. However, the selenium status and selenium intake of the German population has not been recorded in a representative study so far.Thus, literature from the last 50 years was screened in a systematic way and the results of various studies were pulled together to shed light on the selenium status of the German population. Moreover, the selenium content of selected food items that were either found on the German market or grown in Germany was researched and evaluated.Of 3542 articles identified, 37 studies met the inclusion criteria. These 37 studies comprised a total of 8,010 healthy adults living in Germany with a weighted arithmetic mean of 82 μg/l selenium in plasma or serum. The results will form a basis for interpreting upcoming results from national food consumption surveys. Furthermore, 363 selenium values for 199 food items were identified out of 20 data sources—published or analysed between 2002 and 2019. An estimation of the selenium intake of the German population will be possible with this data in future nutrition surveys.The online version contains supplementary material available at 10.1007/s00394-022-02990-0. The trace element selenium is important for the human health: both deficiency and excess will cause substantial health problems. Only 60 years ago selenium was recognised as being essential in the diet of animals and humans. As part of selenoproteins, selenium plays a role in anti-oxidant and anti-inflammatory regulations and in the production of active thyroid hormones . In 2008So far there is no large, representative study on the selenium status of the German population, which makes it difficult to evaluate whether the people in Germany are adequately supplied. Only various smaller studies were carried out over the last decades. In the latest German National Nutrition Survey (NVS) II  the seleUnlike other minerals and trace elements selenium exists as part of various compounds with different bioavailabilities, metabolic pathways and half-lives. In food, selenium is mostly present as selenite, selenomethionine (SeMet), methylselenocysteine (MeSeCys) and selenocysteine (SeCyS)—or proteins containing these –7. The sIn consequence, the selenium content in food is highly variable due to a number of particularities, making it challenging to state precise values of selenium content in specific food items. The literature search of selenium content of selected foods that were either found on the German market or grown in Germany discussed below was part of the BLS review process. With this approach the planned NVS III shall be enabled to provide representative information on the selenium status as well as the selenium intake of the German population.Furthermore, literature from the last 50 years was reviewed in a systematic way to shed light on the selenium status of the German population and to form a basis to interpret new results from upcoming national nutrition surveys.The search strategy aimed to find published data on the selenium status of the German population from 1970 up until March 2021. It included articles obtained through Web of Science, Embase, Pubmed, Scopus, Cochrane, opengrey and grey literature searches. The search term used was  AND (“Selenium[Mesh]” OR “selen*”) AND “german*” AND “human*”. The search term was adjusted to the different requirements of the used databases.To provide reliable estimates for the selenium status in recent decades, number of study participants, mean values of selenium in serum/ plasma and corresponding standard deviations or standard errors, respectively, were extracted from all eligible studies. For studies that did not provide these numbers in the publication but seemed eligible—for instance selenium data were only included as a graph, the data was only stated as median or range, or a German subgroup needed to be extracted out of a pool of participants in a European data set—the corresponding authors were contacted. Data of healthy control groups were used when studies examined the selenium status in specific populations with a certain disease. Where possible the data for men and women were extracted separately.Studies were included when they were published in English or German language as primary study to report the selenium status plus standard deviation/ standard error in blood plasma or blood serum of healthy individuals living in Germany. Information on the selenium status in whole blood samples was excluded for reasons of comparability. To obtain results of general relevance, only values from healthy adults over 18 years of age were used for the present review. Studies were excluded if they did not provide extractable data on selenium status in plasma or serum, only consisted of a study group of less than 10 participants or of pregnant/ nursing women.Intervention studies specifically examining selenium supplementation were excluded or only control data used, as these studies often use pharmaceutical doses. Most observational studies did not provide specific information on selenium supplement use. However, some studies reported a general use of supplements. For example, Burney : 22% of Studies that only provided a mean value without standard deviation or standard error–even after contacting the author—were excluded as the accuracy of their reported results could not been assessed properly. No available risk of bias tool met the specific requirements of our study, thus an own quality assessment was performed for all included studies followed by a sensitivity analysis. The risk of bias was estimated based on the following quality measures: use of reference material/standards, performance of repeat measurements, accuracy of analysis, recovery rate, precision of analysis, limit of quantification LOQ / limit of detection LOD, performance of interlaboratory comparison, accreditation of the laboratory and the representativeness of the study population. All given parameters were considered together to rate the risk of bias as low, moderate or serious. Studies were classed as serious risk if they provided none or only one of the chosen quality measures. An exemption here are studies that were carried out by accredited laboratories as this implies that certain standards are fulfilled. Furthermore, studies that provided two or three of the chosen quality measures were classed as moderate risk, while studies with more than four given quality measures were classed as low risk of bias. A sensitivity analysis was then performed without the studies classified as serious risk of bias.n. Range describes the smallest to the largest value of a given data set.The quantitative data for selenium concentrations in blood serum or plasma is provided in µg/l. Where necessary the atomic weight of 78.97 was used to convert the extracted data to the used selenium unit. Data shown as standard error of the mean (SEM) in single studies were altered to standard deviation (SD) with the formula SD = SEM * √i representing the weight (number of data points) associated with the sample (the selenium concentration) Xi:The weighted arithmetic mean was calculated with the following formula to account for the number of study participants with ωThe time period of sample collection often differed from the year of publication in the found studies. When known, the year of the examination or the midpoint of the examination period was used for the present study. Otherwise the publication date was used or authors were asked for detailed information.Selenium contents of food items were collected through literature search with Web of Science and Scopus. Pubmed and Embase were not included as these databases tend to have a rather medical focus. The search term consisted of "selenium" combined with various food items or food groups. Food items were selected if consumed frequently or in large quantities in Germany based on the results of the NVS II and its longitudinal equivalent NEMONIT. In addition, selenium rich food items such as Brazil nuts were included as they substantially contribute to the daily intake of selenium even if they are only consumed occasionally. Relevant publications were identified through scanning titles and available abstracts. Studies in English and German language were considered. Besides, reports of the German Federal Office of Consumer Protection and Food Safety (BVL) and the German Federal Institute for Risk Assessment (BfR) were screened.Studies were selected when the investigated food samples were bought on the German market or grown in Germany. In addition, the samples had to refer to the edible part of the food item and it had to be clear which part of the food item was analysed, e.g., if the food item was peeled before processing. The data had to be based on precisely described analyses.The quality of the collected data was evaluated based on an adapted quality index developed by the European Food Information Resource. The following categories were assessed: Food description, component identification, sampling plan, number of analytical samples, sample handling and analytical method. Data which received a low quality index were not considered .Minimum, maximum, range and weighted arithmetic mean for the selenium content of foods are presented in µg/ 100 g. The applied weighting factor reflects the number of primary samples which were used in the selenium analyses. To show the relative contribution of specific foods to the reference value for selenium of the German Nutrition Society  , the weiOf 3542 articles identified until March 2021, 37 studies with 47 data points were included in this review  or low (n = 5) risk of bias (Table S2). In a sensitivity analysis where we excluded all studies with a serious risk of bias, the arithmetic mean was robust and remained at 82 μg/l selenium in plasma or serum. Therefore, all studies were included to have a wider range of data points distributed over the last decades.Based on the risk of bias assessment, 10 studies were evaluated to have a serious risk of bias, whereas all other studies showed either a moderate  for 2256 men. Mean serum/ plasma selenium concentration for women was available from 14 studies and the arithmetic mean was 84 μg/l (range: 64–94 μg/l) for 4,124 women.The literature was screened from 1970 to March 2021 with the earliest study found dating back from 1983. Investigations from 1983 to 1990 showed an arithmetic mean of serum/ plasma selenium concentration of 74 μg/l, from 1991 to 2000 of 83 μg/l, from 2001 to 2010 of 73 μg/l and from 2011 to 2020 of 88 μg/l.Out of 20 data sources 363 selenium contents for 199 different food items were identified (see Table S3). The data were published or analysed between 2002 and 2019. Before 2002 no eligible publication could be found. The majority of selenium data was collected from the BVL National Monitoring (2002–2019). Most data were available for vegetables , fruits , meat and meat products  and fish and seafood .The Brazil nut is the food item with the highest selenium content with a weighted arithmetic mean of 277 µg/ 100 g. It is followed by offal: pork kidney 221 µg/ 100 g (range 220–223 µg/ 100 g), beef kidney 123 µg/ 100 g (range 118–154 µg/ 100 g) and veal kidney 98.6 µg/ 100 g. Furthermore, the food group “fishes and seafood” shows notable selenium contents. The highest content  in this group was reported for tuna.The contribution of different food items to achieve the reference value of selenium intake varies widely Table . As a caThis is the first time that data from various studies were combined in a systematic way to estimate the selenium status of the German population. Pulling together the available data indicates an average selenium concentration of 82 μg/l (weighted arithmetic mean) in plasma or serum for a total number of 8010 healthy adults living in Germany. Even though no study representative to the whole German population could be included in the present review, the combination of many different subgroups gives an idea of the approximate selenium status of the German population.A comprehensive review by Fairweather-Tait et al.  concludeSingle nucleotide polymorphisms in genes might improve the ability to metabolise high or low selenium.Populations exposed to harmful elements show no or even beneficial effects of high selenium status. The Inuit in Canada are, for example, exposed to high amounts of mercury as their diets consist primarily of marine mammals and fish. They also show a high mean blood selenium level of 319.5 μg/l. The high selenium status proved to have protective effects on odds ratios for hypertension, stroke and myocardial infarction associated with mercury exposure.The dose and form of selenium determines if the overall effect is beneficial or harmful.The gut microbiota might have a regulating function. Exposure to high amounts of selenium in early life might, for example, alter the composition of the gut microbiota in a way that selenium is more readily excreted.The U-shaped relationship between selenium status and its health effects might not be sufficient to explain the interindividual differences in the effect of selenium on health. Different requirements might exist in populations and individuals. Rayman  recentlyThe earliest studies found in this literature search were conducted in the 1980s. The selenium status over the last 40 years does not follow an apparent pattern. The variations might be due to changes of available food items on the market. An example would be the effect of a reduced import of North American wheat for breadmaking flour in the 1970s, which might have negatively influenced the selenium status in some populations in the European regions  or the iAnother reason could be the different age ranges used in the studies. A decline of selenium bioavailability was shown to occur with increasing age by Olivieri  and BaudArithmetic mean of the selenium status was 80 μg/l for 2,256 men and 84 μg/l for 4124 women. The results are comparable to the results of the EPIC cohort  and bothHowever, a few studies suggest that women are more susceptible to the onset of certain health conditions associated with low or high selenium levels. A study by Arnaud et al.  implies Considering all the facts discussed so far, it becomes clear that it is an enormous challenge to integrate selenium data in nutrient databases, such as the BLS. The selenium content in plant-based foods varies due to considerable differences in the soil selenium. Meat products are affected through the selenium content of the plants/ soils plus the selenium supplementation of specific fodder . TherefoThe high variations in the selenium content in one and the same plant species can be clearly demonstrated using the Brazil nut which is characterised by a naturally high selenium content . The selThomson et al.  emphasizMeat is also a substantial selenium source. Through the supplementation of fodder, meat has considerable selenium contents even in countries with a selenium poor ground . In AustThe implementation of these literature-based data in the nutrient database will offer the opportunity to select the type and calculate the amount of food items necessary to achieve the reference values for selenium intake in Germany. Furthermore, this will support future consumption studies—such as the NVS III—to estimate the actual selenium intake of the German population and to evaluate which foods significantly contribute to the selenium intake in Germany.German nutrition surveys have not covered the selenium intake of participants in the past, since the data on selenium content of food items in applicable nutrient databases were not available for methodical reasons. Therefore, literature from 1970 up until March 2021 was reviewed in a systematic way to display the selenium status of the German population over this time span and to form a basis to interpret new results. Considering our results and the present literature, the majority of adults in Germany seem to be adequately supplied with selenium. However, even if the weighted arithmetic mean of the 37 investigated studies indicates an acceptable selenium status of 82 µg/l in plasma/ serum for a total of 8,010 healthy adults living in Germany, most likely not everyone in Germany will be sufficiently supplied. The planned NVS III with over 10,000 participants will provide highly needed information on the selenium status of the German population in general and of various subgroups (e. g. those following a vegan or vegetarian diet) by determining selenium in blood samples.Furthermore, the selenium content of selected food items that were either found on the German market or grown in Germany was researched and evaluated. The availability of selenium data offers the opportunity to include those in the German Nutrient Database and to estimate the selenium intake of the German population as well as to identify the major selenium sources in future nutrition surveys such as the mentioned NVS III. Moreover, we will be able to further research the link between selenium intake and selenium status in the planned study.Supplementary file1 (DOCX 49 KB)Below is the link to the electronic supplementary material.


The present case report depicts an unusually large desmoplastic fibroblastoma. The diagnosis of the lesion appears to be deceptive clinically. The purpose of this case image is to highlight its size and presenting symptoms, which could easily be mistaken for an odontogenic, salivary gland, or a soft tissue neoplasm. The present case report depicts an unusually large desmoplastic fibroblastoma. The diagnosis of the lesion appears to be deceptive clinically. The purpose of this case image is to highlight its size and presenting symptoms, which could easily be mistaken for an odontogenic, salivary gland, or a soft tissue neoplasm.  Following examination, a soft tissue swelling measuring (10x9x2) cm was noted on the left side of the face Figures . The swe3Microscopic examination from the most dependent part of the lesion revealed a nonencapsulated lesional tissue consisting of proliferation of spindle‐ and stellate‐shaped fibroblasts with large oval nuclei and bi‐ or trinucleation, immersed in the abundant dense collagenous stroma Figures .4Treatment included a wide local excision of the lesion and primary closure under general anesthesia. Following treatment, the patient was observed for 48 hours and then discharged. Postoperative view of the patient is depicted in Figure All the authors contributed to the writing of the manuscript.None.Ethical approval was not required from the institution, in accordance with our country's law, as this was a case report.Written informed consent was obtained from the patient to publish this case image in accordance with the journal's patient consent policy.


Furthermore, the wrong image of IRF3 was used for Figure 2E by mistake. Below is the correct figure. The authors apologize for any inconvenience caused to the readers.


In this contribution, an empirical relationship between the number of review and research articles published per year was searched. The simple idea based on proportionality (linearity) between the numbers of both kinds of articles was expressed in terms of a quadratic relationship, in which the quadratic member can reflect negative or positive deviations from the assumed linearity. The quadratic relationship was able to describe beginning periods of research fields as well as their mature phases and to detect the unpredictably high number of review articles. It was verified by the articles published in 20 various research fields taken from the Web of Science during different time spans.The online version contains supplementary material available at 10.1007/s11192-023-04654-0. Review articles play an important role in scientific publishing. They summarize the current state of specific topics and provide the critical evaluation of existing studies. Review articles can be divided into two main categories, such as narrative and systematic reviews  . The data from 20 various research fields of different duration were collected up to 2021, see Table The data were processed by MS Excel 2019. The statistical analysis including a non-linear regression based on the Gauss–Newton iteration procedure was performed by the QC.Expert software  on the significance level α = 0.05. The outliers were detected by using the Atkinson distance, the Jackknife residuum, and diagonal elements of a projection matrix.NRev) published in one year should be theoretically proportional to the number of research ones (NRes) published in the same year ask is the constant and k < 1 because the number of review articles should be lower than the number of research ones. It is possible to note that NRev and NRes taken in the same years are not, in fact, synchronized in time because the review articles describe the results obtained in recent past. However, some deviations from this ideal model can be expected when the research takes a long time and review articles describe results obtained several years ago and also in an early stage of research when only a few review articles could be written about several research ones. That is why a more general quadratic relationship between NRev and NRes can be suggesteda and b are the constants (parameters). An absolute member c was not taken into account because if NRes = 0 then NRev = 0. If the quadratic member is not significant (a ≈ 0) we obtain the linear relationship again.Supposing that the above-mentioned balance exists, one can assume that the number of review articles  was tested. A weak correlation with r = 0.440 (rcrit = 0.423) between the quadratic parameter a and the time span calculated as the number of years between 2021 and the first year of publishing (Table b (r = 0.165). The correlation shown in Figure S1  was strongly influenced by two points A and B. After their exclusion, the correlation coefficient decreased at r = 0.187, which indicates insignificant correlation. Moreover, all the quadratic regressions given in Table r = 0.950 to 1.000). It can be concluded that the time span has no effect on the quadratic model parameters.The quadratic relationship 2) was tested on the number of annually published research and review articles from different research fields/topics Table . The res was testr = 1.000) with the constants a = 1.76 × 10–5 and b = 0.0747 is demonstrated in Fig. An example of a good fit r = .000 witha = − 1.58 × 10–6, 6.39 × 10–7, and 4.54 × 10–6 respectively) and the linear ones dominate   the unpredictable increase of NRes or, which is more probable, by (ii) restrictions due to the Covid 19 pandemic reducing research activities  is displayed in Figure S6; the results are also shown in Table –2021 is The number of review and research articles depending on time was another part of this study. Two cases with different time courses are shown here: the topics of Neuroimaging and Graphene. In the case of Neuroimaging shown in Fig. On the other hand, the case of Graphene was illustrated in Fig. In this contribution, an attempt to find a relationship between the number of review and research articles was made. The basic idea was based on theoretical proportionality between the numbers of both kinds of articles published per year. The linear model describes a stably developing research. The quadratic member was added to express deviations from the linearity describing beginnings of research (negative deviation) or less intensive long-lasting research (positive deviation). The quadratic regression based on 5-year (3-year) sliding windows was calculated between the number of review articles and the number of research articles published in 20 various scientific fields.2 Photocatalysis, Genetic engineering, Nanotechnology, and Pharmaceuticals in environment were used to show detection of the unpredictably high number of review articles likely due to the Covid 19 pandemic in 2021. The dependence of the numbers of both kinds of articles on time was demonstrated as well. The topics of Neuroimaging and Graphene demonstrated the growth of the number of articles in line with the linear and quadratic models, respectively.Linear regression graphs were obtained for the fields of neuroimaging and the CRISPR technology, which have been dynamically developing. The quadratic correlation graphs were found for other research fields and were demonstrated in details for the fields of Microplastics and Mars exploration. In the case of Robotics, the early stage of this field development was demonstrated. The topics of TiOThe empirical relationship allows to see the state and dynamics of research. It was tested on the data of research fields but it could be further tested on scientific journals and research institutions (universities) to find their publication strategies. Another direction of investigating can be processing review articles without other reviews referred in them.Supplementary file1 (DOCX 462 KB)Below is the link to the electronic supplementary material.


This study measures the increment of health care expenditure (HCE) that can be attributed to technological progress and change in medical practice by using a residual approach and microdata. We examine repeated cross‐sections of individuals experiencing an initial health shock at different point in time over a 10‐year window and capture the impact of unobservable technology and medical practice to which they are exposed after allowing for differences in health and socioeconomic characteristics. We decompose the residual increment in the part that is due to the effect of delaying time to death, that is, individuals surviving longer after a health shock and thus contributing longer to the demand of care, and the part that is due to increasing intensity of resource use, that is, the basket of services becoming more expensive to allow for the cost of innovation. We use data from the Danish National Health System that offers universal coverage and is free of charge at the point of access. We find that technological progress and change in medical practice can explain about 60% of the increment of HCE, in line with macroeconomic studies that traditionally investigate this subject. TThe second objective of this study is to decompose the RI of HCE in the part that is due to delaying time to death (TTD), that is, individuals surviving longer after a health shock, and the part that is due to increasing intensity of resource use, that is, individuals consuming more resources per unit of time. New technologies and medical practices may generate an increase in HCE over time through two different channels: first, the basket of services accessed by patients becomes more expensive to allow for the cost of innovation; second, patients are able to delay the TTD associated with their health condition and thus they can potentially contribute to the demand for health care for longer. Numerous studies demonstrate that approaching TTD prompts an exponential increment of HCE leading to the suggestion that HCE might reduce in the future as individual experience increasing life expectancy over time and hence delay their TTD  that is free of charge at the point of use and offers a universal coverage to its population. The DNHS offers an ideal setting to assess variation in HCE over time as the use of health services is not confounded by variation in ability to pay or access to health insurance.1.1Numerous studies suggest TTD and morbidity are key drivers of HCE, whereas aging captures the effect of these factors when they are omitted from the analysis; hence age has been labeled a red herring , who are the gate keepers of the system, while emergency care can be accessed by calling an emergency number managed by the Emergency Medical Coordination Centers, which assess the urgency of the call and direct the patients to the closest Emergency Department available. Hospital services are reimbursed by the Danish Regions through a system of DRG tariffs centrally determined by the Department of Health on the basis of the average costs reported annually by hospitals. DRGs were initially introduced in 2000 to facilitate payments for patients choosing to receive their treatment in a different administrative area than their area of residence; 3 years later they were extended to all patients as a tool to incentivize hospital productivity and in 2005 were officially adopted as a reimbursement system. The Hospital sector underwent a reorganization in 2007 aiming at reducing costs and improving the quality of services; acute hospitals were reorganized into 21 large multiservice organizations with highly specialized treatments, such as surgery for lung cancer, heart surgery, transplants or treatment of serious burns, centralized in 1–3 locations in the country . Indicators for the primary diagnosis include a total of 1005 distinct indicators based on the ICD‐10 system for classification of diseases reported at the time of the health shock. The Charlson index and comorbidity indicators are calculated by using hospital records at the time of the health shock and 2 years before the shock. Finally, we included indicators for individual HCE occurring 1 year and 2 years before the health shock to control for heterogeneity in utilization of care before the shock.The socioeconomic indicators include individual income, living alone status, and migrant status. Individuals not living alone might receive informal care reducing utilization of other types of care  with gamma distribution and log link function. Box‐Cox tests and Modified Park tests were used to select the appropriate link function and family function:Control for individual heterogeneity is achieved through two channels. First, the calendar year when individuals are exposed to an initial health shock has some degree of randomness with respect to the technology and medical practice available to treat them after the shock. For instance, hospitals decision to invest in acute care for patients with an AMI or a stroke in a particular year has little influence on the probability that individuals will suffer from an AMI or a stroke in that year. Second, we use a large basket of indicators controlling for individual heterogeneity in health and socioeconomic characteristics over the calendar years when individuals are exposed to the health shock. For instance, a health shock might be more severe in late calendars years if the population becomes older and sicker, or if the health system rises the bar for an emergency hospital admission. However, the extent of this potential bias should not be large given the relatively short time window examined by our study, and it should be possible to control for by using the large basket of individual indicators at our disposal. We provide two tests for the extent of such a potential bias in the section for robustness checks.t, following a similar interpretation in macroeconomic studies using a residual approach ; haj is the hazard of death in the interval aj,aj−1 for individuals who survived until aj−1; PrV>aj=Saj is a survival function for the individual i with V indicating her TTD. An appealing property of this model is that the rate of cost accumulation in individuals who die is allowed to differ from individuals who do not, with μ1j representing the expected HCE if the subject dies in the interval j and μ2j the expected HCE if she survives.Basu and Manning  propose Part‐1 estimates the predicted probability of survival Sj^(X) until the start of the period j and the hazard function for death during the period hj^(X) for all person‐period observations. We estimated Part‐1 with a pooled logit model using a discrete‐time approach that allows us to estimate: (a) the time‐varying effects, which enter the model through the interaction between the periods j = 1,…, K and capture the time elapsed after the health shock; and (b) the calendar time t = 1,…,T capturing the RI of HCE. Part‐2 estimates μ^1j(X) in the person‐periods in which individuals die, and Part‐3 estimates μ^2j(X) in the person‐periods in which the individual survives. We estimated Part‐2 and Part‐3 by using a two‐part model with the first part consisting in a Logit model for the probability of positive HCE and the second part consisting in a GLM model for positive HCE with gamma distribution and log link function. The estimated cost function for an interval j for any individual can be expressed as:µ^(X)=∑j=1Kμj^(X)The model in Equation  can be et when individuals experience the health shock, which we include in the matrix of covariates X as a vector of dummies.t captures the RI of HCE that can be attributed to technological progress and medical practice following a similar approach to the model in Equation  that we capture by estimating the HCE for each person‐period observation after the shock, μj^(X), and then cumulating the sum of μj^(X) from the first to the last of the periods j.Formal proof of the consistency of the estimator is in Basu and Manning . EquatioEquation . Second,ΔtThe RI of HCE, which can be attributed to the overall change in technology and medical practice, is obtained by differentiating Equation  with resμ^1j(X) and μ^2j(X) for every subject‐intervals in the data (first part of Equation Sj^(X) (second part of Equation μ^1j(X) and μ^2j(X), for the j person‐periods in which individuals die and in which they survive.The first part of Equation  in curlyX are assumed to have a distinct and independent effect on individual survival, Sj^(X), and cost of care μ^1j(X) and μ^2j(X). This is a key property of the cost function in Equation , but more than 90% is due to increasing intensity of resource use, rather than delaying TTD. This can be explained by a smaller improvement in survival outcomes as compared to cancer Figure  and a reFinally, the RI for AMI is negative suggesting a saving of −1465 € after the first year from the health shock and reducing to −746 € after 3 years. The latter is the result of a large reduction in intensity of resource use and a small increment in survival effect over time. This might be explained by an increment in the offer of rehabilitation services for cardiac patients in Denmark, which reduced the risk of re‐hospitalization and total number of bed days during the period of our study, and by a shift of part of the rehabilitation services from the hospital to the municipality  and the University Research and Ethics Commission.Supplementary Material 1Click here for additional data file.Supplementary Material 2Click here for additional data file.