I argue for an overlooked distinction between perceptual presence and volumetric content, and flesh it out in terms of predictive processing. Within the predictive processing framework we can distinguish between agent-active and object-active expectations. The former expectations account for perceptual presence, while the latter account for volumetric content. I then support this position with reference to how experiences of presence are created by virtual reality technologies, and end by reflecting on what this means for the relationship between sensorimotor enactivism and predictive processing. According to this account, without these embodied action-based expectations, I would not be able to experience the tomato as three-dimensional. Here is one of many passages where Noë presents this view.Consider the following, which we might call “the puzzle of volumetric content”. When I see a tomato, I typically see it as three-dimensional: a roughly spherical object with a rear surface that is occluded from view. How is it that my experience has this volumetric, three-dimensional content given that all that is actually presented to me are the surfaces of the tomato that are facing me?Our perceptual sense of the tomato’s wholeness – of its volume and backside, and so forth – consists in our implicit understanding (our expectation) that movements of our body to the left or right, say, will bring further bits into view. Our relation to the unseen bits of the tomato is mediated by patterns of sensorimotor contingency Noë , p. 63.if I were to act in certain ways? Sure, one might argue, expectations about how the sensorium would change if the object itself were to move in certain ways (with me staying put) are as important, or indeed more so. Thus, if the tomato were spinning on a turntable, the expectation of what I’m about to see, as previously unseen parts of the tomato come into view, would be central to my experience of the tomato as a three-dimensional object. Furthermore, it seems that the cases where my expectations involve my acting are only tangentially to do with my action. They are, at least fundamentally, about the bringing of unseen parts of the object into view, regardless of whether this is about my moving around the object, or the object’s rotating on its own. Such a criticism has been put forward by Cavedon-Taylor . However, should these expectations be restricted to how the sensorium would change n-Taylor . In his perceptual presence on the one hand, and volumetric content on the other. These two things are unfortunately often conflated. An upshot of this is that predictive processing doesn’t simply flesh out Noë’s account: it accommodates its core insights and improves upon it.In this paper, I want to show how a recent way of fleshing out Noë’s view in terms of predictive processing not only addresses Cavedon-Taylor’s criticisms, but also allows for a very neat distinction that Noë’s view cannot accommodate. This distinction is between Seth  has re-cOn this framework, it is not just volumetric content that is underdetermined by sensory input. All perceptual experience, to the extent that it is determined by the model selected to predict future sensory input, is underdetermined by sensory input. Many predictive models are compatible with any given input. What helps with model selection in the face of this multiple compatibility is background knowledge about the probability of the model independently of the input, namely, its “prior probability”.  Crucially, the predictive models that our nervous systems generate include ourselves as part of the world, and how our acting on and in the world will impact on our sensory (and proprioceptive) input.counterfactual richness  a wealth of counterfactual expectation about how the sensorium would change given relevant circumstances – circumstances that needn’t happen and may even be unlikely to happen. In other words, my nervous system isn’t simply “content” with superficially predicting what will happen next, but seeks to “comprehend” more fully the statistical structure of the world, which involves, in part, the tacit positing of the underlying natures and dispositions of things, even if those natures and dispositions are never explicitly revealed, since their being revealed might involve an excessively complicated and/or unlikely set of counterfactual circumstances.Seth presents the connection between the PPF and sensorimotor contingencies as follows. The models that our nervous systems select, and which determine our experience, vary in their A crucial aspect of this picture, which I’ve briefly mentioned, is that predictive models aren’t just about the world, but include ourselves as part of that world. Indeed, bodily action is explained within this framework as a self-fulfilling prediction. More specifically, it involves the expectation that certain body-involving sensory and proprioceptive events will take place, which is then fulfilled by the ensuing action. In a way that is very much in keeping with Noë’s view, exploratory touch can be seen as a nicely illustrative case of perception and how it is fundamentally continuous with action: the movement of my arm and hand as I reach out in the dark to feel something is transparent since the expectations are being effortlessly fulfilled, and a model of the distal object is constructed as parts of the world with which I am less familiar, have less control over, are encountered and generate prediction error that needs to be accommodated.With these two ingredients in place, namely, (i) the counterfactual depth of predictive models, and (ii) the deployment of predictive models that feature ourselves as part of the world, our nervous system has an implicit understanding of sensorimotor contingencies insofar as it deploys predictive models about how the sensorium will change if I were to act in certain ways (even if those ways of acting are unlikely).As Seth puts it,mastery of sensorimotor contingencies relevant to the puzzle of perceptual presence. That is, a counterfactually-rich hierarchical generative model explicitly encodes probabilistic representations of the external causes and expected values and precisions of the fictive sensations conditioned on repertoire of possible actions, thus capturing the key notion within sensorimotor theory of somehow perceiving parts of an object not directly available within ongoing sensory flux. . In short, seeing something as part of my world is quite different to seeing it as three-dimensional, although both are underdetermined by current sensation. Where does this experience of presence come from?Before answering this question, let’s clarify still further the relevant notion of perceptual presence and how it differs from, and can even come apart from, volumetric content. I can perceive a two-dimensional tomato façade as present, although I need not experience it as three-dimensional. Conversely, I might have as my screensaver an animation of a rotating tomato. There is an important sense in which I experience the tomato as three-dimensional, as having volumetric content, but, I do not thereby experience it as having presence .Whereas object-active expectations generate volumetric content , agent-active expectations generate perceptual presence (experiences of things as part of my world). On this account, the experience of the screensaver tomato has volumetric content because I have certain (in this case accurate) object-active expectations about how the sensorium will change as the virtual tomato rotates. However, it lacks perceptual presence because I don’t have the relevant agent-active expectations about the tomato. In fact, I have expectations that contradict presence, e.g., that if I were to walk around it (or rather where it is represented as being), all I would see is, first, an unrealistic foreshortening of the tomato from round to oblong as I see my computer screen from an angle, and then, as I continue round, the back on my monitor. While the tomato on the screen is experienced as having volumetric content but not perceptual presence, the monitor itself of course is experienced as having both.I want to suggest a very simple solution to both puzzles that falls quite naturally out of the PPF. Borrowing Cavedon-Taylor’s  distinctAt this point I’d like to clarify object-active expectations still further, by in particular clarifying their relationship to action.This under-appreciated distinction between volumetric content and perceptual presence, and the different kinds of expectations that underpin the two, offers Noe a way out of Cavedon-Taylor’s criticism: Noe was talking about perceptual presence, not about volumetric content, and it is the former, and not the latter, that is underpinned by sensorimotor contingencies. However, this is unsatisfying for two reasons. First, it is not clear that Noe is restricting himself to perceptual presence in this more specific sense (see the passage at the start of this section). Second, even if we grant that he is, surely we want to be able to accommodate both perceptual presence and volumetric content? I now present account that does just that.I to do something. Many of the relevant expectations are to do with what will happen to the object in certain circumstances that need not involve my acting at all . So here we get the distinction between object-active and agent-active expectations. These expectations, although they are responsible for generating volumetric content and perceptual presence respectively, in being responsible for all experiential content, go well beyond that. They may, for example, generate the experience that something is fragile  or edible  and so on.It is crucial to see that not all counterfactual predictions are about what would happen were So what story does this framework generate for volumetric content and perceptual presence respectively? Let’s return to the rotating tomato screensaver. As the tomato rotates, bringing the back of the tomato into view, the model that my nervous system adopts in order to best predict imminent inputs is that there is an object with a certain shape and volume occupying Euclidean space.there in relation to me. It is, like me and my body, a part of my world, the world that I can navigate through and act upon.For perceptual presence – for example, with a real tomato on the table in front of me – my nervous system selects a model that underpins my embodied appreciation (my “implicit understanding”) that, among other things, as I move around the tomato, previously unseen parts of the tomato will come into view. In short, my nervous system has generated the optimally predictive model that there is an object for the object; it models the object to the extent that it exploits object-centred counterfactual expectations. That very same experience may  also have presence in its content, namely, the object is experienced as part of my world. This quite different feature of the experience is best explained in terms of my nervous system having selected a model for the overall encounter, namely, for the object in relation to me; it exploits agent-centred counterfactual expectations, namely, sensorimotor contingencies. The relevant expectations concern how the sensorium will change if I were to act in certain ways .So, to sum up, then, within the PPF we are to understand the nervous system as fundamentally engaged in the selection of optimally predictive models, and these models determine the content of our experience at a given time. When our experience contains a three-dimensional object, that three-dimensionality  is best explained in terms of our nervous system having selected a model of the subject in the environment, and the presence of the environment to the subject. In short, presence is a two-way relation between subject and environment. If I experience the environment as present to me, I thereby experience myself as present in the environment.One way of putting this account to the test is to examine the ways in which experiences of presence can be created with virtual reality (VR) technologies. In VR research, presence refers to the extent to which a virtual  environment (VE) is experienced as an actual environment that the subject is spatiotemporally located within. The VE usually takes the form of a computer-generated pictorial representation presented to the subject via a head-mounted display (HMD). The ambiguity in the word “presence” of what it is that is present turns out to be rather apt. That is because it refers simultaneously to the presence It has long been acknowledged that what generates experiences of presence in VR is sensorimotor contingencies (viz. agent-active expectations)  and, as discussed, rotation. More sophisticated and immersive forms of three-dimensionality exploit the depth cues that binocular vision provides (see fn. 1), viz., 3D glasses give each eye a slightly different image, namely, the image as it would be from a slightly different location, namely from the location of each eye. This means that a relatively large disparity between the two images corresponds to experiences of proximity, whereas a relatively small disparity corresponds to experiences of distance. This does not exploit action. You get this effect while sitting perfectly still. Indeed, moving your head actually disturbs the effect of 3D glasses since the depth cues don’t vary as they ought to. Having said this, if they did, and you combined VR and 3D, it would add fuller presence to the experience.So much for VR and presence; what about volumetric content? If my suggestion is correct, VR is not necessary for experiences of volumetric content, since what the HMD provides is exploitation of agent-active expectations, not the object-active ones that underpin three-dimensionality. This seems, on reflection, to be an accurate supposition. Rudimentary experiences of three-dimensionality can be achieved through perspective  is testament to that. The illusion, however, is fragile, and movement destroys it rather than strengthening it. But this is perfectly in keeping with the distinction I am trying to sketch. Agent-active expectations are invoked by the careful recreation of embodied binocular vision that 3D glasses (and the appropriate image) provide. But these expectations are broken when movement doesn’t generate the expected sensory change. At the same time, of course, object-active expectations are also broken yielding a loss of volumetric content, as discussed. As the T-Rex’s head appears to jut out of the screen (let’s suppose head-on), if you try (by moving) to look at it from the side, your nervous system will be disappointed, and your 3D generative model of the T-Rex (as a 3D object) will collapse, since the image projected on the cinema screen won’t change to show you the dinosaur in profile simply for your benefit .as around us, what I have said leaves the core of Noë’s sensorimotor enactivism intact. In that respect it’s a defense of Noë against the criticism put forward by Cavedon-Taylor, but one that elucidates the notion of presence. And although in theory Cavedon-Taylor is right that it isn’t agent-active expectations that generate volumetric content, in practice it is hard to separate volumetric content from presence in an experience that is to be genuinely thought of as perceptual . Perhaps more importantly, it is hard to conceive of a conscious, embodied organism that wasn’t constantly making use of sensorimotor expectations to at least some extent. In a related manner, when I talk about volumetric content independently of perceptual presence, this is a theoretical abstraction that never occurs in practice, at least not for embodied organisms (and these are the beings in the universe that perceive and have need to do so). It is nevertheless a theoretical distinction that is worth making since it points to two different components of experience that can be manipulated separately . Certain vivid after-images, or rotating screensavers, might have relatively high levels of three-dimensionality, but low levels of presence. Some low-resolution VR experience might have the opposite: high presence, but low three-dimensionality.In spite of appearances, I don’t think that what I have said here is bad news for Noë’s sensorimotor enactivism. Noë’s view is that our conscious perceptual experience is determined by sensorimotor contingencies, by what I have here called agent-active expectations. To the extent that our perceptual experience is about perceiving the world around us and perceiving it Finally, I’d like to gesture towards two ways in which sensorimotor enactivism and predictive processing are not only compatible, but also deeply similar in spirit. The (related) things that they share (and there a likely more) are as follows.making sense of the world. Second, both the PPF and sensorimotor enactivism, when compared to more orthodox views of perception, play down the importance of sensory stimulation for perceptual experience. To clarify, both entail that my perceptual experience at t1 is not determined by  antecedent sensory stimulation. It is rather, for both views, determined by patterns of expectation, which may be fulfilled or frustrated. The role of sensation for both views is always as a corrective after the experience itself, which is profoundly dynamic. Of course, these expectations are cashed out within the PPF as “models” or “hypotheses”, which is a move sensorimotor enactivists are likely to resist, but that is a question for another day (see Downey First, both the PPF and sensorimotor enactivism explicitly think of perception as, to quote Noë, “a thoughtful activity.” It’s not about passively receiving “impressions” of the world, but of actively In this paper I have presented a distinction between perceptual presence, on the one hand, and volumetric content, on the other, and fleshed it out in terms of predictive processing. Whereas presence is underpinned by what Cavedon-Taylor  calls ag


In healthcare, preceptors act as a role model and supervisor, thereby facilitating the socialisation and development of the preceptee into a professional fit to practice. To ensure a consistent approach to every preceptorship experience, preceptor competencies should be measured or assessed to ensure that the desired outcomes are achieved. Defining these would ensure quality management and could inform development of an preceptor competency framework.This review aimed to evaluate the evidence for preceptor competencies and assessment in health professions.This study followed the PRISMA ScR scoping review guidelines. A database search was conducted in Embase, Medline, CINAHL and IPA in 2019. Articles were included if they defined criteria for competency, measured or assessed competency, or described performance indicators of preceptors. A modified GRADE CERQual approach and CASP quality assessment were used to appraise identified competencies, performance indicators and confidence in evidence.Forty one studies identified 17 evidence-based competencies, of which 11 had an associated performance indicator. The competency of preceptors was most commonly measured using a preceptee completed survey , followed by preceptor self-assessment, and peer-assessment. Preceptee outcomes as a measure of preceptor performance had good but limited evidence.Competencies with defined performance indicators allow for effective measurement and may be modifiable with training. To measure preceptor competency, the preceptor perspective, as well as peer and preceptee assessment is recommended. These findings can provide the basis for a common preceptor competency framework in health professions. Preceptorship may be defined as the formal arrangement, situated within a clinically related setting, between a practicing health professional (the preceptor) and a graduate or student (the preceptee). The preceptor acts as a role model, supervises, provides guidance, learning experiences, and facilitates the socialisation and development of the preceptee into a competent professional, fit for practice during the taught curriculum and pre-registration –3. In soCompetencies comprise a combination of knowledge, skills, abilities or attributes . Multip(i)Evaluate evidence for competencies or performance indicators of preceptors in health professions;(ii)Describe implemented methods of measurement and assessment of competency;The aim of this review was to evaluate the evidence for preceptor competencies and assessment in health professions. The objectives of this review were to:What is the evidence for preceptor competencies in health professions and to how are they assessed?Preceptorship: Preceptorship is the formal arrangement between a practicing health professional (the preceptor) and a graduate or student (the preceptee). Within a clinically-related setting, the preceptor supervises, provides guidance and facilitates the socialisation and development of the preceptee into a competent professional fit for practice –3.Assess: To consider (give careful thought to) someone or something and make a judgement about them or it .Measure: to determine magnitude or quantity based on a standard .Rating: a classification based on assessment of quality, standard or performance .The literature was comprehensively searched using the following databases: Embase, Medline, Cumulative Index of Nursing and Allied Health Literature (CINAHL) and International Pharmaceutical Abstracts (IPA). A search strategy was developed via consensus with all authors and then applied to each database by the primary author (AB) on 19th June 2019 with no date limitation applied. The following PCC  strategy was developed a priori. The study population included medicine, nursing, pharmacy or other allied health practitioners. The concept of preceptor was captured using the terms clinical teacher, clinical educator, clinical supervision, preceptor, preceptorship, tutor or clerkship. The context of professional competence incorporated evaluation, guideline, framework, education, skill or quality. Each term was grouped with the boolean operator “OR”, and each concept with the operator “AND”. The search was restricted to peer-reviewed journal articles and those published in English. The search strategy used for Medline is presented in Additional file The inclusion and exclusion criteria were developed in an iterative fashion as described by Arksey and O’Malley  as more Data were extracted and analysed by the primary author (AB), using a standardised data extraction form containing a predefined set of items. Items included study characteristics ; mode of measurement, measurement tool and scale; competency criteria; results; reliability/validity. The form was pilot tested with three articles, and discrepant items were clarified and resolved by discussion.As the included articles in this review had mixed study designs, two critical appraisal tools were used, the Critical Appraisal Skills Program (CASP) Cohort checklist  and the Methodological limitations were assessed by looking at aspects of each contributing study that may reduce the confidence in the finding .Coherence refers to the extent to which contributing studies fit with the finding in a convincing way. Studies that contain contradictory results to the other contributors would be seen to reduce the confidence in the finding .Assessing adequacy involves making a judgement on the quantity of data along with the quality or richness of the information gained .The confidence in the relevance of the papers contributing to the finding was a matter of examining the setting, context, perspective and phenomenon of interest .To assess the level of confidence in the findings, an approach based on the GRADE CERQual  framework was followed . CERQualAfter these assessments were made, they were considered as a whole to determine confidence in the evidence for the finding. These were then graded on a scale from low to high confidence. All findings were synthesised narratively.The literature search retrieved a total of 1642 citations after removing duplicates. Screening for eligibility based on titles excluded 1463 papers, leaving 179 papers for review of abstracts. A further 69 papers were excluded after reviewing abstracts, with 110 papers carried forward for full text review. Careful screening provided 36 papers fitting the selection criteria. Hand searching found an additional 5 references, resulting in a total of 41 –60 articOf the 41 included articles, 26 were conducted in the United States , 56, 59,Seventeen competencies with associated methods of assessment were identified, as outlined in Table The competency of preceptors was measured in four ways. Most commonly, and with moderate to high confidence as per CERQual, preceptees used a survey instrument to assess the competency of their preceptor , 53, 57.The CASP Cohort checklist was used for the quantitative and validity testing papers, and the CASP Qualitative checklist was used for qualitative studies, descriptive studies and consensus building based on literature review and qualitative synthesis. The results of the CASP assessments tabled with a traffic light legend can be found in Additional file This systematic scoping review of the literature and evaluation of the quality of evidence using GRADE CERQual, informed the development of a 17-item evidence-based set of preceptor competencies and corresponding methods of assessment that is applicable to a diverse range of health professions. This review did not find evidence for significant differences for requisite preceptor competencies across health professions. The identification of the minimum level of performance at which a health practitioner may be deemed a ‘competent’ preceptor requires calibration. These competencies and methods of assessment may form the basis for a competency framework and be applied to recognise preceptors working at an advanced level of practice, thereby enabling a system of quality management and oversight.In assessing the confidence in evidence for these findings using CERQual, it was apparent that 11 of the identified competencies have defined performance indicators that may allow for effective measurement of competence, while six could be described as attributes. Attributes such as being ethical, enthusiastic, or empathetic, were not associated with performance indicators and would therefore to be less conducive to measurement and standardisation. Without adequate measurement, discerning the effect of any potential intervention, such as training is problematic. Interestingly, the competencies or attributes without performance indicators, such as empathy, could be considered as intrinsic to the individual preceptor. Intrinsic traits have been identified as being difficult to modify through training but may develop with personal reflection and maturity . Sutkin A disconnect between the competencies and the mode of measurement of some competencies was identified. For instance, adapting to the learning needs of preceptees had evidence for assessment by peer observation in both simulation and practice environments. This would seem to be a competency that lends itself to evaluation from the perspective of the preceptee, however, in the literature there was no evidence for this mode of measurement. Likewise, demonstrating reflective practice had evidence for assessment via a preceptee survey, whereas self-reflection as a mode of measurement would seem logical, but again, evidence was not apparent. A recommendation is to consider alignment of the mode of measurement with the competency being assessed in a consistent manner across all competencies in the framework.There was a lack of evidence to demonstrate a relationship between competencies or attributes of preceptors and preceptee outcomes. According to Bigg’s framework of constructive alignment, learning outcomes should be clearly outlined at the beginning, then learning activities and assessment aligned, so that the level to which those outcomes have been achieved can be measured . In the An additional consideration in constructive alignment would be to align assessment with assessors who are well placed to provide the assessment. Brookfield describes four lenses through which teachers can view their practice from different perspectives as a tool for critical reflection and ultimately to perform more confidently and at a higher level . A tripaThe strengths of this scoping review are that a rigorous, standardised approach of CERQual was used to assess the confidence in the evidence. This provides credibility to the competencies and methods of assessment identified from the literature search. The nature of the scoping review process allowed for the inclusion of papers of various study design such as validity testing and qualitative studies. A conservative synthesis approach was adopted to facilitate inclusivity of the language used to describe competencies across the literature. Further rationalisation of the identified competencies may be possible. The review followed the PRISMA ScR guidelines and an iterative process was maintained between authors. Limitations of the review are that title and abstract screening, data extraction and evidence assessment were primarily carried out by the primary author, although a random selection of results for all stages were assessed by two additional authors, with points of difference discussed to achieve consensus. An additional limitation was the preponderance of studies from a single country (USA), resulting in a potential risk to generalisability of findings.This review has synthesised a common set of preceptor competencies across health professions. Additional unique preceptor competencies for individual health professions may need to be considered. The relationship between measuring the performance of preceptors and effective outcomes of preceptees has yet to be determined and requires further investigation. It would be worthwhile to examine which of the competencies identified are most relevant to the outcomes for graduates. Retention in the workforce, professional satisfaction, and career progression are all outcomes that may indicate that the model of preceptorship is successful, but this requires evaluation. In addition, the minimum level of preceptor competence has not been determined. A consensus approach, such as the Delphi method , could bA standardised, evidence-based set of preceptor competencies and accompanying methods of assessment has been identified across health professions. Most competencies have an associated performance indicator which allow for effective measurement, while others are more intrinsic to the individual resulting in measurement difficulty. Further research is required to identify the minimum standard of performance that is necessary, as well as to identify the factors that have the greatest influence on the outcomes for preceptees.Additional file 1. Appendix 1 – Example search strategy using Medline.Additional file 2. Appendix 2 – Data extraction table.Additional file 3. Appendix 3 – GRADE CERQual evaluation table.Additional file 4. Appendix 4 Risk of Bias appraisal.


Bolaamphiphiles (BAs) are structurally segmented molecules with rich assembly characteristics and diverse physical properties. Interest in BAs as standalone active agents or as constituents of more complex therapeutic formulations has increased substantially in recent years. The preorganized amphiphilicity of BAs allows for a range of biological activities including applications that rely on multivalency. This review summarizes BA-related research in biomedically relevant areas. In particular, we review BA-related literature in four areas: gene delivery, antimicrobial materials, hydrogels, and prodrugs. We also discuss several distinguishing characteristics of BAs that impact their utility as biomedically relevant compounds. Synthetic bolaamphiphiles (BAs) are segmented amphiphilic molecules that take structural inspiration from archaeal membrane lipids  creates opportunities to combine self-assembly with multivalent ligand presentation. Here, the segmented amphiphilicty facilitates particle organization while the multivalent hydrophilic segments enhance biological function.Archaea microorganisms famously utilize ether-linked BA lipids to assemble and stabilize a range of membrane organizations but especially the monolayer type . As shown in In some situations membrane stabilization is desirable  but in other applications destabilization becomes the goal. The use of BAs as ion-conducting species was one of the earliest and most robust lines of research inside the synthetic amphiphile community , asymmetric BAs are attractive as they can encode a higher density of information vs. symmetric BAs. For example, Jain et al. , 2012 stAnother notable feature of segmented amphiphilicity is the organization of functional groups into dense clusters. Another cross-cutting theme that emerges from the literature is the ability of BAs to impact stability of nanostructures either alone or as a component in a more complex formulation. Archaea-like or archaea-inspired BAs are well-known in this regard. Their membrane spanning ether linked lipid backbone along with hydrophilic head groups stabilize the liposomal membrane  or co-formulated with helper lipids. In 2010, they reported the synthesis and complexation of DNA by asymmetrical BAs featuring ornithine and gluconic acid polar head groups  head groups  to delivery long RNAs  is a threat to global health s including several BA-type structures with central hydrophobic tethers ranging from 3 to 12 carbons s but it was also cytotoxic.In 2016 the Gokel group studied a collection of bis-THA]Cl2, which is structurally similar to dequalinium  block essential microbial transcription and therefore represent a powerful weapon against antimicrobial resistance  then the particular TFD. It was found that nanocomplexes formed in this way preferentially accumulated in bacteria.Gonzalez-Paredes et al.  took a sin vitro antisense treatment to inhibit Clostridium difficile using a bolasome-based approach  that were joined by a hydrophobic isoprene linker see  Caron e. These BHydrogels offer a unique pathway for the conversion of small molecules (low molecular weight gelators) into macromolecular structures. BAs are attractive building blocks for hydrogels as their segmented amphiphilicity promotes both hydrophobic and polar interactions  leading to a rich design space. The self-assembly proclivities of these materials are diverse and influenced by a portfolio of weak interactions including hydrogen bonding, π-π interactions, aromatic interactions, and hydrophobic effects.Romera et al.  show howPhotodynamic therapy is another potential solution to the onset of multi-drug resistant bacteria  to use BAs as a standalone nucleic acid complexing agent (bolaplex) or as just one ingredient of a multi-component lipid formulation? BA-based hydrogels also remain an exciting area of research where creative design can produce multifunctional materials with dynamic properties. Overall, innovative synthetic design will continue to drive discovery. The synthesis of new BA constructs with intermediate molecular weights, falling somewhere between traditional small molecule BAs and segmented polymers, is interesting and somewhat underdeveloped.JH, AM, CW, GV, and PI wrote the paper. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


A recent alert from a well-known scientific journal based on a published retrospective study informed the scientific community that septum incision does not improve reproductive outcome and this operation should therefore not be offered anymore as a treatment, even in symptomatic women unless as part of a clinical trial  .Indeed, such a recommendation from a high-ranked journal, officially representing a Society based on only one retrospective study was, at least, unexpected and scientifically unjustified, particularly considering that the authors of this publication are strong supporters of evidence-based medicine.Currently, nobody (not even the authors of the above mentioned study) denies the fact that women with septate uterus have an increased risk of subfertility, pregnancy loss, preterm delivery, fetal malpresentation and intrauterine growth retardation, resulting in a higher perinatal mortality .Hysteroscopic septum incision represents the surgical solution for these patients; it is also important to mention that currently, the operation should be guided by data obtained by preoperative three-dimensional ultrasound imaging and should be done with mini-instruments, (scissors or bipolar needle) minimising the risk of complications . Thus, cCurrent evidence based on observational studies assessing the pre- and post-operative reproductive outcome of women with septa, on non-randomized comparative studies, in which women could choose between septum resection and expectant management and prospective studies, support the notion that hysteroscopic septum incision has a beneficial effect in the achievement and evolution of pregnancy .Based on that evidence, after many years of discussions and debates, the American Society for Reproductive Medicine (ASRM) and the National Institute for Health and Care Excellence, recommended hysteroscopic treatment of septate uterus in patients with infertility and impaired pregnancy outcomes ; a neutrThus, the question is whether a study could change the current recommended practice and why the scientists should be surprised by that published data.Is the evidence so strong? Going through the details of the study by Rikken et al , it is qIs there a need to change our practice? The published retrospective and biased data do not seem to offer an objective re-evaluation of the current available evidence as it is intergrated in the guidelines and in no way should change our practice. The symptomatic women with septa should be treated hysteroscopically.Are there open issues? Yes there are; there is still a need to evaluate the depth of an indentation which is clinically significant and impairs women’s reproductive potential and, based on that evidence, there is a need to potentially re-evaluate the current available definitions of septate uteri In conclusion, the published data in the aforementioned article should be viewed with great caution and the patients should not be denied the benefits of hysteroscopic septum treatment.Grigoris Grimbizis, ESGE PresidentErtan Saridogan, ESGE Editor-in-Chief FVVOAttilio Di Spiezio Sardo, ESGE SIG Hysteroscopy CoordinatorRudi Campo, Chair, ESGE Board of Directors


New evidence is rapidly identifying multiple pathways by which these dairy nutrients may effect health. Processing, including fermentation and homogenization, may also have positive effects. Conversely, the high saturated fat content of dairy has long raised concern, aligned with international guidelines to minimize dietary intake of animal-origin saturated fatty acids (SFA) to achieve better cardiometabolic health. However, led in part by observational studies and meta-analyses showing dairy to have no or even an inverse association with cardiometabolic health, evidence from randomized controlled trials (RCTs) has been scrutinized over the last 5 years, and focus on low-fat dairy has been challenged. Recent evidence supports the hypothesis that adverse effects of SFAs on metabolic health may be ameliorated when these fats are consumed within a complex matrix such as milk, cheese or yogurt, and that dairy food categories may influence outcomes as much as total fat content. For example, yogurt and high-fat, high-SFA cheese have a negative association with risk of type 2 diabetes (T2D) in many, not all, published trials. However, large sample dairy RCTs of long duration with CVD or T2D incidence as primary endpoints are lacking. This is a clear research gap, with these clinical studies required if a causative link between dairy and improved cardiometabolic health is to be confirmed and in turn promoted through dietary guidelines. Current advisories from national guidance groups such as American Heart Association (AHA) and European Society of Cardiology (ESC) continue to promote consumption of low-fat dairy products, whilst liquid milk and yogurt remain part of nutrition guidelines from joint American Diabetes Association (ADA)/European Association for Study of Diabetes (EASD) reports, and as part of a “no-one-size-fits-all” answer to diet and T2D by the ADA in their most recent 2019 Consensus Report.Cow's milk and dairy products derived from this complex food source have long been proposed as beneficial to human health, yet underlying clinical evidence of direct benefit continues to raise controversy. Limited evidence supports positive cardiometabolic effects of a number of dairy macro- and micronutrient components including whey protein and casein, unsaturated fats, milk fat globule membrane (MFGM) and polar phospholipids, vitamin D and calcium, in addition to non-bovine components including bacterial and yeast probiotics. More controversial remain lipid components  This narrative review aims to present the most recent evidence from both observational cohorts and randomized controlled trials (RCTs) that investigate the relationships between dairy and risk of cardiovascular disease (CVD) and type 2 diabetes (T2D), and to evaluate the evidence provided by these different study types. Also to identify, where possible, potential mechanisms by which dairy nutrients may promote health benefits.Cow's milk and dairy products derived from this complex food source have long been proposed as beneficial to human health, yet underlying clinical evidence supporting direct benefit to cardiometabolic health continues to raise controversy, based primarily on the high saturated fatty acid (SFA) content of whole-fat dairy. Whether high levels of dietary SFAs Concern around dairy and potential adverse health outcomes arose from early epidemiologic data which supported a strong association between animal-origin food groups that provide a major source of dietary SFAs and an increased risk of CVD . In counA number of meta-analyses and systematic reviews have also focused on dairy and T2D , 12–17, Dairy composes about 10% of the energy consumed in, for example, a typical North American diet, of which approximately half is from fluid milk, half from fermented (or “cultured”) cheese, and a small percentage from fermented yogurt . ImportaA literature search was conducted using MEDLINE (via PubMed) to identify observation cohorts and intervention trials that investigated the association between dairy consumption and cardiometabolic health. Medical Subjects Headings (MeSH) included dairy OR milk OR butter OR cheese OR yogurt AND CVD OR diabetes; reviews, including systematic reviews, meta-analyses, umbrella reviews, narrative reviews.Among the various types of animal-based protein foods, a higher intake of protein-rich dairy products has been reported to be associated with a beneficial relationship with a range of CV endpoints in addition to glucose regulation and T2D risk reduction , 27, 28.per se. There however are several systematic reviews of RCTs that identify positive effects of whey protein. Wirunsawanya et al., recently reported on whey supplementation and CV endpoints in 9 RCTs of overweight and obese cohorts, and identified an improvement in serum lipoproteins for total and HDL-cholesterol in addition to improvement in blood pressure  in relation to both T2D and CVD risk, as summarized below.The recent expert panel position paper referred to previously also reported on evidence underpinning relationships between dairy fatty acids and metabolic health. The panel concluded that medium-chain fatty acids/triglycerides (MCFA/MCT), odd chain fats, very long-chain SFAs and c health . They alMCTs are classified as lipids containing medium chain fatty acids of 6–12 carbon chain length. They are minor components of global diets but have long been investigated as a potential dietary lipid substitute for the more abundant long chain triglycerides (LCT). Milk is a reasonable source of saturated MCTs, comprising up to ~15% of total lipid . MCTs unIn vitro studies of skeletal muscle cells show MCTs to enhance oxidative mitochondrial capacity and decrease lipid accumulation relative to LCTs, but not activate NF-κB or decrease insulin sensitivity (IS)  , 52. Premulation  and insumulation . These afat diet , 53. Amefat diet . The Daifat diet .The odd-chain fatty acids (OCFAs), pentadecanoic (C15:0) and heptadecanoic acid (C17:0), are SFAs that are found in dairy. Minor components that comprise ~1.5% of milk fat, with C15:0 reported as approximately twice as abundant as C17:0. Long investigated as potential independent serum biomarkers of dairy intake , 58, theThe MFGM is the biological membrane that surrounds the lipid droplets in liquid milk. This and associated phospholipid (PL) components of milk continue to be associated with health benefits including those of metabolic health, as recently reviewed by Anto et al.  in a narTrans-11 vaccenic acid  is a monounsaturated “natural” trans fat, specific to ruminant-origin products of dairy and meat. There is some evidence  is of particular interest. Associated in recent publications with a lower incidence of T2D  this analysis showed a significant association of trans-palmitoleic with a lower risk of T2D  by the Δ9-desaturase enzyme within the mammary gland to form cis-9, trans-11 CLA (18:2)  . This ismilk fat .cis and trans forms, the most common isomer of which is cis-9 trans-11 linoleic acid. Despite being found in ruminant dairy and meat, and in lesser amounts in plant oils and seafood, CLA is also widely produced industrially for sale as a supplement. Much like vaccenic acid, there are reports of cardiometabolic health benefits  with conjugated double bonds found in both benefits , 87. A sl trials , 89. Thet attack , and 3 Rt attack . There wt attack  and patit attack . There it attack . Conversfat RCTs . In addifat RCTs ] and cytfat RCTs . In addifat RCTs . A recenfat RCTs ; but thafat RCTs .trans-fats is more complex and controversial. Ruminent-origin trans vaccenic acid (trans-VA) may not generate the well-demonstrated adverse response in CV risk endpoints of industrial trans-fats. There is lack of concordance in the evidence base however, with proposed neutral effects of trans-VA observed in cohort studies not being supported by RCT evidence, where systematic review has concluded that all fatty acids containing a trans double bond adversely increase lipoprotein profiles, irrespective of their origin. Conversely there are reported positive T2D risk outcomes for the downstream product of trans-VA, trans-palmitoleic acid (trans-PA) which is also present in minor quantities in dairy, and which cohort studies have correlated with decreased T2D risk. CLA has also been proposed as cardioprotective, with both ruminant-origin and industrial-origin supplements found within the western diet, and highly variable levels of evidence published. From meta-analysis of RCTs showing both significant improvement and significant worsening in lipoprotein risk factors, alongside no significant effects on FPG, to very limited data supporting an association with improved CV incidence in observational studies. There remains no current consensus on outcomes likely due to factors including the highly variable isomers and dose of CLA consumed, size and type of experimental cohorts recruited, and duration of the RCTs.In summary, there are no RCTs evaluating long-term effects of these specific dairy fat components on either CVD or T2D incidence. Very little evidence supports MCTs as cardioprotective, with preliminary clinical findings related only to modest improvements in body composition. In turn, OCFAs have been associated with decreased CV and T2D risk in cohort studies, but no intervention data is available. Conversely, there is limited evidence that MFGM and the associated PL components of dairy may improve CV and T2D intermediary endpoints, in RCTs of 1 day to 12 weeks duration reporting outcomes including lipid metabolism, inflammatory response and insulin resistance. The evidence that underpins Relationships between vitamin D, calcium, and various aspects of cardiometabolic health have long been controversial. In this review, focus has been given to the evidence underpinning relationships between vitamin D and T2D, and calcium and CVD. Dairy naturally contains little vitamin D but is a food category much debated with respect to fortification. Fluid milk and its myriad products have a history of both mandatory or voluntary fortification with vitamin D by the food industry. A recent review reported milk products currently to be systematically, either mandatory or voluntary, fortified with vitamin D only in European Nordic countries of Finland, Norway, Sweden as well as in North American countries of Canada and the United States .There has been conflicting observational evidence for a number of years which has linked low levels of 25-hydroxyvitamin D (25(OH)D) to T2D, and has led to vitamin D replacement interventions conducted with intent to both improve glycemic control and decrease T2D incidence . Both sy1c in T2D patients  and yogurt are commonly consumed fermented dairy products. The fermentation process requires a starter culture, which may vary greatly in order to achieve required texture, flavor and safety profile. Lactic acid bacteria are the major bacteria used in the fermentation process of modern food products, and can include the genera oduction . Acidifioduction , 117. Cooduction . Whilst Lactobacillus and Bifidobacterium. Probiotics are long proposed to have positive health effects achieved through alterations in both composition and function of the host large bowel microbiome, and there is a large literature investigating obesity-related metabolic health outcomes  content of dairy and its myriad of food products has long raised concern , alignedc health .Evidence that underpins the relationship between dairy fat and cardiometabolic outcomes to date exists predominantly from observational studies. This must be noted since association studies cannot determine cause and effect relationships, and are subject to confounding that may bias relationships between diet and disease outcomes. Human clinical trials investigating dairy interventions characteristically have been of short- or moderate- duration, with CV or T2D intermediary risk endpoints, and not disease incidence, evaluated. A summary of both is presented below.CVD: Contrary to prior concerns for high SFA animal-origin food groups . O'Connor et al. have also recently published a review of 38 RCTs, in a heterogeneous meta-analysis of children (>5 years) and adults without T2D, where glycemic endpoints were measured in trials comprising a higher vs. lower dairy arm comparison  and polar phospholipids, vitamin D, and calcium with intermediary cardiometabolic endpoints. Conversely there is no consensus in support of the proposal that both trans and saturated dairy lipids have a consistent adverse effect on cardiometabolic health. Cohort studies report a neutral effect of trans-VA, but are not supported by RCT evidence that shows fatty acids containing trans double bonds to adversely alter serum cholesterol, irrespective of ruminant or industrial origin. In RCTs CLA both significantly improves and worsens CV risk factors but with little effect on glycaemia, and limited association with improved CV incidence reported in observational studies. For dairy SFA, evidence has been growing in support of no association or even a protective inverse relationship with cardiometabolic health, but largely driven by observational cohort studies. A clear research gap is the limited causal evidence of improvements in disease incidence obtained from intervention trials, with RCT evidence obtained predominantly from health individuals in trials of only short- or moderate-duration. In addition, it is proposed that the predicted adverse effects of these dairy lipids may be ameliorated when consumed within the complex food matrices of liquid milk, fermented cheese or yogurt.The contribution of dairy foods to cardiometabolic health has long been controversial. In particular, adverse effects that animal-origin dairy In conducting this wide ranging review of the relationships between dairy and its myriad associated foods and components and cardiometabolic health, there are necessarily a number of limitations. Firstly this is a narrative and not systematic review, hence the ability to formally evaluate bias in its many forms in the large number of publications included both as individual studies or contributing to other narrative or systematic reviews is limited. The quality of the observational studies reviewed was highly variable, as were the design parameters of the RCTs. Study participants age, gender, anthropometric indices, health status and cardiometabolic risk factors also varied greatly between trials, both within and between within study type. It is not clear whether benefits are greatest in individuals identified as at risk of later disease. In RCTs sample size, composition of the comparator (“control”) arm, baseline dairy intake, dairy product and comparator dose, and duration of intervention are examples of important parameters that are not adjusted for in a narrative review.Currently, there is little consensus by International dietary guidelines on the recommended fat content of dairy, and whether continued focus on consumption of low-fat dairy is warranted. The issue is complex, with both the quality and quantity of lipids contributed to the diet through dairy needing to be considered, with potential for higher fat products to promote a high energy density diet , 167 andtrans-fats. Alongside other healthy eating recommendations of consuming a diet high in vegetables, legumes, fruits and wholegrain cereals, EASD makes with no specific reference to dairy, whilst ESC recommends components of the Mediterranean Diet with minimal dairy for CVD prevention, and low-fat dairy for treatment of hypertension. A joint consensus report on management of hyperglycemia from ADA .


The present systematic review and meta-analysis were conducted to find the degree by which the Iranian diabetic patients were informed about their disease in term of health literacy.barakatkns.com), the national publications database (magiran.com) and also Google Scholar and Elmnet search engines. All the original studies published by Oct 20, 2018, in Persian or English, to assess the health literacy of adults with diabetes were included in the study. Ultimately, 17 articles were included in the meta-analysis. The meta-analysis was carried out using the fixed-effects method using Stata-11.2.The search was carried out in databases including the PubMed, MEDLINE (PubMed), Scopus, Embase, Cochrane Library, ProQuest, Web of Science, Science Direct and Wiley and also domestic databases including the Iranian Academic Center for Education Culture and Research (sid.ir), the Iranian Research Institute for Information Science and Technology (IranDoc.ac.ir), Barakat Knowledge Network System (P=0.177). The pooled mean scores with the CI of 95% by gender based on the study population in women and men were estimated as 47.97and 50.06 respectively.The pooled mean score of health literacy was 56.65 out of score of 100, and its 95% CI was estimated as 49.85 to 63.45. No significant heterogeneity could be reported for the articles included in the meta-analysis (I-squared=21.3%, Health literacy is not high in Iranian diabetic patients and is rather inadequate in most of them in both genders. Diabetic women have somewhat lower health literacy compared to diabetic men. Diabetes has always been of interest in medical research as a chronic disease and a major health problem –3. Some Many studies have thus been conducted on health literacy and diabetes –16. The WHO reported health literacy as one of the biggest determinants of health and has recommended all countries throughout the world to establish an association consisting of all those affected by the disease to monitor and coordinate strategic activities for the promotion of health literacy . PatientVarious studies in Iran have also investigated the relationship between health literacy and diabetes , 26. A sMeanwhile, some studies have pointed to the inadequacy of health literacy among diabetic patients in Iran , 34, whiHealth literacy is very important in the prevention and control of diabetes, and the assessment of health literacy in diabetic patients seems necessary for health and medical planning and treatment. Nonetheless, no studies have yet been independently conducted to provide an accurate summary of the level of health literacy in diabetic patients in Iran, and the only study on health literacy in Iran , has detSince many different factors are associated with the health literacy of diabetic patients, which can be widely different from those in patients with other diseases and the general public, the present systematic review meta-analysis was conducted to determine the level of health literacy in patients with type 2 diabetes in Iran.The proposal for this research was first assessed and approved by the University Research Council (Code: A-10-230-17), and the approval of the University Ethics Committee was then obtained (IR.SEMUMS.REC.1397.045). Next, the preliminary stage of the search was carried out and based on the results obtained, the protocol of the systematic review was drafted and uploaded to PROSPERO website. Once the protocol code was issued by PROSPERO (CRD42018098934), the systematic search was carried out as follows:*” and ‘Iran’. The keywords were used both with and without quotation marks and also with wildcards (*) and were combined using the Boolean functions ‘AND’ and ‘OR’. A subject search was also carried out using Medical Subject Headings (MeSH) through Medline (PubMed) database. To access all the relevant articles in gray literature, the core journals and eligible article resources were reviewed. To access the latest published studies, an alert system was activated on a number of databases, including PubMed and Scopus, so that any new articles published during the study could also be reviewed. In this study, the search strategy and the screening and selection of the data were based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.To access the studies conducted on health literacy in diabetic patients in Iran, a search was carried out in databases including the PubMed, MEDLINE (PubMed), Scopus, Embase, Cochrane Library, ProQuest, Web of Science, Science Direct and also domestic databases including the Iranian Academic Center for Education Culture and Research (sid.ir), the Iranian Research Institute for Information Science and Technology (IranDoc.ac.ir), the national publications database (magiran.com) and also Google Scholar and Elmnet search engines. Articles in both Persian and English were retrieved using keywords including “health literacy”, “HL”, “Diabetes”, “Diabetes Mellitus”, “DiabetSince the purpose of this review study was to determine the level of health literacy in adults with diabetes in Iran, no limitations were imposed on the type of study included, and all the original studies published by Oct 20, 2018, in scientific journals, in Persian or English, to assess the health literacy of adults with diabetes, using Test of Functional Health Literacy in Adults (TOFHLA), Health Literacy for Iranian Adults(HELIA) and Short Test of Functional Health Literacy in Adults (S-TOFHLA) were included in the study without any time constraints. The first stage consisted of article search and retrieval. In the next stage, after the elimination of the repeated articles, the titles and abstracts of the retrieved articles were independently assessed by two project collaborators to identify the eligible articles. The assessing team consisted of an epidemiologist, a community medicine specialist and a knowledge and information science PhD. Disagreements about the inclusion of the articles were resolved through discussion and debate to avoid the risk of bias, and in some cases, a third person also made comments. The full text of the eligible articles was then retrieved. The studies that had not numerically specified the level of health literacy in adult diabetic patients were excluded. Duplicated results, irrelevant results, conference abstracts, proceeding papers, books and editorial letters were excluded.The full text of the eligible articles was assessed by two independent project collaborators. The two researchers also assessed the quality of the articles independently based on CASP tools for evaluation of cross-sectional studies. Articles answered “yes” by both of two authors in the first two questions and got at least five” yes “from 8 other questions, were selected. The strengths and weaknesses of each article were assessed and noted. To minimize the risk of bias, a comprehensive search was carried out in various local and international databases.Data were extracted from the eligible articles entered into the study and included the first author’s name, publication year, city studied, type of questionnaires, gender, habitation, sample size and the mean score of health literacy. For the meta-analysis, the mean and standard deviation values were also extracted. Excel was used for data input and notifying other research team members.Ultimately, 17 articles published between 2012 and 2018  were incThe meta-analysis was performed in Stata-11.2 (Copyright 1985–2009) according to the mean command. Publication bias was assessed using the funnel plot drawn based on the data. Heterogeneity was assessed using the I-squared index . Data obtained from the female and male populations were separately included in the main meta-analysis process and the analysis of the subgroups, if available. The meta-analysis was carried out using the random-effects method, and a Forrest plot was drawn for each analysis. To pool the data obtained by different tools, the final score of each study was recalculated in the 0–100 range and included in the meta-analysis.Data pertaining to the sample population of 4115 assessed in these studies were analyzed. The smallest sample size belonged to Rafiezadeh et al  study n study (nP=0.177).The present study is the first systematic review and meta-analysis of the level of health literacy in diabetic patients in Iran. The results of the review of 17 articles revealed a mean health literacy score of 56.65 (out of 100) in Iranian diabetic patients, and since most of the studies had used a rating system of ‘adequate’, ‘borderline’ and ‘inadequate’ to rate the level of health literacy in their subjects  , the majThis result agrees with the findings of a study conducted in Pakistan (a neighboring country of Iran), in which health literacy was inadequate in 67.15% of the patients, which means that the majority of the diabetes patients had poor health literacy . In a stIn the US, to compare health literacy in older diabetic patients and older healthy adults showed that poor health literacy was higher in older male diabetic patients (10.1%) compared to healthy older men (9.3%), which also applied to women (14.7% vs. 6.1%) . Most diHowever, the present findings disagree with the results obtained in Sweden, in which more than half of diabetic patients had adequate functional health literacy . Better The present findings showed that the mean health literacy score was higher in diabetic men (50.06) compared to diabetic women (47.97) although the difference was not significant; in other words, men have higher levels of health literacy. Not many studies have yet been conducted on the differences in the health literacy of diabetic patients in terms of gender, but the few studies conducted on this subject have produced similar results to the present study. In a study conducted in Pakistan  to compaAlthough the differences were not significant, the ratio of men with high health literacy was greater than the ratio of women with high health literacy, which concurs with the present findings . AlthougIn the present study, the PRISMA guidelines were used for the research design and the systematic review steps. To the researchers’ knowledge, this study is the first systematic review and meta-analysis of health literacy in diabetic patients in Iran.This analysis examined cross-sectional studies and therefore could not assess the causal relationship between health literacy and diabetes. The majority of the studies entered into the meta-analysis had not investigated the confounding factors affecting health literacy levels, and their results may, therefore, be biased. There could be some selection bias in some of the studies entered into the meta-analysis due to certain confounding factors or factors affecting health literacy not investigated in those studies, although the overall selection bias and its effect on the results of the meta-analysis cannot be accurately assessed. The dissimilar questionnaires used in the reviewed studies was another limitation of this study due to different scoring system in the studies. Although attempts were made to resolve this issue by recalculating the scores obtained from the different questionnaires (range:0–100), the details examined in each questionnaire were unique, and this limitation should be considered in the interpretation of the results.Health literacy is not high in Iranian diabetic patients and is rather inadequate in most of them. Moreover, diabetic women have lower levels of health literacy compared to diabetic men. Due to the importance of health literacy in the control of diabetes and its outcomes, it is necessary for the health authorities to take effective measures to improve the health literacy of diabetic patients. Policymakers and practitioners in the healthcare system must try on improving health literacy among patients with diabetes. As a suggestion, effective diabetic patient education and engagement will require some simplification, and diabetic patients need more convenient and meaningful access to their health information and to resources that will help them to make informed care decisions.Ethical issues  have been completely observed by the authors.


PDD patients showed increased N2 latency relative to controls, but no significant differences in VEP measures were found for patients reporting complex VH (CVH) (n = 17) compared to those without VH. Our VEP findings support previous reports of declining visual system physiology in PDD and some evidence of visual system differences between patients with and without VH. However, we did not replicate previous findings of a major relationshipVisual hallucinations (VH) are a common symptom of Parkinson's disease with dementia (PDD), affecting up to 65% of cases. Integrative models of their etiology posit that a decline in executive control of the visuo-perceptual system is a primary mechanism of VH generation. The role of bottom-up processing in the manifestation of VH in this condition is still not clear although visual evoked potential (VEP) differences have been associated with VH at an earlier stage of PD. Here we compared the amplitude and latency pattern reversal VEPs in healthy controls ( Visual symptoms are common in Parkinson's disease (PD), and include double vision, dry or painful eyes, poor contrast sensitivity, problems with color vision, and blurring of vision or lowered acuity –5. In 45Visual dysfunction in PD has been linked to the physical decline of retinal function over the course of disease development due to depletion of retinal dopamine , and retModels of VH in Lewy body dementias  have posited that VH are a product of the inefficient integration of multiple perceptual sub-divisions of the visual system including retinal input , 18. HeaIn this investigation we sought to characterize the components of early bottom-up processing in PDD patients, using the pattern reversal visual evoked potential, and to relate the response features to the complexity of the VHs experienced. Based on available evidence of physiological decline in PDD we predicted that we would observe a general reduction in the amplitude of the VEP components, as well as an increase in the P1 latency . In addiA total of 21 healthy controls, and 38 Parkinson's disease with dementia (PDD) patients were recruited from the North East of England. Ethical approval was granted by the Newcastle National Health Service (NHS) Health Research Authority (HRA) . The diagnosis of PDD was confirmed by two independent and experienced clinicians  and met with the standards described in the international PD diagnostic criteria . ParticiAll participants were assessed on their level of global cognitive function using the Mini Mental State Exam . Participants with minor VH  but no complex VH in the last month were included in the PD-NCVH group. This distinction was made due to the different etiologic basis to CVH even though minor VH typically precede CVH. Patients in this study map onto the same categories used in previously published research from our lab [see .Signal processing and measurement was performed using Matlab v2012a , with the EEGLab , ERPLab To account for individual variance in the timing of synaptic communication the VEP components were measured within windows defined by the global field power (GFP) for each individual. The VEP components elicited three GFP maxima following stimulus presentation, each of which was used as the center point for the corresponding component window (GFP maxima ±10 ms). The occipital ROI was defined by measuring the amplitudes of the P1 component for the grand average of the control data set and using the 20 electrodes with the greatest amplitude as the limit for the ROI. Individual subject measurements of peak latency and mean amplitude were taken from the average VEP waveform within the occipital ROI. To account for potential inter-ocular latency differences, we estimated the difference between P1 peak latency measurements for the left and right eyes. Three separate recordings were taken from each participant: viewing with both eyes; viewing with left eye; viewing with right eye. The three recordings were used to help screen for inter-ocular variations that could have indicated undocumented eye disease. The analyses were performed using the both eyes recording.t-tests. We compared the measurements of amplitude and latency separately for each component using univariate analysis of variance controlling for age and interocular latency difference between the left and right eyes. As further validation of the findings, we expanded our model to include UPDRS, CAMCOG, and L-Dopa dose as covariates. Effect sizes were estimated using the partial eta squared measure (η2). To explore the relationship between the variance within our physiological measurements and VH experience in the hallucinating PDD group, we performed parametric correlations between each VEP measurement and NPI hallucination score  and NPI hallucination severity. To help identify any variance in our measurements accounted for by clinical and/or demographic factors we performed additional parametric correlations between the VEP measurements and each value. To investigate the contribution of the minor VH, all the above-mentioned tests were explored with regrouping PDD-NVH vs. PDD-VH. Significance for all tests was determined using an alpha criterion of p < 0.05, and Bonferroni corrected for multiple comparisons . Where appropriate un-corrected correlations are reported to highlight trends within individual results.All statistical tests were performed using the Statistical Package for the Social Sciences . For all comparisons the data were inspected for violations of normality using the Shapiro-Wilk test due to it being more sensitive to small sample sizes. Demographic and baseline factors were compared using independent samples p = 0.09) or levodopa dose (p = 0.27) between the PDD-CVH and PDD-NCVH groups. PDD patients displayed a significant reduction in global cognitive function, UPDRS motor score relative to controls, with the PDD-CVH group global cognitive function and motor function were significantly worse when compared to the PDD-NCVH group. The NPI recorded the severity of hallucinations as mild in 29.4% (5 of 17) PDD-NCVH which were phenomenologically classified as Illusions , presence , shadow , and simple  by the NEVHI. Further stringent grouping into PDD_NVH dropped the reporting of mild hallucinations to 10%.Demographic results are summarized in Cataracts were reported by 20%  of the recruited participants while 19% of the participants had cataracts removed . Other ophthalmological history reported include glaucoma by two participants , macular degeneration by one participant (HC 1.7%), and laser treatment (HC 1.7%).p = 0.001) measurements of visual acuity. As expected, PDD-CVH patients showed a characteristic significant increase in the number of false perceptions (p = 0.047) reported during the pareidolia task compared to PDD-NCVH patients. Interocular latency differences were significantly higher in PDD-CVH compared to the PDD-NCVH (p = 0.028) group.Visual acuity and perceptual scores are summarized in Amplitude N1: −0.844 ± 0.67 vs. −1.27 ± 0.93, P1: 2.34 ± 1.57 vs. 3.61 ± 2.55, N2: −1.12 ± 1.02 vs. −1.64 ± 1.44; Latency N1: 91.79 ± 9.60 vs. 88.28 ± 8.62; P1: 127.21 ± 6.96 vs. 124.50 ± 7.31, N2: 175.54 ± 14.84 vs. 162.26 ± 8.98), although this was only significant for P1 and N2 components. A visual representation of the VEP is presented in p = 0.210; P1: p = 0.120), except N2 latency . A post hoc Bonferroni comparison indicated that N2 latency in controls was significantly less than PDD-NCVH group (p = 0.02) and PDD-CVH (p = 0.018), but the N2 latency did not differ between the CVH and NCVH group while controlling for age and interocular latency differences. Further validation result indicates no significant effect between PDD_NCVH and PDD_CVH on latency and amplitude of N1, P1, and N2 components even after controlling for UPDRS, CAMCOG, and L-Dopa dose along with age and interocular latency.Amplitude tended to be smaller, and latency later in PDD vs controls (Post hoc Bonferroni comparison indicated that N2 latency in controls was significantly less than PDD-NVH group (p = 0.029) and PDD-VH (p = 0.001), but the N2 latency did not differ between the VH and NVH group. The regrouping of minor VH into the PDD-VH group shows a trend toward significant difference for the N1 (p = 0.072) and P1 (p = 0.099) amplitude.Additional analysis with a stringent regrouping of PDD-NVH and PDD-VH show similar results  as in Fir = −0.492, p = 0.045) and P1 amplitude in PDD-CVH patients .Clinical correlation of VEP components for latency and amplitude are shown in r = −0.407, p = 0.028) and N2  latency in PDD patients and was also significant for N1 latency in PDD-CVH patients . False perception in Pareidolia tasks demonstrated significant positive correlation with N1 amplitude in PDD-CVH  patients. Interocular latency showed no significant correlations with NPI hallucination severity , and NPI hallucination frequency .Minimum angle of perception demonstrated significant negative correlation with N1  and PDD-NCVH patients , TMT-A with P1 latency in PDD-NCVH  patients; and categorial fluency scores with all VEP latency components in PDD patients  followed with latency significance in PDD-CVH patients  and PDD-NCVH patients .Executive scores such as CAMCOG Executive demonstrated significant correlations with N1 amplitude in PDD patients r = −0.536, p = 0.026) and P1 latency with age . Correlation analysis with regrouping into PDD-NVH and PDD-VH as shown in In PDD-CVH patients, significant negative correlation was found for N2 amplitude with the duration of PD  are both linked to physical properties of the stimulus such as luminance, brightness, position on the retina, and associated attentional demands –60. FurtSignificant differences in the interocular latency between the CVH and NCVH suggest a difference in low level visual processing between the two groups. Intact low-level visual processing is required to differentiate the different types of inputs projected onto the retina. These interocular differences might be explained by changes within the eye, such as retinal thinning, which is well documented in PD patients (and more prominent in those that experience VH) . It is kIn patients with PDD there are often abnormalities associated with the structure and function of the retina, including changes in morphology and dopaminergic signaling , which hr = −0.555, p = 0.021). The inclusion of minor VH into the PDD-NCVH group potentially explains the correlation with P1 amplitude. Moreover, attentional and perceptual measures (angle detection and pareidolia task) were related to N1 latency and N1 amplitude in patients with complex VH. These reinforce the argument that whilst bottom up dysfunction places individual at risk of VH, it is disruption of these top down processes which are needed for the manifestation of hallucinations.However, our findings are at odds with our hypothesis based on previous work of increased P1 latency  in PD wiGiven the extent of association between the VEP components and major clinical measurements in our study, it is clear that there is a deliberate pattern of communication that occurs between the primary visual cortex and both its bottom-up and top-down projections. However, our experimental design is limited in the scope to which we can draw conclusions on the nature of pathological change within the executive system and the link between attention and passive perception of the VEP stimulus.In the context of a mechanism for VH, our sample results suggest that bottom-up processing is not differentially affected between hallucinators and non-hallucinators. This is not unexpected as it follows that in an integrative model of VH we would expect VH content to stem from the interaction of impaired bottom-up processing with dysfunctional top-down control of perception. In our data, complex VH were associated with greater decline in CAMCOG and UPDRS scores, as well as increased numbers of pareidolia relative to patients without complex VH. The divergence in the cognitive and perceptual profile of the groups supports a deteriorated capacity for effective top-down control, which in this model would be a pre-requisite factor for the generation of complex VH. However, these measures were not significantly correlated with the amplitude or latency of the VEP component measurements suggesting that conduction velocity and basic processing of visual feature information is unimpeded by the integrity of detailed perceptual processing. Our findings suggest that the integrity of visual processing has a complex interaction with the higher perceptual function. To build a stronger mechanistic model of this interaction, future work should study the VEP at its cortical sources, whilst also incorpating structural and functional magnetic resonance imaging data.Within the integrative model of complex VH in Lewy body dementias the importance of bottom-up processing is thought to be its influence on the generation of proto-objects , 18. TheThere are several limitations. Firstly, the sample size within this study was relatively small, which does not allow for strong conclusions. In future, we will use the data to design larger confirmatory studies. Secondly, we used only a single subjective measure for VH severity. The NPI items are typically collected from the carers of the patient, and do not ask questions about the content of the hallucination. It thus remains possible that there could be a relationship between visual health, bottom-up processing, and VH content that could be accessed by quantifying a scale such as the North East Visual Hallucination Interview (NEVHI) . FurtherIn summary, PDD patients demonstrated a diminished profile for visual information processing by way of lowered acuity and reduced visual integrity. This was partially reflected in the outcome of the VEP components, although the broad lack of significant differences between PDD-CVH, PDD-NCVH, and healthy controls implies that bottom-up visual information processing remains reasonably intact. Our findings suggest that while bottom-up processing is not grossly affected by the stage of PDD there is a complex interaction between cognitive, visual, and physiological aspects of visual processing in the generation of VH. To advance our understanding in this field, our findings also support a separation between bottom-up information processing and the mechanism of complex VH generation, and instead imply that the reduced visual integrity might act to place the individual in an at risk state for the development of hallucinations in patients with a deteriorated cognitive profile. Thus, a main contribution to this field of work, lies in redirecting research from low level visual dysfunction to higher level processes. Future work should focus on a multimodal approach to understanding the interactions between top-down and bottom-up perceptual circuitry and how this is impacted by PDD neuropathology.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Newcastle National Health Service (NHS) Health Research Authority (HRA). The patients/participants provided their written informed consent to participate in this study.NM, SG, LR, MRB, CA, DC, and J-PT contributed to the conception and organization of the research. NM and AK participated in the execution and data collection. NM, PU, and MF designed and implemented the data analysis and interpretation. NM and PU wrote the first draft of the manuscript. RG implemented the data analysis and interpretation for the revision. All authors approved the final version of this manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer DF declared past co-authorship and research collaboration with several of the authors DC, J-PT, PU, MF to the handling Editor.


Pelvic fractures, especially when unstable, may cause significant haemorrhage. The early application of a pelvic circumferential compression device (PCCD) in patients with suspected pelvic fracture has established itself as best practice. Ambulance services conduct corresponding performance measurement. Quality indicators (QIs) are ideally based on high-quality evidence clearly demonstrating that the desirable effects outweigh the undesirable effects. In the absence of high-quality evidence, best available evidence should be combined with expert consensus.The aim of the present study was to identify, appraise and summarize the best available evidence regarding PCCDs for the purpose of informing an expert panel tasked to evaluate the validity of the following QI: A patient with suspected pelvic fracture has a PCCD applied.A rapid review of four databases was conducted to identify relevant literature published up until 9 June 2020. Systematic reviews, experimental, quasi-experimental and observational analytic studies written in English were included. One author was responsible for study selection and quality appraisal. Data extraction using a priori extraction templates was verified by a second reviewer. Study details and key findings were summarized in tables.A total of 13 studies were assessed to be eligible for inclusion in this rapid review. Of these, three were systematic reviews, one was a randomized clinical trial (crossover design), two were before-after studies, and seven were retrospective cohort studies. The systematic reviews included mostly observational studies and could therefore not be considered as high-level evidence. Overall, the identified evidence is of low quality and suggests that PCCD may provide temporary pelvic ring stabilization and haemorrhage control, although a potential for adverse effects exists.Given the low quality of the best available evidence, this evidence would need to be combined with expert consensus to evaluate the validity of a related quality indicator before its implementation. Exsanguinating haemorrhage is one of the leading causes of death in patients suffering major trauma . Besidessuspected pelvic ring fracture based predominantly on the mechanism of injury and any visual signs such as bruising around the pelvis is increasingly being advocated as best practice in the prehospital care [Historically, prehospital management in the form of pelvic binding was performed when inspection and palpation of the pelvis revealed deformity, instability and pain. However, the diagnostic reliability of identifying a pelvic fracture by physical examination is questionable, particularly in the patient with decreased level of consciousness –12. Furttal care –15. As ttal care –15. As stal care .A QI is an explicitly defined and measurable aspect of health care services indicative of a desirable structure, process or outcome . That isHowever, this prominent advantage that RAM has over other consensus processes may also be a deterring factor. A systematic review is conducted to provide the expert panel with all pertinent information that will guide evidence-based decision-making . Due to https://www.aspireproject.net).The aim of the present study was to apply rapid review methods to identify, appraise and summarize the best available evidence regarding PCCDs and in doing so provide an evidence summary to inform an expert panel tasked to validate the QI used for the measurement of prehospital trauma care quality. More specifically, this rapid review aimed to investigate current evidence for the effectiveness and safety of non-invasive PCCDs. This study forms part of a larger research project aimed at developing and testing prehospital care quality indicators for the Australian setting  methodology . The scoGuided by the approaches to rapid reviews and evidence summaries by JBI and the World Health Organization (WHO) , a rapidPopulation: Trauma patients with suspected or confirmed pelvic fracture(s)Intervention: Application of a PCCDComparison: No intervention (or wrapping sheet)Outcomes: Clinical endpoints and/or adverse effectsContext: Emergency trauma careStudy designs: Systematic review, experimental and quasi-experimental studies, and observational analytical studies.One author (RP) carried out the literature search, screened the results by title and abstracts using Covidence , and performed full-text review of shortlisted articles based on pre-defined inclusion criteria. The pre-defined inclusion criteria were based on the following population, intervention, comparison, outcome, context, study design (PICOCS) criteria:Following the search, studies selected for retrieval were assessed for internal validity using applicable JBI critical appraisal checklists . This riData were extracted by one author (RP) and verified by another (RM) using a standardized extraction template created a priori in Microsoft Excel for Mac 2019 . For systematic reviews, the following data were extracted: author(s), year of publication, number of studies included their designs, whether meta-analysis was performed and key findings. For primary research studies, following data were extracted: author(s), year of publication, study objectives and design, number of participants, participant characteristics, device(s), and key findings. Each systematic review and primary study was assigned a level of evidence in accordance with JBI .A total of 1194 potentially relevant records were identified through database searching (Fig. Three systematic reviews –31, one Tables Included studies which address the biomechanical effects of PCCDs indicate the devices facilitate a reduction in pelvic volume and improvement in biomechanical stability , 33, 34.The clinical bottom line is that there is no high-level evidence that the application of a PCCD reduces haemorrhage or mortality in suspected or confirmed pelvic fractures. The best available evidence suggests that a PCCD provides temporary pelvic ring stabilization and can serve as an adjunct to early haemorrhage control. The application of PCCD carries a certain potential for iatrogenic harm, however, clinical benefits seem to outweigh this risk. Given the limited data to show undisputable benefit, further research on this topic is needed. In particular, there is a lack of research in the prehospital arena as well as studies which examine the effectiveness and safety of PCCDs in specific pelvic fractures types according to Young-Burgess classification as this mechanistic classification is more practical for the prehospital context.Patients suffering pelvic fractures are at risk of severe and potentially life-threatening bleeding , 44. Espquality indicator and what distinguishes it from a performance indicator – a QI has scientific credibility, i.e. there is evidence and/or expert consensus that the indicator can be used to make a judgement about quality [Health care quality measurement and improvement are complex endeavours. Considering the resources health care organizations invest in them and the potential adverse consequences if conducted poorly , 50, it  quality . Not onl quality . This pr quality , 56. Thi quality , 58.There are several significant limitations that the omission or simplification of systematic review methods induce. The search strategy was limited by restricting the number of databases consulted, excluding all non-English language papers, using more specific search terms and excluding lower levels of evidence. Databases were restricted in line with guidance for rapid reviews and evidence summaries by JBI. Whilst systematic reviewer and meta-analysts should conduct exhaustive searches in multiple databases, rapid reviews commonly omit several databases to focus on those expected to yield best results. This approach is justifiable by studies which have demonstrated only marginal improvement in relevant results by increasing the number of databases searched , 60. TheThis study provides an example of how the timely knowledge synthesis through the deployment of a streamlined rapid review approach can inform QI development. More specifically, the study has reviewed best available evidence regarding the application of a PCCD in patients with suspected pelvic fractures and summarized this into a synopsis for feasible consideration by an expert panel tasked to assess the validity of a related QI. The process of applying a PCCD is not clearly linked to desirable clinical outcomes and does carry a potential for iatrogenic harm. Nevertheless, the clinical benefits seem to outweigh risks. This best available evidence is of low quality strengthening the need for its perusal by an expert panel before possible QI implementation.Additional file 1.


Real-world evidence (RWE) refers to observational health care data beyond clinical trial data. It holds the promise of transforming health care as a new form of evidence to support decision makers in making decisions when developing and regulating medicines. As the importance of RWE is recognized by industry and regulatory bodies, teaching RWE becomes an important matter to evaluate and refine in order to develop future researchers and stakeholders who can better integrate RWE into the routine development of medicine.The aim of this review is to understand how RWE is currently being taught. From this landscape study, the insufficiencies of the current education of RWE can be identified and subsequently inform future education policies around RWE and its subfacets.We will search MEDLINE, EMBASE, PsycINFO, Healthcare Management Information Consortium, Cochrane, and Web of Science for published studies using a combination of keywords and subject headings related to RWE and education. In addition, a Google search to identify grey literature will be conducted. Two authors will independently screen the titles and abstracts identified from the search and accept or reject the studies according to the study inclusion criteria; any discrepancies will be discussed and resolved. The quality of the included literature will be assessed using the Critical Appraisal Skills Programme systematic review checklist.Data from eligible publications will be abstracted into a predesigned form in order to better understand the current state of education of RWE and inform future RWE education directions and policies.The subsequent systematic review will be published in a peer-reviewed journal.PRR1-10.2196/16941 Real-world evidence (RWE) is a subset of evidence-based medicine that refers to health care information gathered through means outside of the typical clinical research settings. Evidence-based medicine (EBM) is the use of best available clinical evidence from systematic research combined with clinical expertise to deliver the best possible clinical care to patients ,2. SinceRegulatory bodies around the world are gaining interest in RWE. Notably, the US Food and Drug Administration has recently announced a $100 million project to build a modern system that will gather RWE from approximately 10 million individuals , and theThe anticipated importance of data collection and analysis of RWE in the future of clinical trials and development of medicines is evident. In order to meet the future demands of RWE researchers in terms of realizing the true potential of RWE in transforming health care, it is important to educate stakeholders such as researchers, clinicians, and policy makers in RWE in an appropriate way.EBM has long been taught to medical professionals, including clinicians and nurses -12, and This systematic review aims to answer the following research questions:What are the current methods used to teach RWE, and what are the effects of those methods?Who are the stakeholders teaching and learning about RWE?This systematic review will be conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines . The proIn accordance with PRISMA Protocols (PRISMA-P) checklist recommendation, the inclusion criteria for this protocol are in accordance with participants, interventions, comparators, and outcomes (PICO). Details of PICO to be included in the review are described in Population:Participants with real-world evidence teachingIntervention:Any form of real-world evidence teachingComparator:No real-world evidence teachingOutcomes:Learner-focused outcomes such as attitudes, cognitive changes, learner satisfactionStudy type:Any study type (study type will not be subjected to any restrictions)Must describe relevance to real-world evidence and its application in health careMust describe a teaching methodEnglish-language publicationsEducation methods that do not describe their relevance to RWE and its applications to health care will be excluded to limit the scope of the review to RWE-focused education and courses. Websites and articles describing RWE  will be excluded as there are no methods of teaching included. Studies not published in English are excluded due to the language barrier.The following databases will be searched: MEDLINE, EMBASE, PsycINFO, Healthcare Management Information Consortium, Cochrane, and Web of Science. In addition, a Google search for grey literature such as blog posts, opinion pieces, press releases, and online courses will be conducted. Online course platforms such as Coursera, edX, FutureLearn, and OpenClassrooms will be searched to identify relevant courses. Real-world evidence:Real world evidence, RWE, big data analytics, real world data, electronic health record*Teaching:Medical education, medical student*, medical curriculum, medical school*, health professionalsEndNote X8 software  will be used for the removal of duplicates. Two reviewers will independently check each article to minimize bias using the Cochrane Collaboration’s risk of bias tool as described in the Cochrane Handbook for Systematic Review of Interventions . All incEligible sources will subsequently be reviewed in detail, and key relevant challenges will be extracted, categorized, and recorded into a predesigned Excel spreadsheet (Microsoft Corp). A sample data abstraction form can be found in A sample search was conducted using PubMed, and the sample search string returned 943 results:  AND . The search string will be further fine-tuned in the review.This study will offer a comprehensive overview of how RWE is taught to different stakeholders of the research and application of RWE in health care. However, traditional means of teaching, such as university lecturies, may not be published and hence may be underrepresented in this protocol.This protocol will be executed in 2020 and published in a peer-reviewed journal in accordance with PRISMA guidelines. Any deviations in the execution shall be noted in the subsequent systematic review publication. The findings from this review will be used to inform the education strategy of RWE.