The soundscape is defined by the International Standard Organization (ISO) 12913-1 as the human’s perception of the acoustic environment, in context, accompanying physiological and psychological responses. Previous research is synthesized with studies designed to investigate soundscape at the ‘unconscious’ level in an effort to more specifically conceptualize biomarkers of the soundscape. This review aims firstly, to investigate the consistency of methodologies applied for the investigation of physiological aspects of soundscape; secondly, to underline the feasibility of physiological markers as biomarkers of soundscape; and finally, to explore the association between the physiological responses and the well-founded psychological components of the soundscape which are continually advancing. For this review, Web of Science, PubMed, Scopus, and PsycINFO were searched for peer-reviewed articles published in English with combinations of the keywords ‘soundscape’, ‘environmental noise/sound’, ‘physiology/physiological’, ‘psychology/psychological’, and ‘perceptual attributes/affective/subjective assessment/appraisals’. Previous research suggests that Electrocardiography (ECG) and Vectorcardiography (VCG) biometrics quantifying Heart Rate (HR), stimulus-locked experimental design, and passive listening with homogeneous populations are predominantly applied to characterize the psychophysiology underlying the soundscape. Pleasantness and arousal are the most frequent psychological descriptors for soundscape subjective appraisals. Likewise, acoustic environments are reported to inconsistently evoke physiological responses with great variability among studies. The link between the perceptual attributes and physiological responses of soundscape vary within and among existing literature. While a few studies detected a link between physiological manifestations of soundscape and the perceptual attributes, the others failed to validate this link. Additionally, the majority of the study findings were limited to one or two physiological responses. Sound is capable of generating powerful reactions in human beings which inform how they interact with and interpret their everyday environments. There is accumulating research indicating how sound affects the activity and functionality of the Central Nervous System (CNS) and the Peripheral Nervous System (PNS) in response to various forms of sounds, such as music ,2, naturFrom a physiological point of view, a sound signal is a detectable change in our external environment that can elicit a series of unconscious responses, unbalancing our homeostasis (the dynamic state of equilibrium). These responses are similar among populations in a similar situation, are automatic, and regulated by the Sympathetic Nervous System (SNS). The Parasympathetic Nervous System (PSNS), on the contrary, is constantly active to maintain homeostasis. It has been long established that both SNS and PSNS are part of the Autonomic Nervous System (ANS), which is per se a division of the Peripheral Nervous System (PNS) . At the The soundscape, conceived as the acoustic equivalent of the landscape, is defined as the human’s perception of the acoustic environment, in context ,13,14,15Humans and soundscapes have a dynamic bidirectional relationship—while humans and their behaviour directly influence their soundscape, humans and their behaviour are in turn influenced by their soundscape. Several scientific communities in the area of neuroscience and psychology, therefore, have begun to pay close attention to our day-to-day exposure to particular sounds and their impact on the mental and physical health of individuals. Researchers in the areas of acoustics, environmental psychology, and auditory neuroscience outline the adverse impact of noise or negative sounds on well-being in an attempt to improve modern living standards ,22,23,24unwanted sound [Within many acoustics-related fields, noise is defined specifically as ed sound ,34. HoweDespite the accumulating evidence of the effects of sound on the human nervous system, the candidate peripheral and central mechanisms underlying its elicitation are far from understood. Although there is a line of robust literature in the areas of urban planning, architecture, noise control and health  pertaining to the assessment and design of soundscapes, the soundscape concept has only recently been introduced to the areas of psychophysiology and neuroscience.As the development of the newly emerging body of psychophysiology and neuroscience research is a necessity, it does not trivialize the psychological approach that has considerably served to enhance our knowledge in the soundscape research domain.The physiological and psychological approaches are two sides of the same coin in the realm of soundscape research, strongly interconnected and equally important. The psychological approach, in soundscape research, strives to depict the acoustic environment through the human behavioural pattern by borrowing a more deductive approach. It translates the underlying mechanisms into explicit behavioural manifestations, resulting from the perception of the acoustic environment.The physiological approach investigates the impact of the acoustic environment through the investigation of fundamental mechanisms of CNS and PNS by adopting a more inductive inferential approach. The physiological approach delineates the causation of the particular behaviour evoked by the environmental sounds.The soundscape is composed of three main components—human interaction, acoustic environment, and perception—so it potentially draws attention across several life-science disciplines such as environmental psychology and public health, psychophysiology and auditory neuroscience. To the best of authors’ knowledge, no previous work has highlighted the explicit psychophysiological underpinnings of the soundscape. The current review of literature is the first work that reflects the fundamental mechanisms of the soundscape rather than its behavioural expressions.Hence, the main research questions are (a) whether consistent methodologies were applied for the investigation of physiological aspects of soundscape; (b) secondly, what were the physiological markers as biomarkers of soundscape; and (c) finally, whether there was an association between the physiological responses and the perceptual attributes evoked by the acoustic environment.The present literature review followed and was reported in accordance with PRISMA, Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) .The inclusion criteria were: (a) including at least one measure of psychological dimensions or perceptual attributes of the soundscape as defined in ISO 12913-2; (b) including at least one physiological measure; and (c) published in English, excluding conference proceedings and books. The rationale of including these journal articles was that they all investigate the SNS and PSNS responses evoked by the acoustic environment.The databases Thomson Reuters Web of Science, MEDLINE/PubMed, Scopus, and PsycINFO were searched for electronic records and studies related to the physiology of soundscape or the perception of environmental sounds, using the following Boolean search terms: ‘soundscape’ OR ‘environmental noise/sound’ AND ‘physiology/physiological’ AND ‘psychology/psychological’ OR ‘perceptual attributes’ OR ‘affective/subjective assessment/appraisals’ mentioned in either the title or the abstract. The time limitation was considered from 1 January 1990 to 1 February 2019, since the existing research is scarce. Journal articles were identified if they collected physiological responses to acoustic environments, regardless of whether they were investigating positive or negative soundscapes. One of the main theoretical frameworks on perceptual attributes has been proposed by Axelsson and his colleagues. Their circumplex model entails two horizontal and vertical axes, representing two different components of the soundscape. The vertical axis demonstrates the eventfulness component, which implies the intensity of soundscapes . The horizontal axis refers to the emotional magnitude of soundscapes, representing the annoyance or pleasantness components  . The pern = 29). Next, if the title or abstract did not provide sufficient information or did not meet the selection criteria, they were removed (n = 71). Then, the remaining 22 full-text articles were assessed for eligibility—of which, 17 were excluded from further inclusion as they were deemed irrelevant . Finally, the exclusion resulted in five relevant journal papers which were read and analysed manually for method and content—of which, the oldest article was published in 2004 [The search results were exported to Mendeley, which identified 122 published research articles. Then, the duplicates were removed  reviewed the titles and abstracts of the journal articles and manually excluded the articles that did not meet the above-mentioned criteria. The second step was selecting the studies in which (ME) assessed the full-text articles for eligibility in accordance with the method outlined in PRISMA. Disagreements between the authors regarding the study selection were resolved by consensus.Although there is a long line of multidisciplinary research on soundscape, the majority of the available literature on soundscape and well-being has focused on the perceptual attributes and psychological components, lacking the conceptualization of its underlying physiological and neural mechanisms’ validity ,40,41. IAlvarsson et al.  were theIn this study, Alvarsson et al. tested university students in a three-part study. The first part began with one 5 min silence baseline, then five 2 min sections of testing or stressor, each followed by a 4 min period of relaxation or recovery. The authors made a 4 × 4 mixed design with relaxation sound as the within-subject variable and the order of the four different sounds as the between-subject variable. A Latin square matrix was applied in which the participants were assigned at random. The participants were given a mental arithmetic task as a stressor. In the task, the participants should decide whether the equation which appeared on the screen was true or false and received feedback as to whether their answer was ‘false’, ‘correct’, or ‘too late’.Aeq, 4 min), high noise , low noise , and ambient sound (referred to in the text as ‘ambient noise’) such as backyard sound including ventilation noise, 40 dB LAeq, 4 min) during the recovery periods.The participants were exposed to 4 min samples of nature sounds  and the recovery period or PSNS activity was measured by High-Frequency Heart Rate Variability (HF HRV). The perceptual attributes assessment was measured by a scale on three dimensions of pleasantness, eventfulness, and familiarity.3 = −0.1111 should be b3 = −0.01111) that does not substantially impact the conclusions of the analysis.We should note that the exponential function coefficients in this work as part of the regression analysis produce a curve which is a factor of 10 off from the data. It is assumed this is a typographical error in the figure  such as people playing tennis, sirens, as well as Western instrumental music  with little acoustic variation over their 30 s, in order to maintain high intra-stimulus homogeneity.All the environmental sounds and music excerpts were ranked from low to high based on a combination of the mean valence and mean arousal level, into groups . Importantly, to ensure ecological validity of the auditory stimuli , the authors did not change or modulate the intensity of the soundscapes presented in the experiments.The physiological responses were extrapolated from SCL, Respiration Rate (RR), and ECG. The affective rating was probed by a 9-point self-assessment Manikin on two dimensions of arousal and valence.Irwin et al.  exploredIn this study, only native English speakers were selected. Here, we will only report the results of the physiological investigation as the outcome of neural responses is not in the scope of this review. For the physiological experiments, the authors selected a set of 8 s stimuli that would broadly range over the pleasantness and vibrancy scales.A set of 219 recordings were selected from different archives and a selected set of 150 sounds was presented to the subjects in a randomized fashion and -in four sequential blocks lasting about 10 min each. Each block comprised a set of sounds with a duration of 8 s followed by 8 s or 16 s of silence. This study did not include any active task and subjects were instructed merely to remain still and listen to the samples. The visceral changes were registered by measuring HR. The perceptual attributes were tested by a self-report assessment on two dimensions of vibrancy and pleasantness.A more recent study by Hume and Ahtamad  employedThey selected their participants among unpaid volunteers. The authors state that a key experimental design consideration was to limit the total time needed for each subject’s experiment to 20 min in order to mitigate potential issues with the experiment and listening fatigue. They also state that the presentation of 8 s sound stimuli was carefully considered in order to limit the prompting of the startle reflex in response to sudden loud sounds. The stimuli consisted of a range of sound-clips with a wide variety or source types such as ‘horses hooves on the road’ and ‘jackhammer plus traffic noise’. The physiological alteration was measured by recording HR, RR, and Electromyography (EMG). The pleasantness and arousal were evaluated by a 9-scale self-report.Another study by Medvedev et al.  investigIn their first study, they included unpaid postgraduate students or members of staff. Initially, Medvedev et al. exposed participants to a thirty-minute sequence with 4 min stimuli. Each sequence entailed five stress periods of 2 min, followed by a stress recovery period of four minutes. During each stress recovery period, the participants were randomly exposed to one of the four different environmental sounds or a silence condition. The stimuli consisted of the sounds of a forest, sea wave, busy motorway, and construction site.In their second study, the objective was to measure the same physiological responses of soundscape during the rest state. Only university students were involved in the second phase of the study. The authors, therefore, exposed their subjects to different 2 min sounds to determine the effects on the ANS by exposing the subjects to unpleasant sounds during the rest period.The sound samples selected for the second part of the study were three unnatural, two natural, and one orchestra piece.The participants’ SCL and HR, representing the ‘fight, flight, or freeze’ response, were measured in both phases of the study, followed by participants’ subjective ratings of their perception of the four presented sound samples. The perceptual attributes in this study were arousal, dominance, eventfulness, familiarity, and pleasantness which were measured by a self-rating questionnaire.The research on the physiological underpinnings of the soundscape is limited and so is the methodology. With respect to the available literature, the majority of the reviewed studies focused on the impact of the acoustic environment on ANS arousal by looking at specific physiological indicators within homogeneous populations, e.g., university students. The most commonly administered study design was passive listening with event-related responses  in which the participants’ physiological and perceptual responses, evoked by environmental sounds, were monitored. In the event-related design, the physiological arousal in response to environmental sounds is measured and evaluated in comparison with their baseline (silence condition). This response is generally more accurately related to the event in higher-frequency measures such as Electroencephalography (EEG), and less so in slower measures such as HR and Electrodermal Activity (EDA). Human, natural, and mechanical sounds reported being commonly used in most of the studies. HR is predominately applied for the quantification of ANS reactivity to environmental sounds. Analysis of heart rate (variability) is acknowledged as a cost-effective method with high validity and reliability, independent of risk factors of any cardiovascular diseases . It has Beyond studies with a primary aim of investigating the psychological markers of the soundscape, a small body of research offers important insights toward a better understanding of the biomarkers of soundscapes by quantifying the physiological manifestations induced by ANS reactivity such as HR/HF HRV, EDA, RR, and musculoskeletal responses.HR is a primary indication of ANS activation which is regulated by SNS and PNS. HR (V) are widely used in medical examinations and can be evoked in response to a variety of factors such as exercise, emotional arousal, and stimulant exposure. Although the outcome of HR and HRV are closely interconnected, they differ from each other in terms of pre-processing and analysis. While HR is measured in beats per minutes, or the average of the beats in a specific the time period , HRV measures the specific change/variability in the time between the beats ,44. OnlySE = 0.48, p = 0.05), although the association was not found between music and HR [In the 2004 study by Gomez and Danuser , the outc and HR . On the c and HR  in the sc and HR  were shoc and HR  is contrAlthough there are inconsistent findings with respect to HR response to soundscapes given a passive listening condition, there is a consensus between the two available studies which employed a stress task condition. Neither Medvedev et al.’s first study nor Alvarsson et al. could validate a significant link between HR and sound exposure during the recovery period after presenting a stress task ,39.Respiration rate (RR) is a vital sign and a widely used metric in medical research as a measurement of SNS reactivity and physiological stability of individuals with high accuracy. Abnormal RR is a serious indication of an imminent health crisis .The study by Hume and Ahtamad  demonstrEDA is a reliable and valid psychophysiological expression of SNS arousal. Physiologically, the activation of the endocrinology system is driven by the interconnection between CNS and PNS, especially by the sympathetic branch of ANS. The increased reactivity of SNS in the epidermis changes its electrical conductance, forming the basis of the EDA that is measured by Skin Conductance Response (SCR) ) and/or Skin Conductance Level (SCL) . HoweverThe second study by Medvedev et al. showed no significant effect of sounds on SCL  which isAeq, 4 min). The authors reported that during exposure to high noise, a minor upturn in SCL was observed during the last 50 s of the 4 min recovery period, implying long exposure to the unpleasant sounds increased arousal [The results of SCL in stress task studies are in less agreement than those with no stress task. Medvedev et al. failed to show significance in measured SCL changes in response to sounds after stress tasks, similar to their findings with no stress task. On the other hand, Alvarsson et al. demonstrated that subjects exposed to natural sounds recovered significantly faster (9–36% faster) from psychological stress in comparison to when they were exposed to ‘high noise’ . EMG measures musculoskeletal activity, from which SNS activity can be derived. The research on musculoskeletal response to soundscape has been confined to Hume and Ahtamad’s work. They showed that there was a significant relationship between attenuated muscle tone and pleasant sounds . However, the significant difference was not consistent among all soundscape excerpts, and no difference between male and female participants could be detected .The ANS is sensitive and responsive to external stimuli such as olfactory, textile, gustatory, vision, and auditory. The reactivity of ANS, triggered by environmental sensory stimulation, manifests in the variation of several systems in vivo, for instance, cardiovascular systems . HoweverThe outcome of the perceptual evaluation of the sounds in the study by Alvarsson et al. indicated that natural sounds were perceived as more pleasant than human and mechanical sounds. Among the latter, low traffic noise and the ambient sound were reported to be perceived as equally pleasant whereas the high traffic noise was reported to be the least pleasant sound. Further analysis showed that the high traffic noise was reported to be the most eventful while the ambient sound was rated as the least eventful and least familiar among all. The rationale of the authors for this finding was that the ambient noise contained no distinctive sound sources and may not be sufficiently salient to be differentiated . This suThe results of emotional magnitude ratings of both environmental sounds and music in the study by Gomez and Danuser showed wide variability in subjective ratings of valence and arousal. For the environmental stimuli, the subjective appraisals tended toward negative valence and high arousal. On the contrary, for the music condition, the subjective appraisals tended toward positive valence ratings and high arousal. In both conditions, faster breathing and high minute ventilation (MV) were related to increased arousal. While this association was reported to be present within the whole emotional magnitude  for music, it was limited to only positive stimuli for the environmental sounds. However, their findings showed that slower breathing, as well as declined MV, were attributed to low-arousal sounds.The thoracic breathing responses to environmental sounds and musical excerpts were demonstrated to be regulated moderately in line with valence ratings and arousal. The authors did not find any link between other physiological responses and perceptual attributes .Irwin et al. could not find a significant HR change associated with pleasantness and vibrancy. The results stayed the same for the association between pleasantness and the length of the sounds .In Hume and Ahtamad’s study, the HR and RR outcomes were reported to be greater in response to increased pleasantness and showed a clear gender difference with larger RR and HR responses observed for males . FurtherThe outcome of the self-reported subjective ratings of the sound stimuli in the study by Medvedev et al. showed substantial variability of the mean response in the perceptual dimension assessing the appropriateness of the selected sounds. Among the presented sounds, ocean and birdsong were reported to be the most pleasant and arousing while construction and traffic were rated as the most dominating and eventful. The results of SCL in the first phase of the study, showed a faster decline in electrodermal activity in response to the more pleasant and less eventful sounds, although the perception of eventfulness and pleasantness differed among the participants. Likewise, sounds associated with the most familiarity and least eventfulness were linked to a decline of SCL. In addition, there was a significant difference in mean HR for the recovery period limited to only the eventfulness domain . In the Altogether, physiological expressions of the soundscape are not always aligned with the perceptual attributes and may remain inconclusive. Notably, it appears auditory stimuli length makes a major contribution to physiological expression and their link with perceptual attributes.The perception of the acoustic environment is the result of ongoing, meticulous, and unconscious interactions between subcortical and cortical brain structures. Consequently, the perception of the acoustic environment is closely correlated with the physiological properties elicited by the acoustic environment. There is a pressing deficiency in the existing soundscape research in which the implication of physiological changes in the context of human health and well-being is missing.Physiological studies have constituted a vital underpinning of conventional approaches to environmental noise control. As the direction of noise control has become progressively more holistic and begun incorporating the soundscape approach, an equivalent understanding of the physiological manifestations of the soundscape is needed. Since research on the physiology of noise pollution is generally more advanced than within the realm of the soundscape, in order to elucidate the physiological underpinnings of environmental sounds the authors briefly look into the physiology of noise exposure and its implications in soundscape research.The majority of the existing body of literature in the physiology of soundscape is limited to HR, which currently indicates that noise or negatively perceived sound exposure significantly contributes to causing tachycardia ,37. HoweAnother study by Elbaz et al. investigating the effect of aircraft noise on HR during sleep shows that increased HR is linked to an increase in Sound Pressure Level (SPL) . These fRR is a physiological metric with mainly consistent results in response to positively and negatively perceived extrinsic auditory stimuli. Regardless of the intensity of the sound, soundscape studies point to an increase of RR evoked by the acoustic environment ,38. SeemThe existing literature also looked into the long-term effects of noise  on physical health in which an association between traffic noise exposure and respiratory morbidities  was demoThe essence of SCL response in soundscape research is to infer psychological descriptors from measured induced EDA. Whereas EDA has been proved to be an accurate manifestation of SNS activation, it does not always show a consistent outcome throughout the soundscape physiology research ,35,37. OThe potential for the examination of soundscape via musculoskeletal system activity is far from limited and understanding it should be deemed highly necessary. EMG, an electrodiagnostic technique which can help to better understand the possible effect of sounds in the musculoskeletal system is limited to one study in the context of soundscape but has been shown to increase in response to pleasant soundscapes . The larIn short, the literature on soundscape and noise appear to have consensus regarding the increase in HR, with less consistency in results among soundscape studies. The RR and EMG outcomes showed more steady patterns in both areas of research indicating the increment of RR in response to sound stimuli, with consideration of the limitation of RR application among soundscape research. On the other hand, there is less agreement on the results of EDA between soundscape and noise research domains since the findings are uncertain among soundscape literature.The limited studies on physiological indices predominantly focus either on the adverse or the favourable aspects of soundscapes. Consequently, an interdisciplinary and holistic probe is deemed necessary to shed light on the entire spectrum spanning positive and negative soundscapes in order to better understand the impact of soundscapes in a general context. Since there is no sufficient evidence to make conclusions about either physiological manifestation related to soundscapes, we suggest that future investigations classify/categorize the types of sound sources. These categories  would function as a steady baseline to which we can attribute the negative and positive responses ,59. InveConsidering distinctions in the physiological responses to single or complex sound sources would also enable future research to better grasp the differences in potential evoked biological responses when considering the different source type characterizations suggested above.Another essential aspect of soundscapes that may lead to invaluable findings and which could strongly reflect on human physiology is the duration of exposure and temporal variation of the acoustic environment, in an experimental context, reflecting in physiological responses ,62. The Given that many of the most promising physiological metrics must be performed in a laboratory setting , the ecological validity of reproduced soundscapes is a vital consideration. Toward this, much work has been carried out within the field of soundscape studies toward reducing artificiality of the controlled acoustic environment and achieving immersion. Two main methods are used: binaural recordings and ambisonic recordings which use multiple microphones to record a sound field at a single point in full-sphere surround. Binaural audio has long been used in soundscape studies, but its use has generally been limited in physiological studies of soundscape and ambisonic audio has not yet been applied to physiological studies. Both binaural and ambisonic audio, which allows the full spherical sound field to be reproduced very close to what would be experienced in situ, can improve immersion and add ecological validity to laboratory studies .In addition to the ecological validity of the acoustic environment, in order to fully research soundscape, it is highly recommended  to take The conceptual framework of the physiological and neural network may be fruitful in order to develop specific candidate physiological and neural mechanisms of soundscape. This approach emphasizes an understanding of basic brain processes at the network level. Applying a network level approach would allow testing hypotheses about different brain regions working in an integrated and coordinated fashion. While the majority of our knowledge of how the brain implements soundscape processing is based on the assumption of assigning a certain role to each region of the brain, there is an emerging realization that shows this approach is not pragmatic in understanding brain function. Instead, it is suggested that functions of the brain in response to soundscape should be understood at the network level. In order to precisely pinpoint the physiological and neural mechanisms behind soundscape, it will not be enough to determine which brain substrates are activated by different sounds. We must also understand how those brain areas work together at a network level.The integration of physiological and psychological approaches known as the ‘body–mind’ model can substantially strengthen our understanding of how and why we experience the soundscape the way that we do. In this model, the mind and body are not seen as separately functioning entities, but as one holistic bidirectional unit, driven by top–down and bottom–up factors. It is for this reason that they consolidate each other’s results as a more complete scientific method. While the psychological component of the soundscape model relies on a wide range of environmental variables such as socio-cultural factors ,70,71, tSoundscape research could also benefit from ameliorating clarity and consistency in the description of the physiological and neurophysiological processes attributed to the soundscape in the context of human well-being. Notwithstanding a few existing studies which strove to unveil the physiological and neurophysiological indications of soundscapes ,37,38,39The present literature review reported on the established psychophysiological outcomes of the soundscape within the existing research, such as HR, HRV, SCL, RR, and musculoskeletal activity underlying soundscape. Hence, a systematic review in accordance with the PRISMA guidelines was performed on four principle databases in the areas of psychophysiology and neuroscience. In this review, we raised three questions: what metrics were used to detect the physiological manifestations of soundscape; whether significant physiological changes occur in response to the acoustic environment; and ultimately, whether the detected changes correspond with perceptual attributes.The outcome of the review indicates that HR measurement and an event-related or stimulus-locked design with passive listening are commonly applied among the existing soundscape physiology research, mostly with homogeneous subject populations. The most frequent subjective assessments used among the studies were based on two perceptual attributes of valence and arousal.The reviewed literature showed the physiological manifestations of the soundscape with wide variability, ranging from rising to fall, which were inconsistently associated with the perceptual attributes. Based on the scope of the discussion provided in the papers themselves and the inconsistency of the results, conclusions cannot currently be drawn about a broader discussion regarding the implementation of the soundscape approach to the design of environments based on physiological manifestations or responses.To advance the research on the psychophysiology of soundscape, we propose a potential classification for the environmental sounds with single and complex sources. It is worthwhile to look into the link of environmental sounds’ temporal variation and length and how they may affect the adaptation, habituation or sensitization of ANS. It is recommended to investigate the psychophysiology aspect of the soundscape in a network level, taking into account all the contributing CNS and PNS factors and how they interact with each other, particularly in the context of health and wellbeing.While the study of physiology and neurophysiology of soundscape is still in its infancy and inconclusive, cross-disciplinary team collaboration is highly recommended to propose an optimum biomarker multi-model for the soundscape investigation. As acoustic design moves further toward the soundscape approach, so should the psychophysiology of soundscape advance, to provide the same underpinning as the physiology of noise provided for conventional noise control.


Primates have long been a test case for the development of phylogenetic methods for divergence time estimation. Despite a large number of studies, however, the timing of origination of crown Primates relative to the Cretaceous–Paleogene (K–Pg) boundary and the timing of diversification of the main crown groups remain controversial. Here, we analysed a data set of 372 taxa  that includes nine primate genomes. We systematically explore the effect of different interpretations of fossil calibrations and molecular clock models on primate divergence time estimates. We find that even small differences in the construction of fossil calibrations can have a noticeable impact on estimated divergence times, especially for the oldest nodes in the tree. Notably, choice of molecular rate model (autocorrelated or independently distributed rates) has an especially strong effect on estimated times, with the independent rates model producing considerably more ancient age estimates for the deeper nodes in the phylogeny. We implement thermodynamic integration, combined with Gaussian quadrature, in the program MCMCTree, and use it to calculate Bayes factors for clock models. Bayesian model selection indicates that the autocorrelated rates model fits the primate data substantially better, and we conclude that time estimates under this model should be preferred. We show that for eight core nodes in the phylogeny, uncertainty in time estimates is close to the theoretical limit imposed by fossil uncertainties. Thus, these estimates are unlikely to be improved by collecting additional molecular sequence data. All analyses place the origin of Primates close to the K–Pg boundary, either in the Cretaceous or straddling the boundary into the Palaeogene. Divergence time estimation is fundamentally important to every field of evolutionary analysis. Reliable estimates of the timing of speciation events across the Tree of Life allow us to correlate these events with both biotic and abiotic phenomena on geological and more recent timescales, thus illuminating those that are most closely associated with periods of rapid diversification , evolutiThough it was A parallel challenge to divergence time analysis can be observed in the development of calibration strategies . Given tWe have reached a state of the art where branch lengths can be estimated with very high precision. The combination of genome-scale data, sophisticated molecular evolutionary models, and ever-increasing computational power has brought us to this point. Advances in DNA sequencing technology are such that virtually every major clade has at least a few species represented by whole-genome sequences, and this trend is rapidly accelerating. Bayesian methods have been developed such that parameter space can be explored during MCMC estimation, and though violations of the molecular clock will continue to present problems, methods for measuring and accommodating rate variation across phylogenies are explicit and generalizable. And finally, the computing power to integrate this information is increasing steadily. But because of the confounding effect of nonindependence of rate and time, the expectation of a conventional Bayesian analysis—that infinite data will eventually overcome prior information and provide posterior distributions with certainty—cannot be met .Thus, the field at present is focused on developing a better understanding of the effects of relaxed clock model choice, and on the impacts of calibration points, both with regard to abundance and placement in the phylogeny. Furthermore, in addressing these challenges, it is an open question as to whether simulation studies or tests of empirical data will be more informative for our understanding of best practices. With regard to clock model choice, an empirical study of three independent data sets showed that autocorrelated models outperform uncorrelated models, though the same study found a “high sensitivity” to the relaxation model employed , while aWith regard to fossil calibration strategies, simulation studies e.g.,  have thuHere, we hope to contribute to this progress by conducting an exploration of model choice and calibration strategy in a classic empirical system: the Primates. Despite the fact that it is a relatively small and biologically uniform clade, primates have been inordinately and repeatedly the subject of divergence time analysis, with the first studies appearing at the very outset of molecular clock studies , up to pOur study explores the effects of an autocorrelated versus an uncorrelated rate model on age estimates, and also explores the consequences of two different interpretations of both the age and the placement of key fossils with the living primate radiation. We apply these two strategies to a large phylogenomic data set for Primates . Until very recently, reliable calculations of branch lengths and age estimates within an analysis of this magnitude would have been beyond the capacity of computational methods. We have tackled many of these challenges by deploying the sequential Bayesian procedure used by The molecular timeline for primate evolution that emerges from this study can be interpreted with confidence. The data set is sufficiently large to provide highly precise branch length estimates, and the methods used are robust in accommodating violations of the molecular clock. The comparison of the two calibration strategies reveals their impact on the results by giving different age estimates within the tree, though the variation in inferred ages is not extreme. Which ages are considered most accurate will depend in large part on the degree of confidence in the fossils and their placement. As an unanticipated result of the study, the difference in age estimates for the deepest nodes of the phylogeny differ markedly when comparing the molecular rate models, with Bayesian model selection supporting the autocorrelated model. As with previous studies over the past several decades, the ancestral primate lineage is hypothesized to have survived the great K–Pg mass extinction event.http://dx.doi.org/10.5061/dryad.c020q.Bayesian estimates of divergence times of Primates were obtained using a supermatrix of molecular data with 372 species and 3.44 million base pairs (Mbp), combined with 17 fossil calibrations. The matrix is the result of merging the 372-species and 61 thousand base-pairs (kpb) data set of Tupaia belangeri), because its complete genome is available in the alignment of We retrieved the sequence alignment of We retrieved the genome-scale sequence alignment of The topology of the 372-species phylogeny was estimated by maximum likelihood (ML) using RAxML v 8.0.19  under th}G model ,b, using}G model  and 100 The two fossil calibration strategies used in this study are summarized in We used the fossil-based prior densities constructed by Tarsius spSahelanthropus, dated to 7.25 million years ago (Ma), to be the oldest member of the human-chimpanzee clade (Orrorin (5.7 Ma) instead. In A, †Chororapithecus is given an age of 10 Ma  . At firset prior .For the 372-species phylogeny, the rate prior was assigned as follows: the mitochondrial substitution rate at third positions is about 20 times the rate at third positions in nuclear genes or MCMC analyses were carried out with the program MCMCTree , using tWe have implemented marginal likelihood calculation by thermodynamic integration (path sampling) in the program MCMCTree. This allows us to calculate Bayes factors (BF) and posterior model probabilities to select for a clock model in the analysis. Details of our implementation are given in  edit 1 Thermodynamic integration is computationally intensive as we must sample from the power posterior estimate , as it hinset of , for theinset of  to perfoIn a conventional statistical inference problem, the variance of an estimate decreases in proportion to 1/brations . For infCalibration strategy B under the AR model gives similar node age estimates for the younger nodes in the tree . The use of the posterior in an analysis as the prior for the next is a well-known feature of Bayesian inference . ConsideThe approach we used here to analyse the primate data is justified because the likelihood model assumes that the sequence partitions are nonoverlapping and independent. However, our approach is approximate. In multiparameter models, the posterior is a multidimensional distribution that may have a complex correlation structure. Here, we ignored the correlation structure of the nine times estimated using the genomic data and approximated the corresponding high-dimensional time posterior as the product of the marginal densities of the times, with a truncation applied to ensure that descendants are younger than ancestors. Note that joint analysis of all the partitions would have been preferable, but it is computationally prohibitive.This Bayesian sequential analysis is different from the use of secondary calibrations in some dating studies , where tAn interesting result from our study is the finding that the AR model fits the primate data better than the IR relaxed-clock model. In the context of previous studies, In the AR model the variance of the log-rate for branches is proportional to the time of divergence, so that the variance is expected to be close to zero for closely related species. In other words, the AR model allows for “local clocks” for closely related species, while allowing the rate to drift substantially across distantly related clades. This model is, from a biological point of view, quite appealing intuitively, and it also fits anecdotal evidence where the strict clock cannot be statistically rejected among very closely related species, for example, among the apes , box 2. Prior to the study reported here, the estimated age of the living primate clade has spanned a 30 My differential, ranging from as young as 55 Ma  to as olAs described at length above, the current study gives added weight to the conclusion that primates are an ancient clade of placental mammals, arising just prior to or millions of years before the K–Pg. And even though lineage diversification within the major subclades is hypothesized not to have occurred until after the commencement of the Paleogene, the separation of tarsiers from other haplorrhines, and the divergence of haplorrhines and strepsirrhines, consistently appear to proceed or nearly coincide with the K–Pg. Given that this event was unequivocally one of the most disruptive and destructive geological episodes in Earth history, the temporal coincidence speaks both to the ecological flexibility and to the evolutionary opportunism of the earliest primates. Although now extinct in North America and in Europe, the primate fossil record shows that the clade was once nearly pan-global, even potentially including Antarctica. Thus, when viewed in the context of divergence date estimates, all of which fall within a temporal window when, as now, continental and island residences would have already been sundered by significant oceanic barriers , we must conclude that early primates would have been able dispersers. In fact, the ability to cross barriers, both terrestrial and aquatic, and to successfully colonize new land masses, are distinct hallmarks of the primate radiation .http://dx.doi.org/10.5061/dryad.c020q. An R package, mcmc3r, that helps the user with marginal likelihood estimation with MCMCTree is available from https://github.com/dosreislab/mcmc3r.Data available from the Dryad Digital Repository:


The inadequate reporting of cross-sectional studies, as in the case of the prevalence of Congenital Anomaly, could cause challenges in the synthesis of new evidence and make possible mistakes in the creation of public policies. This study was conducted to critically appraise the quality of the articles involving congenital anomaly prevalence in Iranian infants with the STROBE recommendations.We performed a thorough literature search using the words “congenital anomaly” “birth defect” and “Iran” in MEDLINE/PubMed, Scopus, SID, Elmnet, Magiran, IranDoc, Iranmedex, and Google Scholar until Aug 2017. In this critical appraisal we focused on cross-sectional studies that reported the prevalence of congenital anomaly in Iranian infants. Data were analyzed using the STROBE score per item and recommendation.The results of 17 selected articles on Congenital Anomaly prevalence showed that the overall accordance of the cross-sectional study reports with STROBE recommendations was about 63%. All articles met the recommendations associated with the report of the study’s rationale, objectives, setting, key results and provision of summary measures. Methods and results were the weakest part of the articles, in which recommendations associated with the participant flowchart and missing data analysis were not reported. The recommendations with the lowest scores were those related to the sensitivity analysis , bias , and funding .Cross-sectional studies about the prevalence of congenital anomaly in Iranian infants have an insufficient reporting on the methods and results parts. We recognized a clear need to increase the quality of such studies. The insufficient reporting of medical research is a long-lasting and potentially serious universal problem that is not evident to many researchers . All sciStrengthening the Reporting of Observational studies in Epidemiology (STROBE) is an instruction whose recommendations have been presented for the purpose of sufficiently report observational studies  ,5. STROBCA is the main cause of infant mortality; therefore, 21% of mortality during infancy results from these anomalies . This tyThis descriptive study was done in two stages. First, a systematic literature search was carried out to recognize the articles to be taken in the study. Then, the quality of the studies was evaluated with STROBE. This study keeps the recommendations of the PRISMA statement for its reporting .MEDLINE/PubMed and Scopus were searched for published cross-sectional studies. Search keywords were “Congenital anomaly”, “birth defect”, “prevalence”, and “Iran.” Persian databases  and Google Scholar were also searched using equivalent keywords from 2007 until Dec 2017. In addition, reference section of relevant studies was manually checked to identify further studies missed by the electronic search. Authors were contacted for additional missing data. This study was performed independently and simultaneously by three researchers  and a list of found objects was made. Then, search results were assessed, and no differences in the outcome were obtained between the three authors.Full-text articles were assessed by three researchers  and those who met the inclusion criteria were selected. Moreover, a secondary search through the bibliographic references of the chosen articles was done, and duplicates were removed. The inclusion criteria included descriptive and cross-sectional studies on the prevalence of congenital the anomalies among infants in Iran; studies were in English and Persian. The exclusion criteria included those studies that mentioned before publishing STROBE’s statement ; studies that investigated the prevalence of congenital anomalies in the animal; qualitative studies, studies presented in conferences; and interventional studies. Short communications, editorials or reviews were excluded.We worked the STROBE items for assessing the quality of the reports. STROBE offers 32 items for the suitable reporting of observational studies. These suggestions express the appropriate method of reporting the title, abstract, introduction, methods, results, discussion, and financing section . Based oTwo methods were used to extract data. The first included information on the general characteristics of each article: first author, name of the study from which the data came from, publication year and language, city, study period, sample size and type of population. The second method is a list of 28 of 32 STROBE items. Three investigators  appraised the full-text of the articles, and the data was extracted. Each researcher considered whether the reports identified met or not the STROBE items. Lastly, the corresponding author of each included article was emailed. In each email, we gave the purpose of the study and the items completed by the article, according to our analysis based on STROBE. This step was performed with the purpose of clarifying potential contrasts with our appraisal. The responses of each author were evaluated based on the methodology expressed above and revisions to our analysis were done as accurate. If no response, a reminder email has been sent 8 d after the first one. We waited for 15 d for the authors to reply, and then our analysis was performed as the ending result.Two kinds of scores were described including score per article and per item. The score per article was described as the number of the STROBE items sufficiently reported, divided by the total of items applicable per article and stated as a percentage. The score per item was described as the number of articles that met each STROBE item, divided by the total of articles for which the item was applicable and stated as a percentage.We obtained 3328 articles within the database search. From these articles, 2548 were excluded for being duplicates and 754 were excluded for screen by title and abstract and the remaining 35 were checked in full-text. Of these, 18 were rejected because they did not meet the selection criteria, as a result, 17 articles were obtained for extracting information –32 Fig..Eleven (56%) out of the 17 corresponding authors answered, mentioning and supporting if they approved (5/11) or opposed (6/11) with our analysis. Most of the conflicts were found in the items associated with the statistical analysis . According to these conflicts, each item was assessed again, and answers were emailed with the respective revisions. The results of this study indicated that the performance of the STROBE items for the reporting of cross-sectional studies on the prevalence of CA was inadequate, the median STROBE score being 63%. Reporting rates were lowest for the methodology and results. These insufficiencies are mainly important for methodologically properly organized studies and correctly analyzed. For that purpose, every precise report, to be reliable, need to afford a strong, complete and obvious showing of what was designed, done and found, that simplify the sufficient understanding and publication of their results . Additionally, we operated a global score for every article to provide a measure of whole reporting. In selecting this system, we do not suggest that all recommendations are of equal significance. On the other hand, we decided to use these policy help readers have an overall view of the quality of the reports and adherence to the STROBE statement in future studies has the potential to improve study reporting, help the appraisal and analysis of CA by reviewers, readers and journal editors, and finally support the practice of evidence-based medicine.Cross-sectional studies about the prevalence of CA in Iranian infants have an insufficient reporting of important parts such as methods and results. This finding indication a strong need to enhance the reporting quality of such studies to make its role to sufficiently inform relevant subjects for the putting into practice of public health policies.Ethical issues  have been completely observed by the authors.


Introduction: Specialist medical assessments fulfil the task of ensuring that physicians have the clinical competence to independently represent their field and provide the best possible care to patients, taking into account the current state of knowledge. To date, there are no comprehensive reports on the status of specialist assessments in the German-speaking countries (DACH). For that reason, the assessment methods used in the DACH region are compiled and critically evaluated in this article, and recommendations for further development are described.Methods: The websites of the following institutions were searched for information regarding testing methods used and the organisation of specialist examinations: Homepage of the Swiss Institute for Medical Continuing Education (SIWF), Homepage of the Academy of Physicians (Austria) and Homepage of the German Federal Medical Association (BAEK). Further links were considered and the results were presented in tabular form. The assessment methods used in the specialist assessments are critically examined with regard to established quality criteria and recommendations for the further development of the specialist assessments are derived from these.Results: The following assessment methods are already used in Switzerland and Austria: written examinations with multiple choice and short answer questions, structured oral examinations, the Script Concordance Test (SCT) and the Objective Structured Clinical Examination (OSCE). In some cases, these assessment methods are combined (triangulation). In Germany, on the other hand, the oral examination has so far been conducted in an unstructured manner in the form of a ‘collegial content discussion’. In order to test knowledge, practical and communicative competences equally, it is recommended to implement a triangulation of methods and follow the further recommendations described in this article.Conclusion: While there are already accepted approaches for quality-assured and competence-based specialist assessments in Switzerland and Austria at present, there is still a long way to go in Germany. Following the recommendations presented in this article, a contribution could be made to improving the specialist assessments in the DACH region according to the specialist assessments objectives. Assessments fulfil a wide range of important tasks: they have a strong effect on learning, they can be used to provide feedback on the effectiveness of education and training programmes and, consequently, they can help protect patients . Until tSociety relies on tests that ensure that patients can place themselves in the care of competent and qualified physicians who have reached a minimum standard . AccordiThe official training regulations for postgraduate medical doctors, which were developed by the BAEK, have the character of a recommendation. Completion of the specialist training is assessed on the basis of documented competences, issued by the respective physician in charge, and an oral examination. According to the BAEK, this “certificate of further training” is proof of the acquired competence and serves as quality assurance for patient care and citizen orientation. The term ‘competence’ is not specified here . https://www.siwf.ch/] for each specialist area. In Switzerland, the FMH (Foederatio Medicorum Helveticorum) is the professional association of Swiss physicians. It is the umbrella organisation of more than 70 doctors' organisations. The Swiss Institute for Medical Continuing Education (SIWF) is an autonomous body of the FMH and ensures high-quality continuing education for doctors in over 120 specialist areas. In cooperation with the professional associations, the SIWF issues a detailed further training programme [https://www.aerztekammer.at/] with the implementation of the medical examination as a prerequisite for the pursuit of a medical profession. The training contents and the corresponding certificates for the acquisition of a specialist title have been drawn up and specified by the ÖÄK [https://www.aerztekammer.at/ausbildungsinhalte-und-rasterzeugnisse-kef-und-rz-v-2015].The Austrian Medical Association (ÖÄK) grants the right to practise as employed, self-employed and self-reliant physicians. The ÖÄK has entrusted the ‘Austrian Academy for Physicians GmbH ). Not only should medical teaching be competence-oriented, but also any successive further education. This includes a competence-oriented examination of knowledge, skills and attitudes.Numerous key competencies are assigned to these roles. The CanMEDS role model has already been integrated into national learning objective catalogues for medical studies in Europe  , SwitzerTo date, there exists no compilation of the extent to which the specialist assessments of the DACH region are competence-based and whether the quality criteria previously mentioned, such as objectivity and reliability, are taken into account. The aim of this work is therefore to provide an overview of the existing summative specialist assessment formats in the DACH region and their organisation, to take a critical look at the formats with regard to quality criteria and to make recommendations on the basis of the international literature. As a first step, this compilation should make the current situation better known and highlight possible directions for the further development of specialist assessments in the DACH region.The following homepages were searched for references to existing assessment formats and the organisation of specialist assessments:https://www.siwf.ch/] Homepage of the Swiss Institute for Medical Education and Training [https://www.aerztekammer.at/]Homepage of the Austrian Academy of Physicians ..Prior deSufficient number of questions, examiners, stations/learning objectives to be examined: A minimum reliability of 0.8 is given for relevant assessments . I. ISufficessments . The morQuality assurance of the created questions/tasks: The content and formal linguistic review and revision of the tasks is necessary to guarantee the unambiguity of the answers and the high quality of the tasks and questions. The validity of the examination results is strengthened by a review process, where experts trained in medical didactics review the questions and tasks ..Quality Quality assurance in the evaluation of the assessment: Quality assurance through test statistical evaluation of examinations makes it possible to revise OSCE stations and examination tasks in a targeted manner, to examine checklists and, if necessary, to draw conclusions about the quality of teaching. The following parameters are recommended: for written assessments at least one evaluation should be carried out with regard to reliability, selectivity and item difficulty . For oral or practical examinations, the better “OSCE-Metrics” . T. T39]. TIn this paper, the question of which specialist assessment methods are used in the DACH region is examined. In addition, the assessment methods used are critically reviewed and recommendations for the further development of specialist assessments are described, based on the current literature.More than 50% of the specialist assessments conducted in Switzerland take the form of MC examinations. The specialist areas of Anaesthesiology, Allergology/Immunology, Cardiology and Vascular Surgery are examined in conjunction with the European Union of Medical Specialists (UEMS). Other departments are planning to do so. Seven different types of MC questions are used, as well as the SAQ, free text examinations (not specified in more detail) and the SQT. Written work, SMP, practical examinations and an OSCE are also used. In total, 50% of the Swiss specialist examinations have a practical component (cf. attachment 1 and attachment 2 ).In Austria, 25% of the specialist assessments are conducted as written examinations (MC questions). Two specialist areas examine in conjunction with the UEMS. SAQ and SMP are also related forms of examination. Blueprinting is used regularly. There is no practical examination yet (cf. attachment 2 and attachment 3 ). In Germany, an unstructured oral assessment takes place throughout the country, which is referred to as a “collegial content discussion“ (cf. attachment 4 ). It is positive to note that in Switzerland 50% of the specialist assessments already have a practical component. In order to be able to test practical and communicative competences within the scope of the specialist assessment, a practical, communication and competence-oriented examination should be used in addition to a knowledge-oriented examination method (written/SMP). The OSCE format could be used here. In order to reduce costs, for example, at least parts of the examinations could be conducted nationwide. According to the literature, it is also positive to note that, in Switzerland and Austria, MC tests with type A pos. questions are used in the majority of cases to objectively test knowledge – including application knowledge – and evaluate it statistically. However, an assessment of the examined competence using these forms of examination is only possible if a detailed insight into the examinations is conducted and their results can be provided. The preparation of written examinations is often underestimated, and it is time-consuming, as review processes must take place in terms of content, formal language and  didactics in order to guarantee the unambiguity of the answers provided. The workload is mainly shifted to the preparation phase (cf. Gerhard-Szep) . In addiIn Germany, oral examinations are conducted in an unstructured manner, although the German Medical Association expressly emphasises on its website that the continuing education designation serves as proof of the acquired competence and quality assurance of patient care and citizen orientation . The curA recommendation with regard to a best practice specialist assessment is made against the background that, so far, only a few articles have taken a stand on assessment methods in the field of postgraduate medical education. A combined use of assessment methods (triangulation) is indispensable in order to be able to cover the necessary competence spectrum. Likewise, the following should be used and documented: obligatory blueprinting , the preparation of questions and horizon of expectations in advance, a sufficient number of questions/tasks, quality assurance measures relating to the preparation and evaluation of examination questions/tasks, examination feedback  and the most cost-effective assessment methods possible. These recommendations are supported by numerous publications , 46]. C. C46]. COn the one hand, this work is certainly limited by the fact that the data researched on the Internet can only be presented descriptively. On the other hand, continuing education curricula, the implementation of continuing education and the design of examinations are closely interlinked in the sense of “constructive alignment”. A further limitation is therefore that, in this article, we have primarily dealt with the presentation of the examinations used in the DACH region and that curricula on further specialist training could only be mentioned in passing. However, a follow-up article could explain the different curricula on further specialist training and their implementation within the DACH region. In the DACH region, the organisation of specialist assessments, the assessment methods used and the quality assurance measures are very different. In contrast to Germany, structured and standardised specialist assessment methods are already used in Austria and Switzerland – as well as practical examinations in the latter. If specialist assessments are to ensure that specialist doctors have the necessary competences for patient care, they must also be designed in such a way that they can actually test competences. This currently appears not to be the case in all specialist areas in Germany, but also in most specialist areas in Austria and Switzerland. Therefore, in order to ensure the quality of postgraduate medical training, it is necessary that even more attention is paid in the three countries to the fact that summative specialist assessments also examine the intended competences of the prospective specialists. A combination of a written examination with a practical examination (e.g. OSCE) is currently recommended, as this not only tests knowledge but also other competences including practical and communicative skills (see table 2 We thank Dr. med. Susanne Frankenhauser, MME, Dr. med. Uta Krämer and Brian Webber for their constructive help in reviewing the manuscript. The authors declare that they have no competing interests.


Background: Depression is the largest cause of mental ill health worldwide. Although interventions such as Dance Movement Therapy (DMT) may offer interesting and acceptable treatment options, current clinical guidelines do not include these interventions in their recommendations mainly because of what is perceived as insufficient research evidence. The 2015 Cochrane review on DMT for depression includes only three studies leading to inconclusive results. In a small and underfunded field such as DMT, expensive multi-centered Randomized Controlled Trials (RCTs) are as yet rare. It is therefore, necessary to not only capture evidence from RCTs, but to also look beyond such designs in order to identify and assess the range of current evidence.Methods: We therefore conducted a systematic review of studies that aimed to explore the effectiveness in the use of DMT with people with depression. This led to a qualitative narrative synthesis. We also performed meta-analyses that calculated the effect size for all included studies, studies with RCT designs only, followed by a subgroup analysis and a sensitivity analysis. In all meta-analyses a random effects model was used with Standardized Mean Differences (SMD) to accommodate for the heterogeneity of studies and outcome measures.Results: From the 817 studies reviewed, eight studies were identified as meeting our inclusion criteria. Three hundred and fifty one people with depression (mild to severe) participated, 192 of whom attended DMT groups while receiving treatment as usual (TAU) and 159 received TAU only. Qualitative findings suggest there was a decrease in depression scores in favor of DMT groups in all studies. Subgroup analysis performed on depression scores before and 3 months after the completion of DMT groups suggested changes in favor of the DMT groups. When sensitivity analysis was performed, RCTs at high risk of bias were excluded, leaving only studies with adult clients up to the age of 65. In these studies, the highest effect size was found favoring DMT plus TAU for adults with depression, when compared to TAU only.Conclusions: Based on studies with moderate to high quality, we concluded that DMT is an effective intervention in the treatment of adults with depression. Furthermore, by drawing on a wide range of designs with diverse quality, we were able to compile a comprehensive picture of relevant trends relating to the use of DMT in the treatment of depression. Despite the fact that there remains a paucity of high-quality studies, the results have relevance to both policy-making and clinical practice, and become a platform for further research. According to the World Federation for Mental Health WFMH, , depressIn England and Wales, the current draft guideline from the National Institute for Health and Care Excellence NICE,  for adulHowever, despite the prevalence of multiple and, often, body-based symptoms in depression, non-verbal and creative types of psychotherapy such as Dance Movement Therapy (DMT)This systematic review is, therefore, not just important for facilitating efficient integration of information into policy making in adult services; it is also necessary to demonstrate clearly and transparently where the effects of DMT are consistent and how they vary across contexts in order to translate research findings to clinical practice. Meta-analysis can provide more precise estimates than individual studies, minimizing bias and reducing chance effects. DMT is a relatively new intervention with an emerging evidence base. It is necessary to evaluate the wider range of available evidence stemming from different types of study designs alongside emerging new data, to allow for decision-making that is based on the totality of available evidence, whilst checking for consistency of results across designs.The definition of what constitutes good evidence is debated at length, especially for psychotherapy. Randomized Controlled Trial (RCT) is the design that is generally perceived as the golden standard for establishing effectiveness , one of the main regulatory bodies of psychotherapists. However, unlike verbal psychotherapy, and unlike the most prevalent forms of psychotherapy recommended for depression such as cognitive behavioral therapy, DMT does not require considerable cognitive and linguistic skills from the client/patient. Therefore, it can potentially bypass social or cultural barriers. Karkou and Sanderson  argue thcreative form of psychotherapy. Following on from her theory-generating doctoral research  or another treatment?Is there evidence of effectiveness of DMT in the treatment of depression based on studies with high quality, i.e., low risk of bias?To synthesize results from all studies of effectiveness of DMT for clients with depressionTo establish effect sizes within groups, comparing pre and post scores on depression immediately after treatment and at the time of follow upTo establish effects sizes between groups, comparing end scores between the experimental and control groups for all RCT designs and for those with low risk of bias.A systematic literature review was chosen as the best way to answer the main research question and as the most highly valued methodology of synthesizing evidence from different studies. According to Higgins et al. , a systeIn this review, conventions and processes used in Cochrane reviews  and focused on pre/post treatment scores of depression for all the studies identified by the systematic review process and synthesized through the qualitative meta-synthesis , while the final calculation involved sensitivity analysis of this last set of studies, retaining only RCTs with low risk of bias (no. 5). Results from this analysis answered the final question of the study which was “Is there evidence of effectiveness of DMT in the treatment of depression based on studies with high quality, i.e., low risk of bias?”All RCTs were considered as well as studies with quasi-randomization or systematic methods of allocation. Unlike the Cochrane review on DMT for depression  in the absence of sufficient evidence to form a firm diagnosis of depression were excluded.The intervention was facilitated by a practitioner who had received formal training, was a dance movement therapist in training or was otherwise accredited in the country in which the study was conducted. In countries where professional accreditation was not available, the available description of the intervention was examined to establish that it demonstrated key relevant characteristics of DMT practice. DMT practice was defined as an active engagement of participants in dance movement in the presence of a therapist. All DMT approaches were considered, but in all cases the intervention had a clear psychotherapeutic intent and fostered a psychotherapeutic relationship. Dance classes with therapeutic benefit were therefore excluded.Studies with all types of comparators to DMT as a main intervention were included such as waiting list, TAU, another psychological therapy, pharmacological interventions, physical interventions or different types of DMT. In this review, and unlike the Meekums et al.  review, Scores on levels of depression were seen as the primary outcome measure. Both self-rated standardized measurements  was used which was not available at the time of the first search.A new search was completed between 2nd October 2014 and 1st March 2018 using the same key words and databases as the first search see . In thisIn the first instance, all known DMT professional associations were contacted through the use of a standardized letter with a request to provide any studies known to them. During the second search, key researchers in the field were contacted to provide any additional new research studies completed since October 2014.With regards to the first set of studies identified during the Cochrane review process we revisited all studies that were excluded on the basis of the study design as indicated on the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) diagram of this original review  extracted data independently from all included studies on the characteristics of the design, the population, intervention and outcomes. Effect size data  for the calculation of meta-analysis was also extracted. Any mismatches between the two sets of data-extractions and discrepancies were resolved through consensus after jointly checking the full-text papers. In case of missing data or incomplete information, VK contacted the authors via email. Permission to include one of the studies that was still unpublished at the time of the review was sought from the authors. Additional information was also requested in order to provide clarification on the methods and procedures followed and complete the assessment of risk of bias.The risk of bias for all the reviewed studies was assessed using Cochrane criteria . The first included all studies and a within-groups calculation. The second involved studies with follow up measures. They were sub-grouped and effect size was calculated considering any long-lasting effects for DMT with this client population. The third calculation included only studies with RCT designs and between-groups scores. Finally, studies with low risk of bias were included in the last calculation that involved a sensitivity analysis.Because of the outcome measures of depression used, the data collected was continuous. For this reason, and assuming that they measured the same construct, outcome measures of depression, such as BDI and HAM-D, were brought together for the calculation of our meta-analysis. Still, given that there were different scales used in each case, Standardized Mean Differences (SMD) were chosen over Mean Differences (MD). The SMD was calculated using Hedges' g method. This method can accommodate for the danger of a small sample size bias .Although data from secondary outcomes were also measured in some of the included studies such as anxiety, quality of life and body image, in this paper our focus remained on results from the primary outcome only.For this paper we also considered the type of subgroup analysis performed in the Meekums et al.  study baN = 817. From these records, 63 were duplicates and were taken out, leaving 760 records to screen at a title and abstract level. From these, 57 records were examined as full text articles, excluding 51 studies due to: the study design (n = 10), the population (n = 21), and the intervention (n = 16).As the PRISMA diagram indicates see , 803 recFrom the six studies that met the inclusion criteria, one by Hyvönen et al.  was consSimilarly, there was more than one reference associated with some of the studies included, e.g., Pylvänäinen et al. , RöhrichA total of 351 participants were involved in all the studies included in this review . From thMethodologically the eight studies ranged from pilot studies with pre/post testing . BDI and SCL are self-reported inventories, while HAM-D is observational. Despite their differences, these tools are regarded as sensitive to capture mood, body image, health anxiety, sleep loss, appetite and many other factors related to the diagnostic criteria of depression.As shown on As The study from China, Xiong et al. , was of The study by Röhricht et al.  was asseIn contrast, the study by Punkanen et al.  had methThe study by Pylvänäinen et al.  is a stuThe value placed on randomization in the conventional hierarchy of evidence  as a sub-group analysisStudies with RCT designs only Studies with RCT designs with lower risk of bias through sensitivity analysis.9), each study included for the analysis was represented by its point estimate with 95% confidence interval. It is noticeable from the plots that the size of the square between the studies varied based on the allocated weight associated with the calculation of each power estimate. The larger studies with less variance and more precise results were given larger weight. The overall measure of effect and the direction of effect is visually represented on the forest plots by the location of the diamond.As per our protocol, only scores until the point of the crossover were considered. In all four cases the effect of DMT in decreasing scores on depression was evaluated. As shown in the forest plots –9, each N = 188). The SMD using a random effects model was 1.10 . As the confidence interval did not contain zero, there was strong evidence of a positive treatment effect. The I2 was calculated which is a measure of heterogeneity amongst studies indicating the percentage of variance amongst studies  and only 11% due to chance. This is visually evident from the wide scatter of effect estimates with little overlap in their confidence intervals . The random effects model provided an estimate of the average treatment effect. It revealed 0.69 SMD with 95% confidence interval . Using Cohen's rule of thumb  effect size was found, suggesting that the lower quality studies dropped the calculated effect size.The meta-analysis performed with all studies and with all designs on scores of depression before and after the DMT interventions also indicate a favorable trend for DMT groups since scores of depression were decreased in all cases. Since scores from control groups were not considered in this calculation, it is not possible to know whether this change took place due to what Eysenck  termed “Similarly, following from arguments in the literature that DMT is not simply a form of dance and/or exercise that provides temporary relief only (Karkou and Sanderson, Although on the basis of both of these two last calculations, we are not able to draw firm conclusions, we can see certain trends which can have useful clinical and research implications. For example, in all cases we can see that the scores on depression decreased, and this decrease continued several months after the completion of DMT.Another important trend relates to the gender of participants. The fact that 81 percent of the participants were women may reflect the fact that dance is seen as an art form that stereotypically attracts women. Research bias can be seen in studies such as Jeong et al.  that invUnlike gender, the age of our sample was widely ranging from 16 to 65 years of age. However, all studies but one (Jeong et al., Similarly, studies with people older than 65 who may be struggling with depression were also missing despite the increased research activity relating to people in this age group (Karkou and Meekums, As indicated in our qualitative narrative synthesis and our first meta-analysis, all the studies included in this review demonstrated a decrease in the levels of depression for the intervention with participants with a range of levels of depression. As Zubala and Karkou  suggest,As presented in our qualitative narrative meta-synthesis, the most common trend amongst the reviewed studies was two sessions per week across 10 weeks. The only Chinese study (Xiong et al., The length of the sessions ranged from 45 to 120 min. On average, and in all the European studies, sessions lasted from 60 to 90 min. The shortest sessions were available in the Korean study by Jeong et al.  that offOn the whole, it is worth considering whether high therapy “dosage” was associated with higher level of severity of depression. In the Chinese study (Xiong et al., Another study that involved participants with similar levels of severity of depression at the baseline was the study by Röhricht et al. . Even wiWith the exception of the study by Pylvänäinen et al. , most stAll the studies except for Punkanen et al.  showed aOn the whole, the studies included in this review used integrative models that combined the interactive model by Chace (Chaiklin and Schmais, The DMT approaches used in the Finnish studies is worth looking at carefully. The Pylvänäinen et al.  study prIn all the studies conducted in Finland and the study in the UK, qualified and registered dance movement therapists delivered the intervention. Due to their training, it is possible that similar methods were used and an overall integrative model of DMT practice was adopted reflecting similar trends in psychotherapy in general (Norcross and Goldfried, The study with the highest quality at the time of writing up this review was the UK study by Röhricht et al. . This waIn contrast, the first review study by Jeong et al.  remainedAll three of the most recent studies came from Finland, a country with particular interest in identifying appropriate treatment for depression due to its high rate of depression and Seasonal Affective Disorder (SAD—Saarijärvi et al., During this systematic review we were able to explore evidence of effectiveness around the role of DMT in the treatment of depression and answer our main research question concerning whether DMT is an effective treatment for clients with a diagnosis of depression. We conclude that there is evidence from high quality studies of a positive effect for DMT in reducing depression in adults. Our positive conclusion offers additional and stronger support to existing evidence from previous reviews of DMT for depression (e.g., Meekums et al., Still, studies that involved children, adolescents and older people were generally missing from this review, confining our positive conclusions to adults with depression only. We were not able to conclude with any confidence whether DMT is beneficial for both men and women. Similarly, in this review, although there were findings relating to secondary outcomes, we did not look at them. Future studies should consider both younger and older populations, men and women and, where available the impact of DMT on secondary outcomes such as anxiety, quality of life, self-esteem and body image next to other clinically relevant outcomes including potentially physiological or neurocognitive changes. Further research attention is also needed on the degree to which positive results, indicated in some of our calculations, can be sustained at a follow up stage and what is the impact of the process of therapy on levels of depression through, for example, mid assessments.The use of dance, the embodied therapeutic relationship, unearthing and working through difficult issues non-verbally and integrating possible discoveries and solutions creatively may be some reasons for the positive impact of DMT. However, further research on the active ingredients of DMT is needed that can offer further confidence about whether these are indeed helpful factors in the treatment of depression. In-depth study of the manuals of the different types of DMT practice used can result in further refinement of what we think is currently responsible for the significant effects of DMT on reducing depression. A new project called “Arts for the Blues” (Haslam et al., Furthermore, we propose that studies need to take place where DMT is not simply added to TAU and compared to TAU alone, but it is also compared with other, regularly available, treatment options. Controlling for other forms of psychotherapy such as counseling, art forms such as dance and music, and either group work or recreational activities will also be of considerable benefit as a way of both narrowing down the active ingredients of the intervention and providing comparable results with other, widely used treatments. A new study recently funded by the UK National Health Service might act as a response to this need where DMT, next to art therapy and music therapy, is compared with person-centered counseling Carr, . This neFinally, the type of approach used, its frequency and overall dosage need to be further explored leading to an associated clinical guideline that takes into account the severity of depression. Such guidelines are currently available for psychological treatment options and exercise (see NICE, VK was responsible for organizing, drafting, and finalizing the current paper. She also completed the systematic search with BM for the Cochrane review, i.e., the first search, and with SA during the second search. She also guided the statistical analysis for the current review. SA contributed to the systematic review, performed the statistical analyses, and contributed to the writing and editing of the text. BM led the Cochrane review, acted as a referee for the current review and edited the final paper. AZ contributed to revisions and edits of the paper.VK and BM are dance movement therapists registered with ADMP UK and as such may be seen as having invested interest in demonstrating the effectiveness of the intervention. SA, originally a speech and language therapist and a dancer, is completing her doctoral studies on DMT. AZ is a psychologist who has been researching arts therapies in her doctoral and post-doctoral work. The submitted work was not carried out in the presence of any other personal, professional, or financial relationships that could potentially be construed as a conflict of interest.