Interprofessional collaboration between general practitioners (GPs) and community pharmacists (CPs) is central to implement antimicrobial stewardship (AMS) programmes in primary care. This study aimed to design a GP/pharmacist antimicrobial stewardship (GPPAS) model for primary care in Australia. An exploratory study design was followed that included seven studies conducted from 2017 to 2021 for the development of the GPPAS model. We generated secondary and primary evidence through a systematic review, a scoping review, a rapid review, nationwide surveys of Australian GPs and CPs including qualitative components, and a pilot study of a GPPAS submodel. All study evidence was synthesised, reviewed, merged, and triangulated to design the prototype GPPAS model using a Systems Engineering Initiative for Patient Safety theoretical framework. The secondary evidence provided effective GPPAS interventions, and the primary evidence identified GP/CP interprofessional issues, challenges, and future needs for implementing GPPAS interventions. The framework of the GPPAS model informed five GPPAS implementation submodels to foster implementation of AMS education program, antimicrobial audits, diagnostic stewardship, delayed prescribing, and routine review of antimicrobial prescriptions, through improved GP–CP collaboration. The GPPAS model could be used globally as a guide for GPs and CPs to collaboratively optimise antimicrobial use in primary care. Implementation studies on the GPPAS model and submodels are required to integrate the GPPAS model into GP/pharmacist interprofessional care models in Australia for improving AMS in routine primary care.  Growing antimicrobial resistance associated with antimicrobial use is an increasing threat to healthcare and the global community ,2. PrimaGeneral practitioners (GPs) and community pharmacists (CPs) are the most important antimicrobial stewards in primary care. Their collaboration, co-ordination, and communication are central to implement AMS strategies and to optimise antimicrobial use in routine GP and pharmacy practices ,7. CPs rGrowing evidence ,12 corroAlthough the literature on AMS is growing in the context of general practice and community pharmacies, AMS research on the GP–CP interface remains scant. To date, there is no AMS model framework elsewhere that guides how to better engage and promote collaboration of GPs and CPs regarding antimicrobial prescriptions and antimicrobial use. The AMS implementation frameworks found in primary care are limited to either general practice  or speciOur study proposes a theory and evidence-informed GPPAS implementation model framework  which coA community pharmacy is the first point of contact for most patients who seek care or advice from a pharmacist for treating minor ailments or self-limiting infection(s). Furthermore, CPs are the most accessible sources for patients to get antimicrobial(s). Pharmacist-patient interactive communications, thus, can play an important role in educating patients about how to prevent minor infections without antimicrobial(s) and safe use of antimicrobial(s). As guided by the SEIPS 2.0 model, an interpersonal trust and dependency between a CP and a patient about antimicrobial-use decisions is critical to reduce a patient’s behaviours of desiring or demanding antimicrobial(s). Pharmacist-patient interactions can impact individual knowledge, provide motivation to act, and change the social norms of both the CPs and patients regarding safe antimicrobial use in primary care.In conjunction with the international evidence ,32,33,34Our GPPAS model stresses that GP-patient interactive communication is as important as CP-patient interaction to collectively identify patient concerns and reduce patient pressure on antibiotic decisions for infections which can be treated without antibiotics or antimicrobials. There is an importance of GP-patient shared decision making on antibiotics. A GP can use CPs an an extended arm, and refer patients to CPs for complete understanding of the antibiotic courses, antibiotic use awareness, food and drug interactions with antibiotics, and possible side effects. This multidisciplinary interactive effort would reduce patient pressure and improve community awareness about optimal antibiotic use. The national and international evidence ,39,40,41An interdisciplinary approach ,43,44 isAn antimicrobial audit and feedback programme is a proven, effective, and sustainable model ,45 whereThis model suggests that a pharmacist would collaborate with the local AMS team to identify the educational needs, to build programme initiatives, to plan for data collection, and to share and discuss the audit-feedback programme outcomes. Sustained funding and involvement of an infectious disease physician, AMS pharmacist, and GP opinion leader to support audit programmes should be a policy decision. In Australia, a few GP clinics, where pharmacists are co-located, could be settings for testing this model as a priori. The implementation feasibility of this model would require better access by general practice and community pharmacist to an AMS pharmacist or infectious disease physician where possible and relevant education, training and practice protocol for CPs.AMS educational and training programmes for GPs and CPs were found to be essential both in the literature ,50,51,52A platform that may help GPs and CPs to learn about AMS from each other’s professional perspectives is lacking in Australia. We propose a GPPAS educational model that can be defined as a community-based model where GPs and CPs would co-construct AMS knowledge by sharing areas of problematic antimicrobial prescribing decisions, exploring dissonance in opinion, and developing consensus about a safer antimicrobial therapy between themselves. The system development approach and theories of interprofessional education back up this model. The support from AMS physicians and AMS pharmacist and their networking are important to newly establish this model in any setting.The proposed model would likely develop a sustainable interprofessional AMS learning process and platform, by utilising the expertise of pharmacists on antimicrobial pharmacotherapy, pharmacokinetics, pharmacodynamics, dosing, antimicrobial spectrum, and resistance to influence GPs’ antimicrobial prescribing. International evidence of such a model ,54,55,56The mode of implementation involves GP/pharmacist regular group meetings and GP/pharmacist co-led workshop training. Research has shown that GPs and CPs in Australia are motivated to be involved in the co-construction of AMS knowledge by collaborative learning processes . A GP–CPThe antimicrobial delayed prescribing strategy has been proven to be an effective AMS approach ,58 to imThe routine review of antimicrobial prescriptions is a useful patient-centric approach to optimise antimicrobial therapy. Thus, routine reviews have become an important part of AMS activities by pharmacists because they identify many aspects of prescribing as compared with a passive antimicrobial audit model. A model in which CPs review GPs’ antimicrobial prescriptions is likely to provide active learning and teaching opportunities for CPs and GPs to adopt AMS activities in routine practices. A key advantage of this model is that each antimicrobial prescription can be assessed for patient safety, AMR risk, and cost savings.General medication reviews are conducted in community pharmacies; however, related training and a checklist that would guide CPs about when, what, and how to commence reviewing antimicrobial prescriptions are not readily available. This might be one of the reasons why CPs less frequently assess guideline adherence of antimicrobial prescriptions and are less likely to communicate with GPs when the choice of an antimicrobial is believed to be suboptimal. Our study found that more than 40% of CPs did not feel confident to assess guideline adherence of prescribed antimicrobial(s). This post-prescription review role of CPs should be a part of routine pharmacy practice to avoid antimicrobial medication errors and to ensure guideline compliance. Advocating these essential roles of CPs could create an opportunity to produce AMS pharmacist stewards, who could support CPs to develop AMS skills and eventually sustainably reduce some problematic prescribing. Using a GP/CP team-based routine antimicrobial prescription review model is one of the approaches that needs future development and evaluation.Pragmatically, an antimicrobial review can be specific to an infection, a patient category, or the type of antimicrobial prescribed . Access to a patient’s clinical indication and diagnostic reports including antibiograms would be important to facilitate this model. For CPs who work as home medicine review pharmacists and co-located pharmacists in general practice, testing this model in those settings might be an immediate practical step forward. The role of CPs in antimicrobial reviews has been supported by the international literature ,33,34,61Diagnostic uncertainty is one of the most cited reasons for inappropriate use of antimicrobials in a community ,63,64. PThe uptake of point-of-care testing by the Australian GPs and CPs was below 20% according to our 2019 nationwide surveys. The evidence indicates that an improved patient referral system, collaborative practice agreements, and user training would help to introduce a new GP–CP collaborative diagnostic stewardship model in Australia. This model would have the following implications: (i) increasing two-way appropriate patient referrals between GPs and CPs and (ii) ensuring that a patient needs either antibiotics or over-the-counter (OTC) or GPs/CPs visits to optimally treat infections. The provision of this model could improve the scope of CPs to be better involved in AMS programmes and to optimise infectious disease patient care through community pharmacies.The active involvement of GPs and CPs in AMS programmes and the implementation of GPPAS strategies require: relevant resources, tools, and technologies; a clinical decision support system prescribing and dispensing software integrated with updated antibiotic guidelines, regional antibiograms, and AMR reports; “My Health Records” providing sufficient clinical and medication information for review by pharmacists; point-of-care tests facilities; the WHO AWaRe antibiotic tool; patient-facing information leaflets; and a checklist defining GP/pharmacist interprofessional AMS activities. These resources will increase the awareness, motivation, and confidence of GPs and CPs to effectively conduct routine AMS tasks. For instance, the use of patient-facing leaflets is an opportunity for both GPs and CPs to provide safety net advice to patients, to revise the decision of antimicrobial use, and to address demands for antimicrobials by patients. Addressing the gaps in tools and technologies would have a significant influence by shaping the organisational set-up for GP–CP collaboration regarding the AMS and implementation of the GPPAS submodels.Organisational support has been deemed as important to set up a GPPAS model for routine patient care and to support GPs and CPs to collaborate with antimicrobial prescription(s). The GP/pharmacy organisational initiatives which have been found as priorities to facilitate implementation of evidence-based GPPAS strategies include: (i) the development of antimicrobial use and resistance data sharing platform between GPs and CPs, (ii) building a local GP–CP network for collaboration, (iii) pharmacist’s access to a patient’s health records including antimicrobial prescriptions, (iv) general practice/community pharmacy practice agreements for AMS, (v) interprofessional organisational structures that ease patient referrals and enable GPs and CPs to follow-up on patients who are using antimicrobials, and (vi) organisational supports for GP–CP collaboration in AMS. There are structural limitations to routinely monitoring the appropriateness of prescribed antimicrobial(s), patients’ clinical and therapeutic outcomes, and providing feedback to GPs. Implementation of a GP/pharmacist antimicrobial audit and feedback model and a routine antimicrobial prescription review model, thus, need a sustainable data solution. The SEIPS 2.0 model component, “tools and technology” recommends that these data should fit into the workflow of GPs and CPs.The potential routine collaborative tasks of GPs and CPs for implementing AMS include: the use of antibiotic guidelines and antibiotic checklists, recording clinical and therapeutic details of patients in available electronic health records and “My Health Records”; ensuring that delayed prescribed antimicrobials are delayed dispensed; GP/pharmacist communication with antimicrobial prescription whenever required to address inappropriate use; use of point-of-care diagnostic stewardship tools  or rapid antigen testing (RADT) for Group A streptococcus (GAS) pharyngitis) to avoid unnecessary use of antibiotics and appropriate patient referral; review of each antimicrobial prescription by CPs and communication with GPs to address any inconsistency in choice, dose, and dose regimen; attempting shared decision making with patients in situations of antimicrobial use to treat infection(s); and providing patient education during consultation using decision support tools such as antibiotic checklist. Strengthening interconnected domains of the GPPAS model would facilitate these routine tasks according to the SEIPS 2.0 model.Having a national governance structure for implementing AMS programmes in primary care is a policy priority. GP and pharmacy representatives in the governance structure would determine and provide a strategic direction to foster GP–CP collaboration in AMS. The external environment such as GP/pharmacy AMS practice guidelines and protocols may drive implementation. The adoption of societal norms and policy on restricted use of broad-spectrum antimicrobials, stopping repeat prescriptions, establishing GP/pharmacy practice agreements, and incentives and/or medicare support for local GP–CP collaboration in relation to antimicrobial prescription and infectious disease management programmes could influence AMS progress in primary care. These societal interventions and policies need greater attention by AMS stakeholders to support implementation of GPPAS model in primary care.According to the SEIPS 2.0 theoretical model, if an AMS supportive work system  has beenThe implementation of AMS programmes in primary care is potentially limited, although most antimicrobials are used in primary care. Acknowledging that primary care practices are everchanging, diverse, and influenced by a lack of interprofessional health service models, it is imperative to develop a sustainable AMS implementation model involving GP–CP collaboration in primary care. Our study, for the first time, has designed a framework for an evidence-based novel GPPAS implementation model that provides important insights into how Australian GPs and CPs could be better engaged in AMS to fight against growing AMR in primary care. The framework for the GPPAS model includes five implementation submodels to foster AMS programmes through improved collaboration between GPs and pharmacists in primary care.E. coli in a community [The GP/pharmacist interprofessional AMS educational submodel is emerging. Such a model in Scotland was effective for reducing the use of broad-spectrum antimicrobials in a large region as part of a national initiative . A systeommunity . In the ommunity . Incorpoommunity . WhetherTo facilitate similar interprofessional AMS educational programmes in Australia, development of a local GP/CP interprofessional team as site champions is a necesary step for implementation. Incorporating AMS educational submodels into existing GP/pharmacist collaboration models such as pharmacist co-located in general practice model  and a hoOur GPPAS model framework proposes a GPPAS implementation submodel for antimicrobial audits and feedback which has enormous importance for antimicrobial surveillance, monitoring and identifying evidence practice gaps and developments of stewardship targets in primary care. Such a model  led by aDiagnostic uncertainty still affects Australian GPs and CPs to avoid unnecessary use of antibiotics for treating infections such as RTIs and UTIs. Our GPPAS diagnostic stewardship submodel would help address diagnostic uncertainty of GPs and CPs potentially for patients with RTIs and UTIs. The use of point-of-care testing  for and rapid antigen diagnostic tests) for RTIs including acute sore throat caused by Group A streptococcal infections has been growing for appropriate clinical decisions on antimicrobial therapy in primary care ,67. HaviOur GP–CP partnership based submodels accelerating implementation of delayed prescribing and routine review of antimicrobial prescriptions by pharmacists could have marked impacts. Australian GPs and CPs were enthusiastic about a partnership-based delayed antibiotic use strategy, and the majority of GPs were receptive to receive CPs’ recommendations on the choice, dose, and duration of antimicrobial therapy where appropriate. Improvements in the organisational structures and technologies that support GP–CP collaboration, and advancement of “My Health Records” could facilitate routine implementation of those submodels.The routine use of antibiotic checklists and leaflets supporting CP-patient and GP-patient interactions for shared decision making on antimicrobial use seems promising. A randomised controlled trial study demonstrated that the use of patient-facing resources  during CPs’ routine consultations was associated with increased self-care advice and decreased patient referrals to GPs . The proIn Australia, apart from developing AMS resources and technologies, a legal framework  can be iThis study has some drawbacks. Methodologically, an in-depth qualitative study  and multi-centered pilot study would also have been ideal to refine the model components and to inform future randomised controlled trials. However, those studies were out of the scope of this project. Although the SEIPS 2.0 model established theories for the GPPAS model, other frameworks such as the theoretical domain framework  and implFuture research is needed to refine the GPPAS model framework using a co-design approach.The implementation evaluation of the GPPAS model, and the submodels needs clinical trials and qualitative studies supported by grounded theory or behavioural approaches ,80,81. LA GPPAS implementation model framework has been successfully designed which will guide and accelerate the implementation of evidence-based AMS programmes by improved GP–CP collaboration in Australian primary care. The GPPAS model could have significant policy implications to foster GP–CP collaboration in AMS. Future implementation trials are needed to deeply understand the feasibility and cost effectiveness of the GPPAS model for national scalability to sustainably optimise antimicrobial use in primary care.An exploratory study design was used to obtain evidence for a prototype GPPAS implementation model. The exploratory studies had different aims and used respective methodologies of systematic review, scoping review, rapid review surveys, qualitative study, and a pilot study with a before-after design. The studies were conducted between 2017 and 2021; the secondary evidence was collected through reviews and the primary evidence in the Australian context was collected through nationwide surveys and a pilot study. Saha et al. (2021)  detailedTheory- and evidence-based approaches were employed to develop a GPPAS model. We identified the Systems Engineering Initiative in Patient Safety (SEIPS) 2.0 model  as a vehHuman factors engineering is the scientific approach to understand interactions among humans and the elemental parts of a system . The SEIThe SEIPS 2.0 model has been increasingly applied to improve the safety of patients and the quality of care in various healthcare settings ,87,88. MA critical synthesis approach was used to collect evidence from multi-method research . We merg


On December 31, 2019, China reported to the WHO cases of pneumonia in Wuhan caused by a novel coronavirus (2019-nCoV). This escalated into an unprecedented outbreak of infections, leading the WHO to characterise it as a pandemic on March 11, 2020. The COVID-19 pandemic is rapidly evolving, and since October 9, 2021, almost 200 000 000 people have been infected with more than 4 000 000 deaths globally . AlthougThis viewpoint aims to summarize how different countries manage the COVID-19 dead and perform autopsies and whether common prevention recommendations can be identified.The PubMed database was searched until October 9, 2021. We used keywords for: deceased covid 19, management of death covid 19, autopsy covid 19 ((deceased covid 19) AND management of death covid 19) AND autopsy covid 19). The selected articles’ references were also screened. Only documents in English were included, while reviews were excluded.For the management of bodies, WHO recommends that health care workers or mortuary staff wear appropriate personal protective equipment (PPE) including gloves, impermeable disposable gowns, medical masks, and eye protection; that the deceased’s family can only view the body without physical contact, always using standard precautions. Furthermore, WHO does not recommend embalming to avoid excessive manipulation of the body .CDC recommends that people not touch the body of a person who died of COVID-19, especially those of older people and people with severe underlying health conditions; wearing at minimum disposable gloves is also recommended. They also recommended embalming bodies and following the standard precautions with additional PPE if splashing is expected (disposable gown and face shield or goggles and facemask) .ECDC states that unnecessary contact with bodies should be minimized and that persons in direct contact with those deceased of COVID-19 should be protected by wearing appropriate PPE: gloves and a long-sleeved water-resistant gown [In Europe, recommendations for funeral services were released from the UK, Ireland, and Italy. The UK Government, quite in contrast with the above-mentioned recommendations, stated that residual hazards from body fluid spillage do not present a risk. It also recommended the use of disposable gloves, disposable plastic aprons, surgical masks, and disposable eye protection .In Ireland, the Coroner Service  recommenIn Italy, Fineschi et al.  publisheRestrictive recommendations were also adopted by other countries in other parts of the world. The National Institute of Forensic Medicine in Malaysia  states tRestrictive guidelines were also adopted by the Government of India : the decThe Washington State Department of Health assessed that mortuary and funeral home workers should use Standard Precautions: nonsterile, nitrile gloves and heavy-duty gloves over the nitrile ones if there is a risk of injuries that break the skin; clean, long-sleeved fluid-resistant or impermeable gown to protect skin and clothing; plastic face shield or a face mask and goggles. .These recommendations are summarized in WHO recommendations  contain CDC released recommendations  focusingThe Royal College of Pathologists’ recommendations  indicateThe UK Government guidance  requiresThe Irish Coroner Service  suggestsen bloc organ extraction to adequately define the respiratory pathological manifestations. They recommended the use of an oscillating saw with bone aerosol aspiration and effective ventilation in the autopsy room. They also recommended the collection of upper respiratory tract swabs  and lower respiratory tract swabs (from each lung) and that organ and tissue samples be kept in formalin for subsequent histopathological investigations.The Italian National Institute of Health  suggest Indian recommendations  firmly aMalaysian interim guidelines  recommenCOVID-19 is the most important health challenge today and the adherence to control strategies to contain the spread of the virus is a global priority. Even if there is no consensus on the spread of the virus from the deceased person, the careful management of the bodies is mandatory, considering that the rate of contamination of personal protective equipment after full autopsies varies between 15% and 65% ,5. Never


To establish reliability and validity of formal intelligence assessment instruments in a multicultural and multilingual society such as South Africa, context needs to be taken into consideration and existing psychological intelligence test instruments need to be surveyed carefully for cultural bias. The aim of this critical review of scientific literature was to critically appraise and synthesize data regarding intelligence instruments applied to South African school learners. The search initially yielded 405 studies of which 15 were finally included for thematic analysis. The following three main themes emerged from the included studies: Applicability of intelligence instruments administered to South African school learners; Contextual and demographic influences affecting performance on administered intelligence instruments; and Intellectual measuring instruments related to developmental and cognitive ability levels. It is recommended that the findings of this research study should be considered in the possible development of a strategic guideline to design an intelligence instrument applicable to South African school learners. The assessment of South African school learners’ cognitive abilities by means of psychological intelligence test instruments has remained controversial, even during the post-apartheid era, where western practices are continuously applied owing to a history of colonialism . Viewed Psychologists in ZA have been administering assessment instruments to school learners from diverse, demographic populations, with the challenge of assessing within low-resourced contexts . In addiAfter the first democratic election in 1994, ZA’s new constitution, which included the Bill of Rights, brought about ethnically fair legislations to cater for a multifaceted, diverse society . This afConsequently, the Human Sciences Research Council (HSRC) investigation of behaviors and needs of test practitioners in ZA, the concerns of outdated, inapplicable psychological tests were raised, accompanied by an urgent appeal to develop psychological tests that are reliable, valid and applicable to the South African population . MitchelThe choice of individually administered intelligence tests, that South African practitioners assessing school learners presently have, range from the limited and outdated few locally developed intelligence tests for school learners to the western-developed, imported intelligence tests that have been standardized according to South African norms . In theiWhat does literature state regarding intelligence assessment instruments applied to South African school learners?Hence, the aim of this critical review was to critically appraise and synthesize data regarding intelligence instruments applied to South African school learners. We pursued to address the following question: A critical review  was applA step-by-step literature search was performed in August 2021 using the electronic databases EBSCOhost, Academic Search Complete, E-Journals, PsycArticles, PsycInfo, Sabinet African Journals, ScienceDirect, Google Scholar, as well as South African Theses and Dissertations. A combination of keywords used in the search included cognition terms (“intelligen*” OR “IQ” OR “cognit*” OR “neuropsycholog*”), instrument terms (“test*” OR “assess*” OR “instrument*”), demographic terms (“learner*” OR “schola*” OR child* OR adolescen*) as well as a geographic term (“South Africa*”). Boolean operators such as AND, OR, and NOT were implemented to help clarify the search. Keywords found in searched texts were applied to search additional research studies.Although this search reviewed peer reviewed works (written in English) from all eras, it predominantly focused on more recent (not older than 10 years) literature works regarding intelligence assessment instruments applied to South African school learners. The search initially yielded 405 studies of which 15 were finally included. Studies were screened and assessed for eligibility by three independent reviewers, namely the primary reviewer (lead author) and co-reviewers (second and third authors), initially by title and abstract, then by full text, according to inclusion and exclusion criteria. Any conflicts were resolved through consensus. This research study  received approval from the Health Research Ethics Committee (NWU-00191-21-A1) of the Faculty of Health Sciences, North-West University (NWU), ZA. The primary reviewer (lead author) performed an independent search, while the second reviewer (second author) monitored the review process by acting as co-analyst of extracted data. The seven-step critical review guideline, as suggested by The thematic data analysis method was applied to analyze the extracted data . First, The following three main themes emerged from the included studies: (i) Applicability of intelligence instruments administered to South African school learners; (ii) Contextual and demographic influences affecting performance on administered intelligence instruments; and (iii) Intellectual measuring instruments related to developmental and cognitive ability levels. It was evident from all the studies that intelligence assessment instruments administered to South African school learners from diverse, demographic populations need to be applicable to that particular population subgroup, in order to be valid, reliable, and fair . When adA few attempts have been made to investigate, adapt, update, and norm the locally developed intelligence test JSAIS, however, not without significant challenges. In the research studies conducted by students at the University of Johannesburg, the researchers respectively administered Sesotho-translated and isiZulu-translated versions of the JSAIS to South African school learners and employed the Rasch model to determine item accuracy (do items measure what they are intended to measure) and applicability . Mawila In reaction to the challenges of assessing South African school learners from multicultural contexts, the LPCAT was locally developed and proved to be a fair and psychometrically sound non-verbal intelligence test, as it was developed and standardized using multicultural samples and yields information over a wide range of abilities .Some reviewed studies noted significant differences on intelligence assessment results among various South African school learner subgroups, and related performance differences to contextual and demographic influences . Some stA trend of South African school learners performing more often in a lower range compared to international norms, were identified by many of the studies reviewed . These sSome reviewed studies found that English school learners from an advantaged educational background performed at the same level or even slightly better than their American counterparts . MitchelThe South African developed LPCAT proved to be a psychometrically sound, culturally fair, time-efficient, and practically useful intelligence instrument which lessens the impact of SES, cultural or educational influences of persons from multicultural contexts by measuring non-verbal fluid intelligence . This dyThe research study by Based on the Piaget-inspired PASS  model, the CAS was administered to South African school learners which revealed findings of a significant correlation between the school learners’ cognitive processes assessed by the CAS, as well as their reading ability (measured by the WDRB) and school marks . FindingIn order to keep updated and suitable intelligence tests for all South African school learner subgroups, normative studies need to continue across the whole country .Most of the subtests in the locally developed JSAIS were found to be valid intellectual assessment measures on South African school learner subgroups, but with the recommendation of refinement in the translation efforts as well as updating, adapting, and standardizing this instrument with norms that are representative of the South African population . Moloi . FoxcrofThe time-efficiency and applicability of the LPCAT instrument  could adViewing intelligence assessment within the unique, multi-diverse ZA context is challenging, but also serves as an opportunity to advance intelligence instruments and their application in practice not only in ZA, but also globally. When used correctly the intelligence assessment is an efficient tool, yet it can be destructive when abused. Besides ensuring that the instrument itself is valid, reliable and optimally designed, the application and use of the instrument should be considered equally important. It is suggested that a thorough and user-friendly manual accompany the intelligence instrument at all times. The manual should cover topics including the specific purpose of the instrument, implied risks and safety measures, client and context limitations, as well as scope of the instrument. Detailed examples of case studies should outline the correct assessment procedure and possible pitfalls. Proper procedure is built on the four pillars of assessment as suggested by While, a critical review does serve to cluster the literature on a topic, the interpretative elements are necessarily subjective and the resulting product is the starting point for further evaluation, not an endpoint in itself . It is rIncreased research has been undertaken in the psychometric field on local and national normative studies regarding various assessment measures in ZA . HoweverAll authors listed have made a substantial, direct, and intellectual contribution to the work, and approved it for publication.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.


Amblyomma americanum tick removed from a resident of Long Island, New York, USA. Tick infection and white-tailed deer (Odocoileus virginianus) serosurvey results demonstrate active transmission in New York, especially Suffolk County, emphasizing a need for surveillance anywhere A. americanum ticks are reported.In July 2019, Bourbon virus RNA was detected in an  Thogotovirus, family Orthomyxoviridae) is a suspected tickborne human pathogen isolated in 2014 from a patient residing in Bourbon County, Kansas, USA  are hosts for the immature ticks. Adults feed on large mammals, such as coyotes (Canis latrans) and white-tailed deer (Odocoileus virginianus). All 3 active developmental stages of the tick will bite humans  revealed the tick was also positive for Ehrlichia ewingii bacteria. Notes on the tick submission form indicated the person was experiencing fever, chills, and fatigue; officials with NYSDOH and Suffolk County Department of Health Services (SCDHS) attempted to contact the resident for a follow-up investigation. No additional information was provided, and no blood samples were available to assess potential infection with BRBV.In July 2019, New York State Department of Health (NYSDOH) epidemiologists were notified that BRBV RNA was detected in an individual, partially engorged female A. americanum ticks for BRBV and Heartland virus (HRTV). HRTV-infected ticks and seropositive deer were detected on Long Island in 2018 and reported in 2021  collected from 145 deer harvested from Suffolk County for BRBV RNA; the virus was not detected.Serologic testing of hunter-harvested white-tailed deer blood submitted for arbovirus serosurveys has been conducted in New York since 2007 using plaque reduction neutralization tests, as described . We seriAmblyomma species ticks in Japan, A. americanum ticks were implicated in local transmission of BRBV  in Japan sampled from prefectures located near the initial detection of the virus  with other tickborne infections, including ehrlichiosis and Heartland virus disease, diagnosis is difficult without specific testing. Currently, testing is only available at the Centers for Disease Control and Prevention and a few state health laboratories. Providers should request BRBV and HRTV testing for patients with history of tick exposure or travel to regions where A. americanum ticks are reported and who are displaying clinical symptoms, including leukopenia and thrombocytopenia, that do not respond with antimicrobial treatment.Our findings emphasize the need to include emerging pathogens such as BRBV and HRTV in surveillance programs wherever lone star ticks are distributed. Clinicians outside of the midwestern United States should be aware of the potential for human disease. It is unclear if the symptoms of the person who removed the BRBV-positive tick were the result of potential infection with BRBV,


Background: Psychomotor agitation as part of the behavioral and psychological symptoms of dementia (BPSD) is one of the common issues found in aged care facilities. The current inadequate management strategies lead to poor functional and medical outcomes. Psychotropic interventions are the current preferred treatment method, but should these medications be the prescribers’ first preference? This review aims to compare pharmacological interventions for psychomotor agitation, judging them according to their effectuality and justifiability profiles. This is to be achieved by retrieving information from Randomized Control Trials (RCTs) and systematic reviews. Objectives: This review evaluates evidence from RCTs, systematic reviews, and meta-analyses of BPSD patients who have taken agitation treatments. Assessing the efficacy of citalopram, other selective serotonin reuptake inhibitors (SSRIs) and antipsychotic treatments were compared to each other for the purpose of improving agitation outcomes and lowering patient side effects. Methods: This review includes RCT that compared citalopram with one or more atypical antipsychotics or with a placebo, along with systematic reviews comparing citalopram (SSRI) with antipsychotics such as quetiapine, olanzapine, and risperidone. Studies were extracted by searching and accessing databases, such as PubMed, OVID, and Cochrane with restrictions of date from 2000 to 2021 and published in the English language. Conclusion: There are still a limited number of studies including SSRIs for the treatment of agitation in BPSD. SSRIs such as citalopram were associated with a reduction in the symptoms of agitation, and lower risk of adverse effects when compared to antipsychotics. Future studies are required to assess the long-term safety and efficacy of SSRI treatments for agitation in BPSD. A large portion of older people who are diagnosed with dementia experience one or more BPSD symptoms during their illness . A recenThere is, however, limited evidence from a direct RCT-double blind study comparing citalopram to other atypical antipsychotics in dementia. Therefore, this review aims to compare systematic reviews and RCTs to evaluate the effectiveness, safety, and acceptability of citalopram compared to other antipsychotics for psychomotor agitation in dementia. Citalopram is frequently used in older people, which has been proposed as an alternative to antipsychotics in the treatment of agitation in dementia . PollockA recent global study on the burden of dementia, published by Lancet Public Health 2022, stated that the number of people with dementia is expected to increase. This study forecast the prevalence of dementia attributable to three risk factors, including the burden of dementia, injuries, and risk factors globally, by world region and at the country level. The outcome of this study estimated that age-standardized prevalence remains stable between 2019 to 2050 at a percentage change of 0.1% , whereas the number of individuals estimated to have dementia will be increased from 57.4 (50.4–65.1) million cases in 2019 to 152.8 (130.8–175.9) million case in 2050, with the highest number of increases in the Middle East and North Africa (367% (329–403)), Sub-Saharan Africa (357% (323–395)), while a lower incidence was reported in Western Europe (74% (58–90)) and in the Asia Pacific (53% (41–67)). Moreover, the estimation in the study stated that globally, there were more women with dementia than men ); this pattern is forecast to continue to 2050. The implications of this study stated that a huge increase in the number of individuals affected by dementia can be expected by 2050 . This term describes the cognitive and neuropsychiatric symptoms severe enough to interfere with the patient’s ability to perform their usual activities and causes a determinable decline from previous levels of functioning. These disorders include cognitive dysfunction, memory loss, reasoning impairment, and visual spatial impairment, along with language and communication issues; these symptoms are usually associated with symptoms of psychosis and agitation. Moreover, a recent qualitative study by Larsson et al. 2020 recognized four core additional symptoms of dementia (Alzheimer’s and Lewy body dementia): (1) wakefulness in attention and cognition abilities, (2) animated and recurrent visual hallucinations (3) rapid eye movement (REM) sleep behavior disorders leading to recurrent vivid dreams, and (4) parkinsonism, muscular slowness, rigidity, and increased risk and incidence of falls . The pheThere are four common types of dementia , while many pathological autopsy cases reported Lewy bodies combined with Alzheimer’s disease changes  and the Fronto-temporal lobar degeneration (FTLD): The age incidence of this kind of dementia occurs between 40 to 65 years, FTLD symptoms show marked changes in personality and behaviors and difficulty with producing and comprehending language, and memory . This kiStudies were retrieved by searching electronic databases, including PubMed, OVID MEDLINE, and Cochrane Central Register of Controlled Trials for literature appurtenant to pharmacological interventions for treating agitation in dementia from 2000 until 2021. Search strategies are outlined in Published in the English language;Randomized controlled trials RCTs, both experimental and non-experimental studies, non-RCTs, non-randomized  studies, observational, retrospective and prospective cohort studies, and analytical and cross-sectional studies;Published in peer-reviewed journals;Included any type of dementia and any level of severity in any setting;Focused on treatment and management of behavioral and psychological symptoms of dementia ;Included pharmacological interventions, compared different kinds of pharmacological interventions or compared to placebo;Included the outcomes of the pharmacological interventions or adverse effects.Inclusion criteria of selecting clinical studies:Any study focused on non-pharmacological interventions only;Studies focused on non-dementia population, such as health professionals or care givers;Low level of evidence, such as case reports, study protocols, commentaries, or design interventions;Population aged 17 years old or younger;Paper of other mental health or psychiatric disorders (not including dementia).Exclusion Criteria of selecting clinical studies: Were written in English;Focused on all types of dementia;Focused on the behavioral and psychological symptoms of dementia (BPSD);Presented recommendations in regard to agitation, psychosis, and aggressive behaviors;Were established in developed countries with reputable healthcare systems.Inclusion Criteria of selecting guidelines:Six RCTs were excluded as four of six RCTs compared only antipsychotics and two RCTs compared antipsychotics with benzodiazepines. Six systematic reviews were excluded, as four focused on antipsychotics and other antidepressants and two were comparisons of antipsychotics. Thus, the remaining three RCTs and two systematic reviews were included. Chaiyakunapruk et al. 2018  designedThe Cochrane intervention review performed by Seitz et al., 2011  intensivThere are three recent RCT studies that have explored citalopram as treatment for agitation and aggression in dementia. p = 0.935); citalopram vs. olanzapine . Citalopram demonstrated lower all-case hospitalizations than quetiapine  and olanzapine . Moreover, citalopram also demonstrated a decreased occurrence of falls in comparison with olanzapine , but no difference was noted regarding instances of falls between citalopram and quetiapine. In addition, citalopram had the lowest incidence of orthostatic hypotension compared with quetiapine  and olanzapine . This trial revealed no differences observed regarding QT wave prolongation and infections [In a six-month RCT , 75 partp = 0.57); NBRS psychosis score ; Udvalg for Kliniske Undersogelser side effect scale (UKU) total score ; UKU psychotic subscale score ; UKU neurological subscale score . Additionally, the trial stated that there were significant side effects with risperidone but not with citalopram [A twelve-week randomized, double-blind controlled trial done by Pollock et al. was conducted at the University of Pittsburgh Medical Centre , comparip = 0.04. The results of mADCS-CGIC shown 40% of the citalopram group showed improvements with OR 2.13 95% CI = 1.23, 3.69 at p = 0.01. Moreover, CMAI and NPI scales revealed significant improvements for citalopram group participants. However, QT intervals prolongation were seen at higher rates in the citalopram group than placebo  [The CitAD randomized clinical trial is another study examining the effect of citalopram on agitation in Alzheimer’s dementia. The study was conducted by Porsteinsson et al.  as a ranThe systematic reviews by Seitz et al.  and ChaiThe review by Seitz et al. applied the ‘risk of bias tool’ to assess bias in the results by methodological quality and summary graphs. Moreover, bias in this review was assessed by visual screening of funnel plots of the primary outcomes. The review by Chaiyakunapruk et al. examined the selected study bias by using the revised Cochrane risk of bias tool for randomization trials (RoB version 2). This tool measures deviation from intended interventions, bias in the measurements, bias due to results outcomes, and bias due to missed outcome data. In general, the risk of bias of the selected studies in this review was classified at low risk. The authors of both reviews provided a satisfactory explanation and a discussion of the results. Both reviews reported potential conflict of interest, but there is no information about the sources of funding they received for conducting the reviews. The trial by Viscogliosi et al.  was condThe objective and the hypotheses of the trial by Pollock et al.  are wellMarano et al. conducted an RCT study that showed that citalopram reduced agitation when compared to placebo . The objTraditionally, atypical antipsychotics have been used as the primary method for treating episodes of agitation and psychosis for people with dementia. However, despite the effectiveness of these agents in managing the agitation, they still provide undesirable side effects and an increased risk of mortality. As a result, there are continued campaigns to reduce the use of antipsychotics in older people and promoting the use of alternative agents such as SSRIs. Although there is limited evidence collected in this review, the findings from the two systematic reviews and the three clinical trials indicated that SSRI antidepressants  not only showed efficacy for treating BPSD, but were better tolerated compared to antipsychotics. This review also showed that citalopram reduces the symptoms of agitation when compared to placebo and it has fewer adverse effects compared with atypical antipsychotics, such as risperidone, quetiapine, and olanzapine. The outcome of this review suggests that further studies involving more participants from aged care facilities should be conducted, with a longer duration of the trials to assess the safety and the efficacy of citalopram for managing agitation in dementia in long-term use.


Introduction: Concerted efforts to optimize outcomes and data transparency in shoulder arthroplasty have led to the creation of the American Academy of Orthopaedic Surgeons (AAOS) Shoulder and Elbow Registry, the first nationwide registry of its kind. We used online crowdsourcing to explore the general public’s perceptions and beliefs toward the disclosure of quality and price data in shoulder arthroplasty.Methods: A total of 498 participants recruited using Amazon Mechanical Turk (MTurk) completed a survey regarding beliefs about public disclosure of quality and price data in shoulder arthroplasty. The MTurk is an online marketplace for crowdsourcing tasks  to a pool of over 500,000 registered workers in exchange for financial compensation. Requesters post human-intelligence tasks, and workers can respond to those that they are interested in completing. This web-based platform is an efficient survey tool for medical research, with comparable national representativeness to traditional convenience samples.Results: The majority (95%) of respondents believed surgeons and hospitals should share their data with national registries such as the AAOS Shoulder and Elbow Registry. Most believed that patients considering shoulder arthroplasty should have public access to surgeons’ outcomes and complication rates (96%), years of experience (95%), and case volume (92%). Most respondents desired price transparency in implant costs (95%), surgeon reimbursement (80%), and hospital reimbursement (84%). In decreasing order of importance, the top three factors guiding surgeon choice were: (1) surgeon included in the insurer’s network, (2) annual case volume, and (3) publicly available outcomes.Conclusion: Increased quality and price transparency in shoulder arthroplasty may empower patients to make better-informed decisions about their care and ultimately enhance value. Given the strong public desire for data transparency and the notion that public disclosure of data is intrinsically associated with performance improvement, surgeons and hospitals should strongly consider submitting their data to national registries such as the AAOS Shoulder and Elbow Registry. Optimizing health outcomes and the care experience after discretionary orthopaedic surgery has become a major priority in the shift toward value-based care ,2. ShoulRecent efforts spearheaded by the American Academy of Orthopaedic Surgeons (AAOS) to enhance outcomes and data transparency have led to the creation of the Shoulder and Elbow Registry, the first nationwide registry of its kind. Conceived in 2018, the AAOS Shoulder and Elbow Registry collects procedural and patient-specific data (including patient-reported outcome measures) for shoulder arthroplasty, elbow arthroplasty, and rotator cuff repair procedures , there wThis study sought to explore the United States general public’s perceptions and beliefs toward disclosure of quality and price data in shoulder arthroplasty.Survey designWe conducted an online cross-sectional survey to explore the United States general public’s perceptions and beliefs toward the disclosure of quality and price data in shoulder arthroplasty. The survey was developed using Qualtrics  and consisted of 21 questions designed to be completed in less than 10 minutes (Supplementary Appendix).We collected basic demographic data including age, sex, race/ethnicity, primary language, education level, marital status, annual income, insurance status, and region of residence. We also gathered data about perceived overall health status, health literacy  , and patAll the questions used to assess perceptions and beliefs towards public disclosure of shoulder arthroplasty data were based on a four-point Likert scale ("strongly disagree/disagree/agree/strongly agree") to optimize symmetry and balance. This scale was chosen as an effective means of assigning a numeric value to the opinions of a sample population. An iterative consensus process was used to formulate them. The answers "agree" and "strongly agree" were considered together when reporting general result trends. These questions asked respondents whether surgeons and hospitals offering shoulder arthroplasty should share their data with national registries, and whether patients considering shoulder arthroplasty should have public access to surgeons’ outcomes, complications, years of experience, annual case volume, and surgery-related costs Table . In thisThe last question of the survey asked respondents to choose the main factor guiding surgeon choice among six options: (1) online patient reviews, (2) publicly available outcomes, (3) bedside manner, (4) fellowship training, (5) annual case volume, and (6) surgeons included in the insurer’s network.Participant enrollmentAmazon.com, Inc., Seattle, WA), an online crowd-sourcing marketplace that allows people to complete human intelligence tasks  for small amounts of money [Participants were recruited using Amazon Mechanical Turk  with valid social security numbers currently residing in the United States. Each participant was awarded US$ 0.12 for completing our survey. To maximize demographic representation and therefore generalizability of the survey results, we targeted enrollment of 550 participants. At the end of the survey, we included a randomly generated unique completion code as an attention check and to ensure that respondents were humans and not bots. Respondents were not included in our study if the typed code was different from that generated by our algorithm. The survey was administered over a two-day period in May 2020. This study was exempt from review by our Institutional Review Board.The responses of 498 participants were considered in our study Table . Most reThe majority (95%) of respondents believed surgeons and hospitals should share their data with national registries such as the AAOS Shoulder and Elbow Registry Table . Most beIn decreasing order of importance, the top 3 factors guiding surgeon choice were: 1) surgeon included in the insurer’s network, (2) annual case volume, and (3) publicly available outcomes (Figure  surgeon Patients considering elective orthopaedic surgery are expected to make complex health decisions with limited information available to them. Recent nationwide efforts to optimize outcomes and standardize data collection in shoulder arthroplasty have led to the creation of the AAOS Shoulder and Elbow Registry in 2018. With the transition of high-quality data to actionable knowledge, ensuring patient access to this information has the potential to maximize value in shoulder arthroplasty. But it is unclear the degree to which the public finds this information important and useful when making healthcare decisions. In this context, we used online crowdsourcing to report large-scale public perceptions and beliefs toward the disclosure of quality and price data in shoulder arthroplasty.The principal strengths of our study include the national representativeness provided by MTurk. This crowdsourcing platform is a powerful and relatively inexpensive way of obtaining survey results that have arguably closer generalizability to the US population than those derived from traditional survey methods ,16. NoneOur findings highlight the strong public desire for quality and price transparency in shoulder arthroplasty. The vast majority of respondents felt that providers should share their data with national registries, and believed that patients seeking shoulder surgeons should have access to their outcomes, complications, years of experience, annual case volume, and procedure-related fees. It is interesting that there are very little data available to patients considering shoulder arthroplasty, despite the notion that informed patients make more value-driven decisions. This information void suggests ample opportunity for optimizing value in shoulder arthroplasty. Recent efforts to collect high-quality data, such as the AAOS Shoulder and Elbow Registry, have the potential to improve patient engagement and reduce decisional conflict. In addition to the Shoulder and Elbow Registry, the AAOS houses three other registries: the American Joint Replacement Registry, the Musculoskeletal Tumor Registry, and the American Spine Registry ,19. PublThere is also growing evidence that publicly reporting performance motivates clinicians to improve performance ,21. For We observed that the biggest factor guiding surgeon choice was in-network coverage, which is not surprising given that out-of-network bills can be very large and extremely impactful for those who receive them. A recent study by Chhabra et al.  raises aThere are several limitations to this study. First, as the majority of study participants were young, healthy, and college educated, the risk of selection bias was high. The generalizability of our study could be improved by including patients who had previously undergone shoulder arthroplasty. Second, while our survey data indicates that insurance type is the most heavily weighed factor in choosing a shoulder arthroplasty surgeon, this claim is not based on surgeon data or outcomes. In addition, despite the assessment of public desire for price and quality information for shoulder arthroplasty, our survey did not include specifics pertaining to cost or national registry data.This study used online crowdsourcing to underscore the strong public desire for health data transparency and choice. Increasing quality and price transparency in shoulder arthroplasty may empower patients to make better-informed decisions about their care and ultimately enhance value. Given the strong interest in data transparency and the notion that public reporting of data is intrinsically associated with performance improvement, surgeons and hospitals should strongly consider submitting their data to national registries such as the AAOS Shoulder and Elbow Registry.


Consumers and stakeholders are increasingly demanding that the meat industry guarantees high-quality meat products with stable and acceptable sensory and safety properties. To achieve this lofty goal, it is prerequisite for meat researchers to address current meat quality issues and consider certain important goals. First, it is essential to decipher the unknowns concerning the underlying mechanisms of meat quality determination and development. Second, we need a better understanding of the biochemical pathways behind the conversion of muscle into fresh meat and those related to the manufacturing steps and their impact on processed meat products. Third, it is more than necessary to refine our knowledge on the impact of pre- and post-harvest procedures on both the molecular aspects of muscle foods and the final quality and safety of meat products in order to develop management and decision tools. Over the last two decades, sophisticated OMICs technologies—genomics, transcriptomics, proteomics, peptidomics, metabolomics and lipidomics, also known as foodomics—have been powerful approaches that extended the scope of traditional methods and opened up impressive possibilities to explore the above objectives in significant ways ,3,4,5,6.Longissimus thoracis et lumborum (LTL) to evaluate the most reliable protocol for the identification of biomarkers of dark-cutting beef condition, also known as dark, firm, and dry (DFD) meat [In the frame of the discovery and evaluation of beef quality biomarkers, González-Blanco et al.  assessedFD) meat . By meanFD) meat  focused FD) meat ,10. The FD) meat  applied FD) meat . FurtherFD) meat  aimed toLongissimus lumborum  and Psoas major  from Small-tailed Han sheep in relation to color stability during post-mortem storage . The study revealed that the main differentially abundant proteins were from the glycolysis, others belong to the energy metabolism enzymes, chaperones and heat shock proteins, and proteins of structure. Thanks to correlation analyses, proteins such as adenylate kinase isoenzyme 1 (AK1), Pyruvate kinase (PKM), Carbonic anhydrase 3 (CA3), and Creatine kinase M-type (CKM) were significantly related to color stability in agreement with the available proteome repertoire of meat color [In lamb research, two papers evaluated the variation in color  using prat color  performeinterleukin 2 (IL2) gene. Similarly, eight independent laboratories proceeded with the validation and certification of the proposed methodMeat and processed meat products have high nutritional value and economic importance, which makes them appealing commodities for fraudulent activities. Fraud activities associated with meat and meat products include addition , dilution (addition of water for yield increase and cost reduction), substitution, and mislabeling or misdescription, which are critical issues for economic, health, and religious reasons. Therefore, meat authentication is an important concern to protect consumers from illegal and unwanted ingredients. Accordingly, three papers dealing with meat authenticity, origin, and detection of meat adulteration using OMICs methods were published ,16,17. CSparus aurata) using metabolomics [Two other research papers aiming to evaluate the freshness in gilthead sea bream (bolomics  and a bebolomics  were pubIn summary, the content of this Special Issue fits in with the current trend toward the use of foodomics to ensuring the quality, safety, and authenticity of meat and meat products. We hope that this Special Issue will attract the interest of the community of meat scientists, as well as students and scholars, by inspiring them to undertake more research in this emerging and important area of research towards the development of methods and decision tools to ensure more sustainable muscle foods. Special thanks go to the authors for their valuable contributions to this Special Issue and to our colleagues who devoted their time to review the papers. We sincerely hope that readers will find this Special Issue on meat OMICS-based approaches motivating and informative.


Nonhuman primates (NHPs) mimic most aspects of the human and play a critical role in translational research of neurological diseases. Functional connectivity is frequently examined using resting-state functional MRI (rsfMRI) to assess the functional abnormality in the anesthetized animal brain. As anesthetics show different effects on physiology and neural activity in a dose-dependent manner, specific and safe anesthesia procedures must be considered and applied to keep the animal from stress and motion during rsfMRI scanning. In this review, typical anesthesia protocols and rsfMRI techniques for NHPs are summarized. An optimal anesthesia protocol and rsfMRI scanning protocol for NHPs are introduced.Nonhuman primates (NHPs) are the closest living relatives of humans and play a critical and unique role in neuroscience research and pharmaceutical development. General anesthesia is usually required in neuroimaging studies of NHPs to keep the animal from stress and motion. However, the adverse effects of anesthesia on cerebral physiology and neural activity are pronounced and can compromise the data collection and interpretation. Functional connectivity is frequently examined using resting-state functional MRI (rsfMRI) to assess the functional abnormality in the animal brain under anesthesia. The fMRI signal can be dramatically suppressed by most anesthetics in a dose-dependent manner. In addition, rsfMRI studies may be further compromised by inter-subject variations when the sample size is small (as seen in most neuroscience studies of NHPs). Therefore, proper use of anesthesia is strongly demanded to ensure steady and consistent physiology maintained during rsfMRI data collection of each subject. The aim of this review is to summarize typical anesthesia used in rsfMRI scans of NHPs and the effects of anesthetics on cerebral physiology and functional connectivity. Moreover, the protocols with optimal rsfMRI data acquisition and anesthesia procedures for functional connectivity study of macaque monkeys are introduced. Resting-state functional MRI (rsfMRI) can examine the intrinsic synchronous activations between regions that are spatially distinct in the brain and has become a robust tool to assess the functional organization and status of the central nervous system in preclinical and patient studies. In particular, with the advancement of contemporary neuroimaging techniques with high and ultrahigh-field MRI, it is increasingly used to examine brain function and disorders in small and large animal models, including mice, rats, pigs, and nonhuman primates (NHPs). However, animals are usually scanned under general anesthesia to keep them from stress and motion and minimize motion artifacts . Due to General anesthesia is used in both humans and animals to induce unconsciousness and keep the subject from feeling pain or stress during medical procedures. In functional MRI studies, the human is usually scanned awake for a short period. In contrast, animals are generally anesthetized for structural and functional MRI study using total intravenous anesthesia (TIVA) or inhalational anesthesia to keep them from stress and moving during scanning for up to several hours. Extensive studies have demonstrated that cerebral blood flow (CBF), metabolism, and neuronal function are substantially affected by anesthesia ,7,8. In NHPs are our closest living relatives and resemble most aspects of humans in neuroanatomy, physiology, immunology, metabolism, etc. Rhesus macaques share 93.5% of the human genome . NHP modAltered functional connectivity of the default mode network (DMN) is seen in the brain with neurological disorders and correlated with cognitive status ,39. DMN The aim of this review is to summarize anesthesia protocols used in functional connectivity studies of NHPs with rsfMRI and the effects of anesthetics on cerebral physiology and functional connectivity. As the neural activity in the brain is closely associated with cerebral physiology, the information about the effects of anesthesia on physiology and rsfMRI signal could be helpful in rsfMRI experimental design and data interpretation of neuroscience studies using NHP models.www.pubmed.gov, accessed on 1 September 2022) was conducted with keywords including ‘nonhuman primate (or nonhuman primate), functional connectivity, resting state’. Articles published from 2005 to 2022 (31 August 2022) were considered, and 137 results were found. These articles were manually sorted through. In addition, the site of Web of Science  was searched using the same keywords and periods, and 6 additional publications were identified manually and included. Fifty articles were confirmed and selected in this review.A literature search on the NIH national library of medicine website  can detect the spontaneous fluctuation of the blood oxygenation level-dependent (BOLD) signal in the brain and provide an indirect measure of brain activity . FunctioIt is well known that anesthesia usually suppresses the neural activity of the brain in a dose-dependent manner compared to the awake state of the brain ,11,12. IHowever, ultrahigh-field MRI scanners are mostly built with small-bore sizes for small animals (such as rodents) and are not applicable to large animals in most institutes. In contrast, clinical 3T high-field MRI scanners are installed widely in imaging research facilities or clinics. They are mostly used for scanning macaque monkeys, one of the mostly used primate species in neuroscience and biomedical research. Previous studies have demonstrated that the multiband MRI technique can substantially improve the rsfMRI detection sensitivity and statistical power in studies of the human connectome. One previous study indicated that the multiband MRI technique could also improve the sensitivity for rsfMRI examination in anesthetized macaque monkeys using a clinical 3T setting  62]..62].CBF quantifies the blood supply to the brain and is closely associated with neural activity ,9,63,64.ASL perfusion can be conducted for monkeys using a three-coil or two-coil setting in which a separate labeling coil is applied to tag the blood water using a clinical 3T scanner ,69. MoreInhalational anesthesia, including nitrous oxide, halothane, isoflurane, sevoflurane, desflurane, and intravenous/intramuscular anesthesia, including ketamine, alphaxolone-alphadolone, propofol, barbiturate, and alfolaxone, have been used for diagnosis purpose or biomedical research of NHPs. To date, isoflurane, ketamine, and propofol are among the most used anesthetics for general anesthesia of laboratory animals  and neurCompared to structural MRI, rsfMRI of animals often requires stable control of physiology and accurate maintenance of depth of anesthesia during data collection. As seen in the selected 50 literatures for functional connectivity studies using NHPs , six studies of NHPs, such as marmosets ,76 and rPrevious human studies have demonstrated the effects of isoflurane and propofol on CBF and the metabolism of the brain by using PET ,89 or peIsoflurane is a volatile inhalation anesthetic agent commonly used in medical procedures and in vivo neuroimaging examinations of experimental animals for its low blood gas solubility , precise control of anesthetic depth, and minimal hepatic metabolism . Inducti2 or ambient air, is normally used as the maintenance dose for sedation purposes during MRI scanning. A prior Xenon-133 study of anesthetized baboons has shown that isoflurane produces vasoconstriction in cerebral vessels in low doses (~0.5% or less) and vasodilation in high doses (~0.95% or higher) [The 0.75–1.5% isoflurane, mixed with 100% O higher) , indicat higher) ,107. Li  higher) . They fo higher) , indicat higher) ,108,109.In addition, monkeys may be anesthetized for several hours for neuroimaging data collection, as seen in prior studies that reported the exposure of neonatal monkeys to sevoflurane for 5 h  and to iSevoflurane and desflurane also provide good control of anesthetic depth and rapid recovery from anesthesia  and are As an NMDA receptor agonist in the thalamoneocortical and limbic systems, ketamine is a fast-acting dissociative anesthetic used as an induction and maintenance agent in veterinary anesthesia, with neuroprotective and antidepressant effects . KetaminIt is a typical procedure to use ketamine as an induction agent prior to inhalation anesthesia in large animals such as NHPs. Additionally, ketamine showed a vasodilation effect and increased CBF in large animals such as spontaneously-breathing goats  and rabbFurthermore, ketamine’s suppression effect on functional connectivity of the default mode network was seen in humans  , and theLi et al. also investigated the effect of ketamine on the functional connectivity of rhesus monkeys when ketamine was used alone as an induction and maintenance agent and later switched to isoflurane . InteresKetamine can be combined with medetomidine during the anesthesia of macaque monkeys as medetomidine provides muscle relaxation but not causing cardiovascular and respiratory effects . In addiPropofol is a popular anesthetic used in animals, including NHPs. It was applied previously for general anesthesia of NHPs in long structural and diffusion MRI scans of stroke macaque monkeys  and a stAlfaxalone  is a synthetic neuroactive steroid anesthetic, and Alfaxalone-2-hydroxpropyl-β-cyclodextrin  is its newest formulation and was approved by the FDA for use in dogs and cats in 2012 . Alfaxaln = 4) showed no significant difference in functional connectivity was observed in the interested default mode networks of the brain anesthetized by comparing alfaxalone to ketamine  and isoflurane (~0.8%) [n = 4).Li et al. investigated the effects of alfaxalone on CBF and intrinsic neural activity in rhesus monkeys and compared it to ketamine . Dramati (~0.8%) , probablCompared to ketamine, alfaxalone showed an evident vasoconstriction effect, as reported in a pig study . The comPrevious studies have reported that anesthesia exposure in young children (<3 or 4 years old) is an important factor in developmental deficits such as learning disabilities  and an iDue to the substantial suppression effects of isoflurane on neural activity, a better anesthesia protocol is highly demanded to improve the BOLD signal detection sensitivity. Medetomidine and dexmedetomidine are alpha-2 adrenoreceptor agonists and showed improved sensitivity to detect BOLD responses ,170. DexNHPs are among the most challenging species and play a key and unique role in neuroscience research . As NHPsCompared to rodents, the option of anesthesia protocols for the rsfMRI study of NHPs is limited. The protocol with ketamine (IM) and isoflurane is a well-established and popular procedure and has been used for most rsfMRI studies of anesthetized NHPs, including infant and adult macaque monkeys, squirrel monkeys, and marmosets which are the primate species mostly used in neuroscience research. It is worth mentioning that this anesthesia protocol is generally being used in routine structural and fMRI scans of macaque monkeys aged from one week to over 20 years old in the author’s institute. However, due to the strong vasodilation effect of ketamine, it may be adverse and not applicable in some models of NHPs and alfaxalone could be an alternative to induction agent prior to isoflurane administration accordingly.


This article provides a stocktake of the adaptation literature between 2013 and 2019 to better understand how adaptation responses affect risk under the particularly challenging conditions of compound climate events. Across 39 countries, 45 response types to compound hazards display anticipatory (9%), reactive (33%), and maladaptive (41%) characteristics, as well as hard (18%) and soft (68%) limits to adaptation. Low income, food insecurity, and access to institutional resources and finance are the most prominent of 23 vulnerabilities observed to negatively affect responses. Risk for food security, health, livelihoods, and economic outputs are commonly associated risks driving responses. Narrow geographical and sectoral foci of the literature highlight important conceptual, sectoral, and geographic areas for future research to better understand the way responses shape risk. When responses are integrated within climate risk assessment and management, there is greater potential to advance the urgency of response and safeguards for the most vulnerable.  •Compound climate impacts are particularly hard to adapt to•Compound vulnerabilities and exposures constrain adaptation capabilities•Inappropriate responses to climate change can lead to maladaptation•Compound impacts can have cascading effects on response options Earth sciences; Climatology; Safety engineering; Business; Decision science These include significant investments in institutions for improved risk management governance and high integrated management such as improved early warning and emergency response to complement structural measures such as levees.,,These compound effects, and their amplification of risk, present greater challenges to the risk-reduction outcomes of human responses to climate change. We currently do not know if existing or future adaptation options, including technologies, behaviors, and practices over space and time, are going to be sufficient to safeguard human and environmental needs at current and future global warming levels.It is with these climatic and response imperatives that we set out to explore what we know about implemented adaptation and how best to respond to compound climate impacts.The 53 studies we analyzed spanned 39 countries with over 45 documented types of adaptation-related responses to 24 types of compound climate events . While t,,,,,,,,,More than half (56%) of the adaptation literature describes the compound interaction between hazards qualitatively. However, quantitative description is provided for 23% of articles that show temporally compounding interactions and 15% that show spatially compounding interactions. Using the literature’s identification of qualitatively and quantitatively compounding events, the highest number of compounding hazards in the adaptation literature is associated with changes in rainfall. Notable climate hazards that compound with drought include extreme heat across the USA, Philippines, Nepal, Zimbabwe, and South Africa,,,Climate hazards that commonly compound with river flooding in the adaptation literature include extreme heat in Ghana,,,Across compounding hazards at the coast, sea level rise is observed to compound with coastal erosion in Cameroon and with increased salinity in Vietnam.Temporally compounding hazard interactions may be particularly challenging for adaptation when there are multiple timescales involved. For example, hydrological drought, extreme heat, and excessive evapotranspiration all act at different timescales, but they may interact to create additional challenges for response. As was the case in the case of a Great Plains drought that forced over 80 unprecedented water conservation measures in McCook, Nebraska, USA.Spatially compounding interactions present their own challenges to adaptation. For example, the interaction of agricultural drought and pluvial flooding over large areas in Laos and the Philippines spatially compounded with each other and with climatic preconditions of increasing average temperature and evapotranspiration that had particularly severe impacts on livelihoods and food security of small-scale rice farmers.Exposure is a physical condition resulting from being in dangerous proximity to a climate hazard without adequate protection and can be affected by the duration, intensity, and spatial extent of the event. The primary exposure characteristics affecting responses to compound climate events are relatively evenly split between duration of exposure to climate hazard (34%), spatial extent of exposure to climate hazard (32%), and intensity/magnitude of climate hazard (26%).Length time of exposure to climate hazard is well demonstrated in three rice-growing areas of Pemba Island, Tanzania, where rice farmers were highly exposed to sea level rise and coastal floods, whose severity will increase over time as sea levels rise.,,Spatial extent of exposure to climate hazard has a significant effect on responses to compound climate events. For example, pastoralists whose livelihoods cover a large mobility range extent have been noted to experience risk to food security and risk of loss of livelihoods under drought conditions that restricted mobility.The adaptation literature does not commonly describe the interactions between multiple exposures. When they do, interactions between the primary and secondary exposure are more commonly qualitatively described with reference to either spatial or temporal dimensions rather than both time and space (55% of articles), while quantitative descriptions of spatially compounding exposures are provided in 15% of articles and temporally compounding exposures in 11% of articles. It is also common for the adaptation literature to reference the intensity of the hazard rather than being specific on time or space dimensions of exposure (26% of articles).Across the adaptation literature, the most common vulnerabilities that affect responses to compound climate impacts include low or no income, food insecurity, limited access to institutional resources, and limited access to finance. However, there are at least 23 dimensions of vulnerability which affect responses under compound climate events, highlighting the diversity of contexts and multiplicity of aspects affecting vulnerability to climate change . The freImportantly, many vulnerabilities interact with each other in compounding and intersecting ways. For example, lack of credit facilities, inadequate climate change information and adaptation knowledge, access to water for farming and livestock, inadequate government support for smallholder farmers, lack of property rights of female smallholders, and lack of access to markets all affected smallholder farmers' adaptation responses to combined mean precipitation decrease and drought in the Upper East Region of Ghana.,The importance of how multiple non-climate stressors affecting vulnerabilities interact with compound climate events is also highlighted in more recent studies of human responses to super cyclones. Cyclone Amphan hit the Bay of Bengal in May 2020, when COVID-19 was at its peak in India and Bangladesh.In Uganda, farmers with more land, education, access to governmental extension, a non-farm livelihood, larger households, and older age had more capacity to buffer shock from drought and increased precipitation variability through increased assets and entitlements than poorer farmers who were more likely to engage in opportunistic behavior like casual laboring.Interactions between vulnerabilities are generally described in the adaptation literature qualitatively (68% of articles). Spatially compounding vulnerabilities are described in the interactions between food insecurity, low income, and dwelling in high-risk areas for coastal communities in Tanzania affected by impacts of sea level rise and coastal flooding.,,,,Inequality and injustice are often underlying patterns behind differential vulnerabilities, such as the intersection of multiple aspects of identity altering the way people experience discrimination or how historical injustices such as colonialism, racism, and sexism have shaped current exposure patterns and access to adaptation resources.Although it is common for articles to list more than one vulnerability that is relevant to the response to compound climate event, they rarely list all the relevant dimensions of vulnerability or the differential effects they have on other vulnerabilities or on responses. It is also common for indicators of vulnerability and exposure to be conflated across qualitative and quantitative studies reducing the accuracy and specificity of information for risk assessment. This information would be valuable to understand the constraints that contextualize the potential efficacy of response options across multiple contexts. This is particularly important given how frequently key dimensions of inequality (11 articles), governance (9 articles), government responsiveness (5 articles), informality policy/practices (5 articles), and migration policy (5 articles) were identified to affect responses to compound climate events through their impact on the background conditions driving vulnerability.in situ adaptation.,,,,,,,,,,,There are at least 45 types of adaptation response to compound climate events documented in the adaptation literature  . The sev,,When linking the observed impacts documented in the articles to the IPCC AR6 Key Risks, compound climate events in the adaptation literature most commonly present severe risk to food security,,,,There is increasing evidence of adaptation constraints, including both soft (68%) and hard (18%) limits.,,,,,,Examples of soft limits to compound climate hazards include lack of access to finance,Examples of adaptation reaching hard limits include dislocation and relocation of households due to combinations of riverbank erosion and tropical cyclones,,Responses to compound climate events are generally reactive at first, but the literature shows that over time there is potential for responses to become more proactive A. For ex,Only 9% of articles describe anticipatory and proactive responses A. For exEighty-seven percent of articles provide evidence of vulnerability reduction B. ChangiMost articles demonstrated how responses reduced (78%) or avoided exposure (5%) C. For ex,However, 7% of articles exhibit evidence that the response to compound climate events increased vulnerability. For example, in Bukavu, DR Congo, increased irrigation in response to extreme heat and decreased precipitation led to increased evapotranspiration losses with marginal benefits to productivity. The climate hazards, combined with a lack of alternative livelihoods, led to livelihood loss and a deepening poverty cycle.,,The complex relationship between hazards, exposures, social vulnerabilities, and responses is shown in Isle de Jean Charles, Louisiana, USA. This island is being inundated by sea level rise, hurricanes, coastal erosion canalization of the wetlands by oil and gas exploration, and the levees starving the Mississippi delta of sediment and through delta subsidence.How responses affect other responses is important for informing better adaptation to climate change and avoiding negative trade-offs in response options. Eight percent of articles indicated responses had no effect on other responses, while 25% of articles did not report on how responses affected each other D. Over h,,,However, 11% of articles also identified how selected responses reduced the effectiveness of other response options , highligOf the documented adaptation responses, behavioral or cultural adaptation-related responses were the most common type reported (33%), followed by ecosystem-based or nature-based (25%), technological or infrastructural (25%), and institutional (17%). Articles frequently reported responses that involved multiple types of adaptation, for example, the installation of urban green roofs for cooling  or government-supported planting of drought-resistant seeds among subsistence farmers . A typical behavioral response for smallholder farmers is the combination of crop diversification, diversification of income sources, and increased irrigation in response to extreme heat and mean precipitation decrease.,,These categories of adaptation-related responses to compound climate impacts matter because behavioral, ecosystem-based or nature-based, technological or infrastructural, and institutional types of responses have varying effectiveness and feasibility across different contexts. For example, at current global warming levels, the IPCC 6th Assessment assessed human migration in Africa to have high potential effectiveness as a behavioural response but low feasibility due to economic, institutional, and technological barriers.,A similarly differentiated pattern emerges for technological responses, like bulk water infrastructure development and financial investment in agriculture. For both of these, potential effectiveness is high, while feasibility is low due to institutional and technological dimensions constraining adaptation.The adaptation literature identifies a range of cascading effects between determinants of climate change risk under conditions of compound climate events E and 5F.Two other cascade effects are identified. Over one-third of articles describe a type of compounding interaction, where two or more determinants of risk act together to severely affect one determinant E. For ex,Two articlesThe Black Summer fires of 2019–2020 in eastern and southern Australia demonstrate the far-reaching cascading impacts across natural and human domains that were exacerbated by resource constraints in response capacity which have been identified as a barrier to containing fires effectively.Maladaptation is observed in 41% of articles F. For exThe 53 articles reviewed here focused on compound climate hazards and are a very small fraction of the vast literature on adaptation to climate change impacts and to climate risk more broadly.,,,,,,,,This article has focused on human responses to compound climate impacts. Where the literature has identified a role of ecosystem-based adaptation or nature-based solutions has been highlighted. However, responses to compound climate impacts are necessary for all of life on earth including ecosystems,,The greatest risks from a changing climate may not come from individual climate impacts and risks but from the interactions and interdependencies between cascading and compound climate impacts and socio-economic and geopolitical vulnerabilities—in other words, the nexus between compound climate hazards, exposures, existing intersectional vulnerabilities, and multiple types of human responses. These interactions can be mapped via available tools and analytic methods such as the Circle tool for infrastructure and system interactions,Kemp et al.These findings highlight the importance of understanding how context, including system capital and connectedness, affects differential effectiveness and feasibility of responses to compound climate events. Addressing many of the factors affecting the soft limits to adaptation can provide an entry point for more effective responses to compound extreme events—for example, improving access to finance, affordability of new technologies, and good governance and government responsiveness; enhancing social, gender, and cultural capital; reducing poverty and inequality; and boosting climate change literacy and education and safeguarding indigenous and traditional knowledge, while better addressing inequality and other economic vulnerabilities to improve climate change responses.nick.simpson@uct.ac.za).Further information and requests for resources and reagents should be directed to and will be fulfilled by the lead contact, Nicholas P. Simpson .The team set out to identify compound and cascading hazards and response interactions affecting climate change risk in the scientific climate change adaptation literature published between 2013 and 2019. GAMI had already coded all individual hazards and adaptation-related responses documented in the articles. However, the full GAMI dataset needed to be screened to find which articles documented responses to compound climate events or their impacts and for specific analysis concerning responses to compound climate impacts. We therefore screened 1682 GAMI articles using NVivo key word search (compound∗ OR cascad∗) and selected the sub-set of human adaptation papers that displayed responses to compound climate events. This initial step identified 113 articles for potential full text coding for compound effects. A team of 11 coders then explored this set of papers with a full text readthrough of each article for responses to compound climate events, and how responses compound with each other to affect risk. After this second round of screening, a further 60 articles were excluded based on their lack or insufficient documentation of responses to one or more compound climate events. This left 53 articles for full analysis.Each article was coded through a blinded process by two different coders see . Codes wIn order to locate empirical responses within a broader understanding of risk, the observed impacts in each paper were categorized by the coding team according to the ‘key risks’ identified by the IPCC sixth Assessment, such as risk to biodiversity or food security.Recognising that the adaptation literature may not include the breadth of illustrations of compound climate events, nor responses to them necessary to enhance our understanding of adaptation to climate change, we also include 11 extended examples in the discussion of the results through reference snowballing from the underlying literature of the recent IPCC sixth assessment Working Group 2 report.