Numerous forms of psychotherapy have demonstrated effectiveness for individuals with specific mental disorders. It is, therefore, the task of the clinician to choose the most appropriate therapeutic approach for any given client to maximize effectiveness. This can prove to be a difficult task due to at least three considerations: (1) there is no treatment approach, method or model that works well on all patients, even within a particular diagnostic class; (2) several treatments are equally efficacious  when considered only in terms of the patient's diagnosis; and (3) effectiveness in the real-world therapeutic setting is determined by a host of non-diagnostic factors. Typically, consideration of these latter, trans-diagnostic factors is unmethodical or altogether excluded from treatment planning – often resulting in suboptimal patient care, inappropriate clinic resource utilization, patient dissatisfaction with care, patient demoralization/hopelessness, and treatment failure. In this perspective article, we argue that a more systematic research on and clinical consideration of trans-diagnostic factors determining psychotherapeutic treatment outcome  would be beneficial and – with the seismic shift toward online service delivery – is more feasible than it used to be. Such a transition toward more client-centered care – systematically considering variables such as sociodemographic characteristics, patient motivation for change, self-efficacy, illness acuity, character pathology, trauma history when making treatment choices – would result in not only decreased symptom burden and improved quality of life but also better resource utilization in mental health care and improved staff morale reducing staff burnout and turnover. Despite the large variety of factors influencing psychotherapeutic treatment outcomes, when making treatment choices, diagnostic factors are usually prioritized when following clinical practice guidelines published by internationally recognized consortiums such as the National Institute for Health and Care Excellence (United Kingdom) , the CanSome guidelines/algorithms reference a small number of non-diagnostic factors such as severity of illness and patient preference, but to the best of our knowledge, none provide explicit direction or recommendations related to (a) how to choose from amongst treatment modalities within a single tier, (b) how to assess for and weigh non-diagnostic factors when selecting within (or across) tiers , and c) the relative importance of non-diagnostic factors in relation to treatment outcomes [cf. ].Without this more detailed guidance, consideration of non-diagnostic factors is most often unmethodical, superficial, or altogether excluded from treatment plan decision-making. In the limited number of cases where these factors are indeed considered, they are typically evaluated only once a patient has been deemed “treatment-refractory” or “treatment-resistant”  and, theBeyond the limitations of current, diagnosis-centered treatment guidelines, the small number of available treatment options at clinics or individual service providers has also limited the practical relevance of the question of treatment selection. Namely, in everyday clinical practice, most clinicians and (private or government-funded) mental health clinics have been able to provide a single or a very limited number of treatment approaches  decreasiThis state of the matters presents the intriguing possibility that the very foundation of clinical practice guideline development and their use in everyday clinical practice may have a disorienting influence on treatment selection. That is, orienting practitioners to use diagnosis as the primary determinant in differential psychotherapeutic treatment consideration and selection implicitly assumes  that diagnosis is the fundamental determinant of treatment response and, accordingly, should be the primary guide to psychotherapeutic treatment selection.However, a large array of non-diagnostic factors have been proposed and/or evaluated as potential determinants  of optimal psychotherapeutic treatment selection and response e.g., –10]. Man. Man10)]Importantly, it has also been noted that most psychotherapeutic research of the last three decades has been focused on outcomes, rather than mechanisms of action . This foFurther, the diagnosis-oriented nature of treatment guidelines is strongly influenced by the literature upon which such guideline recommendations are based: the vast majority of studies assessed when constructing clinical practice guidelines are randomized controlled trials comparing a single treatment  to placebo or treatment-as-usual in a diagnostically homogeneous sample. Thus, there are only very few studies that could be used by guideline developers to substantiate recommendations as to the relative probability of effectiveness of one active treatment over another. Moreover, because of the difficulty in accessing  the literature on non-diagnostic factors, it is not surprising that this literature is rarely cited or systematically considered in the development of treatment guidelines and algorithms.Research has identified a large array of non-diagnostic factors that have been evaluated as potential determinants (predictors and moderators) of optimal psychotherapeutic treatment selection/response. When choosing among psychotherapeutic modalities, practitioners ideally should consider all or at least several of these patient-, clinician- and clinic-specific factors that can potentially impact treatment outcomes. These include – among others – sociodemographic characteristics , patient motivation or readiness for change, patient self-efficacy, illness acuity, specific comorbid illnesses , overall amount of psychopathology [cf. the p-factor ], traumaIn cases where these non-diagnosis-related factors are assessed and taken into consideration at clinic intake, patients may be more responsive to treatment  and motivated to initiate change in emotion regulation, cognitions and behaviors. In the most ideal situation, instead of treatment assignment based on diagnoses, implicit clinician preference/bias or immediate resource availability , a set of evidence-informed predictors of treatment acceptability and response is to be used to perform personalized and holistic treatment recommendation/selection.We anticipate that mental health treatment recipients could benefit considerably from such an evidence-based/informed systematic process for treatment selection, which would permit treatment recommendation(s) to be tailored to the individual's goals and broader characteristics predictive of treatment response. Even if no factors clearly predict a single best treatment modality , patientTo remedy the suboptimal status quo, there is increased interest in applying concepts of stratified medicine in psychotherapeutic treatment selection. Stratified medicine  specificThe process of identifying and validating moderators of treatment response in mental health should ideally begin with a comprehensive and rigorous evaluation  of studies with direct comparisons of active psychological interventions in order to identify candidate factors with the best evidence as trait- or state-  moderatoWe believe that the seismic shift toward virtual psychotherapeutic service delivery due to the COVID pandemic – despite the numerous challenges – offers a huge opportunity to move toward more systematic treatment selection; both in terms of generating research evidence and allowing a more client-centered clinical practice. With virtual service delivery, the limitations of a given clinician or particular clinic now pose significantly smaller barriers than in the past as more distant service providers with a better match to client characteristics have recently become realistic alternatives. While it may be true that certain client populations [most likely those with more severe pathology cf. ] are lesvia  clients was not feasible in the past, the current landscape of online service delivery allows organizations or clinician networks to assess and diversify the therapeutic modalities available within their systems and use them in an economic way for the benefits of all  clients, therapists, and the mental health care system as a whole.Psychotherapeutic treatment selection is a largely neglected topic within the mental health care literature. Given that diagnosis alone is insufficiently predictive of psychotherapeutic treatment outcome, it is clear that non-diagnostic factors contribute to differential effectiveness and efficiency. Despite this fact, clinical practice guidelines are organized entirely around diagnosis and rarely reference non-diagnostic factors in recommending or prioritizing treatment options. We propose that this diagnostically-oriented framework for psychotherapeutic treatment selection omits critical patient-, therapist- and clinic/contextual factors that could help increase the overall effectiveness of psychotherapy, which – some argue – are much more limited , 41 or aNo datasets were generated for this study.KA developed the concept of the paper. KA and BKT wrote the first draft of the manuscript. All authors contributed to reviewing and interpreting the extant literature, final version as well as read, and approved the submitted version.


To decelerate antibiotic resistance driven by inappropriate antibiotic prescribing, a prescription review and feedback (PRF) policy is implemented in primary healthcare institutions (PHIs) in Beijing, China. However, evaluation of PRF implementation in PHIs is scarce. This study aims to systematically identify the barriers and facilitators of PRF policy implementation to provide evidence for antimicrobial stewardship.We conducted key informant interviews with 40 stakeholders engaged in the implementation of PRF in Beijing, including physicians, pharmacists and administrators. Interviews were audio recorded and transcribed verbatim. We coded the interview transcripts and mapped informant views to domains of the Theoretical Domains Framework. We then used a behaviour change wheel to suggest possible behavioural interventions.Knowledge) and skills (Skill) of PRF were possessed by stakeholders. They felt responsible to promote the appropriate use of antibiotics  and believed that PRF could help to change inappropriate provider behaviours  in prescribing antibiotics (Beliefs about consequences) under increased intention on antibiotic use (Stages of change). Moreover, informants called for a more unified review standard to enhance PRF implementation . Frequently identified barriers to PRF included inadequate capacity (Skill), using punishment mechanism (Behaviour regulation), reaching consistently lower antibiotic prescription rates , lack of resources  and perceived pressure coming from patients .Procedural knowledge (Stakeholders believed that PRF implementation promoted the rational use of antibiotics at PHIs in Beijing. Still, PRF was hampered by inconsistencies in review process and resources needed for PRF implementation. It has been used in hospitals and proved effective to promote rational antibiotic use in the USA, France, Japan, and in low- to middle-income countries (LMICs), including Nepal, India and Lebanon.11–16 However, little evidence is available regarding the effectiveness of PRF in primary healthcare settings in China.Antibiotics are the most frequently prescribed therapeutic agents worldwide.17 one of the core objectives of which was to strengthen the capacity of PHIs to conduct PRF. This included interventions of providing training programmes to promote the rational use of drugs based on national guidelines and incorporating PRF into performance appraisal management.In China, PRF was implemented as a pragmatic tool in primary healthcare institutions (PHIs) to constrain the inappropriate use of antibiotics, with Beijing being the first pilot area. A three-level PRF system Figure  for PHIs18 Moreover, a systematic review found that knowledge of factors associated with behaviour changes could address the barriers and enablers of antimicrobial stewardship (AMS), including audit and feedback in hospitals. In addition, social and contextual factors were also assessed as factors affecting antibiotic prescribing and engagement of AMS.19According to our previous study, after BMHC launched the PRF policy in 2017, decreases were seen in the antibiotic prescription rate (17.9% to 15.1%) and the irrational antibiotic prescription rate (14.0% to 9.2%) between 2017 and 2019.As a core strategy of AMS, the implementation of PRF in PHIs is essential. Therefore, this study aims to systematically identify the barriers and facilitators of the implementation of PRF policy to provide evidence for further improvement.JAC-AMR Online).This qualitative study was conducted according to the Standards for Reporting Qualitative Research (SRQR); the list content is shown in Table As the capital of China, Beijing had 21.5 million residents and 2075 PHIs with 68.3 million visits in 2019 . PHIs are designed to be the first point of contact for patients with the national health system. All PHIs in Beijing are outpatient clinics with very little inpatient capacity (only 26 000 patients were discharged from PHIs in 2019), providing basic outpatient clinical care and public health services to individuals and families residing in the community.To facilitate the implementation of PRF, the Beijing Prescription Reviewing System of Community Healthcare Institutions (BPRSCHI) database was established. The BPRSCHI database covered 327 PHIs. Sampling software is embedded in the information system of all PHIs. A total of 100 prescriptions were randomly selected from each PHI monthly using a systematic sampling method, with the sampling interval calculated by dividing the number of total prescriptions by 100. Due to the vast number of prescriptions resulting from numerous visits to Beijing, this methodology is used to select representative prescriptions for prescription review across the city.We used a three-step sampling method Figure  to selecEach informant from all 40 stakeholders participated in a KII (May 2021 to June 2021), and the interview was held online due to the COVID-19 pandemic. One member of the research team would ask questions of the informant and another research member would record the interview. Each interview lasted 30–60 min. The interviews focused on exploring the implementation, barriers and potential solutions to address inappropriate antibiotic prescriptions at PHIs. The interview content is shown in All interviews were audio-recorded and transcribed verbatim using iFlyrec software. All analyses of interview research codes were coded for both technical and management perspectives and thematic/category content analysis was also conducted by two researchers (K.D. and W.Z.). Analysis of qualitative data on implementation facilitators and barriers of PRF was conducted using a deductive coding approach and through an iterative process to the constructs of the Theoretical Domains Framework (TDF). Occurrences of capabilities (C), opportunities (O) and motivations (M) model of behaviour change (B) (COM-B) components relevant behaviour change techniques (BCTs) were coded and mapped directly onto the relevant TDF domains to illustrate how the findings could be used to inform intervention design. The ranking of the domains we identified through the TDF is shown in Table 20 The TDF consists of 14 domains . Verbal informed consent with a waiver of documentation was approved by all participants to protect confidentiality.We interviewed 40 stakeholders using semi-structured interview guides. Informants included 10 physicians, 14 pharmacists and 9 PHI administrators from these 12 selected PHIs for further interview. We also invited seven county-/district- and city-level administrators (Beijing Prescription Review Group) to participate in our study. The interview recordings were transcribed verbatim. Table PRF policy was believed to promote the rational use of antibiotics since the antibiotic prescribing rate (APR) had been reducing for nearly 10 consecutive years in primary care. Systematic barriers and facilitators of PRF implementation are shown in Figure ‘…conduct prescription reviews based on drug instructions, guidelines, and professional books related to prescription review’ (N32 Pharmacist)All stakeholders had heard that PRF was rolled out as a measure of AMS in their geographical area, while administrators were more knowledgeable about the management and organization of PRF in PHIs, like holding meetings to provide feedback on PRF work to pharmacists and physicians. Physicians and pharmacists were more knowledgeable about the actual procedures on how to review a certain prescription, such as applying drug labels, adhering to guidelines, and technical publications related to the infectious disease.‘Through the PRF process, the physicians realized that they need to improve technical competence…’ (N27 District/County Administrator)Both physicians and pharmacists recognized the importance of their professional ability to conduct PRF well. Therefore, administrators offered training sessions for pharmacists and physicians at PHIs to enhance their skills. For instance, physicians and pharmacists at PHIs could attend educational meetings with specialists from tertiary hospitals and online training programmes. Through the implementation of PRF, pharmacists and physicians were inspired to learn more about the rational use of antibiotics and to communicate with each other to better cooperate during PRF.‘…which can improve the clinical level of doctors, increase the knowledge base and better carry out our work.’ (N17 Physician)Measures were taken at all levels to promote the appropriate use of antibiotics through recording and making public the unqualified prescriptions found in PRF. Furthermore, technical support was provided to PHIs from tertiary and secondary hospitals.All stakeholders acknowledged that PRF was critical to their work. Physicians and pharmacists generally felt motivated and responsible to promote the rational use of antibiotics through engaging in PRF. Pharmacists considered themselves ‘gatekeepers’ of care for patients.‘Review support was conducted by pharmacists from secondary and tertiary hospitals…’ (N5 District/County Administrator)‘Prescription reviews have a positive impact on antibiotic use, with antibiotic use declining every year for both adults and children.’ [N1 BPR working group administrator]Positive consequences resulting from PRF implementation were mentioned by the BPR administrator, such as reducing the APR, reducing irrational antibiotic use, enhancing guideline adherence for diagnosis, enhancing the professional level of physicians and pharmacists in PHIs, and enhancing the trust between physicians and pharmacists, which would be favourable for the future transformation of pharmacists in PHIs in China from pharmacy services to clinical services.PRF conducted as a measure to promote inappropriate antibiotics was recognized by stakeholders, and PRF was considered an essential tool to enhance the quality of care as well as the pharmacy service at PHIs. Furthermore, administrators believed that PRF could help to intervene in the irrational clinical behaviour of inappropriate prescription of antibiotics.‘Prescriptions are more standardized and rational, with fewer prescription errors and less duplication of medications.’ (N23 Physician)‘Favourable to the future transformation of pharmacists is a good policy for pharmacy services.’ (N34 Pharmacist)‘Some district health committees take it seriously and allocate specific funds for PRF.’ (N1 BPR working group administrator)The implementation of PRF led to an increased intention of antibiotic use among physicians, pharmacists and administrators to fulfil responsibilities pertaining to PRF to ensure rational antibiotic use, like using extra funds for PRF.‘Beijing has unified a prescription pre-vetting platform to interface with the existing treatment systems of PHI to unify the review standards’ (N2 District/County Administrator)District administrators identified unified management processes were essential to establish a harmonized standard for conducting PRF. Moreover, one district-level administrator specifically pointed out the importance of designating specialized staff, ideally fulfilled by a clinical pharmacist or a paediatrician, as essential to conducting PRF successfully.‘Supervision of the uploading of this community health service is included in the performance appraisal to ensure the completion of the quality of this work.’ (N5 District/County Administrator)To break irrational prescribing habits, facilities in the Haidian district had an initial review before conducting PRF to further identify and avoid medical errors during prescribing. For example, paediatric antibiotic prescriptions with a target APR ratio were used as a focus to correct irrational prescribingManagement tools targeted at the change of prescribing behaviour were developed to help physicians and pharmacists identify the inappropriateness of prescriptions. For example, performance appraisal was considered a major influence on physicians’ prescribing behaviours by all types of stakeholders alike. Under the pressure of performance appraisal, physicians would pay more attention to make sure prescriptions were appropriate to avoid being financially sanctioned.‘Paediatric antibiotics are reviewed separately; a ratio for each department is developed…’ (N9 Administrator of PHI)‘Pharmacists and review specialists do not have a high enough level of expertise, and personnel have a lack of professionalism and may not have as much experience with more specialized diseases.’ (N13 Administrator of PHI)The capacity of pharmacists at PHIs to review physicians’ prescriptions for patients diagnosed with specialized diseases was questioned by the administrators. Meanwhile, the inadequate capacity of pharmacists to communicate with physicians to correct irrational antibiotic use was admitted by administrators of PHIs as the bottleneck to conducting PRF.‘The number of pharmacists is low and the workload is high.’ (N32 Pharmacist)Pharmacists have an essential role during the PRF process. However, insufficient funding and professional staff hindered the promotion of pharmacists to invest themselves in PRF.‘Pharmacists are required to juggle dispensing and prescription review duties, which puts more manpower pressure.’ (N33 Pharmacist)Different management standards between districts or counties made it even more difficult to evaluate performance consistently across 16 districts in Beijing.‘Performance review criteria may not be consistent across districts.’ (N1 BPR working group administrator)The lack of equipment, systematic training and human resources were obstacles to better conducting of the PRF, as mentioned previously. Furthermore, when Chinese herbal medicines were involved in the prescription, it was hard to conduct PRF since there were no specific review criteria for this category of medicine.‘There are no better and finer rules when it comes to pointing out herbal medicines; there are no more detailed criteria for drug interactions.’ (N13 Administrator of PHI)The lack of human resources  and information systems limited PRF from reaching its full potential. In most PHIs, pharmacists only had Associate’s and Bachelor’s degrees and little work experience at large public hospitals, where freshmen were trained in more sophisticated programmes. Therefore, pharmacists in PHIs were only trained to dispense drugs and could have limited capacity to review prescriptions through a clinical lens. In addition, due to limited funding, the information system was not installed in some PHIs and therefore the pharmacists could only manually check the prescriptions, which was inefficient.‘Doctors will compromise to meet the needs of their patients and to not cause complaints. The community is simply using the drug for patient satisfaction.’ (N1 BPR working group administrator)Patients and their family members were widely recognized as social influences on the prescribing of physicians. Sometimes physicians felt pressured by patients and their families to prescribe antibiotics.‘Performance-based intervention can be a double-edged sword that may cause some people to become rebellious and resistant to the prescription review process.’ (N16 Administrator of PHI)Obstacles were found from both management and technical perspectives. First, PRF results would affect performance appraisal, which was related to the salary of physicians in PHIs. This caused some controversies since some physicians would, therefore, pay more attention to their prescribing behaviour. However, some physicians were resistant to PRF, worrying that their salaries could be affected.13 increasing justified antibiotic use, de-escalation and adherence to guidelines in Nepal,15 decreasing antimicrobial use in India,9 and reducing antibiotic utilization in Lebanon.16 However, little attention was paid to how PRF, as a core strategy of AMS, exerts influence on the appropriateness of antibiotic use in primary care.22To the best of our knowledge, this is the first study in the primary care setting to identify the systematic facilitators and barriers of PRF implementation in LMICs. Previous studies merely focused on the effect of PRF to reduce the inappropriateness of antibiotic use in a hospital setting, including optimizing carbapenem use by promoting a de-escalation strategy in Japan,In line with studies abroad, we found that some of the informants (42%) mentioned that PRF policy made antibiotic use more reasonable with the reduction in APR in nearly 10 consecutive years in the primary care setting (APR data from seven informants). Facilitators, including more prudent prescribing behaviour and attitude towards antibiotics, deeper communication with patients, and enhancement in expertise under management, were achieved through PRF. However, barriers to the expertise capacity of pharmacists and physicians, specialized human resources in PHIs, and discordant prescription standards across different districts still block the further enhancement of PRF.23–25 A systematic review conducted in France show that, apart from knowledge and skill, other factors such as patient satisfaction and pressure, time constraints, diagnostic uncertainty and externalized responsibility could be driving factors of antibiotic prescribing decisions.27 Consensus of studies showed that a ‘culture of expectation’ could explain why patient satisfaction makes physicians compromise with an antibiotic prescription. Furthermore, the perception of patient pressure could be exacerbated by economic concerns or patient satisfaction scores.27 Time constraints resulting from work overload could be another factor in inappropriate antibiotic prescribing.27 Since symptoms of bacterial and viral infections could present similarly, diagnostic uncertainty could lead to antibiotic prescribing as a measure for physicians to avoid potential risks when diagnostic tests were not available.26Knowledge and skill were commonly documented factors in the well-studied knowledge-attitude-practice (KAP) model to exert a positive effect on physicians’ clinical choices when facing presumed infections in PHIs.28 Likewise, our qualitative analysis also identified patient pressure as an underlying factor contributing to inappropriate antibiotic use. In addition, under the co-effect of patient influence under the ‘Social influence’ TDF subdomain and knowledge under the ‘Knowledge’ TDF subdomain, physicians would compromise an antibiotic prescription to alleviate the pressure from the patients. When considering the condition of paediatric visits, parental pressure such as reassurance and advice regarding children’s illnesses, along with other parental factors like poor antibiotic knowledge and personal past experiences influencing decision-making between parents and healthcare professionals,29 could cause an inappropriate prescription for children.An umbrella review across PHIs worldwide showed that social influence factors could be a predictor of antibiotic prescribing of physicians, such as pressure from patients resulting from patient economic condition or other demographic characteristics.31 Furthermore, factors such as physician beliefs about patient demands could affect the clinical decision of physicians, and inappropriate antibiotic prescribing would therefore drive antibiotic abuse.32 Furthermore, clinical guidelines in PHIs were issued by authorities around the world to conduct the right antibiotic use for clinical decisions. However, unsatisfactory adherence to clinical guidelines was found not only found in PHIs in LMICs, but also in PHIs in high- to middle-income countries (HMICs) like England and Denmark.34 Regarding medical as well as non-medical considerations, physicians developed and rely on their experience and habits in decision-making on antibiotic prescribing.34 This phenomenon highlighted the need for effective targeted intervention. For example, as our stakeholders implemented their PHI, they held a morning meeting to read up and share the Chinese guidelines for common infections (N10 Administrator of PHI), which enhanced the level of awareness and practice of adherence to the guidelines in the long run. However, lack of access to relevant antibiotic prescribing guidelines could also be considered a barrier in some HMICs.35Barriers identified include a shortage of human resources and low capacity of information technology for pre-prescription review  in PHIs in China. This finding is similar to what has been identified in other LMICs like India; non-clinical factors in this domain were found to contribute to antibiotic abuse, such as financial incentives and time pressure affecting the decision processes of physicians.36 Nonetheless, successful practices targeted at reducing and optimizing antibiotic prescribing could be reached under health system organizations and resources in Beijing, China.Overall, factors at the individual, community, health system and societal levels in mainland China were found to contribute to inappropriate antibiotic use in communities.Our study had limitations. First, the sample size was small due to the limited sources, which could undermine the representativeness of the results; however, we included all economic levels of all districts in Beijing and all types of stakeholders engaged in PRF to moderate the effect. Second, we did not provide the data on antibiotic resistance to show the consequence of PRF on prudent antibiotic use. Further study could focus on exploring the effect of PRF on antibiotic resistance. Third, the demographic data of the informants were not provided due to the limit of data accessibility.Our study identified facilitators and barriers to PRF implementation through the TDF framework in PHIs, in Beijing, China. However, focus on barriers is needed, including further improvement in harmonizing unified standards, and information technology, strengthening the guideline of PRF.dlad128_Supplementary_DataClick here for additional data file.


Music therapy has seen increasing applications in various medical fields over the last decades. In the vast range of possibilities through which music can relieve suffering, there is a risk that—given its efficacy—the physiological underpinnings are too little understood. This review provides evidence-based neurobiological concepts for the use of music in perioperative pain management.The current neuroscientific literature shows a significant convergence of the pain matrix and neuronal networks of pleasure triggered by music. These functions seem to antagonize each other and can thus be brought to fruition in pain therapy. The encouraging results of fMRI and EEG studies still await full translation of this top-down modulating mechanism into broad clinical practice.We embed the current clinical literature in a neurobiological framework. This involves touching on Bayesian “predictive coding” pain theories in broad strokes and outlining functional units in the nociception and pain matrix. These will help to understand clinical findings in the literature summarized in the second part of the review. There are opportunities for perioperative practitioners, including anesthesiologists treating acute pain and anxiety in emergency and perioperative situations, where music could help bring relieve to patients. Pain is a fundamentally subjective experience. This is reflected in the revised International Association for the Study of Pain (IASP) definition of pain , where pThe primary nociceptive path of this ascending system is the spinothalamic tract. Information on this path travels either towards reticular formation (RF) to modulate arousal, the periaqueductal gray (PAG) in the mesencephalon  , or is fSpinal trigeminal projections travel to the RF and continue with other afferents, ending close to the PAG or in the ventroposteromedial nucleus  and intralaminar nuclei of the thalamus. The VPM also has connections to the primary somatosensory cortex.pain matrix [The spinoreticular tract carries information to nuclei in the reticular formation and rostral ventromedial medulla (RVM) and from there to the intralaminar nuclei of the thalamus. These pathways create a multisynaptic circuit, the n matrix . Signal n matrix .Following a noxious stimulus, information on the tissue injury is transmitted from the periphery to the posterior horn of the spinal cord, where primary pain nerve fibers end and synapse. The secondary neuron crosses over and ascends contralaterally in the ascending spinal pathways of the anterolateral system. Here, the signal can travel one of three ways:Descending pathways originating segmentally in the spinal cord , as wellWhen Gardner et al. published their study on auditory analgesia in dentistry in 1959 , a vividMusic as part of a multimodal intra- and postoperative pain management concept has significant effects on both subjective pain levels and analgesia requirements postoperatively . The modPain perception is dependent on the emotional valence  of a stimulus . By chanThe provoked change in emotional appraisal of an unpleasant stimulus can be viewed in the context of the positive valence musical sounds can have on the state of emotional arousal. Musical sounds perceived as pleasant by an individual can trigger a dopamine-fueled reward cascade. It leads to positive emotions and so-called musical chills as the highest state of pleasure caused by music –52 and cThe second pain-modulating component of listening to music presents as a shift in attentional focus (distraction). In neuroimaging methods , this seems to be characterized by a decrease in pain-induced delta-amplitudes in the cingulate gyrus and the insular cortex. This shifts attention away from pain towards music .Present-day experimental findings speak for more complicated neuropsychological processes involving preexisting expectations responsible for the analgesic effect of pleasant sounds •. This iFunctional magnetic resonance imaging (fMRI) analysis has shown different activation patterns of spinal and cortical areas to painful stimuli with music compared to without music . This caaffective pain component of the amygdala, insular cortex, and PAG), though not the perceived pain intensity  [EEG signals obtained during and after a painful stimulus furthermore suggest that preferred music decreases the unpleasantness  •, 48, 61mponent) • could nmponent)  found thmponent) ) was mosmponent)  or incremponent) , 64). Thmponent) . For examponent) , 65, 66.Brain regions involved in pain processing, namely, the PFC, amygdala, and hippocampus, are also involved in stress response . These iMeasuring cortical electrical signals has been shown to be a useful and accessible tool to determine effects of both musical  and painTo objectify the clinical analgesic effect of perioperative music interventions, the following outcome parameters seem to have been most useful: the effect on postoperative pain during the first 24 h after general anesthesia , the eSo far, no significant reduction in length of hospital stays, time spent in the intensive care unit, or overall costs during hospitalization through music-analgesia could be demonstrated •, 74.Most of the systematic reviews and meta-analyses, including recent publications by Fu et al. • and DalThe currently available body of literature is very heterogeneous, which makes concrete conclusions for practice only possible to a limited extent. In order to make use of music as a tangible co-analgesic, a feasible framework for such intervention needs to be defined. Further research needs to determine the differences and optimal timing of the intervention . Compelling evidence for preserved auditory sensory perception under general anesthesia  suggestsAcross all systematic reviews and meta-analysis currently available, no adverse effects of musical interventions have been reported.ClinicalTrials.gov on perioperative musical intervention during general anesthesia [There are currently two ongoing studies registered with esthesia , 88.There appears to be some consensus that auditory stimulation with music during or after surgical interventions, under sedation or general anesthesia, can be considered an effective and low-cost, low-side-effect complimentary treatment to alleviate procedural and postoperative pain. Musical interventions have a low-threshold applicability in everyday clinical practice. Offering music via headphones during operations under regional anesthesia, with or without sedation, is already common practice. Anesthesia providers seem to hope for a relaxing and distracting effect, especially during operations with high noise levels, such as orthopedics. Patients can play their own music via their mobile phones or choose from a provided music library with a selection of genres and artists. In our experience, clinicians do not seem to have concrete expectations of reduced intraoperative opioid or sedative requirements when offering musical stimulation to their patients in the operating room. Our aim was to concretize anecdotal assumptions of musical analgesia, encourage anesthesia teams to systematically use music as a co-analgesic, and suggest ways in which future research in this area can unite neuropsychological and biological, philosophical, and anesthesiologic theories of pain and consciousness and further establish pain modulatory approaches.


Current American College of Sports Medicine (ACSM) exercise guidelines for exercise oncology survivors are generic one-size fits all recommendations, which assume ideal or prototypic health and fitness state in order to prescribe. Individualization is based on the objective evaluation of the patient’s baseline physiological status based on a linear dose response relationship of endpoints. This is only a partial snapshot of both the acute and chronic responses exercise can provide. Each acute exercise session represents a unique challenge to whole-body homeostasis and complex acute and adaptive responses occur at the cellular and systemic levels. Additionally, external factors must be considered when prescribing exercise. Network physiology views the human organism in terms of physiological and organ systems, each with structural organization and functional complexity. This organizational approach leads to complex, transient, fluctuating and nonlinear output dynamics which should be utilized in exercise prescription across health states. Targeting health outcomes requires a multi-system approach as change doesn’t happen in only one system at a time or in one direction Utilizing a multi-system or person-centered approach, allows for targeting and personalization and understands and targets non-linear dynamics of change. Therefore, the aims of this review are to propose a paradigm shift towards a Network Physiology approach for exercise prescription for cancer survivors. Cancer treatment affects multiple systems that interact to create symptoms and disruptions across these and therefore, prescribing exercise utilizing both external daily factors and internal physiological networks is of the highest order. Cancer diagnosis and treatment has a number of well documented physiological, psychological, and physical changes and challenges. A number of studies have demonstrated that cancer treatments are associated with either short-term or chronic dysfunction which includes an accelerated aging phenotype which can include multi-system declines . RegularOne reason for recommending this lack of precision it that results of randomized trials, focus on individual components of response and endpoints . These endpoints only offer a partial snapshot of both the acute and chronic responses exercise can provide. Understanding how each acute (daily) exercise session represents a unique challenge to whole-body homeostasis is important to understand the complex adaptive responses that can occur at the cellular and systemic levels. Whole body exercise is a dynamic challenge that precipitates change in numerous cells, tissues and organs in response to each specific acute exercise challenge. It is important to understand that each acute session will offer an additive effect to facilitate eventual chronic change. Network physiology views the human organism in terms of physiological and organ systems, each with structural organization and functional complexity . The outOptimizing exercise training to improve post-treatment health and reduce risk of comorbid chronic disease/and recurrence is imperative for long term treatment and survivorship in the cancer continuum. However, much like those studies testing the benefits of exercise for healthy persons, the clinical guidelines for cancer patients closely adhere to the exercise guidelines of World Health Organization (2019) and American College of Sports Medicine  . OverallExercise oncology studies using prescriptions based on the national exercise guidelines have often shown physiological, psychological and physical function non-responses, leading authors to conclude a given intervention is not effective and/or not strong enough evidence to base future exercise recommendations on. . This is2 max as a linear process that is trainable. Using this reasoning, every person who trained hard enough would be running the Boston marathon. This is of course not the case, as interactions change in time, both quantitatively and qualitatively. There is not a clear dose response relationship to VO  and thus the aim of prescription becomes a decrease in variability and improvements in quality of life. A daily exercise session needs to consider a patient’s health status beyond disease state and consider daily mood, nutrition, previous night’s sleep, illness , stress levels and the in the moment environment. These factors all individually contribute to how each exercise session will affect the physiological systems as a whole. Thus, a person-centered perspective that considers daily external variables and internal physiology  would coGiven the multitude of different responses that changing one of the four steps of exercise prescription  can elicOver 50 years of exercise research has informed practice in athletic and general populations, however these findings have rarely been used in clinical trials and populations  AthleticA person-Centered Exercise Prescription offers an ideal framework in cancer populations due to the heterogeneity across cancers . This heterogeneity can have profound effects on daily motivation, readiness and also capacity for physical activity . Cancer 1) Completion of a Person-Centered Needs Analysis2) Person Centered Exercise Goals Co-Created with Patient3) Daily Readiness Assessment and Score to Inform Acute Exercise Prescription4) Daily Exercise Prescription Based on a Daily Readiness ScoreTherefore, exercise prescription in the cancer continuum should be centered around a four-step process. This four-step process is a combination of understanding how acute exercise sessions combine to affect chronic change .1) Compl-more efficient recovery patterns (ie stress to recovery ratio)-add more or less volume per week (dependent on daily fatigue or other symptoms)-increase training frequency (by responding to in the moment feeling)-decrease plateaus that lead to discontinuation of exercise (increased adherence)This Person-Centered approach to autoregulation is based in flexible nonlinear periodization and considers an individual’s daily readiness to prescribe acute exercise. This approach uses the nonlinear training model framework but changes daily training based on the daily readiness of a trainee to perform in a specific training zone . Daily tDespite over 50 years of research into manipulation of non-linear exercise program design, these exercise prescriptions are not currently used in exercise oncology practice and research. To date, only one study had examined nonlinear periodized training in a clinical population . The stuUnderstanding symptoms and side effects of cancer treatment requires an understanding of complex, nonlinear systems within individuals with dynamic day to day and in the moment states. In order to support targeted outcomes across systems we must improve our prescriptive pproach to allow for an understanding of nonlinear health This understanding allows adaptations to daily contexts and creates training programs that have less stress and less risk of attrition  A non-li


Emotional clarity is one facet of emotional intelligence that refers to one’s meta-understanding of and ability to identify and describe feelings. The existing research has largely focused on trait emotional clarity and its benefits for greater psychological well-being, more successful emotion regulation/coping, and diminished psychopathology. Researchers have begun to examine state or momentary emotional clarity in daily life. In this paper, we situate emotional clarity within the larger literature on emotional intelligence abilities. Then, we argue that state clarity relies on the ability to incorporate information from the dynamic contexts that emotions unfold in and should more closely reflect one’s emotional intelligence ability relative to traditional trait measures. In addition, we review and make recommendations for measuring state emotional clarity in daily life and propose future research directions, focusing on how state emotional clarity could inform the study of emotion regulation, decision making, and goal pursuit in daily life. Conceptions of emotional intelligence frequently involve sets of abilities related to one’s own and others’ emotions. Among the abilities proposed to comprise emotional intelligence, abilities related to perceiving emotions, understanding emotions, and using/regulating emotions are some of the most frequently cited . EmotionLike emotional intelligence, emotional clarity has received attention across disciplines in psychology, including, but not limited to, clinical, cognitive, personality, social, and industrial/organizational psychology. Though emotional clarity can be understood as a standalone construct, it is also a dimension of several multidimensional constructs, including alexithymia  and identifying emotions conveyed through pictures of artwork and landscapes (the Pictures test). The understanding facet of emotional intelligence is also measured with two tests: identifying emotions that are intensifications of other emotions (the Changes test) and identifying emotions that are blends of other emotions (the Blends test). Though the emotion perception facet is defined as being the ability to recognize emotions in the self, others, and other stimuli, the MSCEIT only measures the ability to recognize emotions on static faces and in stimuli such as landscapes. Likewise, the emotion understanding tests do not test the ability to identify changes in intensity or blends of emotions in the self. However, this issue is not unique to the MSCEIT. Other tests of emotion perception  representation of their emotional experiences, should be considered an indicator of fluid emotional intelligence ability. Empirical evidence suggests that emotional clarity facilitates the healthy processing of emotional experience. Higher emotional clarity has been linked to faster processing of negative emotional information . Lower eResearch has also unambiguously linked trait emotional clarity to a host of psychological processes and outcomes that one would expect a facet of emotional intelligence to be linked to. Low trait emotional clarity has been linked to several indicators of psychopathology, including depression , worry , panic , and proDespite primarily being studied as a trait, emotional clarity is a dynamic process . That isWe argue that fluctuations in emotional clarity may be especially important to study because they could also reflect differential access to one’s fluid emotional intelligence abilities across various contexts. Reports of state or momentary emotional clarity rely on the abilities to incorporate information from various sources at a given time  and indicate one’s online ability to clearly represent their emotional experiences. To date, only a handful of studies have assessed state emotional clarity in daily life. Below, we review how state emotional clarity has been operationally defined and measured across these studies. We also provide recommendations for measurement and situate these measurement issues within the emotional intelligence ability field.Direct measures of examining state emotional clarity involve relatively straightforward self-reporting about one’s experience. These measures prioritize face-validity  versus between-subjects (at the person level). Each of these studies examined the proportion of variance of the momentary emotional clarity was at the within- versus between-person levels using the intraclass correlation (ICC). A final concern regarding measuring state emotional clarity over the course of an experience sampling study is whether being asked to report on one’s emotions and one’s level of emotional clarity will systematically increase the emotional clarity over the course of the study. To illustrate the lack of systematic time effects on momentary emotional clarity, we present data from 12 randomly selected participants from the authors’ most recent experience sampling study. Indirect measures of state emotional clarity capture the performance or speed of information processing that is relevant to a target characteristic . These mAlthough RT has the advantage of being unobtrusive and less subject to desirability bias, this measure of state emotional clarity has some important limitations. First, clear data processing rules are needed when working with RTs ; for exaWhen measuring state emotional clarity, several factors should be considered. Given the brevity of state and momentary measures, they are unable to capture the same amount of construct coverage that longer trait scales can. Consequently, measuring state emotional clarity using a combination of direct and indirect measures may be superior to using either in isolation. When using direct measures, single-item measures strongly limit how broadly and reliably a construct can be measured , which uThough self-report items have typically been avoided in the assessment of emotional intelligence abilities, it may be necessary to include this method in bridging fluid and crystallized emotional intelligence. In avoiding a self-report methodology, the current measures of emotional intelligence ability  are unable to assess the experiential employment of emotional intelligence. Within-person approaches to understanding psychological phenomena are becoming increasingly popular for explaining behavior e.g., . EmpiricAs described above, the current body of studies examining state emotional clarity estimate that about one-half to two-thirds of the variance in emotional clarity is at the within-person level. This indicates that, on average, each person’s state or momentary emotional clarity varies across time and contexts. Fluctuations in momentary emotional clarity likely reflect the extent to which one’s abilities to be clear in the moment are either enhanced or hindered by factors such as the context in which emotions are unfolding. The broader literature on personality traits and states provides some clues as to why people vary in emotional clarity and how to understand the relation between the trait and state levels. Whole trait theory  argues tA second assertion from whole trait theory that helps to characterize fluctuations in emotional clarity is that the stable mean of the density distribution reflects a descriptive trait level, while the spread of states reflects the influence of social-cognitive mechanisms  that rise in response to one’s situation/context. The process of clearly identifying one’s emotional state is one of signal detection . To percThe extent to which one can clearly understands their emotions should be linked to how intense those emotions are. When examining RTs to emotion items, Emotional clarity should vary based on the intensity of the emotional signal that one is detecting . ClearerSocial interactions often elicit emotions, and emotions impact social interaction . TherefoAppraisal theories e.g.,  argue thState emotional clarity concerning the type of emotion one feels may in part depend on how clear the source of that emotion is. Interoception refers to the processing and representation of bodily signals . EmotionThe usefulness of interoceptive cues may also depend on age. The physiological hypothesis of emotional aging  argues tFunctional theories of emotions  propose Understanding the variability and fluctuations in one’s ability to clearly understand their emotions has important implications. Over the last two decades, many efforts have been made to increase socioemotional skills and emotional intelligence abilities  and incidental  have both been shown to impact the decision-making process . In situBehavior is directed by goals  this ability and the downstream effects that being clear in the moment have will be important for understanding how to best cultivate the ability to be emotionally clear.


Globally, crickets are gaining recognition as a valuable alternative protein source for human consumption due to their lower resource requirement and ecological footprint compared to traditional livestock. In this paper, we examine strategies that may expedite the sustainable domestication of crickets as a food source. Using survey data from 306 households in western Kenya, we find that supplying cricket production starter kits, granting access to credit facilities, encouraging participation in farmer groups, and fostering partnerships can enhance the adoption of cricket farming. Moreover, we provide new evidence that institutional training significantly increases cricket yields while embracing cricket consumption (i.e. entomophagy) increases market supply. These findings underscore the importance of technical training, provision of production starter kits, and raising awareness about entomophagy to achieve sustainable mass production and adoption of cricket farming. The United Nations (UN) projects a global population growth of approximately 9.5 billion by 2050, which will result in an unprecedented increase in the global demand for food UN . Preciseicipe) and other partners have over the past decade invested in research and technologies to increase awareness, acceptance, production, and consumption of insects both for food and livestock feed in sub-Saharan Africa (SSA). This collaboration has led to the discovery of a new, previously scientifically undescribed edible cricket (Scapsipedus icipe) with great promise for mass production for human consumption and inclusion as an alternative protein ingredient in chicken feed  and the probability of adopting cricket farming. Conversely, factors such as group membership, household acceptance of crickets as food, and the provision of cricket production starter kits post-training are positively correlated with the likelihood of household adoption. In the second stage of the model, we find that remoteness negatively impacts yield, while access to credit appears to boost yield.In the second research question, we examine the impact of institutional training sources on cricket production the multinomial endogenous treatment effects (METE) model. We find that access to training from NGOs and a public research university increase cricket yields by 55.4% and 70.8%, respectively. Lastly, we examine the impact of consumption behavior on market supply using an endogenous switching regression (ESR) model. The first stage ESR estimates reveal that geographical remoteness and market inaccessibility negatively correlate with the likelihood of cricket consumption. In contrast, the awareness of crickets as a nutritious food source is positively linked to consumption rates. Furthermore, collective cricket farming activities show a positive correlation with market supply among cricket-consuming households. We also observe a marginal association between higher education levels and increased market supply among non-consuming households. Estimates from the second stage of the ESR model reveal that cricket consumption boosts market supply by 20.5%. Additionally, we find suggestive evidence that if non-consuming households were to adopt cricket consumption, there is potential to augment their market supply by 29.5%.The rest of the paper is organized as follows: We briefly present a literature review in “Livestock value chains are already an ecological stressor and a threat to global ecosystems. For instance, there is a growing consensus that animal-based foods cause more greenhouse gas (GHG) emissions as compared to insect-based foods  in Kenya is not well established, and consumption is likely constrained by various factors. Firstly, most insects are still harvested from their natural environments , implying that their supply is dependent on location and seasonality Nonaka . SecondlWe conducted household surveys across three counties in Western Kenya: Kisumu, Siaya, and Homabay  survey tool. The questionnaire contained different modules that captured detailed information on household socioeconomic characteristics, awareness and perceptions on insects farming and consumption, access to cricket farming training, cricket production, marketing and associated constraints, and institutional support services.The data collection exercise was conducted by well-trained enumerators supervised by Domestic cricket farming being relatively new  cricket farming after receiving training and Yi = 0 if otherwise (non-adopters). β0 is the intercept, βij is a vector of parameters to be estimated; Xij is a vector of explanatory variables which explain cricket farming adoption behavior; Xij and symmetrically distributed about 0.The first (selection) equation in a Heckman model is a probit estimator. We, therefore, specify our selection equation as:λ which is the ratio of the ordinate of a standard normal distribution to the tail area of the distribution  n Greene  as shownAccording to Heckman , if the Xij is a vector of explanatory variables, The second stage (outcome equation) estimated using OLS estimator and is specified as:i will therefore choose a training source or a bundle of training sources j, over any other alternative source k, if Vij > Vik, k ≠ j where Vi is the indirect utility derived from any of the training sources.In this study, potential cricket farmers had two main cricket production training sources: Public university and non-governmental organizations. In addition, due to high possibility of knowledge spillovers, farmers are also likely to receive training from fellow farmers who have receieved institutional training. Nonetheless, our aim is to evaluate the effects of institutional training sources. We theorize that farmers will choose a training source that maximizes expected utility subject to socio-economic and institutional constraints. A farmer However, when the farmers are required to choose from available cricket production training sources (providers), selection bias and endogeneity problems may arise as the choice decision could be influenced by other unobservable characteristics. Failure to account for endogeneity and selection bias can either overestimate or underestimate the actual effects of the treatment variable on the outcome variable of interest. As a result, we follow Deb and Trivedi  and applVij, specified as:zi is a vector of household socioeconomic characteristics; The METE model estimation proceeds in two stages. The first stage applies a multinomial logit which models potential cricket farmers’ adoption decisions for the two main training sources. This first stage assumes that farmers are rational and will therefore choose a training source that maximizes their indirect utility yi is the quantityi; xi represents exogenous covariates with parameter vector β. Parameters γj denote the treatment effects of participating in training relative to the non-participants. If the farmer’s decision to participate in training is endogenous and assuming dij to be exogenous, estimates of γj would be biased and inconsistent thus necessitating exogeneity tests in outcome Eq.  of crickets harvested. We specify the outcome equation as:Estimation of cricket production and supply gains from pre-existing consumption behavior of households based on non-experimental data is not trivial because of the need to find a good counterfactual. What we cannot observe is the production effects of those households that are already cricket consumers should they have chosen not to be cricket consumers. Neither can we observe the effects on non-consumers had they been consumers. Experimental and quasi-experimental studies would effectively address this problem by having two non-consuming insect groups to begin with: treatment and control. With this approach, the treatment group would receive adequate training on how and why they should eat crickets including how to prepare the crickets as food and the benefits of consuming insects in general (entomophagy). We would then presume that the outcomes observed on the control are statistically representative of what would have occurred without adoption.However, routine cricket consumption is not well established in Kenya and therefore not randomly distributed into two well-defined groups of the consuming and non-consuming households, but rather the households themselves decide to consume or not to consume based on their awareness and perceptions towards crickets as an alternative food. As such, there may exist systematic differences between consumers and non-consumers due to observable household characteristics such as education, household size, access to information, income levels, etc. Further, unobservable characteristics such as attitudes, skills, and individual motivations may influence cricket consumption decisions and subsequently affect potential yields and market supply by the households  and E(ε2 |C = 0) are given as shown:1 and λ2 which represent the selectivity terms. If the estimated covariance In light of the above-mentioned issues, we follow Maddala and Nelson  to estimWhile the model parameters can be identified through interpretation of the selectivity terms (inverse mills ratio coefficients), it is recommended to adopt a plausible instrument(s) in the outcome equation for more robust identification  and untreated group on market supply is computed as:In Eq.  the termFinally, we estimate the transitional heterogeneity effects (TH), which is whether the effect is larger or smaller for the households that practice cricket consumption or for the households that did not practice cricket consumption in the counterfactual case that they did practice cricket consumption [i.e. the difference between Eqs.  and 11)11)]. A cGiven the assumption that the error terms have a trivariate normal distribution Eq. , the ESRTable About 26%, 35%, and 39% of the sampled farmers received training on cricket farming from a public university, NGOs, and fellow farmers respectively. This finding underscores the important role of rural networks in generating knowledge spillovers (positive) necessary for the adoption of new farm enterprises and technologies (Pratiwi and Suzuki The average age of the farmers was 48 years with non-adopters older (49 years) than adopters (46 years) with a marginal statistical difference. Years of formal education and household size were averagely 9 and 5 years, respectively, and no significant statistical difference was observed between adopters and non-adopters. The average statistically significant difference in annual income between adopters  and non-adopters  emphasizes the economic importance of cricket farming in transforming rural incomes.With regard to access to institutional support services, 35% of both adopters and non-adopters reported having accessed credit. Interestingly, there was a significant difference (at 5% level) between the two groups with regards to membership in a rural group with about 86 and 77% positive responses among adopters and non-adopters, respectively. This finding is consistent with existing literature on the role of social networks and rural institutions in the adoption of new farming enterprises such as cricket farming  equation reveal that distance to main road, group membership, insect consumption, and provision of rearing equipment affects the probability of adoption of cricket farming after receiving training. Notably, holding all other factors constant, longer distance to the main road undermines adoption of cricket farming as it is associated with a reduction in the probability of adopting the enterprise after exposure to training by 2.4%. Previous studies have shown that poor rural road network could potentially limit timely access to inputs, technical support and financial resources necessary for agricultural production  on other farm or non-farm activities. Finally, the negative association between inaccessibility to roads (remoteness) with cricket yields corroborates evidence from existing studies that poor road network in rural areas limits farmers’ access to both factor and output markets thus undermining farmers’ full production potential  respectively. The differential effects could be attributed to differences in skill-set endowments and specialization among trainers from the two sources of training, although this assessment is beyond the scope of the current study.The estimates of the first stage of the ESR model are presented in Table The statistically significant likelihood ratio test of independence of the selection and outcome equations indicates that there is a positive correlation between cricket consumption and market supply. This implies the presence of endogeneity problem hence justifying the use of ESR model. Additionally, the Wald test is statistically significant indicating the goodness of fit of our ESR model.First stage ESR estimates show that determinants of cricket consumption are distance to the main road, distance to the main market, nutritional perception, and entomophagy awareness. Both distances to main road and the market had negative effects on the decision to consume crickets. This is probably because access to roads and shorter distances to markets may facilitate access to information. As a result, households that are favored by this proximity may be relatively more informed on alternative food sources compared to their remote counterparts. Besides, existing literature points out that good road networks and market accessibility in rural areas improve household decision making and economic outcomes due to increased access to agricultural information services Jacoby .Farmers’ awareness of crickets as source of food and perceing them as nutritional had positive effects on consumption decisions. These findings are consistent with current literature on drivers of insect consumption. For instance, Schouteten et al.  observedWith regard to determinants of market supply, the mode of operating cricket farming affected market supply among cricket consumers. As such, operating cricket farming/enterprise with partners or as a group with other farmers increases the quantities sold among the cricket-consuming households. This could be attributed to efficiencies resulting from labor pooling and diverse skill-sets when operating with partners as cricket farming is labor-intensive  is significantly different from zero. The results suggest that both observed and unobserved factors influence market supply gains (welfare outcomes) given the consumption decision. The significance of the coefficient of correlation between the consumption equation and the outcome equation indicates that self-selection occurred in the decision to accept and consume crickets as an alternative food/protein group.The estimates for the average treatments effects (ATT and ATU) and the heterogeneity effect (HE) are presented in Table The results reveal that cricket consumption (entomophagy) significantly increased market supply and has the potential to increase that of non-consuming producing households. Interestingly, the results in Table In this study, we analyzed socio-economic and institutional factors that would sustain the adoption of edible cricket farming and estimated the effects of institutional training and cricket consumption on production and market supply. Firstly, in assessing what determines how much adopters produce, we hypothesized that this hurdle is dependent on the decision to take up cricket farming after receiving training. We applied the Heckman sample selection model to assess socio-economic and institutional factors that influence adoption and production. Secondly, we hypothesized that the training provider determines the ultimate quantities produced. To that effect, we estimated the effect of the training sources on the production of edible crickets using a multinomial endogenous treatment effects model. Lastly, we deploy an endogenous switching regression to estimate the effects of household consumption of crickets (entomophagy) on market supply.Our findings confirm that after being exposed to training, cricket adoption is enhanced by shorter distance to the markets, membership in rural institutions, provision of rearing equipment (starter kits), and practicing entomophagy. The implication is that uptake of new cricket farming enterprises would require both national and county governments in Kenya in collaboration with development partners to implement policies that address road infrastructural challenges to the market. The policies should further encourage and promote rural institutional capacity building of community members on cricket farming technologies for food and feed. Lastly, sensitization and awareness creation on the nutritional and health benefits of entomophagy to households and economic wellbeing of youth and women is crucial.Cricket yield is significantly higher for adopters that received technical training from various institutions. This implies that future programs should take a collaborative approach in providing specialized training and technical backstopping to assist cricket farmers in overcoming adoption barriers. Research and development partners should endeavor to provide support through the provision of affordable production equipment, entrepreneurial skills, financial support, value addition, professional training and market access.Our results further confirm an effect of cricket consumption on market supply. Thus, commercial cricket mass production and market demand would readily be achieved if frequent sensitization campaigns on cricket consumption are widely carried out to encourage adoption, acceptability, and practices of entomophagy in the various communities and beyond. Nevertheless, despite the aforementioned insights and policy implications, this study has some limitations that can be addressed by future research. Firstly, the current study focuses on the cricket enterprise from a supply-side only. Secondly, this study does not look into the cricket farmers’ disadoption behavior and lastly the study relies on cross-section data which has empirical limitations in estimating causal effects. Future studies should therefore address these limitations by assessing the cricket demand drivers, farmers’ disadoption behavior and endeavor to overcome data and study design limitations to analyze the dynamics of adoption, demand and supply as well as causal effects of institutional and behavioral interventions on consumption and yields.


Pharmacogenomics (PGx) aims at tailoring drug therapy by considering patient genetic makeup. While drug dosage guidelines have been extensively based on single gene mutations (single nucleotide polymorphisms) over the last decade, polygenic risk scores (PRS) have emerged in the past years as a promising tool to account for the complex interplay and polygenic nature of patients’ genetic predisposition affecting drug response. Even though PRS research has demonstrated convincing evidence in disease risk prediction, the clinical utility and its implementation in daily care has yet to be demonstrated, and pharmacogenomics is no exception; usual endpoints include drug efficacy or toxicity. Here, we review the general pipeline in PRS calculation, and we discuss some of the remaining barriers and challenges that must be undertaken to bring PRS research in PGx closer to patient care. Besides the need in following reporting guidelines and larger PGx patient cohorts, PRS integration will require close collaboration between bioinformatician, treating physicians and genetic consultants to ensure a transparent, generalizable, and trustful implementation of PRS results in real-world medical decisions. Precision medicine aims at tailoring disease prevention and management to identify optimal therapies by considering individual factors, such as genetic profile, health conditions, environmental exposure, and lifestyle. Although very promising, developing and reaping the rewards of precision medicine has proven to be a challenging task, as it requires dealing with the complex interplay between many non-linear associations from factors that result in individual variability.Many studies have shown that many complex diseases, such as mental disorders, addiction, pain responses, etc., can have strong genetic underpinnings. By considering patient-level genetic information, such as significant genomic loci and associated genes, genomic medicine is a rapidly emerging field that is dedicated to improve healthcare practice using an individual’s genomic information . Over thAn adverse drug reaction (ADR) can be defined as “an appreciably harmful or unpleasant reaction resulting from an intervention related to the use of a medicinal product; adverse effects usually predict hazard from future administration and warrant prevention, or specific treatment, or alteration of the dosage regimen, or withdrawal of the product” . In addiPharmacogenomics (PGx) is the study of how an individual’s genetic makeup affects the response to drugs. It can contribute to the development of precision medicine by selecting drugs with better efficacy while lowering the risk of ADRs during clinicians’ prescription decision making process. Many drug-gene pairs are currently used in clinical practice to help in finding the beneficial regimen for a specific patient with a specific condition. Evidence-based guidelines have been developed for more than a decade to advise prescribers in daily clinical practice on an optimal drug regimen according to genotypes or predicted phenotypes . UnfortuOne promising approach in PGx is the use of patient-level polygenic risk scores (PRS). In simple terms, PRS reflects the genetic predisposition for a phenotype of interest. More precisely, PRS calculates the sum of genome-wide risk alleles that are weighted by their corresponding effect size estimates  derived from GWAS summary statistic data . ImportaThe clinical utility of PGS has already been highlighted in recent research. For example, Khera et al.  demonstrLike what has been done in genomic medicine, most progress from pharmacogenetic studies has allowed to identify rare mutations carrying high-risk of poor outcomes. Some examples of common drug-variant pairs implemented in clinical practice to decrease ADR risk are abacavir and HLA-B*5701, thiopurines  and TMPT, among many others. It is also well established that allelic variations of genes involved in drug elimination, such as CYP2D6, can impact drug response both in terms of efficacy and toxicity depending on the metabolic profile of specific drugs. Moreover, predicting PGx endpoints like pain response with a polygenic polymorphisms combination and related gene set involved both in drug response (OPRM1) and disposition  has already been proposed .While showing great promise, the potential impact of PRS in PGx remains largely unknown. This may be not surprising since using PRS with PGx endpoints (safety or efficacy) is more challenging. High fidelity of patients’ response phenotypes to drugs is one of the major limiting factors for this type of research. In addition to compare uniformly treated patients, PGx studies must rely on well-defined endpoints  which requires patient data with high level of granularity in a strictly-defined time duration. This type of information is often only available or recorded patient-level clinical databases. Another difficulty resides in polypharmacy  that increases the risk of drug-drug interaction, or underlying diseases like kidney failure, both may increase susceptibility to toxicity and then modulate estimation of genetic effect sizes.n = 31/50), followed by circulatory and digestive conditions. Among the 105 drug phenotypes that were analyzed, 82 were related to drug efficacy and response and 23 were related to ADR phenotypes. Phenotypes for which GWAS summary data were used to compute PRS were grouped in three distinct categories, i) disease-related phenotype , ii) pharmacogenomic-related phenotype , and iii) ADR-related phenotype .More specifically, a review by  found thCross et al. have also reviewed common drugs associated with PRS studies in ADR and efficacy prediction . FrequenAs briefly mentioned before, PRS construction is based on the weighted sum of risk alleles across the genome. More specifically, PRS analyses need two independent datasets: i) a discovery (base) dataset, that is made of summary statistics  obtained from GWAS and made available online, and ii) a target dataset, that is made of genotypes from individuals for whom we want to compute PRS. The PRS are then estimated for target samples from information obtained in discovery samples. Of note, although incorporating only genetic variants reaching genome-wide significance level may sound intuitive, improving PRS predictability by including many variants showing weaker associations with a phenotype has also been described . This apSNP effect size estimation must be done cautiously given their uncertainty, the fact that not all of them influence phenotypes under study and independence between SNP is not guaranteed. Unadjusted values could result in poor estimation and high standard error. To mitigate this risk, different methods can be used to construct PRS .shrink) model complexity by adding a penalty factor to focus on more important variables. Differences between both techniques reside in the way parameters are tuned to create penalty. Briefly, LASSO regression can reduce variable effect to zero (decreasing the number of variables in a model), while Ridge regression tends to decrease large effects more than LASSO but keeping all variable values more than zero. While combinations of LASSO and Ridge exist, the most appropriate regression methods that should be applied may depend on the underlying phenotype under study and effect size distribution. These are very commonly in machine learning applications (not the scope of this paper), and model parameters can be optimized through iterative process.These techniques, such as Lasso or Ridge regression, are commonly exploited (not only in PRS) to reduce , the second filtering step, consists in removing variants with a p-value that exceeds a predetermined level of significance  . This isificance .Although C + T approach looks attractive because of computational and conceptual simplicity, some authors mentioned that prediction accuracy can be limited . AnotherRecent simulation studies by Zhai et al.  using PGClinical implementation of PRS is a topic of active research . HoweverFirst, a significant well-established bias resides in the predominance of European ancestry in GWAS effect size estimation, limiting the generalizability of PRS results to other populations that are already underserved . Second,Converting good intentions and existing promises into concrete actions necessitates to understand clinicians’ expectations about PRS and the way to develop their trust in genetic clinical tool. As proposed by Hao et al., a transparent PRS report containing directive-free guidelines, along with evidence and limitations about PRS interpretation may be beneficial. This is important at least for two reasons: 1) in order to establish trust, laboratory choices and associated resources that were used to define risk thresholds and interpretation  must be clearly explained, also knowing that these interpretation parameters may vary between risk phenotypes; 2) considering the current absence of demonstrated clinical utility on patient outcomes, physician support through educational resources and genetic counseling should be provided since they are responsible for making the final medical decisions. The importance of reporting informational guidelines is primordial given the need to contextualize PRS results with patient’s medical history.a posteriori when ADR or drug unresponsiveness are suspected but also preemptively when optimal dosage of a drug with a narrow therapeutic index  must be determined as quickly as possible. However, like for many chronic conditions, pharmacological drug response depends on a myriad of factors, whether related to drug properties, patient’s pharmacokinetic profile , or patient’s pharmacodynamic profile . We can therefore easily imagine that multiple variations in the genome can affect drug response, and this is the reason why PRS looks promising in PGx.Genetic variants are nowadays commonly analyzed in PGx, both However, as already mentioned earlier, PGx data are not as available for PRS as is disease information. In addition, as mentioned by Kumuthini et al. , furtherEven though phenotype variance explained by PRS is frequently low, this number is expected hopefully to increase with larger cohorts of patients, predominantly in ethnic population under-represented in currently available biobanks, including UK Biobank and All of US research program . MoreoveAn important issue has emerged due to the lack of reporting guidelines in PRS, along with gaps in data transparency and availability. As previously described, different approaches and parameters thresholds are available to estimate effect sizes. This makes difficult the comparison between PRS and some authors have proposed the Polygenic Risk Score Reporting Standards (PRS-RS) to facilitate translation of PRS research into clinical care .From a clinical perspective, confidence in generalization of research-derived PRS to real-world patients would be essential to ensure appropriate medical decisions. In addition, it will be essential to determine how to deliver this information in ways that providers will find acceptable. Another issue is that careful attention must be paid in a similar way to what must be done when extrapolating the results of clinical trials to a population frequently suffering from additional comorbidities that the one used to derive GWAS effect size data. Despite the above-mentioned barriers in implementing PRS, the effort in developing PRS guidelines and promising examples of reporting workflow are preparing the ground for an effective PRS integration in electronic health records.In conclusion, PRS have the potential to move pharmacogenomics a step further by providing a more personalized and comprehensive view of an individual’s genetic susceptibility to drug response. As illustrated by promising examples of PRS integration into clinical workflow, and while awaiting more robust genetic data across a bigger spectrum of genetic architecture, transparent information about the promise and limitations of PRS interpretation is key to help in its implementation for patient care. As PRS is expected to keep on improving in their ability to capture heritability of polygenic traits, there is good reason to expect that appropriate clinical trials will soon prove their clinical utility.


Advances in sequencing technologies and bioinformatic analyses are accelerating the quantity and quality of data from all domains of life. This rich resource has the potential to reveal a number of important incidences with respect to possible exchange of nucleic acids. Ancient events have impacted species evolution and adaptation to new ecological niches. However, we still lack a full picture of processes ongoing within and between somatic cells, gametes, and different organisms. We propose that events linked to acceptance of alien nucleic acids grossly could be divided into 2 main routes in plants: one, when plants are exposed to extreme challenges and, the second level, a more everyday or season-related stress incited by biotic or abiotic factors. Here, many events seem to comprise somatic cells. Are the transport and acceptance processes of alien sequences random or are there specific regulatory systems not yet fully understood? Following entrance into a new cell, a number of intracellular processes leading to chromosomal integration and function are required. Modification of nucleic acids and possibly exchange of sequences within a cell may also occur. Such fine-tune events are most likely very common. There are multiple questions that we will discuss concerning different types of vesicles and their roles in nucleic acid transport and possible intracellular sequence exchange between species. The question of a continuous flow of genes between prokaryotes and between prokaryotes and eukaryotes beyond endosymbiotic-related events involving mitochondria and plastids has received much attention . Is thatLand plants (embryophytes) have evolved from freshwater communities, particularly from streptophytes . NumerouEukaryotic cells contain many different compartments in the cytosol and nucleus. They can grossly be divided into membrane-enclosed and membrane-less organelles. First, we will discuss the membrane-enclosed vesicles. The vesicle membrane composition varies between species as well as the vesicle content and cargo target . In gramThe endomembrane system is a fundamental cellular organization composed of 2 main routes, 1 for outgoing traffic (exocytosis) and the other for incoming traffic (endocytosis) . It is bPseudomonas species has been shown to generate broad-spectrum immune responses to bacterial species and oomycetes in Arabidopsis and tomato  is an example of a single-stranded DNA virus that mediates the transfer of sugar beet DNA to other plant hosts  granules, including the so-called SGs . SGs areMost information on SGs in plants so far derives from virus infections. One example is the cauliflower mosaic virus. This virus manipulates the host cell and alleviates translational repression by targeting the PBs, which are aggravated under uninfected conditions (Lotus burtii allowing nodulation by 5 Rhizobium species classified into different taxonomic genera (The flow of nucleic acids between plants and organisms in immediate close proximity seems to occur with different intensities and host acceptance levels. First, during extreme challenges, new traits and even organelles have been accepted by taxa in Viridiplantae, resulting in fitness advantages that eventually lead to survival of individual species (Reports from a multitude of eukaryotic organisms including plants point to the fact that nucleic acids are transported within and between cells and organisms as a rapid response to changed environments. Plants do acquire nucleic acid from invading organisms, but the expression can be suppressed by host-induced gene silencing . There aThe picture is complex and many questions remain to be answered about sequence selectivity, intracellular transmission, and modification processes. The frequency of transient influences in somatic cells is most likely much greater than an impact on gametes. It is unclear if, when, and how the latter step is taken. To advance our understanding of these dynamic events, we foresee progress based on new microscopic advances (