The new ICD-11 introduces a fully dimensional classification of personality disorders representing a fundamental change in personality disorder diagnosis with major implications for clinical practice and research. The new system centers on the evaluation of the severity of impairment in the areas of self and interpersonal functioning. This focus on personality functioning converges with long-standing psychoanalytic/psychodynamic conceptualizations of personality pathology. In a detailed conceptual analysis and review of existing empirical data, points of convergence and notable differences between major exponents of the psychodynamic tradition—object relations theory as developed by Kernberg et al. and the Operationalized Psychodynamic Diagnosis—and the ICD-11 system are critically discussed. Personality functioning can be considered to be the current “common ground” for the assessment of personality disorders and constitutes a considerable step forward in making personality disorder diagnosis both clinically meaningful and suitable for research purposes. The upcoming 11th revision of the ICD includes “the most radical change in the personality disorders classification history” . The “trOne of the key issues is the new focus on personality functioning as the essence of personality disorder classification. The ICD-11 fundamentally defines personality disorders by “problems in functioning of aspects of the self , and/or interpersonal dysfunction ” . This deImpairment in personality functioning constitutes the core component of personality disorders distinguishing it from healthy personality as well as from other forms of mental disorders, thus demarcating the “genus of personality pathology” . ICD-11 This article focuses on a discussion of the newly introduced severity measurement of the ICD-11 classification of personality disorder from a psychodynamic viewpoint and compares it with established psychodynamic assessment instruments and their underlying concepts. A comprehensive analysis of the advantages and limitations of the complete ICD-11 system including a discussion of the complex issue of pathological personality traits is beyond the scope of this article.The focus on self and interpersonal functioning as the central tenet of personality pathology is shared by many theoretical orientations and evidence-based treatments for personality disorders . NotablyPersonality functioning as defined in the ICD-11 and DSM-5 is related to the psychoanalytic notion of personality structure or organization . Personality structure or organization are theoretical concepts characterizing the fundamental “operating system” or underlying, stable configuration of personality, which in turn manifests itself in specific modes of personality functioning which can be phenomenologically observed and assessed. The precursors of the modern psychoanalytic understanding of personality structure can be found in Freud's “structural theory” of the psyche as composed of Id, Ego, and Super-ego and the analysis of the interaction between these entities in psychic functioning . AnotherArguably, the most important contemporary psychoanalytic model of personality structure was developed by Otto Kernberg et al. over the past decades –16. Kernvia an assessment of personality styles based on underlying dynamic themes and conflicts , a collaborative effort for the comprehensive, psychodynamically informed assessment of personality, –21. The onflicts , 22, 23.onflicts .In the German-speaking world, the most important psychodynamic model for the assessment of personality structure is provided by the Operationalized Psychodynamic Diagnosis (OPD-2) . ConceptThere is considerable overlap between the domains of personality functioning deemed relevant by the ICD-11 and psychoanalytic conceptualizations of personality. Besides considering the domains of self- and interpersonal functioning for the evaluation of personality disorder severity, the ICD-11 also takes into account emotional, cognitive, and behavioral manifestations of personality dysfunction. This includes the “Accuracy of situational and interpersonal appraisals, especially under stress,” which ranges from adequate reality testing to dissociative or psychotic-like perceptions and beliefs in the most severe cases. The capacity for reality testing also constitutes a core element of the level of personality organization as developed by Kernberg, with impairment in reality testing being the hallmark of a psychotic functioning, and a propensity for paranoid reaction with otherwise intact reality testing being indicative of borderline personality organization , 26, 27.Despite the significant similarities there are also noteworthy differences. Generally, the psychodynamic models encompass a broader definition of personality functioning and consider several further dimensions essential for the accurate appraisal of personality organization. Some of these domains of psychodynamic personality functioning are evaluated in the trait section of ICD-11, including aggression against self and others. Other dimensions are not represented in the ICD-11, notably including the predominant quality of defense mechanisms and the level of moral functioning. The mechanisms used by an individual to defend against unbearable feelings and mental states range from mature and adaptive processes like intellectualization and repression to primitive and maladaptive ones such as splitting and projective identification. These immature mechanisms are deemed pathognomonic for personality pathology and provide clinically relevant information for appropriate treatment planning and therapeutic technique , 30. AddAnother remarkable facet is the almost complete absence of any mention of sexuality in the ICD-11 guidelines. From a psychoanalytic point of view, sexuality constitutes a highly relevant dimension of object relations/interpersonal functioning and difficulties in the establishing mutually gratifying sexual relationships are considered to be core features of personality pathology and should be part of a comprehensive assessment. The ability to integrate intimacy and sexuality in a trusting relationship is one of the cornerstones of a healthy personality .One of the key differences between a psychoanalytic approach to personality disorder assessment and the ICD-11 proposal is that the first one is grounded in a comprehensive theoretical system as opposed to the atheoretical, predominantly descriptive ICD-11 system , 34. ObjFrom a psychodynamic viewpoint, the inclusion of severity of impairment as the core feature of personality disorder classification represents a major improvement over previous classification systems. Multiple studies have confirmed global severity as the single most important predictor for current and future dysfunction –39. The The general description of the different levels of personality functioning are very similar between the ICD-11 system and psychodynamic diagnostic approaches providing convergent validity to the model. However, as noted above, the ICD-11 system provides a purely descriptive approach and in line with its overarching goals does not include any information of etiology and pathogenesis for the different levels of personality pathology. It has been suggested that this atheoretical approach leads to an overemphasis on readily observable behavioral symptoms while somewhat neglecting the intrapsychic dimension which psychodynamic approaches deem crucial for personality pathology. Compared to the DSM-5, it has been noted that the ICD-11 personality classification system predominantly focuses on externalizing behavior and the “dangerous patient” as a criterion for the assessment of personality pathology , 41. ArgPsychodynamic approaches consider the intrapsychic dimension an irreducible aspect of personality functioning which is reflected in the detailed assessment strategies of the presented models. They each provide a theoretical framework for understanding the developmental pathways leading to the different levels of personality organization and thus go beyond a purely descriptive approach. Notably, object relations theory sees Borderline personality organization as the outcome of the predominance of excessive splitting mechanisms, which impede the development of an integrated view of oneself and significant others, leading to the observable deficits in self- and interpersonal functioning. The predominance of these splitting mechanisms is in turn associated with constitutive (genetic) factors linked to excessive levels of aggression and to environmental containment deficits of primary attachment figures. In normal development, splitting mechanisms gradually diminish and more mature modes of defense mechanisms  take center stage leading to increased identity integration . TherefoOne of the central purposes of a diagnostic classification system is to inform clinical decision making including risk assessment and differential treatment planning . The ICDHowever, ICD-11 remains at its core an atheoretical  and predominantly descriptive diagnostic system, therefore arguably reducing its immediate clinical utility . In contFurthermore, the more comprehensive nature of the dimensions of personality functioning assessed in object relations theory and OPD consequently provide more extensive clinically relevant information. For example, the level of moral functioning is considered to be a crucial factor for prognosis and treatment choice with antisocial personality functioning indicating a particularly poor prognosis. Equally, the predominance of immature defense mechanisms will have an impact on all stages of treatment and its assessment will help the clinician to better understand the often rapidly shifting and apparently chaotic behavior of patients suffering from severe personality disorder.Notably, the assessment of the severity of personality disturbance constitutes only one step of the ICD-11 diagnostic procedure, and careful consideration needs to be given to the aptitude of the supplementing trait model to provide a clinically meaningful picture of the individual personality style or type of a patient , 47. ManOf course, the most important objection to a more comprehensive model of personality functioning is the limited time available in daily clinical practice. This was a major focus of the ICD-11 working group in developing the new system and it certainly is a crucial factor .While a number of self-report and interview-based instruments have already been developed for the AMPD of DSM-5 , no offiBoth psychodynamic approaches covered here, object relations theory and OPD, provide both, self-report and interviewer-based assessment instruments. The Structured Interview for Personality Organization . EspeciThe influence of contemporary psychoanalytic object-relations theory, most prominently advocated by Kernberg et al., on the development on the AMPD of DSM-5 has been frequently highlighted . While tVB and SD conceptualized the manuscript. VB wrote the first draft of the manuscript. SD substantially revised the initial draft. Both 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.


To encourage multidisciplinary team learning by introducing Child & Adolescent Mental Health (CAMHS) in-situ simulation training.To provide focused Human Factors feedback through the expertise of senior airline pilots.The integration of the WingFactors in-situ simulation programme to multiple departments at Whittington Health NHS Trust has transformed the education landscape. The programme has received unanimously positive feedback, and the potential benefits for not only physical, but also mental health training, have been quickly recognised. A total of 90 simulations have been performed. A number of CAMHS scenarios have been designed with the primary aims of encouraging multidisciplinary training and increasing the focus on Human Factors in Psychiatry.Simulation scenarios were performed in real clinical environments with primed actors, thus enabling high-fidelity in-situ simulation. Immediate ‘hot’ debriefs were delivered by clinical faculty and uniformed airline pilots, with emphasis on psychological safety to encourage participation from all team members. The key learning points were then detailed in written documents and circulated to the wider team as a valuable learning resource.The first CAMHS simulation involved the acute management of a collapsed patient in the Emergency Department toilet, with a ligature tied around her neck and accompanied by a distressed patient. Another scenario addressed de-escalation techniques when dealing with a patient presenting with an overdose, who was threatening to leave the ward and posing potential risk to herself.The nature of these in-situ simulations enabled the multidisciplinary team to analyse practical considerations in the management of acute clinical situations. Scenarios were designed to focus on areas which had been identified as needing improvement for patient safety.The observations provided by airline pilots increased the focus on Human Factors training. A number of key themes were identified, including the importance of effective team-briefing, distraction management and task allocation. This is of particular significance when managing a distressed patient and anxious relative, in a busy high-stress clinical environment.In-situ simulation is a newly emerging concept in the field of Psychiatry, and the success of this programme has been highlighted through consistently positive feedback from participants, and nomination for the HSJ Award (Best Education Programme 2021). The involvement of airline pilots has promoted collaborative learning amongst the multidisciplinary team, and increased the focus on Human Factors in Psychiatry, clearly demonstrating the value of in-situ simulation training in this field.


Increased demand for in vitro fertilization (IVF) due to socio-demographic trends, and supply facilitated by new technologies, converged to transform the way a substantial proportion of humans reproduce. The purpose of this article is to describe the societal and demographic trends driving increased worldwide demand for IVF, as well as to provide an overview of emerging technologies that promise to greatly expand IVF utilization and lower its cost. Since its clinical introduction in 1978, in vitro fertilization (IVF) has redefined the ability of the human species to procreate. Initially developed to aid the infertile couple, clinical indications for IVF have since rapidly expanded to include medical and genetic conditions, as well as fertility preservation. While IVF access and utilization vary widely globally, the practice now accounts for the conception of over 5% of all newborns in some European countries where IVF is more affordable and/or is covered by insurance , 3. InfeChanging demographics and societal norms are driving increased IVF utilization. Improved access of women to educational and career opportunities, as well as effective contraception has contributed to progressively delayed childbearing and overall lower fertility rates worldwide. In many countries and in virtually all US states, fertility rates are now substantially below population replacement levels of 2100 births per 1000 women. In a growing number of metropolitan areas as well as in entire highly developed countries, the average age at first birth now exceeds 30 years, that is, well beyond peak fertility which occurs in the mid 20s. Inadvertently, a growing proportion of women is delaying childbearing to a point where age-related fertility decline contributes to the prevalence of infertility and to increased demand for fertility treatments including IVF and oocyte cryopreservation. These trends will likely accelerate due to the socio-economic impact of the COVID-19 pandemic, which has forestalled new family formation. Indeed, preliminary data from Chinese cities indicate that birth rates declined between 9 and 32.6% in the second half of 2020 compared with 2019, reflecting effects of the COVID-19 lockdowns . Declinifertility is a basic human right is just starting to gain traction and is sure to accelerate wider adoption of such policies [The utilization of IVF is closely linked to its affordability and accessibility . Indeed,policies . AnotherThe distribution of established fertility clinics thus closely corresponds to affluent metropolitan areas with the lowest fertility rates and the most advanced maternal ages at birth. Conversely, less densely populated and less affluent areas are characterized by relatively poor IVF access. Moreover, racial and ethnic disparities in the utilization of IVF, largely due to socio-economic factors, are inversely correlated with fertility rates . An addiThe IVF process is complex and stressful, it consists of multiple steps which can take up to several months to complete. The main reasons patient prematurely drop-out of IVF prior to achieving a pregnancy are the financial, physical, and psychological burdens of the treatment regimen . Here, wControlled ovarian hyperstimulation (COH) is performed to increase the number of oocytes available for IVF. COH involves multiple injections of gonadotropins and serial visits to the fertility clinic for the conduct of transvaginal ultrasound evaluations and the measurement of circulating hormone levels. It follows that COH is complex, time sensitive, and intensive. Various strategies intent on reducing the number of injections by utilizing long-acting gonadotropins or oral medications are already available and are gaining increased acceptance in the field for the treatment of select patient populations , 11. Simidentification and separation of sperm and oocytesfertilizationembryo cultureembryo selection for transfercryopreservation of surplus embryos and gametesPerhaps the most promising technological development that might democratize IVF access in the near-term is the automation and miniaturization of the IVF laboratory. Building, staffing, and manually operating an IVF laboratory account for much of the high cost, maldistribution in access, and variability of outcomes. The basic steps in the IVF laboratory include:Great progress has already been made towards the automation of these individual steps by way of new technologies. Still, the IVF process in its entirety remains highly manual. The altogether novel IVF lab-on-a-chip concept has the potential to revolutionize IVF by enabling the automation of virtually all of the steps involved in a single system –18.Microfluidics is defined as a multidisciplinary field of study and design whereby fluid behaviors are accurately controlled and manipulated with small scale geometric constraints that yields dominance of surface forces over volumetric counterparts. Past procedures in the IVF laboratory, though successful, apply a macroscale approaches to microscale cellular biological events . IntegraMicrofluidic sperm-sorting devices –21 and aMicrofluidic in vitro insemination has been demonstrated , whereasEmbryo culture has already been fully automated with use of time-lapse incubators which allow continuous monitoring of embryo development. Data generated from time-lapse incubators can be analyzed with machine learning to aid in the selection of embryos with the highest pregnancy potential –38. AddiFinally, cryopreservation of sperm, oocytes, and embryos has become the standard of care. Vitrification has become the dominant method for oocyte and embryo cryopreservation. While semi-automated/automated systems for oocyte/embryo vitrification have been reported and are now in early stages of clinical adoption –56, thesFigure Fertility preservation research has steadily increased our understanding of the mechanisms that govern folliculogenesis . The devPerhaps the most revolutionary concept in modern reproductive science is that of in vitro gametogenesis (IVG). IVG comprises various approaches, including organ culture systems, embryonic stem cells (ESC), induced pluripotent stem cells (iPSC), and spermatogonial stem cells (SSCs). Several of these approaches led to the creation of functional gametes in rodent models . JapanesThe existence of human oogonial stem cells (OSCs) capable of giving rise to new oocytes has been an area of some controversy for nearly a decade. Reports to the effect that cells isolated from human ovarian tissue using fluorescence-activated cell sorting and an antibody against the DDX4 protein constituted OSCs challenged the long-standing dogma that the ovarian reserve is finite , 72. MulSSCs constitute the progenitor cells in the process of spermatogenesis. As such, these cells are the focus of in vitro spermatogenesis (IVS) and in vivo restoration of male fertility. While IVS has been achieved in rodent models, it has proven far more difficult to realize in primate counterparts . One recThe convergence of IVF with reproductive genetics has been at the forefront of the field for the past few decades. The development of next generation sequencing has expedited the adoption of PGT of embryos with an eye toward detecting the presence of chromosomal abnormalities. Moreover, increased use of carrier screening of infertile couples has increased the use of PGT for monogenic diseases. As cost of carrier screening decreases and the number of detected mutations expands, a substantial new population of patients identified as carriers may pursue IVF with PGT to build their families. Indeed, population genomic screening of young adults may offer significant healthcare savings through the prevention of rare disorders and cancers . Future The growing utilization of IVF will transform the way a substantial proportion of the human species procreates. It is likely that in the near future, as many as 10% of all children will be conceived through IVF in many parts of the world. Given the rapid scientific and technological evolution of IVG and of reproductive genetics, it is imperative that both the public and regulatory bodies be engaged in establishing a framework for the ethical evaluation of emerging technologies –84. Such


Objective: We propose a MATLAB-based tool to convert electrocardiography (ECG) waveforms from paper-based ECG records into digitized ECG signals that is vendor-agnostic. The tool is packaged as an open source standalone graphical user interface (GUI) based application. Methods and procedures: To reach this objective we: (1) preprocess the ECG records, which includes skew correction, background grid removal and linear filtering; (2) segment ECG signals using Connected Components Analysis (CCA); (3) implement Optical Character Recognition (OCR) for removal of overlapping ECG lead characters and for interfacing of patients’ demographic information with their research records or their electronic medical record (EMR). The ECG digitization results are validated through a reader study where clinically salient features, such as intervals of QRST complex, between the paper ECG records and the digitized ECG records are compared. Results: Comparison of clinically important features between the paper-based ECG records and the digitized ECG signals, reveals intra- and inter-observer correlations of 0.86–0.99 and 0.79–0.94, respectively. The kappa statistic was found to average at 0.86 and 0.72 for intra- and inter-observer correlations, respectively. Conclusion: The clinically salient features of the ECG waveforms such as the intervals of QRST complex, are preserved during the digitization procedure. Clinical and Healthcare Impact: This open-source digitization tool can be used as a research resource to digitize paper ECG records thereby enabling development of new prediction algorithms to risk stratify individuals with cardiovascular disease, and/or allow for development of ECG-based cardiovascular diagnoses relying upon automated digital algorithms. I.Electrocardiography (ECG) is a diagnostic tool used by medical professionals to record the electrical activities of the heart There have been attempts to standardize ECG records, and as summarized in the review paper by Waits and Soliman To advance the digitization of ECGs, we build upon our previous work We propose the use of Optical Character Recognition (OCR) In addition, we present a semi-automated segmentation procedure using a method based on CCA to extract ECG row waveforms in the records. Moreover, the proposed CCA partly aids in character removal by discarding non-overlapping characters. While previous studies utilize a connected components based approach to extract ECG lead segments The second barrier is the lack of open accessible software for digitization of ECG records. This is hampered by the lack of generalizability across vendors of digital ECG systems To address this issue, vendor-specific information is bounded by a template. For example, ECG templates contain characteristic information, such as patients demographics , the locThe culmination of our effort is the realization of a tool for digitizing paper ECGs as an open source standalone executable tool with a graphical user interface (GUI) designed in MATLAB . To support the utility of the tool, ECG digitization results are validated through a reader study conducted at Emory University Hospital. Cardiologists (observers) exercised the tool to measure the correlation of the clinical features between the digitized ECG record and the paper ECG record using a kappa coefficient The remainder of the paper is organized as follows. II.This section describes the process of converting scanned paper ECG records in JPEG (Joint Photographic Experts Group) format into digitized ECG signals. Methods of optical character recognition (OCR) to extract patient demographic information and removal of ECG lead characters are also detailed.A.A typical ECG record is comprised of 12 ECG leads, superimposed on a background grid for ease of readability and clinical feature measurement . The proB.The preprocessing functions for a batch of scanned ECG records are described in the blocks of Step A . The scaNext, an automatic thresholding technique utilizing the histogram profile of the background gridlines is carried out on the portion of the ECG records containing the waveforms, based on our prior work C.bwconncomp and regionprops, respectively. Subsequently, the CCA based method results in a number of labelled connected components which need to be combined and reorganized into ECG row waveforms.Step B of the flowchart contains blocks describing the segmentation of ECG row waveforms in the binarized ECG records, using a CCA based method . The binThe reorganization of the ECG waveforms is complicated by the discontinuities in the ECG waveforms, which are in part attributed to thresholding and the extent of degradation of the ECG records. To overcome this, connected components within a fixed distance threshold are fused together. This distance threshold is set such that all the connected components belonging to the same ECG row waveform are combined. Having too large a threshold may lead to inclusion of stray pixels near the ECG signal, which may introduce distortions in the digitized ECG waveforms.The choice of the distance metric determines the computational efficiency of the digitization process. For example, using Hausdorff distance To further increase the computational efficiency of the digitization process, connected components whose number of pixels is lesser than a threshold, which is typically around 100 pixels, can be discarded. Inclusivity of a greater number of connected components lead to smoother ECG waveforms, ultimately leading to increased time for digitization of ECG records.Thus, the following three main parameters can be modified to efficiently identify connected components comprising ECG row waveforms: (1) the threshold distance between each of the connected components, (2) the metric chosen for distance computation between the connected components, and (3) the number of connected components retained for distance computation. These parameters are chosen to optimize digitization accuracy, and the connected components are designated to their corresponding ECG row waveforms . The ECGD.Step C utilizes optical character recognition (OCR) to identify characters to extract patient demographic data, and to removal of overlapping ECG lead characters. OCR utilizes correlation as a metric to identify text, using a predefined template-based library. MATLAB contains a built-in OCR application which facilitates the creation of custom OCR template-based libraries. The OCR application in MATLAB contains a predefined library of numeric characters (Zero - Nine), and the lower-upper cases of the English alphabet. The OCR application also provides the option of creating custom libraries which are created using character extraction, training, and annotation on sample records. Manual annotation of characters is necessary sometimes due to misidentification of characters by the OCR software.The binarized ECG records obtained from Step A are then subjected to morphological operators such as erosion, followed by dilation. This clarifies the underlying skeletal structure of the characters. OCR is utilized to identify and remove the overlapping ECG lead characters to ensure only the ECG waveforms are present . The ROIFollowing this, the patient demographic information present in the ECG records is extracted using OCR and may be linked to the patient’s research records or EMR. The extracted characters are stored in a text file or in the header information and available to the user.However, with respect to character removal of ECG lead characters, occasionally a few characters are only partially identified and removed. The cause has been traced to imperfect alignment of scanned ECG records due to human error. The ROIs are shifted around, and character removal is sub-optimal for these ECG records. To circumvent this, the scanned ECG records are compared with standard templates, which are the original scanned paper ECG records without anomalies either obtained from a public repository or selected by the user from the available records. The difference in alignment is addressed by adding the offset to the ROIs. Thus, using OCR, the overlapping ECG lead characters are removed.E.The segmented ECG row waveforms, obtained from Step B, are extracted and converted to voltage-time pairs in Step D . The colF.To confirm the quality of digitization of paper ECG records, we conducted a reader study identifying five clinically important features of the ECG signal. The features included the interval . The \dost interpretation session, cardiology observer A measured the 5 parameters from the odd-numbered standard ECG records, and even-numbered digitized ECG records. Cardiology observer B measured the 5 parameters for the odd-numbered digitized ECG records, and even-numbered standard ECG records. During the second interpretation session, the observers interpreted the remaining ECG records from the two sets. Upon the completion of the study, the results were tabulated, and pearson correlation coefficients computed.The study was carried out by two cardiology observers, Observer A and Observer B with 2 and 4 years of experience in interpreting ECGs, respectively, to calculate the inter-observer and the intra-observer measurements. For the purpose of this study, the intra-observer measurements are defined as the scanned paper and digital ECG measurements obtained by the observer on 2 separate days. A total of 10 ECGs randomly selected from a subset of 53 ECG records were examined retrospectively upon approval from the Emory Institutional Review Board (IRB00086259). Five parameters from 10 printed scanned ECG records and 10 digitized ECG records were measured by the two cardiology observers in two-interpretation sessions, between which there was 1-week of washout period. During the 1III.This section details the results obtained from the ECG digitization process and the validation study.A.B.Five clinically important features, namely C.Apart from the results of the reader study, the OCR application successfully obtained the text of the patient demographic data contained in the paper ECG record such as the name of the university, patient ID, date, time, and clinical parameter details. The text is obtained with an accuracy of 93.56% which is expected to increase with the inclusion of more training samples for the OCR template library.D.IV.The aim of this work was to extract the ECG signals and produce a digitized format from the scanned ECG records, and consequently create an open source standalone executable tool that is independent of equipment vendor. Importantly, the correlations obtained in the reader study results indicate that the process of digitization of ECG records preserves the critical clinical parameters of ECG signals. Furthermore, the results of the reader study also corroborate the results put forth by our previous study which show high correlation of clinical data extracted from paper and digitized ECG formats Although most correlations were > 0.9, some of them were slightly lower. Discrepancies remain in the correlations between the paper ECG signal in the paper and digitized records, which we hypothesize can be attributed to differences in the thickness of the ink used to print the ECG signal. Furthermore, small differences in the sampling rate of the signals between the paper and digitized records, can also contribute to imperfections in correlations. The relatively lower correlation values associated with the inter-observer values of the The main contributions of this work include the removal of overlapping ECG character lead segments using morphological processing and OCR, segmentation of ECG row waveforms using CCA and batch processing of ECG records which can be generalized across manufacturers of ECG systems. Primarily, in the removal of overlapping ECG character lead segments, the utilization of OCR and morphological processing allows for accurate demarcation between the ECG signal and ECG lead characters. Based on the reader study results, OCR can identify the remnants of a lead character fused with that of a signal, while ensuring that the vital features of the ECG signal such as Another contribution of this work is the segmentation of the ECG waveforms using a connected components based method. This approach is designed to ensure maximum retention of the saliency of clinical features previously mentioned. An additional advantage is character removal. That is, a significant portion of the ECG lead characters that do not bleed into the ECG signals are discarded, since they fall into the category of connected components, which contain too few pixels. Additionally, during the process of combining the connected components to form ECG row waveforms, the components which are deemed to be at a distance greater that the threshold are discarded. Therefore, stray non-overlapping ECG lead characters identified to be a connected component are often removed. This aids OCR in discarding ECG character leads overlapping with the ECG signals.https://github.com/ECG-Digitization-Project.Batch processing of ECG records is another key feature in this work. A one-time creation of template corresponding to each unique type of ECG record is necessary, to store information regarding the location of ECG contours, patient demographic information, and ECG lead characters. These templates facilitate the batch processing of multiple ECG records, to convert them into digitized records. An online library of publicly available ECG templates, along with a user manual and the application installation files, will be available on Github at Finally, this work has been packaged into a standalone executable tool, available to the public. The tool was designed utilizing ‘App designer’ available on MATLAB R2019b. This application was designed utilizing ‘App designer’ available on MATLAB R2019b and also incorporates Multi ROI/Mask Editor Class package With regards to tradeoffs in the methods, the quality of ECG digitization using this work is dependent on the parameters chosen in the CCA. These parameters can be modified for a template, to control the trade-offs between the time taken for digitization and quality of digitized ECG records ECG records that are of relatively lower quality due to graininess of the paper require the parameter corresponding to the minimum number of pixels selected per connected component to be also lower. In contrast, higher quality ECG records containing smoother ECG signals require the parameter to have a higher number of pixels as the threshold. This would prolong the digitization time for grainy ECG records, but would also ensure the thorough inclusion of all the signal components. Similarly, the distance computed between each of the connected components helps determine the ECG waveform to which the connected components belong. The larger the distance computed,the more likely it is for the ECG waveform to include stray pixels that do not belong to the signal. Conversely, the smaller the distance computed, the slower the digitization with increased robustness.A limitation of utilizing inter-observer and intra-observer correlations is the introduction of bias, as observed in our earlier work While manual intervention is required, such as entering the ECG template-based information and calibration, once the template information is entered, the user can continue to use the tool for that batch of records. Additionally, the template approach for the segregation of the patient demographic information and ECG waveform region, inherently assumes the presence of a DC pulse at the beginning of ECG lead segments. Thus, the recalibration of the parameters with respect to the template ECG records will now be more difficult to implement in the absence of a DC pulse. Another limitation of the proposed work is the difficulty in digitizing overlapping ECG waveforms across consecutive ECG rows, in the presence of high signal amplitudes. Using the current approach, the separation of the overlapping waveforms remains to be addressed.Furthermore, use of the ECG digitization tool may result in reduced accuracy of waveform tracings in areas that overlap with text. This may lead to misclassification of beat type , and further testing is needed on the impact of this signal deformation on computerized outcomes of programs that analyze the signal. Finally, due to limited ECG records available for the construction of the custom library, the OCR module did not contain many template characters. With the availability of more records, the OCR process will result in higher accuracy of character recognition and extraction. An additional disadvantage is that some portions of the waveform may be altered due to OCR error. This is also one of the current limitations of the algorithm.The proposed digitization method can be improved in several ways in the future. For instance, subtractive clustering techniques and principal component analysis can be utilized for the separation of overlapping high amplitude waveforms V.We developed an open-source MATLAB-based GUI tool for the conversion of paper ECG records to digitized ECG waveforms. The important features of this method include the use of OCR to perform character removal of ECG lead characters, and a tool to improve the generalizability of ECG record digitization regardless of the ECG vendor. The validation study conducted revealed negligible differences between the clinical features, such as


Mesenteric ischemia (MI) is a condition characterized by compromised intestinal perfusion, leading to varied patterns of bowel hypoxia that requires prompt diagnosis and surgical intervention. Here, we report a case in which indocyanine green (ICG) was utilized to evaluate intestinal blood flow in a patient with acute-on-chronic MI. A 65-year-old underweight female presented with abdominal pain out of proportion to exam and was found to have diffuse aortic atherosclerotic disease with chronic occlusion of both superior and inferior mesenteric arteries with distal reconstitution. After multidisciplinary evaluation, elective treatment with vascular surgery was planned; however, on day three of her hospitalization, the patient's abdominal pain acutely worsened. She was taken to the OR for exploratory laparotomy. Under white light, the small bowel from the ligament of Treitz (LOT) to the terminal ileum and the large bowel from the cecum to the splenic flexure appeared ischemic with patchy areas of necrosis. Fluorescence angiography was then performed; injection of indocyanine green (ICG) dye and imaging with the SPY-PHI near-infrared camera system demonstrated appropriate blood flow into the bowel mesentery, with complete absence of flow into the bowel mucosal surface from the LOT to the splenic flexure, confirming irreversible bowel necrosis. Introduction of ICG intraoperatively decreased the uncertainty associated with white light assessment of bowel viability, leading to a definitive intraoperative diagnosis and clear plan of care. The use of fluorescence guidance to diagnose fulminant small and large bowel necrosis prevented the surgical team from having to perform multiple takebacks to the operating room in the setting of a nonsurvivable injury. Had the surgical team relied on the white light appearance of the bowel, they would not have been able to diagnose the true extent of bowel demise. The patient was placed on comfort care for this devastating nonsurvivable injury. Despite being approved for medical uses in the 1950s, only in the past decade has the use of Indocyanine green (ICG) become commonplace in the field of general surgery. Its amphipathic properties allow it to bind lipoproteins and plasma proteins once injected into the blood stream or biliary system. Once distributed throughout the body ICG absorbs and emits light in the near-infrared range (750-800 nm) that penetrates deep into tissue and is detected by an imaging system , 5. The A 65-year-old white female with past medical history of chronic obstructive pulmonary disease and a one-year history of chronic abdominal pain presented to the Emergency Department with a 2-day history of worsening epigastric pain. She had no prior abdominal surgeries. Her social history was significant for daily tobacco use. Despite having a normal appetite, the patient lost 30 pounds  over the past year. The patient's abdomen was soft and only mildly tender to epigastric palpation with negative rebound tenderness or guarding. Lab work demonstrated a normal white blood cell count and a normal lactate level. Abdominal CT angiogram revealed diffuse atherosclerotic processes, including a large mural thrombus within the aorta at the thoracolumbar junction, complete occlusion of the celiac trunk and superior mesenteric artery with distal reconstitution, and several splenic infarcts. The patient was admitted to the hospital and underwent evaluation by gastroenterology, general surgery, and vascular surgery. An upper endoscopy was performed to look for peptic ulcer disease; none was found. The care team concluded that symptoms were likely due to chronic mesenteric ischemia and the patient was scheduled for an open mesenteric bypass with vascular surgery, to be completed in several days.On hospital day five, the patient's abdominal pain acutely worsened in severity and lab work revealed leukocytosis of 14,400/L and a lactate level of 6.8 mmol/L. An emergent exploratory laparotomy was performed. Under white light alone, the small bowel from the ligament of Treitz (LOT) to the terminal ileum and the large bowel from the cecum to the splenic flexure appeared ischemic with patchy areas of necrosis . To obta2Mesenteric ischemia is a condition in which abdominal vasculature is compromised leading to some degree of intestinal hypoperfusion. Acute mesenteric ischemia (AMI) is the more malevolent form in which blood flow is so restricted that bowel inflammation and necrosis results , 7. AMI Diagnosis is made based largely on clinical suspicion, results of CT angiography, and visual inspection of the bowel via laparotomy or laparoscopy. Early detection is vital, as bowel that has not undergone extensive necrosis can be saved through revascularization techniques, increasing overall survival. If the bowel becomes necrotic, bowel resection is the only surgical option , 10, 12.The high mortality rate of AMI can be partly attributed to the anastomotic network formed between the celiac trunk, SMA, and IMA. This interconnection helps minimize damage in situations where there is reduced flow through one of these major branches. However, when major occlusions do occur, it introduces a large degree of variation in the pattern of intestinal hypoperfusion that is produced . TherefoIn the case above, the patient initially presented to the emergency department with indicators of CMI. Despite having definitive CT angiography results, her transition towards AMI was not readily apparent. On hospital day 5, an acute change occurred, shifting her disease process to acute-on-chronic mesenteric ischemia. During exploratory laparotomy, using white light visualization, the degree of necrosis of her small and large intestine was not readily apparent. Under white light alone, the small bowel from the ligament of Treitz (LOT) to the terminal ileum and the large bowel from the cecum to the splenic flexure appeared ischemic with patchy areas of necrosis; however, some areas appeared to be viable. The use of ICG Figures –6 demonsThe application of ICG provided several immediate benefits. The contrast between the dye and surrounding tissue provided clear and almost instantaneous results, confirming that irreversible bowel necrosis had already occurred. The use of fluorescence guidance increased the surgical team's certainty in declaring the patient had suffered from a nonsurvivable injury and eliminated the need for an interval second-look laparotomy. Although not a pleasant decision by any means, using fluorescence guidance to confirm of the extent of bowel necrosis spared the patient from any futile trips to the operating room.Acute mesenteric ischemia (AMI) is a devastating condition in which prompt surgical intervention is crucial to the wellbeing of the patient. Unfortunately, the unpredictability of patient symptoms and the lack of a distinct diagnostic test makes recognition of the disease difficult. This uncertainty often follows the patient into the OR as surgeons must quickly determine the extent of bowel ischemia, which is difficult to see under white light alone. This case demonstrates how indocyanine green (ICG) and fluorescence guidance enabled the surgical team to diagnose a devastating bowel injury and minimize additional futile operative interventions.


Background: Medication adherence can prevent health risks, but many patients do not adhere to their prescribed treatment. Our recent trial found that a digital intervention was effective at improving medication adherence in non-adherent patients with Hypertension or Type 2 Diabetes; but we do not know how it brought about behavioural changes. This research is a post-trial process evaluation of the mechanism by which the intervention achieved its intended effects.Methods: A mixed methods design with quantitative and qualitative evidence synthesis was employed. Data was generated by two studies. Study 1 used questionnaires to measure the underlying mechanisms of and the medication adherence behaviour, and digital logfiles to objectively capture intervention effects on the process of behaviour change. Multilevel regression analysis on 57 complete intervention group cases tested the effects of the intervention at modifying the mechanism of behaviour change and in turn at improving medication adherence. Study 2 used in depth interviews with a subsample of 20 intervention patients, and eight practise nurses. Thematic analysis provided evidence about the overarching intervention functions and recommendations to improve intervention reach and impact in primary care.Results: Study 1 found that intervention effectiveness was significantly associated with positive changes in the underlying mechanisms of behaviour change ; and this effect was heightened twofold when the tailored intervention content and reporting on medication taking  was interested into the regression model. Study 2 suggested that the intervention supported motivation and ability to adherence, although clinically meaningful effects would require very brief medication adherence risk appraisal and signposting to ongoing digitally delivered behavioural support during clinical consultations.Conclusion: This post trial process evaluation used objective methods to capture the intervention effect on the mechanisms of behaviour change to explain intervention effectiveness, and subjective accounts to explore the circumstances under which these effects were achieved. The results of this process evaluation will inform a large scale randomised controlled trial in primary care. Medication adherence can prevent morbidity and mortality associated with Hypertension and Type 2 Diabetes , 2. HoweWe have therefore developed a highly tailored and interactive behavioural intervention, the Medication Adherence for Patients Support (MAPS) to support treatment adherence in primary care. To develop the intervention, we have reviewed theory, evidence, and obtained insights from Patients and Public Involvement and Engagement –9.The MAPS intervention aims to support medication adherence by modifying the theoretical determinants that underpin behaviour change; that is, the non-intentional and intentional non-adherence, the health outcome expectations, the medication adherence self-efficacy and the social norms. One way to effectively modify the underlying mechanisms of behaviour change is to provide highly tailored advice to the individual and further support reports on behavioural performance . The intThe MAPS intervention was evaluated at a pragmatic randomised controlled trial with 135 non-adherent patients with Hypertension or Type 2 Diabetes recruited from eight primary care practises in the UK; and it was found to be effective at improving medication adherence and reducing blood pressure and glucose levels . HoweverDisentangling the effective and replicable intervention processes that bring about improvements in medication adherence could inform effective and scalable medication adherence programmes in primary care. Though, to date our knowledge about the ways by which medication adherence is improved is based on self-reports, which makes the identification of effective and replicable interventions challenging.This research is a post-trial process evaluation of the MAPS intervention which utilised the technology to collect objective evidence to inform knowledge about the ways by which the intervention achieved its indented effects. It has also obtained subjective accounts to explore the implementation conditions that enabled intervention reach and impact in primary care setting. The ultimate aim of this research was to inform evidence for effective and replicable medication adherence interventions real-world practise .The Medication Adherence for Patients Support (MAPS) is a highly tailored and interactive behaviour change intervention: the content of the intervention was tailored to each patient's values of intentional non-adherence, non-intentional non-adherence, health outcome expectations, medication adherence self-efficacy and social norms. The content, intensity and schedule of the intervention messages was pre-specified based on theory, qualitative and quantitative evidence, consultations, and Involvement and Engagement of the Public . The digThe intervention included three broader categories of messages: (1) advice messages tailored to the theoretical determinants of medication adherence, (2) reminder messages about the prescribed regimen, and (3) query messages that included behaviour change strategies to prompt active engagement with the tailored intervention content by asking patients to report whether or not they have taken their medications as prescribed  and intensity  of the intervention was pre-specified as following: during the first week, each patient was asked to complete questions about the determinants of medication adherence behaviour and was sent highly tailored feedback aiming to address these behavioural determinants. During the first month, the intervention included more reminder messages, which were gradually reduced during the second month and were stopped during the third month of the intervention. Advice messages followed a reverse delivery sequence: they were introduced during the first month and gradually replaced the reminder messages during the second and the third intervention month.We adopted a flexible approach to intervention delivery: the number of the reminder messages and the timing of all messages were pre-selected by participants, and participants could change these options during the 3-month intervention i.e., they had the option to request less or more messages, or to stop receiving messages.The trial was implemented in eight primary care practises in the UK. Recruited primary care practises were located at different areas of deprivation, with the majority of them in deprived or highly deprived areas, ensuring that the trial reached patients from a wide range of deprivation areas. Practise nurses who advised patients about medication adherence, blood pressure checks or other similar consultations, were invited and participated in the trial.Patients were eligible to participate if they met all four inclusion criteria: (1) were above 18 years old, (2) had a diagnosis of either Hypertension or Type 2 Diabetes mellitus, or both health conditions; (3) had been prescribed at least one antihypertensive medication or glucose lowering medication; and (4) had either poorly controlled blood pressure or glucose levels as logged in their medical records, or had gaps in collecting repeat prescriptions during the six months before study invitation. Patients were excluded if they were taking part in another medication adherence intervention or had a health condition that could impair their participation.Eligible patients were identified from the practise database by a practise manager and confirmed for eligibility by a practise GP. Patients were then approached opportunistically by practise nurses during usual care consultations or proactively by sending text message or postal invitations. Patients were prompted to contact their practise nurse or the research team, to book their baseline consultation. During baseline consultation patients provided written informed consent and completed baseline data measurements. All methods and procedures have been approved and were carried out in accordance with the guidelines and regulations of the Ethics Committee of East of England, Essex Research Ethics Committee (REC Reference number 17/EE/0203) and Health Research Authority.At completion of baseline measurements, patients were randomised to either the digital intervention as an adjunct to usual care or to usual care only. The random sequence was generated by a centralised web-based service and was stratified by two important confounders: medication adherence intention as measured by the Medication Adherence Report Scale  and burdA mixed methodology was employed in line with recommendations for the process evaluation of randomised controlled trials , 13. In We collected data, using questionnaires, digital log files and in-depth interviews, to triangulate data synthesis and generate findings.The population for this process evaluation was (1) the intervention group patients only, selected due to the data utilised for the process evaluation i.e., digital log files to objectively capture intervention effects, and (2) both intervention group patients and health care facilitators , given the importance of this evidence to inform future medication adherence programs in primary care.Specifically, the process evaluation aimed to respond to the following research questions:a) Was intervention effectiveness associated with improvements in the theoretical determinants that underpin behaviour change i.e., intentional and non-intentional non-adherence, medication adherence self-efficacy, health outcome expectations and social norms?b) Did tailoring and reports on behaviour moderated the effects of the theoretical underpinnings at improving medication adherence?c) What were the overarching intervention functions that supported intervention effectiveness?d) What were the conditions under which the intervention achieved reach and impact of non-adherent patients in primary care setting?Study 1 provided evidence to respond to research question a and b; and study 2 provided evidence to respond to research questions c and d.To evaluate the underlying mechanisms of behaviour change we collected data using a baseline and 3-month follow up questionnaire measuring non-intentional non-adherence, intentional non-adherence, health outcome expectancies, medication adherence self-efficacy, social norms and medication adherence behaviour.Non-intentional non-adherence refers to patients' non-conscious consideration of performing a behaviour; such as forgetting or misunderstanding the prescribed treatment. Intentional non-adherence refers to patients' conscious consideration of performing a behaviour; such as not taking their medications as prescribed because they decide not to take a dose or stop taking their medications , 16. NonHealth outcome expectations refers to patients' outcome expectations, such as the perceived reduction in risks of developing health complications that follows medication adherence . Health Medication adherence self-efficacy refers to patients' perceptions about their ability to take all the doses of their prescribed medications as prescribed, as well as their optimistic beliefs about their ability to sustain their behaviour regardless the barriers specific to long-term medication adherence . Such baSocial or subjective norms refer to perceptions about others' views about taking medication or others' adherence to medication  . Social Medication adherence was measured by one single item .To disentangle the intervention content that brought about change, we coded the data objectively captured by digital log files during the three months intervention based on the following operational definitions: we coded the variable “tailoring” when there was a confirmation of receipt of the tailored intervention advice. The median score for tailoring was used as a threshold to indicate low  or high (above threshold) tailoring.We coded the variable “report behaviour” when there was a “yes” or “no” response to intervention query messages to report medication taking. Report behaviour was coded as “high” when all responses confirmed medication taking, “medium” when at least half of the responses confirmed medication taking and “low” when less than half of the responses confirmed medication taking.Tailoring and report on behaviour were conceptualised and coded as different variables, because tailoring required confirmation of the tailored intervention advice, whereas report on behaviour required confirmation of the behavioural performance .We have also coded “overall intervention usage,” that is a combined score of the objectively measured intervention components received i.e., confirmation of receipt of the tailored intervention content, responses to intervention query messages, and interactions regarding the intervention delivery options —to explore potential effects of the overall intervention usage on intervention effectiveness. Data that captured usage of the intervention regarding the study procedure  were excluded.Data captured at digital log files during the three months intervention were extracted and coded. Each patient's digital log files were coded separately. Data summarising tailoring, report on behaviour and overall intervention usage across all participants was then grouped into one coding and included in the analysis.The qualitative evaluation explored two aspects of intervention impact; (a) the overarching intervention functions that supported intervention effectiveness; and (b) the conditions under which the intervention reached non-adherent patients with Hypertension or Type 2 Diabetes in primary care.We conducted in-depth interviews with a subsample of the intervention group patients and all practise nurses or health care assistants who took part in the trial, to obtain multi-perspective views about the individual and context-specific elements of the intervention reach and effectiveness.The patients semi-structured interview guide was developed by a researcher based on theory and aimed to explore views about the intervention content and prompt recommendations for improvement. Patients were asked their views about specific intervention messages, whether and how messages supported medication adherence and under what circumstances. When patients could not remember or elaborate about a specific intervention message, an example of a received message as recorded by digital log files was provided.Each of the patient's interviews lasted from 90 to 180 min. Longer interviews with patients were required to establish rapport and overcome potential bias regarding the role of the interviewee and the interviewer. The first 13 interviews were conducted face-to-face at patient's home until main codes were created, the remaining seven interviews were conducted by phone to confirm or further explore the elicited codes.The semi-structured interviews with practise nurses aimed to explore elements that impacted on intervention reach and obtain recommendation to improve intervention scalability in primary care. Practise nurses were asked about patients' characteristics for whom the intervention was acceptable and potentially effective, and the practise-level conditions that could facilitate intervention reach and scale up  conducted the interviews independently. AK conducted the interviews with practise nurses, AK and VM conducted the face-to-face interviews with patients, and CAC and VM conducted the telephone interviews with the patients. All interviews were audio-recorded and transcribed by an independent transcription service. Transcripts were double checked for accuracy against recordings by the researchers, and all personal identifiable data were removed before analysis. Field notes were collected during the face-to-face interviews to inform data analysis. One of the researcher's had experience in developing and evaluating medication adherence interventions, including process evaluation using quantitative and qualitative methods, and the two others had training on qualitative data collection and analysis. The researchers had no previous knowledge or relationship with the participants.Questionnaires and interviews were completed by patients at the end of the 3-month intervention; from June 2018 to April 2019. Data were recorded at the digital log files during the 3-month intervention; from March 2018 until March 2019. Quantitative data coding and analysis was conducted during December 2019. Qualitative coding was conducted by two researchers, and analysis were conducted during September 2019. Data triangulation and mixed methods analysis was completed during January 2020. The trial was first registered at ISRCTN on 08/08/2017 and the reference number is 10668149.In total 77 patients were randomised and enrolled into the intervention group, and 57 of them provided complete data and included in the quantitative analysis.The selection of patients who were invited to take part at a post-trial in depth interview was informed by the coding of the digital log files: invited participants were selected based on level of intervention engagement  and basic demographics  to ensure that a variety of views were explored. From those meeting the eligibility criteria, we randomly selected 25 and invited them to take part in the interview using phone calls. Five participants refused to participate, three because of time constraints and two because of lack of interest. In total 20 patients completed the end of intervention interview: 13 face-to-face and seven over the phone.Eight practise nurses, one from each of the eight primary care practises, who either identified or invited patients during usual care consultations, were invited by phone and took part in the in-depth face to face interview.Principal component analysis suggested that multi-collinearity was not an issue for the variables. Histograms explored continuous variables' distribution, and the Levene test assessed the assumption of equality of variance. Regression analysis explored whether intervention effectiveness was associated with the underlying mechanisms of behaviour change. Multivariable regression analysis tested whether, and to what extent, intervention tailoring and report on behaviour modified the effects of the theoretical underpinnings at improving medication adherence. Data were inserted into the regression model, with medication adherence as a dependent variable and each of the theoretical determinants as an independent variable. Interactive effects were explored between the theoretical determinants with tailoring and report on behaviour. The variables measuring theoretical determinants were adjusted for baseline values. Analysis was conducted using SPSS v26.Qualitative data were analysed thematically  using NVP = 0.04; 6.85 ± 0.47 vs. 6.36 ± 1.59). Similar direction of effects was observed for improvements at both the systolic blood pressure  and glucose levels  favouring the intervention group.The majority of patients were registered with primary care practises located at highly deprived areas and were above the age of 50 years. The 3-months follow up results on behavioural and clinical outcomes have been reported previously . Medicatb = 0.46, P = 0.03), non-intentional non-adherence  and medication adherence self-efficacy  within the intervention group. There was a trend towards positive associations between medication adherence and improvement on each of the health outcome expectations  and the two specific self-efficacy variables , but these effects were not statistically significant. There were no effects of the social norms on intervention effectiveness . Reports on medication adherence was 26.8% low, 60.7% medium and 12.5% high, and it was positively and significantly associated  with improvements in medication adherence within the intervention group , which was significantly associated with improvements in medication adherence , and this effect was heightened further when tailoring  and report medication adherence behaviour  was included in the regression model  facilitated motivation to medication adherence; (b) enabled medication adherence behaviour, and (c) prompted social integration. To improve intervention impact and scale up, participants recommended the integration of the behavioural intervention into usual care consultations to facilitate control over the long-term clinical indicators of the health condition.Patients reported that their motivation to take medication was embedded in improving their health condition and thus achieve health benefits, whereas barriers to adherence were mainly influenced by their everyday lifestyle; and that the intervention supported them to sustain adherent by reinforcing their motivation and by prompting them to specify and address the barriers to adherence . Intervention tailored advice and reporting on behaviour captured objectively by digital log files significantly amplified these effects by twofold (heightened explanation of intervention effectiveness at 59%).Qualitative data supported that the intervention increased motivation to adherence, enable patients to sustain adherent and prompted integration of medication adherence behaviour into social context. To improve intervention reach and scale up, the intervention could provide very brief behavioural risk appraisal during usual care clinical consultations and signpost patients to an ongoing digitally delivered behavioural support.The results of this research were based on data obtained by the intervention group of patients taking part in a pragmatic randomised controlled trial implemented in primary care setting. To our knowledge, this is the first process evaluation of a medication adherence digital intervention in the primary care. This study elucidated the mechanism by which the intervention brought about behaviour change in non-adherent patients and provided the evidence-base of effective medication adherence interventions in primary care.A strength of this research is the measurement of intervention content captured objectively by digital log files, which provided objective data about patients' engagement with the tailored intervention content. The research has also obtained data from multiple perspectives and facilitated data triangulation. Another strength of this research is its mixed methodology approach. This process evaluation synthesised both quantitative and qualitative evidence to provide comprehensive responses to our research questions.A limitation of this research is the lack of evaluation of the underpinnings of health behaviour change against the control group of the trial. However, between group comparisons were not possible due to the primary aim of this study and the data required to respond to the research questions. The evidence of this research is based on a subsample of patients, and the results should be treated with caution when interpreted to larger population. Although the sampling was stratified and controlled for important confounders, quantitative process evaluation might require data from larger samples to provide the necessary power to detect the impact of digital interventions on modifying the determinants of medication adherence and on subsequently improving adherence.This research study did not control for the effect of other potentially important cofounders on the intervention effectiveness, like the effect of the health care provider or patient demographics . Future research could explore the effect of these cofounders on intervention effectiveness, to increase knowledge about the scalability of the intervention to non-adherent patients.This research provided evidence about the process by which a behavioural intervention improved medication adherence. It was found that the intervention effectiveness was supported by improvements in non-intentional non-adherence, intentional non-adherence and medication adherence self-efficacy. This finding suggests that intention to adherence and positive appraisals about the capability to medication adherence are important mechanisms of effective interventions. Furthermore, this study found that the intervention tailored advice and reports on behaviour heightened this effect twofold at improving medication adherence. Positive improvements were observed for the perceived reduction in risks of developing health complications that follows medication adherence and beliefs about ability to adherence regardless the perceived burden of pills, suggesting that these could potentially be effective mechanisms of medication adherence.Future research could usefully investigate the effects of these mechanisms using larger sample size and against the control group to provide rigorous evidence about the mechanisms of medication adherence. A combination of highly tailored and interactive digital intervention with very brief health care provider behavioural advice about medication adherence could act synergistically to strengthen the impact of the intervention in the primary care.Participants actively engaged with the tailored intervention daily for an average of 11 min, during the intervention (duration of daily messages was ~1 min). Considering the challenges to engage non-adherent patients with usual care advice , and theTo our knowledge this is the first research that has evaluated the mechanisms by which an interactive text and voice message intervention has supported medication adherence within non-adherent patients in the intervention group of a randomised controlled trial in primary care. It was found that tailored intervention content and reports on behavioural performance doubled the effect of intentional non-adherence, non-intentional non-adherence, and adherence self-efficacy in explaining improvements in medication adherence. Patients reported motivation and ability to be important intervention effects in improving medication adherence behaviour. Practise nurses recommended very brief medication adherence risk appraisals followed by signposting to additional digitally delivered behavioural intervention to support non-adherent patients as part of the time constrained usual care consultations. Future research could usefully investigate and evaluate the effects of active and objectively captured intervention content at modifying the mechanisms of behaviour change and at improving medication adherence and clinical outcomes using rigorous designs.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.All methods and procedures have been approved and were carried out in accordance with the guidelines and regulations of the Ethics Committee of East of England, Essex Research Ethics Committee (REC Reference number 17/EE/0203) and Health Research Authority. The patients/participants provided their written informed consent to participate in this study.AK and SS have developed the intervention and designed this study. CC and VM assisted with patients' invitation to the telephone interviews, qualitative data collection, and data coding, supervised by AK. JB and SE developed the digital platform to facilitate the delivery of the tailored behavioural intervention and to capture data about patients' intervention usage at digital log files. AK conducted the analyses and drafted this publication, with comments and advice by SS. All authors have read and approved this manuscript for publication.This paper presents independent research funded by the National Institute for Health Research (NIHR) under the Research for Patient Benefit program [grant number PB-PG-0215-36032].The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The visible and near-infrared (Vis-NIR) reflectance spectroscopy was utilized for the rapid and nondestructive discrimination of edible oil adulteration. In total, 110 samples of sesame oil and rapeseed oil adulterated with soybean oil in different levels were produced to obtain the reflectance spectra of 350–2500 nm. A set of multivariant methods was applied to identify adulteration types and adulteration rates. In the qualitative analysis of adulteration type, the support vector machine (SVM) method yielded high overall accuracy with multiple spectra pretreatments. In the quantitative analysis of adulteration rate, the random forest (RF) combined with multivariate scattering correction (MSC) achieved the highest identification accuracy of adulteration rate with the full wavelengths of Vis-NIR spectra. The effective wavelengths of the Vis-NIR spectra were screened to improve the robustness of the multivariant methods. The analysis results suggested that the competitive adaptive reweighted sampling (CARS) was helpful for removing the redundant information from the spectral data and improving the prediction accuracy. The PLSR + MSC + CARS model achieved the best prediction performance in the two adulteration cases of sesame oil and rapeseed oil. The coefficient of determination ( Edible oils are rich in essential nutrients for human beings and thus are some of the most common cooking ingredients in our daily lives . HoweverCamellia oleifera [Although edible oils have obvious characteristics, such as odor and color, which can be used in preliminary artificial discriminations, the judgments are too subjective and susceptiblebased on these natural characteristics. Some researchers developed sensors to accurately sense the external characteristics of oils. For example, the electronic tongue was developed to qualitatively detect adulteration based on tasting fingerprints ,11. Howeoleifera , identifoleifera . Nevertholeifera .The visible and near-infrared (Vis-NIR) reflectance spectrum is generated by the absorption of radiation, which causes the molecular vibration from the ground state to a higher internal energy level. Therefore, it reflects the internal and external features of the objects. In previous studies, the Vis-NIR reflectance spectroscopy has been used to develop a hybrid proximal sensing method to quickly identify oil-contaminated soil  and measIn this study, we presented a nondestructive and effective method for identifying the adulteration of edible oil using Vis-NIR reflectance spectroscopy. The experimental workflow of oil adulteration detection is shown in In order to obtain pure samples of rapeseed oil, sesame oil, and soybean oil, the rapeseed seed (Yangguang 198), sesame seed (Xinyuzhi 10), and soybean (Wandou 33) were processed with an oil press. The soybean oil was taken as the adulterated oil to blend with sesame oil and rapeseed oil, respectively. The doping ratios were set as 0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, and 100%. The 0% represented the pure soybean oil, and the 100% represented the pure sesame oil or rapeseed oil. In our experiment, five groups of adulterated samples were generated to ensure the independence of the oil samples. Each group included nine adulterated sesame oils, nine adulterated rapeseed oils, and four pure oils . Therefore, there were a total of 110 oil samples for the adulteration experiments of sesame oil and rapeseed oil.In order to obtain the Vis-NIR reflectance spectra, a simple spectrum measurement platform was constructed. The platform was mainly composed by a black box, four halogen lamps (75w), an automatic lifting sample system, a PSR-3500 portable spectroradiometer, spectrum acquisition software, and so on, as shown in The SNV, MSC, SG smoothing, and WT are commonly used to remove the negative effect of various spectra data . The SNVIn order to eliminate redundant information and simplify the prediction models, the PCA, VIP, SPA, and CARS were adopted to select the effective wavelengths . PCA is To identify the different adulteration types of oil samples, the SVM, RF, and KNN methods were employed to build the classification models, respectively. SVM maps spectral data into high-dimensional space by using kernel function and seeks for the optimal hyperplane to separate samples. RF is a classifier with multiple-decision trees to classify samples and assess the importance of variables. KNN is a classifier insensitive to outliers that can classify by measuring the distance between different feature values. KNN predicts new sample according to its K-nearest neighbors.In addition, three regression models including PLSR, SVR, and RF were adopted to predict the oil adulteration rate, which was a very important quantitative indicator for oil quality inspection. PLSR is a commonly used multivariate analysis method in the Vis-NIR spectrum analysis, which constructs a regression model of multiple dependent variables against multiple independent variables. SVR was developed based on the structural risk minimization principle. It is suitable for the analysis of high-dimensional spectral data with a small sample set. RF can be used for regression modeling, and the predicted value in RF regression model is the average output of each decision tree. RF can reduce the risk of overfitting by the process of averaging decision trees. Therefore, it is commonly applied for the modeling and analysis of various spectral data.n is the total number of samples.In the analysis of the adulteration type, the performance of prediction model was evaluated by accuracy R2=1Furthermore, a 10-fold cross validation was applied to evaluate the robustness and generalization of predictive models. In this paper, the spectral data were randomly divided into ten partitions with equal size. Nine of the ten partitions were combined as the training data , and the remaining one partition was used as validation data (prediction set). The crossvalidation procedure was repeated 10 times with each of the 10 partitions used exactly once as the validation data. The 10-fold crossvalidation of the Vis-NIR spectra analysis was shown in The Vis-NIR reflectance spectra of the 110 adulterated oil samples were shown in In our study, the experimental samples were divided into seven classes, i.e., pure sesame oil (100%), low-adulterated sesame oil (60% ≤ ratio ≤ 90%), high-adulterated sesame oil (10% ≤ ratio ≤ 40%), pure soybean oil (0%), high-adulterated rapeseed oil (10% ≤ ratio ≤ 40%), low-adulterated rapeseed oil (60% ≤ ratio ≤ 90%), and pure rapeseed oil (100%). Due to the adulteration rate of 50% being rare in practice, the samples with adulteration rate of 50% were excluded from the experiment of qualitative analysis. In order to eliminate the external interference and noise, four pretreatment methods were used to preprocess the spectral data. The SVM, RF, and KNN were adopted to construct the prediction models for identifying an oil adulteration type based on the spectral data. The 10-fold crossvalidation was conducted to the each of the models, and the average prediction results were shown in To further evaluate the performance of the model (SVM + SNV/MSC) in independent samples, six pure oils including two brands of sesame oil, two brands of rapeseed oil, and two brands of soybean oil were collected from the local Walmart stores for experiments. The Vis-NIR reflectance spectra were measured on the platform as described in The reflectance spectra were used to construct the PLSR, SVR, and RF regression models to determine the accurate adulteration rates of sesame oil and rapeseed oil. For accurate quantitative analysis, the adulteration rates of sesame oil and rapeseed oil were analyzed separately in our experiments. Similar to the identification of the adulteration type, the four pretreatment methods and raw spectra were applied to compare the prediction accuracy of the adulteration rates. The prediction result of each model was the average prediction results of 10-fold crossvalidation.In the study of sesame oil adulterated with soybean oil, the Vis-NIR spectra were analyzed by the PLSR, SVR, and RF methods combined with different pretreatments. In the study of rapeseed oil adulterated with soybean oil, we adopted the same analysis procedure as the sesame oil adulteration case. The analysis results were shown in In this section, we intend to evaluate whether effective wavelengths could help to promote the prediction accuracy of adulteration rates. The full wavelengths of the Vis-NIR reflectance spectra inevitably comprised the irrelevant features. Extracting optimal wavelengths can remove the influence of noncritical factors and reduce the complexity of prediction models. Furthermore, a simplified model can contribute to the downstream analysis of oil quality detection. Therefore, four effective spectral selection algorithms  were applied to extract the effective wavelengths. The obtained effective wavelengths were then applied to the PLSR, RF, and SVR regression models. Similarly, the 10-fold crossvalidation was adopted to calculate the average prediction result of each model. In the experiments of sesame oil adulterated with soybean oil, the numbers of effective wavelengths extracted by four effective spectral selection algorithms were 83 (PCA), 97 (SPA), 90 (VIP), and 94 (CARS), as seen in On the whole, the experiment results demonstrated that the effective wavelengths were beneficial for accurately predicting the adulteration rates of edible oils. The model of PLSR with MSC pretreatment was the best model which achieved the highest accuracy with CARS algorithm in both cases of sesame oil adulteration and rapeseed oil adulteration. It showed good versatility and robustness. The triple pattern (PLSR + MSC + CARS) was the recommended model for predicting the adulteration rates of sesame oil and rapeseed oil. Based on the extracted effective wavelengths, the complexity of prediction model was significantly reduced with the very limited effective wavelengths. In general, the experiment results demonstrated the feasibility and effectiveness of the CARS effective wavelength selection algorithm and highlighted the necessity of eliminating redundant data of the spectra. Therefore, we further investigated the distribution and characteristics of the screened effective wavelengths.The overlap of the effective wavelengths is an important indicator to compare different spectral selection algorithms. In the experiments, the numbers of the effective wavelengths extracted by the four spectral selection algorithms were approximate equilibrium, as shown in Then, the distribution of the selected effective wavelengths in the whole spectra was analyzed, as shown in In order to investigate the contribution of individual effective wavelength on adulteration rate, Pearson correlation coefficient (PCC) was employed for evaluating the association relationship between the adulteration rate and the reflectivity in individual wavelength. Based on the best model of the sesame oil adulterated with soybean oil, two representative effective wavelengths  were selected for analysis. This study evaluated the reliability and feasibility of Vis-NIR reflectance spectroscopy for the rapid and nondestructive discrimination of edible oil adulteration. A Vis-NIR spectroradiometer system was constructed to obtain the reflectance spectra of the sesame oil adulterated with soybean oil and the rapeseed oil adulterated with soybean oil. Four commonly used methods  were applied to evaluate the impact of pretreatments on spectra data. In the qualitative detection experiments, the accuracy in the prediction set were 100% with the SNV and MSC pretreatments, which suggested that the SVM was a powerful model for oil adulteration type identification. In the quantitative prediction experiments of sesame oil adulterated with soybean oil and rapeseed oil adulterated with soybean oil, the RF method with MSC pretreatment achieved the best prediction effect on the two groups experiments with full wavelengths. Then, the PCA, VIP, SPA and CARS methods were applied to extract the characteristic spectra from the Vis-NIR reflectance spectra. Compared with the prediction performance of full wavelengths, the prediction performance of effective wavelength was slightly improved. According to our results, the model of the triple pattern (PLSR + MSC + CARS) was the recommended method for predicting the adulteration rate of sesame oil adulterated with soybean oil and rapeseed oil adulterated with soybean oil. The Vis-NIR spectra of different edible oils have significantly different amplitudes at a series of characteristic wavelengths. Therefore, the presented methodology can be applied to the adulteration discrimination of other kinds of oils. According to the results reported in this paper, a practical and efficient detection system could be constructed for the fast discrimination of edible oil adulteration in a wide range of application scenarios. To achieve this goal, a simplified reflectance measuring instrument can be designed based on the effective wavelengths. Then, the Vis-NIR spectra data of different edible oils should be measured to retrain the presented model for the nondestructive discrimination of various edible oils adulteration. The enhancement of these related technologies is helpful for the popularization and application of the Vis-NIR spectroradiometer system for oil adulteration detection.


On the Origin of Species. Previous hypotheses predict that developmental constraints make some morphologies more likely to arise than others and natural selection discards those of the lowest fitness. However, the quantification of the role and strength of natural selection and developmental constraint in shaping convergent phenotypes on macroevolutionary timescales is challenging because the information regarding performance and development is not directly available. Accordingly, current knowledge of how embryonic development and natural selection drive phenotypic evolution in vertebrates has been extended from studies performed at short temporal scales. We propose here the organization of the tetrapod body-axis as a model system to investigate the developmental origins of convergent evolution over hundreds of millions of years. The quantification of the primary developmental mechanisms driving body-axis organization  can be inferred from vertebral counts, and recent techniques of three-dimensional computational biomechanics have the necessary potential to reveal organismal performance even in fossil forms. The combination of both approaches offers a novel and robust methodological framework to test competing hypotheses on the functional and developmental drivers of phenotypic evolution and evolutionary convergence.Convergent evolution is a central concept in evolutionary theory but the underlying mechanism has been largely debated since  These mexternalist view claims that convergent evolution is the result of the unfettered ability of natural selection to produce optimal solutions to repeated environmental problems, and the internalist view argues that convergence is the result of ‘constraints’ that hamper the production of phenotypic variants, hence leading to the more likely evolution of similar features [Convergent evolution is a quasi-ubiquitous phenomenon but its origin has been largely debated in evolutionary theory ,4. Most features –7. The ‘features .endless, quantifying the strength of natural selection and developmental constraints in shaping convergent phenotypes over hundreds of millions of years is challenging because the information regarding performance and embryonic development is not directly available. As a consequence, although some studies have used an approach bridging palaeontology and developmental biology [a).Although both views present evidence that the diversity of Life is not  biology –11, our . 2b): (i)somitogenesis [The total number of vertebrae informs about the speed of the budding of the presomitic mesoderm in the formation of the new somites during the process of ogenesis . As the ogenesis . (ii)Hox gene expression patterns [Hox genes in patterning axial skeletal regions has been demonstrated not only in mammals but also in other tetrapods [Hox genes (and other patterning genes) leading to variation in the distribution of vertebrae among morphological regions [The relative numbers of vertebrae present in each region inform about changes in the patterns –21 acrosetrapods –27, as wetrapods ,29. A ma regions .The diversity of tetrapod body-axis proportions is enormous even for taxa adapted to the same physical environment. Surprisingly, this diversity results from the combination of three variables that are easily quantifiable in both recent  and fossfigure 1Hox-expression in Actinopterygii is well known [Hox-code expression and regionalization in the cartilaginous fish, Leucoraja erinacea [Hox-based vertebral regionalization at the common ancestor of jawed vertebrates. (iii)Finally, vertebral lengths inform about differential post-patterning growth of somites among axial regions, which determines the relative lengths of vertebrae within regions. Differential growth of somites among regions can result in evolutionary change in body proportions in the absence of other changes .The axial skeletons of fishes are simply subdivided into trunk and tail regions ,29, and ll known . Recent erinacea  and in eerinacea  predict Tanystropheus) [Therefore, the vertebral formula (number of vertebrae per region ) is a suropheus) .The response of the thoracic region of cetaceans and sirenians  to selective agents is similar to that of short-necked reptiles; the number of presacrals increases while retaining the ancestral cervical count. The axial system of pinnipeds and close terrestrial taxa is similar, as in placodont reptiles, suggesting that marine adaptations do not need to be coupled with changes in vertebral number .Despite the low meristic variation of mammals , their v. 3a) allows testing for developmental triggers of body-plan diversity at large-temporal scales. This can also manifest theoretical combinations of developmental variables with the potential to answer how much variation in the organization of the tetrapod body-axis has been explored by organic evolution (figure 2a). Different methods have been developed to study and quantify patterns of morphospace occupation [The three variables that account for developmental changes in axial organization of the tetrapod axis could be analysed using theoretical morphology  to invesfigure 2cupation –39 and pcupation  allowingcupation .Figure . 4c). Accordingly, they experienced profound morphological  changes in their body plans, including the acquisition of streamlined bodies with fusiform shape, characterized by a rounded front and a tapered end [A direct consequence of body-axis organization is the shape of the external body, which has profound implications for locomotion . Aquaticfigure 1ered end . This deered end . Streamlered end  because ered end .Computational fluid dynamics (CFD) is increasingly being used to investigate the relationship between body shape and locomotory performance in both living  and extiet al. [CFD has been applied to infer swimming performance in extinct taxa such as in ichthyosaurs , plesioset al.  used CFDet al.  demonstret al. [Alternatively, analyses of osteological maximum range of motion (oROM) of virtually assembled vertebral columns in a specific pose ,49 can bet al.  investiget al. .. 5a) can be combined with those parameters that account for (hydrodynamic) efficiency—e.g. drag and lift obtained from CFD—(b) into performance landscapes [c). Performance landscapes allow testing for functional drivers of morphological convergence quantifying the functional optimality of both occupied and unoccupied regions of the morphospace [et al. [The combination of morphospaces obtained from the three developmental parameters that account for the diversity of the tetrapod axis a can be from CFD—b into pendscapes  to quantphospace ,52. For  [et al.  investiget al. [et al. [Optimal designs are usually constrained by the existence of trade-offs between more than one task/function , impossiet al.  used PETet al. . Moreove [et al.  to invesc) can be used to explicitly test whether evolution has explored all functional optimal morphologies, whether many species are functionally suboptimal, whether unrealized morphologies are functionally poor and whether some optimal morphologies have never been achieved in evolutionary history.The combination of adaptive landscape evaluation and PET c can be . 6The developmental mechanisms governing the tetrapod axis have been already studied in living and fossil taxa ,16,34 ansensu [Our proposed approach could be of potential application to decipher the relative contributions of development and adaptation in the generation of convergent body-axis in a wide variety of taxa beyond marine tetrapods. For example, this could be the case of putatively convergent tetrapods towards an airborne locomotion such as birds, pterosaurs and bats or secondarily adapted species of mammals and reptiles towards specific locomotory demands . Beyond tetrapods, the investigation of developmental changes in the body-axis of fish as a response of different aquatic adaptations (sensu ) could bAltogether, this approach offers a novel methodological framework to test competing hypotheses about the functional and developmental drivers of phenotypic evolution and morphological convergence, using the body-axis as a model system.