To determine whether the Centralized Chronic Medication Dispensing and Distribution (CCMDD) program in South Africa’s differentiated ART delivery model impacts clinical outcomes, we assessed viral load (VL) suppression and retention in care between patients participating in the program compared to the clinic-based standard of care.Clinically stable people living with HIV (PLHIV) eligible for differentiated care were referred to the national CCMDD program and followed for up to six months. In this secondary analysis of trial cohort data, we estimated the association between routine patient participation in the CCMDD program and their clinical outcomes of viral suppression (<200 copies/mL) and retention in care.Among 390 PLHIV, 236 (61%) were assessed for CCMDD eligibility, 144 (37%) were eligible, and 116 (30%) participated in CCMDD. Participants obtained their ART in a timely manner at 93% (265/286) of CCMDD visits. VL suppression and retention in care was very similar among CCMDD-eligible patients who participated in the program compared to patients who did not participate in the program . VL suppression alone  and retention in care alone  were also similar between CCMDD-eligible PLHIV who participated in the program and those who did not.The CCMDD program successfully facilitated differentiated care among clinically stable participants. PLHIV participating in the CCMDD program maintained a high proportion of viral suppression and retention in care, indicating that community-based ART delivery model did not negatively impact their HIV care outcomes. As high volume clinics devote resources to diagnose HIV and initiate patients on ART, service delivery models that reduce the burden of unnecessary clinic follow-up visits are needed.4 Differentiated, community-based ART delivery models may reduce the burden on the healthcare system, while also giving clinically stable PLHIV greater access to ART.5The UNAIDS has established the 95-95-95 targets to end the HIV epidemic by 2030, with the goal of having 95% of all people living with HIV (PLHIV) who are accessing antiretroviral treatment (ART) maintaining VL suppression.6 In 2014, the National Department of Health (NDoH) in South Africa established the Centralized Chronic Medication Dispensing and Distribution (CCMDD) program which is a public-private partnership that allows clinically-stable patients referred by healthcare workers in government clinics to collect ART refills at private pharmacies or community-based organizations.9 The CCMDD program supports patient ART adherence and retention by enabling convenient access to treatment at pick-up points, averting lengthy wait times at high volume HIV clinics, as well as diverting patients from overwhelmed clinic settings. CCMDD provides access to ART for over 1.7 million people and has become the largest differentiated care program in the world.9Almost one in five adults are living with HIV in South Africa, with an estimated 66% (5.1 million) PLHIV having suppressed VL in 2020.12 Additionally, there is growing need to better understand how patients progress along the cascade of care to access ART through alternative delivery models in routine national programs. An evaluation of the delivery of community-based ART for maintaining viral suppression and retention in care in South Africa may establish the impact of CCMDD on clinical outcomes as well as better understand the patients who are able to enroll and access differentiated care. In this dataset from a trial cohort in Durban entering the national differentiated care program in South Africa under routine conditions, we sought to evaluate participation and identify gaps in the CCMDD program enrollment cascade, and ultimately determine the impact of CCMDD program participation on HIV care outcomes among clinically stable patients compared to standard treatment within health clinic facilities.However, there are mixed findings on whether decentralized community-based models of care results in similar patient loss to follow-up and adherence.Simplifying HIV TREAtment and Monitoring) Study cohort, an open-label randomized controlled trial in Durban, South Africa from February 2017 to October 2018. Details of the research protocol have been published elsewhere.13 The study received ethical approval from the University of KwaZulu-Natal (BFC296/16) and University of Washington (STUDY00001466), and was registered with ClinicalTrials.gov (NCT03066128).Participant data in this analysis was collected from the STREAM , WHO violence against women instrument , and Patient Health Questionnaire-2 (PHQ-2) to screen for_depression. Participants received care according to South African HIV treatment guidelines, including testing for VL and creatinine at enrollment, and VL, creatinine, and CD4 cell count after six months. Any participant with a VL>1,000 copies per mL received enhanced adherence counselling and repeat VL testing after two months. If the repeat VL was >1,000 copies per mL, the participant was offered to switch to a standard second-line ART regimen. Participants in both comparison groups were reimbursed 100 South African Rand (ZAR) per clinic visit, per South African research guidelines.13The data used for the current study was collected as part of a randomized trial of quarterly point-of-care VL testing on retention in care and VL suppression (the STREAM parent study).15 PuPs are contracted by the NDoH and include private pharmacies and community-based adherence clubs and organizations separate from clinic settings, as well as fast-track lanes at registered health facilities.15 Eligible patients may voluntarily register and select a PuP from which to collect medication every two months, and return to the clinic every six months for clinical review and prescription renewal.15 The NDoH distributes and dispenses medication through government tender across PuPs in eight provinces in South Africa. There is no cost for patients to participate in the CCMDD program.15At least one year after initiating ART, stable participants in both arms of the trial qualified for the CCMDD program in South Africa, which allow clinically-stable participants to collect ART at decentralized pick-up points (PuPs).16 Once referred, participants collected ART every two months at a community pick-up point of their choice and were reviewed at the clinic by a professional nurse after six months. All blood testing occurred at the clinic. Participants not eligible for the CCMDD program or who chose not to participate continued with bi-monthly clinical visits. Any participant more than two weeks late for a scheduled clinic or community PuP visit received one phone call from the clinical team and resumed ART collection at the clinic, per South African guidelines.13 Laboratory and clinical records were used to assess the timing of participant referral into the community-based ART delivery program.Participants were able to be assessed for CCMDD eligibility starting from 12 months post-ART initiation. Whether the participant was assessed for CCMDD eligibility as part of the national algorithm for differentiated care, and the outcome of this assessment, was captured in electronic CRFs by study staff. In accordance with South African guidelines, participants in both trial arms were eligible for referral into the program if they were non-pregnant, clinically stable on the same treatment regimen for at least 12 months, had CD4 count >200 cells per μL, no current TB, no uncontrolled diabetes or hypertension, and had two consecutive undetectable (<20 copies/mL) VL results.The primary outcome for this analysis was a composite measure of retention in care with viral suppression, defined as <200 copies per mL, at 12 months. We used this composite outcome because both components are necessary to achieve positive treatment outcomes for adults living with HIV. Patient retention in care was defined as collecting ART at the study clinic or a community pick-up point between 44-56 weeks after enrollment. Participants not retained in care at 56 weeks were tracked by the study team up to 60 weeks for VL testing. All VL testing for the primary outcome was performed using a laboratory-based Cobas 6800/8800 machine . We also analyzed retention in care, viral suppression , and undetectable VL at study exit.If a participant was ever formally assessed for CCMDD participation prior to the Month 12 study exit visit, they were considered “Assessed”. Of those who were considered “Assessed”, those formally deemed eligible prior to the Month 12 study exit visit were considered “Eligible”. Of those ever considered “Eligible”, participants formally referred to the CCMDD program prior to the Month 12 study exit visit were considered “Referred”. Among those referred, participants who have documentation that they picked up ART from a CCMDD pick-up point within the defined window prior to the Month 12 study exit visit are considered to have “Participated”.17The primary outcome was compared between two groups who were eligible for the CCMDD program: 1) Those who participated in the program and 2) Those who did not participate. Relative risks and 95% confidence intervals were estimated using relative risk regression via modified Poisson regression with robust standard errors. Our pre-specified analysis adjusted for study arm, continuous age, and sex in the final model based on prior literature. We conducted two sets of sensitivity analyses: (a) adding adjustment for distance from the clinic (<5km vs ≥5km), and high alcohol use, to ensure that these factors, which differed between groups by more than 7.2% , were not confounding our results, and (b) using a modified Poisson model with identity link to model risk differences (RDs) rather than RRs, in order to ensure that modeling a common outcome did not obscure the magnitude or importance of potential differences. Statistical significance was determined using a two-sided type one error rate of 0.05. Statistical analysis was performed using SAS 9.4.th 2017 and August 23rd 2017, the study enrolled 390 PLHIV. Among study participants, 236 were assessed for CCMDD. Of these, 144 were deemed eligible, and 140 were formally referred to the CCMDD program  of STREAM trial participants were not assessed for CCMDD program eligibility. Further investigation into baseline characteristics of patients not assessed showed they were similar to patients who were assessed for CCMDD eligibility, with a median age of 33 years (IQR: 27-38) and 34 years (IQR: 29-39), respectively. Public transportation was the main mode of transport to the clinic (88%), and the majority of unassessed patients had to travel at least 5 km to the health clinic (77%), though travel time was usually less than an hour (92%). Comparison of social-demographic characteristics, as well as mental health, drug/alcohol use, and ART adherence indicators, show this unassessed patient population was very similar to patients who were assessed, as well as patients deemed eligible for CCMDD . The maiAt study exit after 12 months of clinical follow-up, 94% (109/116) of PLHIV who were eligible and participated in the CCMDD program had achieved both VL suppression and retention in care, compared to 93% (26/28) among those who were eligible but did not participate after adjusting for study arm, age, and sex  . ResultsVL suppression alone  or retention in care alone  were also very similar between CCMDD-eligible PLHIV who participated and those who did not participate . Among PIn this cohort of South African adults living with HIV, the majority of patients who participated in the CCMDD program picked up ART within the expected time window and remained eligible for the CCMDD program. Enrollment in differentiated care did not negatively impact clinical outcomes as levels of VL suppression and retention in care were equivalent between those who had received the standard-of-care compared to those who had participated in the CCMDD program. However, less than half of participants in the parent study were assessed for CCMDD program eligibility.22 In these studies among stable adult patients, participants greatly preferred decentralized pick-up points and reduced clinic visits, leading to fewer patients lost to follow-up and better retention outcomes.21 However, community-based treatment is not always preferable to the clinic as there were also dissenting findings from a randomized control trial in South Africa that concluded that patients had better clinical outcomes in clinic-based adherence clubs compared to those in the community, though retention in both club models was poor.11 Our study adds to this growing body of evidence, and is one of the first to assess the impact of the CCMDD program on the clinical outcomes of viral suppression and retention in care.The observed effectiveness of CCMDD participation for maintaining the clinical outcomes of viral suppression and retention in care aligns with the expectation the CCMDD program would yield similar outcomes to the standard clinic-based ART provision in South Africa, and are consistent with findings reported in other studies across different global contexts.23 However, access to these alternative service delivery models are often predicated on prior clinical stability from national guidelines, thus introducing a catch-22 where patients who demonstrate poor clinical outcomes of viral suppression are ineligible to participate in programs that may increase their access to medication. Although we cannot conclude whether CCMDD participation may improve clinical outcomes for those currently excluded, research is needed to further understand the mechanism by which PLHIV drop out of care and fail to suppress VL so that implementation of ART delivery strategies can be optimized.Broad models of providing monitoring and treatment to millions of unique PLHIV are not likely to adequately support patients in the long-term, thus we must consider adapting HIV services to specific population needs and contexts. Reviews on different models of differentiated care which include facets of the CCMDD program such as community-based ART groups, decentralized and more infrequent ART pick-ups, and task-shifting, suggest that adapted ART delivery strategies are acceptable alternatives to traditional clinic-based care for PLHIV.25 Assessment and eligibility criteria may hamper access to the CCMDD program for patients who potentially have the most to gain from adaptive services. Additionally, there is also opportunity to use differentiated care not just for ART delivery, but for providing additional TB prophylaxis and screening that support both TB and HIV control measures.Our findings also show that unassessed participants had almost 2-fold higher prevalence of tuberculosis compared to assessed participants. Current tuberculosis (TB) is an exclusion criteria for CCMDD, which may explain why these participants did not have assessment of CCMDD eligibility recorded in the study database. Studies have shown that among PLHIV with comorbidities, particularly TB, there were benefits to extending intervals between clinic visits and ART pick-ups from pharmacies, however, routine TB screening was still needed and risk assessment at treatment initiation to identify factors associated with poor clinical outcomes was recommended.29 Lack of social support, stigma, and prior loss to follow-up events were identified as essential factors that negatively impacted retention in care in a cross-sectional study that recommended home and community-based care services be incorporated into HIV service delivery models.30 Further research is needed to determine whether widening access to such differentiated care services through the CCMDD program could provide these disenfranchised patients with multi-month refills and lower costs for patient travel and time through decentralized ART collection.Our study, and the CCMDD program in general, focused on non-pregnant, adult PLHIV who are stable on ART. This is a potential limitation of existing differentiated models of ART distribution. Key populations, such as adolescents, people who use injection drugs, and pregnant people, are particularly vulnerable to non-adherence and elevated VL.13 In addition, there is potential for selection bias as our study did not randomize participants into enrollment for the CCMDD program. However, randomization of participants was logistically and ethically objectionable as CCMDD is a national program provided across South Africa and we studied the program as it was implemented.There were several limitations in this study, starting with the external validity of our study population. First, our study population consisted of participants from the STREAM trial, which reduces generalizability to other populations due to the types of people who are likely to join trials, and trial selection criteria. Second, retention in care in the STREAM parent study may be higher than the general population as all participants were reimbursed for study visits.Analysis of baseline socio-demographic characteristics as well as health behaviors among CCMDD-eligible participants who participated in the program and CCMDD-eligible participants who did not participate in the program did not show major differences. We have adjusted for observed differences in those who participated compared to those who did not, but unmeasured differences could remain. The trial intervention (point-of-care VL testing and task sifting to enrolled nurses) may have influenced assessment procedures for CCMDD and treatment outcomes, but we also adjusted for treatment arm in the regression model. Study reimbursements may also have impacted retention in care, however, identical incentives were provided for participants in comparison groups to minimize differences.31Our study reports outcomes six months following earliest possible CCMDD enrollment, thus there could be limitations as to how these findings translate to long-term retention in care. Some participants only participated in the CCMDD program for one month which may not be long enough to adequately capture changes to VL and retention in care. Further qualitative studies on patient preferences should also be conducted to determine feasibility and acceptability of the CCMDD program and provide data on barriers to participation. A relatively small sample size, particularly among eligible participants who did not participate in the CCMDD program, as well as the fact that participants are from a single clinical site serving an urban population of PLHIV in South Africa are also noted and may encourage further studies to determine outcomes across other contexts. These research gaps will be further explored in the STREAM HIV study currently conducted in both urban and rural clinics in KwaZulu-Natal, South Africa.As universal access to ART becomes more established for millions of PLHIV worldwide, there is growing consensus that a blanket model of care is no longer an acceptable strategy for providing life-long HIV services. The CCMDD program in South Africa is an effective model for providing differentiated care for clinically stable patients, however, understanding and adapting ART delivery to unique patient contexts and needs is still needed to achieve undetectable VLs and long-term retention in care. There is a gap for a needs-based approach to servicing more vulnerable sub-populations unable to presently suppress VL, as opposed to a performance-based differentiated care model that caters exclusively to clinically stable patients.In conclusion, we show that participation in the CCMDD program allowed stable adults living with HIV to suppress VL, be retained in care, and have undetectable VL levels that were similar to those who received standard-of-care treatment in a clinic-based setting. These findings support national implementation of CCMDD. Further research on the long-term effectiveness of the CCMDD program on VL suppression and retention in care is needed among representative sub-populations living with HIV, and not just among clinically stable patients.


Orientia tsutsugamushi. Immunochromatography (ICT) and IgM ELISA are two of the routinely employed antibody based assays for diagnosis of Scrub typhus fever in Nepal, although the recommended gold standard diagnostic test is IgM Immunofluorescence assay (IFA). This study evaluated InBios Scrub Typhus Detect™ Immunoglobulin M (IgM) ELISA and IgM Immunofluorescence assays in single serum sample at the time of admission.Scrub typhus is an acute febrile illness caused by the obligate intracellular bacterium, Orientia tsusugamushi was detected by using Scrub Typhus Detect™ Kit and an in-house IgM IFA. The IFA assay was performed with the Gilliam, Karp, Kato strains and O. chuto antigens following the ARRL protocol.Study participants (1585 suspected cases), were enrolled based on acute febrile illness with suspected scrub typhus cases in central Nepal. Blood sample was collected from the suspected patients of scrub typhus, presenting with acute febrile illness. IgM antibody to Statistical analysis of IgM ELISA results when compared to reference test, IgM IFA results demonstrated the following characteristics, sensitivity 84.0% (95%CI: 79.73–87.68%), specificity 94.82% (95% CI: 93.43–95.99%), positive likelihood ratio 16.21% (95% CI: 12.71–20.67%), negative likelihood ratio 0.17% (95% CI: 0.13–0.21%), disease prevalence 22.08% (95% CI: 20.06 -24.21%), positive predictive value 82.12% (95% CI: 78.28–85.42%) and negative predictive value 95.44% (95% CI: 94.27–96.38%) respectively.Although IgM IFA is considered the gold standard test for the diagnosis of scrub typhus cases, it is relatively expensive, requires trained personal and a microscope with fluorescence filters. Scrub typhus IgM ELISA may be the best alternative test and possible viable option for resource limited endemic countries like Nepal. Orientia tsutsugamushi. Scrub typhus is an arthropod-borne illness with the larval stage of several species of trombiculid mites called as chiggers; act as vectors for the transmission of the disease to the human beings. The species of the genus Leptotrombidium, particularly leptotrombidium deliense is considered to be primary cause of disease transmission in most countries [Orientia tsutsugamushi via the bite of an infected chigger, which act as both the vector and reservoir of Orientia tsutsugamushi.Scrub typhus is an acute febrile illness caused by the obligate intracellular bacteria ountries . Humans Traditionally, the scrub typhus was considered to be endemic in the part of world described by ‘tsutsugamushi triangle’ which consists the northern most point in Korea, Japan and the far eastern Russia in the north, reaching to tropical northern Australia in the south and Pakistan and Afghanistan in the west . HoweverO. tsutsugamushi from blood and eschar of the patient are also utilized, however culture is not commonly utilised.Nepal is considered as an endemic area of tsutsugamushi triangle and the outbreak of this disease is reported from different districts . Early dO. tsutsugamushi-specific recombinant 56-kDa antigen is now available as a commercial ELISA kit.Antibody based diagnostic assays are important for the diagnosis of scrub typhus in resource limited countries like Nepal. Although the gold standard test for diagnosis of acute scrub typhus is IgM IFA , 6, ICT Despite the wide use of ICT and IgM ELISA, data on their performance and efficacy in resource limited countries like Nepal, is not widely available. Hence this study was designed to evaluate the performance of the ELISA in comparison with an in-house IgM IFA in an acute serum sample taken at the time of admission.A prospective study was conducted among hospitalized acute febrile illness patients with suspected scrub typhus in central Nepal for a period of one year, April 2017 to March 2018. Cases of uncharacterized acute fever for more than 4 days were included in the study after excluding the confirmed cases of other febrile illness caused by malaria, dengue, leptospirosis, and enteric fever. Single blood sample were collected from this subset of acute febrile illness patients that were hospitalized. The blood samples were centrifuged at 3000 rpm for 5 min to separate the serum. Serum samples were stored at − 80 °C until they were analyzed.Orientia tsutsugamushi was detected by using Scrub Typhus Detect™ Kit, InBios International, USA containing the recombinant p56kDa type specific antigens of Orientia tsutsugamushi Karp, Kato, Gilliam and TA 716 strains according to the manufacturer’s instruction. Optical density was measured by HumaReader HS, ELISA reader, optical densities (ODs) > 0.50 was considered positive. The cut-off was calculated following recommendations for determining the endemic cut-off titre in the kit protocol. The cut-off calculated from healthy volunteer was mean OD (0.23) + 3 standard deviation (0.09) =0.50. We proposed a cut-off OD value of > 0.50 for chitwan and surrounding region based on our finding.IgM antibody to Orientia tsutsugamushi  strains and Orientia chuto antigens. The antigens were prepared in the Australian Rickettsial Reference Laboratory, Geelong, Australia by culturing the organism in L929 cell line and RPMI media (Invitrogen) supplemented with 5% fetal bovine serum. Individual antigens were coated onto rickettsial screening slides containing 40 individual wells, air dried and fixed in acetone. Serum samples were diluted 1:128 in 2% casein buffer and spotted onto the slide in duplicate and incubated at 37 °C for 40 min in a moist chamber to allow for the binding of antigen and antibody. With each slide tested, positive and negative controls were included. Slides were washed 3 times in PBS and dried. An anti-human FITC labeled IgM conjugate was then added and slides incubated at 37 °C for 40 min in a moist chamber. Slides were washed once more, air dried, mounted and observed under the fluorescent microscope. Positive results are indicated when fluorescence intensity was equal to or greater than the positive control. The diagnostic cutoff > 1:128 was considered positive which was derived after testing the serum samples of healthy controls from that particular region. Negative results were reported when the sera didn’t fluoresce at a dilution of 1:128. Positive serum samples were serially titrated 1:128, 1:256, 1:512, 1:1024, 1:2048, 1:4096, 1:8192, 1:16384 etc. to end point titers with individual antigens.Antibodies against Scrub Typhus Group were tested using Positive and negative controls were included with each slide that if either failed in a screening or titration slide, tests were repeated. In instances of continuation of assay failure both the antibody and antigen controls were re-titrated to see if there had been a shift in the antibody endpoint or if the antigen had lost its reactivity. Whenever necessary fresh controls and antigens were optimised prior to repeating of the assay with the specimens.The collected data were entered in Epi info 3.5 from CDC and exported to IBM SPSS version 16.0 . The sensitivities, specificities, positive predictive values, negative predictive values of the serological tests were calculated using MedCalc for windows, version 18.11.3 . STARD 2015 guidelines for reporting diagnostic accuracy studies was strictly followed [Orientia tsutsugamushi IgM ELISA Positive samples are summarized in Fig. Orientia tsutsugamushi antigens IgM ELISA positive samples are listed in Fig. Standard for Reporting Diagnostic Accuracy (STARD) flow chart of suspected scrub typhus cases enrolled in the study is given in Fig. Statistical analysis of ELISA IgM results when compare to IgM IFA results demonstrated the following characteristics, sensitivity 84.0% (95% CI: 79.73–87.68%), specificity 94.82% (95% CI: 93.43–95.99%), positive likelihood ratio 16.21% (95% CI: 12.71–20.67%), negative likelihood ratio 0.17% (95% CI: 0.13–0.21%), disease prevalence 22.08% (95% CI: 20.06 -24.21%), positive predictive value 82.12% (95% CI: 78.28–85.42%), negative predictive value 95.44% (95% CI: 94.27–96.38%) respectively. Calculation of statistical values of IgM ELISA test compared with IgM IFA are summarized in Table Scrub typhus is an endemic/reemerging acute febrile infectious disease prevalent in Nepal. The diagnosis of scrub typhus was generally done by clinical presentation and history reporting prior to its serological diagnosis. The common clinical manifestations of other acute febrile illness make it difficult for its clinical diagnosis. The mortality rate varies from 0 to 30% if left untreated in the endemic areas .In this study we compared the results of the Scrub Typhus Detect™ IgM ELISA against the gold standard IgM IFA.The overall sensitivity and specificity of the IgM ELISA was 84.0% (95% CI: 79.73–87.68%) and 94.82% (CI: 93.43–95.99%) respectively in our study. Various studies have demonstrated a similar performance, with sensitivities in the range of 85 to 93% and specificities 94 to 97.5% –12.The dInBios IgM ELISA is a sensitive and specific test and could be substitute for the IgM IFA in resource limited countries like Nepal. ELISA is comparatively cheaper and easier test with high throughput of the specimens.Orientia tsutsugamushi are mixed to antigen on a slide, then detected using a fluorescently labeled anti-human antibody. Karp, Kato and Gilliam serotypes are the most commonly used antigens [Indirect immunofluorescence assay (IFA) is considered to be the gold standard test for the diagnosis of scrub typhus , in whicantigens , local santigens . Among 1antigens , 14, 15.antigens .Local cut off titer must be determined in the endemic countries based on the seroprevalence rate in the healthy population while using IFA and ELISA, which enables to distinguish the acute infection and previous exposure if only single serum sample is available . AlthougOrientia tsutsugamushi Karp, Kato, Gilliam, TA 716 and Orientia chuto may not be representative of the infecting Orientia from this region which may lead to lower sensitivity of both ELISA and IFA used. The antigens used for ELISA test (TA716) and IFA (O. Chuto) may lead to minor inaccuracies in the result and validation between the IFA and ELISA.The various limitations of this study include the collection of single serum specimens for the detection of IgM antibodies during the acute phase of the disease. A rise in the antibody titer in paired sera could not be detected in our study. The circulating strains of Orientia species in Nepal are not known so antigens used in the serological assays Scrub typhus is the common acute febrile illness present in our country Nepal. Although IgM IFA is considered the gold standard test for the diagnosis of scrub typhus cases, it requires trained personal and fluorescent microscope. IFA is gold standard test which need to be utilized for all research purposes. It may be difficult to use this method for the routine diagnosis of scrub typhus in resource limited countries. Scrub typhus IgM ELISA may be the best alternative test for routine use currently available in Nepal.


Phytophthora small extracellular proteins that consists of conserved subfamilies that are widely recognized by solanaceous plants. Remarkably, one subclass of SCR74 proteins is highly diverse, restricted to the late blight pathogen Phytophthora infestans and is specifically detected in wild potato plants. The diversification of this subfamily exhibits signatures of a coevolutionary arms race with surface receptors in potato. Insights into the molecular interaction between these potato-specific receptors and the recognized Phytophthora proteins are expected to contribute to disease resistance breeding in potato.Immune receptors at the plant cell surface can recognize invading microbes. The perceived microbial molecules are typically widely conserved and therefore the matching surface receptors can detect a broad spectrum of pathogens. Here we describe a family of  Phytophthora infestans. A subclass that includes the conserved effector PcF from Phytophthora cactorum activates immunity in a wide range of plant species. In contrast, the more diverse SCR74 subclass is specific to P. infestans and tends to trigger immune responses only in a limited number of wild potato genotypes. The SCR74 response was recently mapped to a G-type lectin receptor kinase (G-LecRK) locus in the wild potato Solanum microdontum subsp. gigantophyllum. The G-LecRK locus displays a high diversity in Solanum host species compared to other solanaceous plants. We propose that the diversification of the SCR74 proteins in P. infestans is driven by a fast coevolutionary arms race with cell surface immune receptors in wild potato, which contrasts the presumed slower dynamics between conserved apoplastic effectors and PRRs. Understanding the molecular determinants of plant immune responses to these divergent molecular patterns in oomycetes is expected to contribute to deploying multiple layers of disease resistance in crop plants.Plants deploy cell surface receptors known as pattern-recognition receptors (PRRs) that recognize non-self molecules from pathogens and microbes to defend against invaders. PRRs typically recognize microbe-associated molecular patterns (MAMPs) that are usually widely conserved, some even across kingdoms. Here, we report an oomycete-specific family of small secreted cysteine-rich (SCR) proteins that displays divergent patterns of sequence variation in the Irish potato famine pathogen  Cladosporium fulvum (–The plant apoplast is the battlefront of the plant-pathogen interaction . To colom fulvum . Plants m fulvum . Most RLm fulvum –9. Recen fulvum –.Phytophthora cactorum-Fragaria), SCR74, and SCR91  and plant NLR genes have been reported to follow the arms race model, such as the ATR1 from Hyaloperonospora parasitica and RPP1 from Arabidopsis  were obtained from InterPro. The PcF/SCR proteins were only present in oomycetes, including dopsidis , Phytophcactorum , Phytoph were obtrasitica , Phytophnfestans . Eleven nfestans , and 20 nfestans . Our dat10.1128/mBio.00947-20.8TABLE S1P. cactorum isolates used in this study. Download Table S1, XLSX file, 0.02 MB.List of PcF/SCR proteins and Copyright © 2020 Lin et al.2020Lin et al.Creative Commons Attribution 4.0 International license.This content is distributed under the terms of the P. cactorum was included as an outgroup. Based on the alignment and network analysis, the PcF/SCR proteins were classified into three clades, i.e., a PcF clade, an SCR74 clade, and a PcF/SCR clade, respectively . A highly variable region from amino acid position 31 to 51 is present in these PcF/SCR proteins; members of the SCR74 clade share an AINA/PD/EPV/IA motif, that is different in the other clades  of 65 PcF/SCR proteins. The 65 PcF/SCR proteins are classified into 3 clades, i.e., a PcF clade, a PcF/SCR clade, and an SCR74 clade. PcSCR96 was used as outgroup for phylogeny analysis. Download Copyright © 2020 Lin et al.2020Lin et al.Creative Commons Attribution 4.0 International license.This content is distributed under the terms of the P. cactorum were reported , and another synonymous mutation was found in the effector domain of NL2003-3  Amino acid alignment of PcF proteins from nine P. cactorum isolates from the USA and Europe. (B) Flanking sequences of 500 kb of PcF from P. infestans and 200 kb of PcF from P. sojae, P. ramorum, and P. capsici, along with a short contig from P. cactorum, were aligned by Mauve. Regions of significant synteny are displayed as colored locally collinear blocks (LCBs) based on Mauve’s progressive algorithm. The LCBs are connected by colored lines between the species. The PcF orthologs  from the 5 Phytophthora species are shown with black arrows. Download FIG S2, TIF file, 1.7 MB.Copyright © 2020 Lin et al.2020Lin et al.Creative Commons Attribution 4.0 International license.This content is distributed under the terms of the PcF loci are conserved in diverse Phytophthora species, we extracted the PcF loci and the flanking 250-kb region from the genome of P. infestans, the 100-kb flanking sequence from P. sojae, P. ramorum, and P. capsici, and a short contig containing PcF from P. cactorum. Sequence alignment of the PcF loci  the sequences of Scr74 genes are highly diverse and display a marked signature of positive selection as previously reported by Liu et al. , and a 53-amino-acid mature protein (black bar). The cysteine residues are highlighted in yellow and they are conserved in most of the variants. Other conserved amino acids with no change or only synonymous mutation are highlighted in blue. The highly diverse amino acids with nonsynonymous mutations are highlighted in red. Download FIG S3, TIF file, 2.6 MB.Polymorphisms of SCR74 genes from 52 sequenced Copyright © 2020 Lin et al.2020Lin et al.Creative Commons Attribution 4.0 International license.This content is distributed under the terms of the Scr74 genes in the P. infestans reference genome, we extracted three Scr74-containing supercontigs   from supercontigs 1.73 and 1.4 showed a high level of identity   from theidentity . This obScr74 and PcF localize in GSR or gene-dense regions (GDRs), we plotted two Scr74 genes and PiScr70, the PcF ortholog of P. infestans, as well as known apoplastic effectors Inf1 and Epi1, and the well-characterized cytoplasmic Avrblb2 and Avr3a on the flanking intergenic regions (FIRs) map of P. infestans reference genome (T30-4). The Scr74 genes localize to the extreme GSR region, similar to the Avr genes Avrblb2 and Avr3a. In contrast, the P. infestans PcF ortholog PiScr70 lands closer to the GDR, similar to Inf1, which shares features with MAMPs (P. infestans reference isolate T30-4-infected samples were plotted for various stages (Scr74 genes peaked at 2 to 3 days after infection (dpi), which is similar to typical Avr genes, whereas the expression pattern of PiScr70 rather resembles Epi1 (Most oomycete genomes have gene-dense housekeeping regions (GDRs) and gene-sparse repeat-rich regions (GSRs), and rapidly evolving effectors tend to be located in the GSR . To visuth MAMPs   in the cytoplasm, and stably expressed either SCR74-B3b or a cysteine mutant SCR74-27A, both with monomeric red fluorescent protein (mRFP) under the control of the constitutive Ham34 promoter  The expression of SCR74-B3b-mRFP and a cysteine mutant SCR74-B3b-27A-mRFP were confirmed in mycelium (M) and culture filtrate (CF) using immunoblotting with αmRFP antibody, and αGFP primary antibody was used to detect intercellular protein GFP to show there was no leakage in the CF with cellular proteins. Ponceau stain (PS) was used for protein loading control. Protein size markers are indicated in kDa. (B) Confocal projections reveal that both fusion proteins of SCR74-B3b-mRFP and SCR74-B3b-27A-mRFP are secreted at haustoria (H) in infected tissues by P. infestans transformants expressing SCR74-B3b-mRFP and SCR74-B3b-27A-mRFP, respectively. Download FIG S4, TIF file, 2.3 MB.Copyright © 2020 Lin et al.2020Lin et al.Creative Commons Attribution 4.0 International license.This content is distributed under the terms of the Solanum section Petota), 23 tomato, 7 eggplant, 10 pepper, and 8 Nicotiana genotypes. PcF and SCR96 from P. cactorum, SCR68 from P. sojae, and 13 SCR74 variants from P. infestans were cloned into potato virus X (PVX) vectors pGWC-PVX or pGR106, and transformed into Agrobacterium tumefaciens strain GV3101 for transient expression. The Agrobacterium clones carrying single PcF/SCR genes were toothpick-inoculated onto at least 6 leaves from 3 plants. The general necrosis-inducing CRN2 and the empty vector were used as positive and negative controls, respectively. The symptoms were scored 12 to 14 days after infection, on a range of 0 to 10, reflecting no visible response up to clear cell death in all replicates, respectively. After removing genotypes that showed unspecific cell death to pGR106 treatment, or failed to show cell death to pGR106-CRN2, there were a total of 4 Nicotiana, 2 pepper, 3 eggplant, 17 tomato, and 136 potato genotypes that were scored for their response to the effectors , dark orange (score 7 to 8), light orange (score 5 to 6), to beige (score 0 to 4). CRN2 and empty pGR106 vector were used as positive and negative controls, respectively. Download Table S2, XLSX file, 0.03 MB.Effectoromics screening on Copyright © 2020 Lin et al.2020Lin et al.Creative Commons Attribution 4.0 International license.This content is distributed under the terms of the P. cactorum caused cell death responses in a wide range of diverse Solanaceae. Recognition was detected in various wild potato species, as well as tomato, pepper, eggplant, and some tobacco accessions  PVX agro-infection of PcF in Capsicum annuum (CGN16796), Solanum incanum (CGN18575), Solanum hjertingii (HJT350-1), and Solanum polytrichon (PLT789-6), and agro-infiltration in Solanum lycopersicum (CGN14330). (B and C) PVX agro-infection of SCR74 variants on S. polytrichon (PLT378-1) (B) and Solanum microdontum subsp. gigantophyllum (GIG362-6) (C). CRN2 is included as a positive control for PVX agro-infection, and coinfiltration of R3b and Avr3b for agro-infiltration. The empty PVX vector is used as negative control. Download FIG S5, TIF file, 2.4 MB.PcF and SCR74 responsiveness in the Copyright © 2020 Lin et al.2020Lin et al.Creative Commons Attribution 4.0 International license.This content is distributed under the terms of the Solanum genotypes  Protein alignment of SCR74-D4, -B4, and -C10 The predicted S-S bridges (yellow bars) and the α-helix (green bars) are indicated. (B) Predicted structure of the mature SCR74 protein, where the polymorphic amino acid between SCR74-D4, - B4, and -C10 at position 28 is shown. (C) PTA767-1 recognizes SCR74-D4, -B4, and -C10, whereas PLT378-2 can only recognize SCR74-C10. (D) Two SCR74 cysteine mutations SCR74-synB3b-27A and SCR74-synB3b-47A were synthesized and PVX agro-infected on GIG362-6 leaves together with SCR74-B3b and a codon-optimized SCR74-B3b. CRN2 and empty vector were used as positive and negative controls, respectively. The photo was taken 14 dpi. Download Copyright © 2020 Lin et al.2020Lin et al.Creative Commons Attribution 4.0 International license.This content is distributed under the terms of the Solanum microdontum subsp. gigantophyllum genotype GIG362-6 plants. The mutants failed to cause cell death, showing that S-bridges are critical for SCR74 function  genes, a putative reticulate-related 1 like gene, a serine/threonine-protein kinase ATG1c-like (autophagy-related protein) gene, a prenylated rab acceptor family gene, and a uracil phosphoribosyltransferase-encoding gene , we mapped the response to SCR74 to a locus at the top of chromosome 9 in GIG362-6 . Based oing gene , Fig. S7ing gene , here weectively .10.1128/mBio.00947-20.7FIG S7G-LecRKs are upregulated after UK3928A infection. (B) Differential expression of candidate genes in the mapping interval. The raw read counts and transcript per million (TPM) for each sample, as well as the differential expression ratio and the P value, are shown for the four treatments of GIG_water versus GIG_UK3928A and MCD_UK3928A versus GIG_UK3928A. The upregulated genes are highlighted in red, the downregulated genes are highlighted in blue. The significant (P < 0.05) differential expression P values are shown in red font, otherwise in blue font. Download FIG S7, TIF file, 2.3 MB.Differential expression of candidate genes on haplotype 1 of GIG362-6. (A) The mapping interval on GIG362-6 with the RNA-seq reads from GIG362-6, mapped to haplotype 1 (BAC03-H3 and BAC01-3A). The blue peaks present the coverage of RNA-seq reads. The samples of water treatment and UK3928A inoculation are shown. The two Copyright © 2020 Lin et al.2020Lin et al.Creative Commons Attribution 4.0 International license.This content is distributed under the terms of the G-LecRK loci are conserved among different Solanaceae, we analyzed the G-LecRK loci from various other available solanaceous genomes. We found that Solanum chacoense, which is closely related to S. microdontum and clone DM1-3, contains four partial and three full-length G-LecRK genes in the locus. In another wild potato, Solanum verrucosum, we detected four G-LecRK genes  experiment on the mapping parents GIG362-6 and MCD360-1, 48 h postinoculation (hpi) with P. infestans isolate UK3928A or mock-inoculated with water. The RNA-seq reads were mapped to the BAC sequences of GIG362-6 and show that the G-LecRK genes are upregulated after infection  sensing    that recity (SI) , 37. Thiity (SI) .G-LecRK genes show CNV in the two haplotypes of GIG362-6, with two or five copies, respectively. The copy number of these G-LecRKs in different potato genomes varies dramatically, namely, three, four and seven full-length or partial G-LecRK genes were found in the DM1-3 potato, Solanum verrucosum, and Solanum chacoense genomes, respectively, which suggests this locus has been under evolutionary pressure in wild potato species. Other, more distant Solanaceae, such as tomato, pepper, and eggplant, only contained one or a maximum of two G-LecRK genes in their genome. Our genetic data provide further evidence about the coevolution hypothesis that the highly diverse apoplastic SCR74 effectors coevolve with the receptors in their wild potato host species.The P. infestans and potato. We showed that the PcF/SCR effector family acts as “invasion patterns”  were obtained from InterPro. The protein sequences were aligned by MAFFT v7.309  and Genehttp://protists.ensembl.org/) or JGI genome portal (https://genome.jgi.doe.gov), including P. infestans (ASM14294v1) (P. sojae (P. sojae V3.0), P. ramorum (ASM14973v1) (P. capsici (LT1534 v11.0) (P. cactorum strain LV007 can be obtained from GenBank (NBIJ01000000) (The oomycete genomes were obtained from EnsemblProtists (ans ASM144v1 (29),tans ASM194v1 (P. 4 v11.0) . The draPhytophthora isolates.Phytophthora cactorum isolates that were used in this study are listed in in vitro Solanum collection of Plant Breeding at Wageningen University and Research.The seeds of tomato, pepper, and eggplant were obtained from the Centre for Genetic Resources, Wageningen, The Netherlands (CGN). The potato genotypes were clonally maintained at the Agrobacterium tumefaciens strain GV3101 for PVX agro-infection or into pK7WG2 for agro-infiltration. More details are in the Materials and Methods section of the supplemental materials.The effectors were cloned into pGR106 vector and then transformed into 10.1128/mBio.00947-20.10TEXT S1Text S1, DOCX file, 0.04 MB.Detailed Materials and Methods used in this study. Download Copyright © 2020 Lin et al.2020Lin et al.Creative Commons Attribution 4.0 International license.This content is distributed under the terms of the


In conclusion, cancer survivors were positive about the NutriCare program and its integration into practice.Nutrition is an essential part of oncology care; however, nutrition advice and guidance are not always provided. This six-week pilot pretest-posttest intervention was designed to test the feasibility and effectiveness of integrating a nutrition education program (NutriCare) into outpatient oncology care. Twenty breast cancer survivors were recruited through Tufts Medical Centre. Nutrition impact symptoms and demographics were collected at baseline, dietary quality and quality of life measures were collected pre and post-intervention and an evaluation form was completed post-intervention. Forty-four percent of eligible participants were recruited, and 90% of those completed the study. The NutriCare program was well received with participants reporting that goals were feasible (94.4%), the program had a positive impact on their diet (77.8%), and over 80% would recommend the program. There was an interest in continuing with the program (89%) and in receiving additional guidance from the healthcare team (83%). There was a significant improvement ( Nutrition is extremely important in the management of cancer. It is well recognized that some treatments could have detrimental effects on patients’ dietary intake ,2, whichContinued active clinical support and education for cancer survivors should be considered an essential element in the cancer journey to address patient well-being . The NutNutriCare is a program designed to integrate nutrition into oncology care. The components of this intervention have been published elsewhere  and haveAs mentioned previously, the NutriCare model has previously been reported, but in short, it utilizes the 5-A model  to integrate nutrition care into the oncology setting. This model has previously been utilized in smoking cessation , obesityAn information sheet was provided to all participants by the oncology team in Tufts Medical Centre prior to consent. All participants gave informed written consent before commencing any aspect of the study. The baseline visit coincided with a clinical visit to the Breast Clinic to make it more convenient for the participants. After consent, participants provided information on socioeconomic demographics as well as completing two quality of life questionnaires – the Patient-Reported Outcome Measurement Information System (PROMIS) -57 Profile v2.1  and PROMFollow-up was six weeks after the in-person visit and consisted of a brief phone call and the mailing of the two quality of life questionnaires to be recompleted and new login details being provided to complete the DHQ III online again. The program’s feasibility was assessed in a number of ways, including using participants’ satisfaction ratings on an evaluation form provided at the six weeks follow-up, using the participants’ ratings for understanding and ease of use of the provided resources, and the study’s retention rates.The PROMIS -57 Profile v2.1  and PROMFor the components of the PROMIS -57 Profile v2.1 questionnaire, for the United States general population, a score of 50 is average with a standard deviation of 10. For concepts within this questionnaire that are positively worded, therefore, such as mobility, a T-score of 60 represents one standard deviation above average and a T-score of 40 represents one standard deviation below average. Conversely, with negatively worded concepts such as anxiety, a T-score of 60 represents one standard deviation below average, while a T-score of 40 represents one standard deviation above average .The PROMIS Scale v1.2-Global Health gives values for both Global Mental and Global Physical Health. When reporting on Global Mental Health the cut-offs for poor, fair, good, very good and excellent are 29, 40, 48 and 56, respectively . For GloDietary quality was assessed using the Healthy Eating Index (HEI)-2015 and its component score calculated by the Diet*Calc software developed by the National Cancer Institute , based op < 0.05.Data were analyzed using SPSS version 24. Descriptive statistics were used to describe the demographic and health information and are presented as means, SDs, ranges, frequencies and percentages. The study was not powered to detect statistically significant differences, but pre-post intervention differences in dietary intake and quality of life measures were assessed using t-tests. Significance was set at This project was approved by the Institutional Review Board of Tufts University . The researchers obtained written informed consent from all study participants prior to enrolment in the study. All data was stored in password-protected computers and locked filing cabinets in Tufts University and only the first author and principal investigator had access to this data.2 (±6.4). 30% of the cohort reported weight gain since diagnosis, and 15% reported weight loss in this timeframe. 80% previously underwent surgery, 75% underwent chemotherapy, and 75% underwent radiation therapy. 75% were receiving hormonal therapy at the time of the pilot. Additional characteristics can be found in The results of the NACP questionnaires are outlined in n = 8), increase vegetables by one portion on most days (n = 5), increase dairy by one portion on most days (n = 7), have breakfast (n = 6), include an extra portion of oily fish per week (n = 4), increase fruit by one portion on most days (n = 4) and increase fiber by introducing more wholegrains (n = 4).The main goals chosen based on the results of the NACP  and in cPhysical health scores ranged from 39.8 (fair) to 57.7 (very good) at baseline and from 39.8 (fair) to 67.7 (excellent) at follow-up. Mental health scores ranged from 31.3 (fair) to 67.7 (excellent) at baseline and from 33.8 (fair) to 67.7 (excellent) at follow-up .p = 0.04). There were no additional statistically significant changes in quality of life or in overall dietary quality as measured by the HEI-2015 and its component scores from pre-test to post-test  and were enrolled in the study. In all, 18 of these 20 participants (90%) completed post-testing.Participants were very positive about the NutriCare program . They ren = 10, 55.6%) of the enrolled participants by phone to follow-up (Recruitment of participants occurred primarily by phone which proved difficult as not everyone could be reached or responded to phone messages. Focus groups to refine this program were carried out prior to implementation  and thesollow-up .p = 0.04) in physical function over the six weeks; however no additional significant differences in quality of life or dietary quality were seen.The NutriCare program was well-received by breast cancer survivors in this study. There was an interest in continuing with the program and in receiving additional guidance from HCPs. There was a significant improvement . The impact that high levels of fatigue, as demonstrated in this group, could have on the ability to shop for and prepare food and therefore, overall dietary intake should not be ignored. A large meta-analysis of 12, 327 breast cancer survivors who had completed treatment reported that one in four suffered from severe fatigue post-treatment, with the prevalence reducing substantially in the first 6 months after treatment . This isn = 11) at the six-week follow-up. We also did not assess specific laboratory values, which could have served as risk surrogates indicating short-term changes and could also have acted as motivational tools.There were a number of limitations in the study. First, the survivors who enrolled in the study were highly educated, white, breast cancer survivors of high socioeconomic status and so the results of this pilot will not be applicable to broader cancer groups, cancer types or ethnic groups. This bias has been demonstrated regularly in previous work also ,30. In aIn conclusion, cancer survivors were positive about the NutriCare program and its integration into practice. There was an interest in continuation with the program and additional guidance from HCPs. There is warrant in investigating the delivery of this program through different mediums, e.g., online, to ensure that patients and survivors who are attending centers that do not have the resources to run such a program will still be able to take part and get access to evidence-based nutrition guidance.


Chatbot, a type of digital healthcare tool, is used in various medical fields but has never been developed for follow-up management of WGHE in Korea. (2) Methods: The database containing results and explanations related to WGHE was constructed. Then, the channel, which connects users with the database was created. A user survey regarding effectiveness was administered to 23 healthcare providers. Additionally, interviews on applicability for occupational health services were conducted with six nurses in the agency of occupational health management. (3) Results: Chatbot was implemented on a small scale on the Amazon cloud service (AWS) EC2 using KaKaoTalk and Web Chat as user channels. Regarding the effectiveness, 21 (91.30%) rated the need for chatbots as very high; however, 11 (47.83%) rated the usability as not high. Of the 23 participants, 14 (60.87%) expressed overall satisfaction. Nurses appreciated the chatbot program as a method for resolving accessibility and as an aid for explaining examination results and follow-up management. (4) Conclusions: The effectiveness of WGHE and the applicability in the occupational health service of the chatbot program for follow-up management can be confirmed. A health examination provides an effective screening and medical evaluation strategy that has been scientifically shown to facilitate early detection and treatment, even among asymptomatic patients, thereby preventing disease and promoting personal health . In KoreFollow-up management for the general health examination entails additional interventions, such as diagnosis confirmation, education, and counselling, regarding results of the examination for those who need further action after the screening . The impChatbot, a type of digital healthcare tool, is a rule-based or artificial intelligence-based communication software that uses a mobile device to provide answers and relevant information in response to questions posed through text or voice conversations . This teBecause chatbots are optimised for mobile devices and can therefore obtain the necessary information without the need to install a separate app, the number of users and the service area are becoming increasing significantly. However, no chatbot program has yet been developed that explains the results of the general health examination explicitly and provides methods for follow-up management, that are easily understood by the general public. This pilot study is the first step in a plan to develop a chatbot program for follow-up management of the WGHE. The study develops an early version of a chatbot program that generates health status information and health management methods based on individual results from the WGHE. Furthermore, this study investigates the effectiveness of the chatbot program to healthcare providers who have undergone WGHE program in 2018 and the applicability of the chatbot program to nurses in the special agency of occupational health management in charge follow-up management of WGHE.Research participants were recruited from October to November 2019. The research director visited three hospitals and explained the purpose of the study, the contents of the study, and the method of participation for those who received the WGHE in 2018. In addition, consent was obtained from those who agreed to participate in the study. Subsequently, chatbot authentication and personal data were collected after using the chatbot program for a week, a survey was conducted online. Research participants submit their own phone number, and the researcher sends a channel subscription message to the participant’s phone number. It is authenticated through the consent of the channel subscription, and data is generated based on the inputted health examination results and information appropriate to one’s health status is sent to the individual. Also, the chatbot program was explained to nurses working at the agency of occupational health management. They checked the entire contents of the chatbot program for a week and then participated in the interview. The study was approved by the Institutional Review Board of Busan Paik Hospital, Inje University (No. 19-0189). The chatbot program was developed based on the rule-based or scenario method that is most often used to describe professional content. The development process is as follows.Requirements analysis: Define business requirements for program development.Scenario flow definition: Define the flow of core tasks to which the program is applied and the flow design for providing examination results.Database construction: Design and build the schema for the examination results and additional explanation database. At this time, construct images and videos that will be useful for explaining the examination results.Channel establishment: Set the channel where the user and chatbot will meet.Chatbot program development: Develop a content-provided chatbot program and a chatbot program that extracts and provides necessary answers.The chatbot program for follow-up management of the WGHE is implemented on a small instance of the Amazon cloud service (AWS) EC2 and web server; the development language node is 7.0, and the database management system is MySQL 5.7. KakaoTalk and Web Chat are used as user channels. After the user performs personal authentication through a smartphone, the program provides follow-up information based on individual results. Using the health examination results, a scenario-based process is used to create a response by linking to or searching the database, web search engine, and YouTube API (Application Programming Interface) for data suitable for the patient’s status and examination results . Personal authentication is required only once, at the first access, and subsequent identification is automatic based on the phone number. After authentication, only the authenticated user’s information is displayed on the corresponding smartphone. Smartphone implementation is shown in Information on study participants’ examination results was extracted from the examination results server if that server was accessible. In the case of subjects who have undergone the WGHE program at other hospitals, who would not have access to the examination results server, the examinee printed the examination results and then submitted them. The collected examination results were then stored on a different server. A separate database was built, and after the testing and service period, it was discarded to protect personal information. To test the business logic and accuracy of the data display, a separate web program was developed  to enterThe target diseases of the WGHE in Korea are hypertension, obesity, anaemia, diabetes, dyslipidaemia, liver disease, kidney disease, pulmonary tuberculosis, other chest diseases, and cardiocerebrovascular disease. The history-taking and physical examinations cover past personal and family history and lifestyle factors, body measurements, chest radiography, blood tests, urine tests and risk assessment for cardiocerebrovascular disease. The content of the program comprises two stages. The first step explains the examination results according to the test items  and basic recommended follow-up management . The second step requires researching and organising more detailed information than that presented in the basic results  and more detailed follow-up methods than those provided as basic follow-up management .This information is provided by government agencies , National Cancer Control Institute in Korea), professional medical associations in Korea , and homepages of universities or general hospitals . Five occupational and environmental medicine specialists reviewed the summary of examination results, details of follow-up management, and specific information for each disease.An eight-question survey addressing satisfaction with the chatbot was administered, including its necessity and convenience, to 23 medical personnel working at hospitals in Korea . They haSix nurses were interviewed, in charge of follow-up management of WGHE  regarding the possibility of using the chatbot program for follow-up management at the agency of occupational health management. They reviewed all the contents of the chatbot program for follow-up management and applied the chatbot program through an app before they took part in the interview. The interview had three aims: (1) the reason why follow-up management was difficult; (2) to evaluate the chatbot program for follow-up management; and (3) to assess the possibility of using the chatbot program in the occupational health service. The questionnaire was constructed using a 5-point Likert scale, but in the results, responses were aggregated into three categories. Very high and slightly high were classified as high, middle as moderate, and slightly low and low as low, and the results in the applicability interview were decided through a meeting of the researchers. Similar opinions were organized into one content and independent opinions were described as they were in the interview.The program content is divided into two parts. The first includes the examination results, reference value for each test, a basic explanation of the result and actions to be taken. The second part contains detailed information about the examination results (definition and complications of target disease) and recommended managements . Detailed information and sources are shown in Of the 30 medical personnel who agreed to use the chatbot program for follow-up management, 23 were selected as participants. Four who reported normal results (A) on all examinations (and thus did not require follow-up) and three who did not complete the survey were excluded. There were 14 males and nine females; the largest proportion (39.12%) were in their 30s. In terms of content comprehension and content specificity, 17 (73.91%) and 18 (78.26%) participants were satisfied , respectively. However, in terms of ease of use and ease of completion, 11 (47.83%) and 13 (56.52%) respondents, respectively, were satisfied , respectively, reflecting less satisfaction with the program’s ease than with content comprehension and specificity. In terms of the need for follow-up management chatbots, 21 (91.30%) respondents indicated that chatbots are needed ; fewer respondents  said that such chatbots could contribute to healthcare . Finally, 14 respondents (60.87%) reported overall satisfaction  .Nurses working at the agency of occupational health management highly appreciated the chatbot program, as it was especially useful as a tool for solving accessibility among the difficulties in follow-up management and as an aid for explaining examination results and recommended actions. Furthermore, they suggested that accessibility and applicability would improve if question-and-answer functions were added. However, they expressed concern about the chatbot’s inconvenience for use and accessibility for elderly workers. A summary of the interview results is shown in This pilot study aimed to develop an early version of a chatbot program for follow-up management after WGHE. Another purpose was to investigate the effectiveness of use among healthcare providers and to check applicability in occupational health services among nurses in the agency of occupational health management.The developed chatbot program is a system that generates information of follow-up management appropriate to the participants’ condition by matching the participants’ collected information  with the results of the health examination. It then checks the contents of the participants’ interest from the generated information. Such a system has the advantage of first showing the overall information of follow-up management necessary for the individual’s situation. Then, from among the data provided, the participant can search more intensively for additional information of interest. Follow-up management in a health examination is not just about the individual’s interests; rather, it is an additional intervention that includes steps such as diagnosis confirmation, education, and counselling for those who need further action as a result of screening. Thus, the first step of health examination should be to provide all of the follow-up management information required by the individual.The results of our user survey regarding the chatbot program for follow-up management showed that medical practitioners were generally satisfied in terms of content comprehension  and content specificity . About 50% of the information comprised videos or animations less than 4 minutes in length that have been provided to the general public by professional societies affiliated with the Korean Academy of Medical Science; thus, their source may be one reason for the high level of satisfaction with content and specificity due to their evidence based evidence level. Infographics, which combine information and graphics, have attracted attention as a method for effectively delivering large amounts of data and complex information . InfograIn terms of ease of use and ease of construction, 11 (47.83%) and 13 (56.52%) participants, respectively, were generally satisfied, reflecting less satisfaction than with content comprehension and specificity. Previous studies mentioned that ease of use positively affects the intention to use smartphone healthcare applications , and theRegarding the need for follow-up management using chatbot programs, 21 (91.30%) participants said that such chatbots were generally needed, whereas a lower proportion  believed that they could contribute to healthcare . This result is similar to previous research findings showing that, although respondents were interested in healthcare applications, they did not expect them to have any effect . HoweverInterviews with nurses working in the agency of occupational health management suggested that the chatbot would improve patient access. This improvement is because information on follow-up management could be checked at any time on a smartphone. Furthermore, they highlighted the chatbot program’s usefulness for explaining necessary follow-up management information and its value for reducing the time needed for follow-up management. Moreover, considering a previous study showing that most occupational health management agencies have difficulty developing the necessary textbooks for safety and health education in Korea , this chThis study has some limitations. First, it was a pilot study using a preliminary version of the chatbot program. The initial version of the chatbot program developed in this study provided appropriate information when a participant pressed a button. However, recent years have seen attempts to replace text input with speech recognition technology, even aiming to grasp the intention of a question using natural language processing techniques. In the next step, technologies that can facilitate a question-and-answer process will be applied. Second, a satisfaction assessment for the general public was not performed, although there are clear differences between medical providers and members of the general public from the point of view that you are already familiar with the terms of WGHE and the content that the chatbot will provide in response. However, it was necessary to test the program after creating the initial version of the chatbot program. Because it is a follow-up management program based on one’s results of a health examination, medical providers would be little significant difference to the general public at the point. In the next step, it should be planned to increase the completeness of the chatbot program and conduct satisfaction assessments among the general public. Third, the sample size is too small while proceeding with the pilot study. Likewise, no statistical analysis was performed. So, we cannot confirm statistically meaningful results. We plan to conduct large-scale research in the future to confirm statistical significance. Fourth, the chatbot program developed here focuses on comprehensive and detailed explanations of the information necessary for follow-up management. Follow-up management takes effect only when there is a change in behaviour, such as measuring blood pressure periodically or continuously exercising. However, this chatbot program cannot directly manage or support lifestyle improvement efforts. Recently, an app that helps manage smoking  or obesiIn summary, a follow-up management program using chatbots in WGHE was developed for the first time in Korea. Chatbot users were generally satisfied, and it was confirmed that there are positive aspects in applying chatbot programs to occupational health services. For more practical follow-up management, in the future, it is necessary to develop an upgraded version of the chatbot program that includes a personalized question-and-answer process that supports behaviour changes with a large number of the general public.


Orientocardiochiles Kang & Long, gen. nov. , is discovered and described. This genus represents the ninth genus in the Oriental region. Two new species  are described and illustrated, and a key to species of the genus, with detailed images, is added. Diagnostic characters of the new genus are analyzed and compared with several other cardiochiline genera to allow the genus to key out properly using an existing generic treatment. The scientific names validated by this paper and morphological data obtained from this project will be utilized and tested in the upcoming genus-level revision of the subfamily based on combined morphological and molecular data.For the first time in 21 years, a new genus of cardiochiline braconid wasp,  Cardiochilinae Ashmead, 1900 is a relatively small subfamily of Braconidae Nees, 1811, comprising 221 described species in 16 genera   . Four cain, 1912 . In Vietreported . OrientoPyralidae and Noctuidae, among other families, are typically hosts and include important crop pests such as the tobacco budworm, Heliothisvirescens , and cotton bollworm, Heliocoverpaarmigera     . Of the ralidae) .Braconidae Collection of the Institute of Ecology and Biological Resources , the Hymenoptera Institute , and Museums Victoria . Other materials were borrowed from HIC and Illinois Natural History Survey . All HIC material will be deposited in the Canadian National Collection of Insects , including the holotype of Orientocardiochilesjoeburrowi Kang sp. nov. and the holotype of Orientocardiochilesnigrofasciatus Long, sp. nov. is housed in IEBR.The type specimens for the present work were provided by the Hymenoptera Ontology website . Terms for sculpture are based on The morphological terminology mostly follows O.joeburrowi sp. nov., morphological analysis was conducted using a Leica MZ75 stereomicroscope. Color habitus images were captured using a Visionary Digital BK Plus imaging system , equipped with a Canon EOS 5DS R DSLR camera. Images were stacked in Zerene Stacker v. 1.04 (Zerene Systems LLC.). All images were made by IK and edited in Adobe Photoshop CS 6 . Body parts of the specimen were also measured using Adobe Photoshop CS 6 .For the specimen of O.nigrofasciatus sp. nov., morphological analysis was conducted using an Olympus SZ61 binocular microscope; measurement were carried out using an Olympus SZ40 binocular microscope; the photographs were produced by KDL with a Sony 5000 digital camera attached to a Nikon SMZ 800N binocular microscope at IEBR and processed with Adobe Photoshop CS5 to adjust the size and background.For the specimen of Cardiochilinae in the collection at IEBR; NP: National Park, S: South.Abbreviations used in this paper are as follows: POL: distance between posterior ocelli; OOL: distance between posterior ocelli and eye; OD: diameter of posterior ocellus; T1: first metasomal tergum; T2: second metasomal tergum; T3: third metasomal tergum; MT: Malaise trap; “Card. + number”: code number indexing for specimens of the Orientocardiochiles gen. nov. and descriptions of the two species are based on females. Distribution maps were produced using QGIS 3.10.0  cell broad. M+CU in hind wing distinctly shorter than 1-M. Hind wing with 6 hamuli. T1 widened apically, with lateral suture clearly defined throughout. T2 mostly rugose except for plateau-like projection . Body large and stout, finely sculptured, whitish to yellow pale in color with black spots and stripes. Head in dorsal view transverse. Antenna 41- or 43-segmented. Eyes sparsely pilose. Clypeus with distinct suture and two clypeal tubercles present apically. Malar suture present. Mandible bidentate and angularly bent ventrally. Mouthparts  short. Maxillary palpus 5- or 6-segmented. Labial palpi 4-segmented. Notauli deep, crenulate, meeting posteriorly in deep smooth area. Scutellar sulcus curved, with 5+ crenulae. Scutellum more or less elevated medially, without carina laterally and apically. Propodeal areola completely developed and kite-shaped or elongated pentagonal. Epicnemial carina absent. Mesopleuron mostly smooth; precoxal sulcus well-defined and crenulate, not reaching posterior margin. Metapleuron rugulose. Mesosternal sulcus finely crenulate. Hind tibia without apical projection; inner tibial spur distinctly longer than outside spur, subequal to half of hind basitarsus. Tarsal claws pectinate. Forewing with elongated pterostigma; vein r reaching at apical fourth of pterostigma; SR1 sharply angled at basal fourth; basal fourth of vein SR1 almost perpendicular to apical vein 3-SR. Vein 1a present as a spectral short trace; 1ion Figs , 5G; plaOriental .Unknown.Cardiochiles from the Oriental region. From “orientum” (Latin for the eastern region) and the generic name “Cardiochiles Nees, 1819.” Gender: masculine.The name for the genus refers to Orientocardiochiles gen. nov. will run to couplet 9 in the key to world genera by Austerocardiochiles in the couplet 9b of the key as follows:Taxon classificationAnimaliaHymenopteraBraconidaeKangsp. nov.C6C0A498-FC35-580B-A693-6E227D16571Ehttp://zoobank.org/C653D411-AED6-45FA-8BE7-254DBDA02BD9Holotype Malaysia • ♀; female, Perlis, Wang Kelian; 6°40'40.94"N, 100°11'23.94"E; xi.2008; Sharkey & Norliyana.Head. Antenna 41-segmented; length of scape 1.3 × longer than its width (30:23); third segment  2.2 × longer than second segment (pedicel) (29:13); apical segment 1.9 × longer than subapical segment (15:8). Clypeal suture distinct . Notauli present . Length of hind femur, tibia and basitarsus 3.8× (210:55), 7.1× (320:45) and 6.0 × (18:3) longer than maximum width of each. Basal spur of mid tibia 0.58× longer than length of mid-basitarsus (67:115). Basal spur of hind tibia 1.8 × longer than length of apical spur (88:49), and 0.49 × longer than length of hind basitarsus (88:178). Hind basitarsus 0.56 × longer than length of hind tibia (18:32), and 0.96 × longer than length of remaining hind tarsi 2–5 (178:185). Hind tarsal claws pectinate with 10 teeth . Length of pterostigma 4.4 × longer than its width (191:44). Forewing r:3-SR:2-SR= 33:165:99; 1-M 2.4 × longer than m-cu (88:36); 2-SR+M 1.63 × longer than m-cu (59:36); 1-CU1 0.23 × longer than 2-CU1 (22:96) and 0.37 × longer than cu-a (22:59). Length of hind wing 5.2 × longer than its maximum width (78:15); second submarginal cell trapezoid, maximum length of the cell 3.15× longer than its maximum height (262:83) .  Fig. . Hind wi5). Fig. . T2 dors5). Fig. . T3 enti5). Fig. . Hypopyg5). Fig. . OviposiColor. Body mostly whitish pale and appearing striped; the following areas melanic: antenna, vertex, median mesonotal lobe (mostly melanic except for posterior area), lateral mesonotal lobe , scutellum, anterior propodeum, fore trochantellus, basal fore femur, mid trochanter (mostly) and trochantellus, hind coxa with a large melanic spot posterolaterally, entire hind trochanter and trochantellus, hind femur , mid and hind tarsi, median tergum 1, entire tergum 2, anterior terga 3–6, posterior tergum 7, ovipositor and external ovipositor sheaths. Wings entirely lightly infuscate, stigma dark brown but centrally pale.Male. Unknown.Named in honor of Joseph Lee Burrow, the world-class college football quarterback for the LSU Tigers and the 2019 Heisman Trophy winner.Unknown.Orientocardiochilesjoeburrowi sp. nov., is known from only one female specimen collected from Wang Kelian, Malaysia, which is near the Thailand–Malaysia border  forewing entirely lightly infuscate; ii) propodeum without short longitudinal carina anteriorly; iii) propodeal areola quadrate (kite-shaped); iv) hind tarsal claw pectinate with 10 teeth; v) hypopygium entirely sclerotized and without median enfold; vi) scapus entirely brown.Taxon classificationAnimaliaHymenopteraBraconidaeLongsp. nov.7F1AAC72-BFDB-594B-8501-81F5A2662298http://zoobank.org/7F9CC61E-28E0-45A2-B6C4-40FA9F4231A9Holotype, Vietnam • ♀; female, “Card.101” (IEBR), S. Vietnam: Lam Dong, Cat Tien NP, forest; 11°18'N, 107°26'E, 100 m; 8.iv.2007; MP Quy.Head. Antenna with 43 segments; length of scape 1.4 × longer than its width (18:13); third segment 1.5 × longer than second segment (15:10); apical segment 2.25 × longer than subapical segment (4:10). Clypeal suture distinct; ventral margin of clypeus evenly convex with indistinct tubercles  . Length of hind femur, tibia and basitarsus 3.0, 7.0 and 8.0 × longer than their maximum width, respectively. Hind coxa shiny, smooth. Hind femur sparsely punctate. Hind tibia without apical projection; inner hind tibial spur 1.6 × longer than outer spur (16:10) and 0.5 × longer than hind basitarsus (16:32). Hind basitarsus 0.5 × longer than hind tibia (32:63), 0.9 × longer than hind tarsus 2–5 (32:37). Hind tarsal claw pectinate, with 4 teeth . Pterostigma elongate; length of pterostigma 5.0 × longer than its width (45:9)   Fig. . Pronota35) Fig. . Lobes o35) Fig. . Propode35) Fig. . Precoxa35) Fig. . Mesople35) Fig. ; propodeeth Fig. . Wings. :9) Fig. . r:3-SR::9) Fig. . Subdisc:9) Fig. . Hind wi:9) Fig. . Metasom29) Fig. ; coriace29) Fig. ; median 29) Fig. . Hypopyg29) Fig. . Oviposi29) Fig. ; setose Color. Pale yellow; antenna black, except scape yellow; stemmaticum and vertex posteriorly black , and “fascia” , because of black stripes basally on metasomal tergites 4–6.Unknown.Orientocardiochilesnigrofasciatus sp. nov., is known from only one female specimen collected from Cat Tien NP, S. Vietnam.  forewing apically strongly infuscate; ii) propodeum with short longitudinal carina anteriorly; iii) propodeal areola pentagonal; iv) hind tarsal claw pectinate with four teeth; v) hypopygium with median longitudinal fold; vi) scape mostly yellow, except for the dorso-apical region.Orientocardiochiles Kang & Long, gen. nov., Austerocardiochiles Dangerfield, Austin, & Whitfield, 1999, Hansonia Dangerfield, 1996, Heteropteron Brullé, 1846, and Wesmaelella Spinola, 1851 share the presence of lateral sutures on the first metasomal tergum that are clearly defined throughout the length of the tergum , are recorded from the region. Five genera have been recorded from Malaysia and Vietnam in each country. More genera will be likely to be found in Malaysia and Vietnam after further collecting.As mentioned in the Introduction, members of n region . As a reBraconidae. However, a genus-level phylogeny of Cardiochilinae based on molecular data is lacking. This shows the necessity of a novel phylogeny. Therefore, IK is in process of conducting a new genus-level revision of Cardiochilinae to elucidate the genus-level relationships of the subfamily using a novel phylogeny based on combined molecular and morphological data.In the past two decades, molecular data combined with morphological data has been widely utilized to improve resolution of the species-, genus-, tribe-, and subfamily-level relationships of


Recommendations for risk reduction of dementia and cognitive decline emphasize addressing modifiable risk factors including physical activity, cognitive stimulation, and socialization. However, existing resources and programs to promote brain health through multifaceted risk factor reduction are often costly, challenging to individualize, and limited in their delivery format, narrowing their accessibility among older adults. To address community identified needs for brain health promotion resources, we applied a user-centered design approach to develop, implement, and evaluate feasibility/acceptability of a community-based brain health promotion program: Strength & Resilience Brain Health and Wellness Program. Design requirements were specified through ongoing end-user feedback via structured and open-ended surveys, group dialogue, and facilitator memoing which informed needed iterative refinements of program components. The resultant program incorporates information about brain health/dementia prevention, physical exercise, and cognitively-stimulating activities targeting attention, focus, problem solving, and communication. Integrated across components are deliberate adaptations for physical/cognitive abilities and activities to facilitate group cohesion and reduce stigma. Across two 10-week offerings, we found the program to be feasible as demonstrated through high enrollment (N=44) and retention (75%). A quarter of participants self-disclosed a dementia diagnosis in baseline surveys. Participants rated program components as acceptable, and perceived positive influences on target risk factors particularly social isolation, sense of self-worth, and cognitive stimulation. The current study provides a platform for a feasible and scalable group, community-based brain health promotion program, and suggests participant-centered outcomes extend beyond cognitive domains. More rigorous evaluation of the program is needed to evaluate fidelity across components and standardized outcomes.


Global Positioning System (GPS) stations installed in and around the epicenter of the Lushan earthquake (Mw 6.7), which occurred almost 5 years after the 2008 Wenchuan earthquake, recorded preseismic deformation corresponding to the Lushan earthquake within the southern Longmenshan thrust belt. A half-space dislocation model is used to simulate the theoretical values of the postseismic displacements caused by the 2008 Wenchuan earthquake, and after transforming the reference frame and filtering the GPS displacement time series, the theoretical and observed GPS values are compared to identify the geodetic anomaly preceding the Lushan earthquake. The abnormal extent of this geodetic anomaly decreases with increasing epicentral distance for each GPS site. This geodetic signal reflects preslip along a locked section of the 2013 seismogenic fault, which caused the accumulation of elastic strain energy until the faulting strength was overcome, thereby generating the Lushan earthquake. Hence, this anomaly might be used as an observable and identifiable precursor to forecast an impending earthquake within a period of less than two and half years before its occurrence. At present, earthquake forecasting is a very difficult issue because very little about the earthquake mechanism is understood; moreover, the instruments needed to observe an earthquake are often not situated sufficiently close to the epicenter at the correct time6. Since the Global Positioning System (GPS) technology, some researchers have tried to detect possible precursors before an earthquake by analyzing preseismic strain rate7, baseline distance8 or ionospheric maps9. However, researchers have difficulty explaining the relationship between the observed precursors and the epicenters. Furthermore, the location of the epicenter cannot be forecasted before an earthquake. Consequently, whether an observable and identifiable precursor anomaly precedes an impending earthquake has yet to be resolved11.Predicting the magnitude and location of an earthquake prior to an impending seismic event has been a controversial subject of research over the past two decades13. The LTB has attracted considerable attention in the last 10 years, particularly as a result of the 2008 Mw 7.9 Wenchuan and 2013 Mw 6.7 Lushan earthquakes that occurred along the thrust boundary19. The Wenchuan earthquake produced a complicated 240-km-long surface rupture zone in the middle segment of the LTB, while the Lushan earthquake occurred along the southern segment as a blind reverse-faulting event22. The distance between the rupture zones of these two earthquakes is 90 km24, and few earthquakes have occurred within this gap. During the Wenchuan earthquake, a significant stress increase resulted from coseismic oblique slip, which had the potential to trigger or hasten the occurrence of a destructive earthquake on the southern segment of the LTB19. Therefore, a well-designed temporary continuous GPS network comprising 10 stations  is a N42° ± 5°E-trending crustal shortening boundary between the Bayan Har Block and the South China Block along the eastern margin of the Qinghai-Tibet Plateauons Fig. . All of 14, the Wenchuan earthquake was a thrust fault earthquake. Thus, the westward component is reasonable because most of these stations, except LS07, are located on the footwall of the Beichuan fault (F2) , followed by station LS06   Fig. . Before (B) Fig.  or accum(B) Fig. ; consequ32. The seismicity recorded by the Sichuan Seismic Network confirms that the seismic activity at the epicenter is weak, but more seismicity occurred in the epicenter and its adjacent areas during the period from 2011 to 2013 before the Lushan earthquake than during the period from 2008 to 2010 . We obtained the preseismic displacement time series data from the 2005 International Terrestrial Reference System (ITRF2005) that were processed by GAMIT/GLOBK. Then, we transform the observations into the South China Block framework and filter time series with stacking and the least-squares collocation method (see the Supplementary).36. A Maxwell body and a layered structure model  are used in the simulation.The Lushan earthquake occurred on the southern segment of the LTB almost 5 years after the Wenchuan earthquake, and its epicenter is located within the domain of the newly installed continuous GPS network Fig. . Since mSupplementary Information.Supplementary Figure 1.Supplementary Figure 2.Supplementary Figure 3.Supplementary Figure 4.


This study investigates leadership skills and Canadian Medical Education Directives for Specialists (CanMEDS) competencies acquisition within the General Surgery Residency Training Program (GSRTP). The Saudi Commission for Health Specialties (SCFHS) incorporates the CanMEDS Competency Framework into its curriculum to prepare the resident for healthcare needs.This is a descriptive-analytical study. A questionnaire was used to collect data from 117 General Surgery residents (GS) at seven institutes in Jeddah, Saudi Arabia.The GS residents reported an acceptable self-perceived level of Clinical Leadership Skills (mean ± standard deviation). The most dominant skill was working with others (1.98 ± 1.03), followed by demonstrating personal qualities (2.07 ± 0.88), the ability to manage services (2.21 ± 1.37), improving services (2.22 ± 1.84) and last, setting directions (2.39 ± 0.95). Regarding the CanMEDS competencies, the respondents showed a generally positive perception with an “agree” level (Mean = 1.83). Of the CanMEDS competency roles, Collaborator ranked first followed by Professional and then Communicator. Leader competency ranked fourth followed by Health Advocate, Medical Expert and last, Scholar.The GSRTP residents showed satisfactory self-assessed clinical leadership skills and acquirement of the CanMEDS competencies during their training, which will prepare them to lead in the future. In 1995, the Saudi Commission for Health Specialties (SCFHS) established the General Surgery Residency Training Program (GSRTP) in Saudi Arabia. It is a five-years structured program. By the end of the program, the trainee shall acquire basic surgical knowledge, clinical surgical skills, and the general principles of professionalism. The program aims to graduate competent surgeons with a high level of cognition, psychomotor skills, and affective and attitudinal experience in the different branches of General Surgery so they can competently vie in the international market. Another important aim of the program is to teach trainees the concepts of professionalism and medical ethics, as well as total quality management and cost-conscious practice.Anecdotal reports show that few surgery programs officially include leadership skills programs in their curriculum. In 2015, the SCFHS integrated and incorporated the CanMEDS Competency Framework into the GSRTP curriculum. The content of the framework was defined and a shorter developed version of the curriculum was then given to the program designing committee for approval. Furthermore, a manual containing the CanMEDS was distributed amongst GSRTP program directors and residents.1The CanMEDS framework was designed by the Royal College of Physicians and Surgeons of Canada (RCPSC) in the 1990s and formally adopted in 1996. It describes the abilities required for physicians to effectively meet the healthcare needs. These are grouped and integrated under seven domains: Medical Expert, Communicator, Collaborator, Leader, Health Advocate, Scholar and Professional.2In the UK, the National Health Service (NHS) mentioned that physicians’ leadership competency needs to be actively involved in the process of healthcare system transformation and the General Medical Council (GMC) considers engagement in quality improvement as “very important.”9A questionnaire was distributed among the GS residents in seven training institutions in Jeddah, a city located in western Saudi Arabia. It was designed to elicit their impression of whether the CanMEDS leadership skills and competencies were well explained, properly expressed and eventually implemented in the GSRTP. and 3) the GSRTP competencies based on the CanMEDS. A Likert scale of a five-point ordinal scale was used  demographic data, 2) a resident’s clinical leadership competencieswas used .r = 0.932) and in the second round (r = 0.928), therefore, no modifications were done.Before the final questionnaire was given to the residents, the text and the statement’s clarity were reviewed by a professional academic staff and a statistician. The statements among each variable were analyzed by Pearson Correlation test. Pilot studies were conducted twice with a sample size of 81 respondents and rounded twice for greater reliability. The purpose of the pilot study is to test for comprehensibility and ensure that the respondents will understand the questionnaire. The consistency of the questionnaire was determined using alpha coefficients . In the first round the Alpha Coefficient reliability was  Version 21. A chi-square test was used to find the relationship between independent and dependent variables, whereby p-value = 0.05 was considered significant. For dependent variables, we calculated the mean, standard deviation (SD) and ranked the statements.One hundred seventeen GS residents from seven training centers received the questionnaire and consented to read and fill it out. All the training centers apply the same curriculum which is sited by the SCFHS. A total of 95 (81%) questionnaires were received and analyzed and the demographic data are shown in Clinical Leadership Competency Framework was tested with an aim to evaluate residents’ clinical leadership skills, including their ability to work with others, demonstrate personal leadership qualities, manage and improve services as well as the ability to set directions .p < 0.05). The mean, SD, rank and significances value for each competency can be found in The third section of the questionnaire assessed each resident’s opinion on acquiring the CanMEDS competencies during their residency training and its relationship with Clinical Leadership. Each competency was examined with four to seven statements. A chi-square test of independence was performed to examine the relationship between each CanMEDS competency as one of the components of the Saudi GSRTP and Clinical Leadership competencies. The results between these variables were significant  reported that leadership in medicine is in great need and currently at a void.Surgical trainees among the theater team in South Yorkshire, UK, demonstrated acceptability for the introduction of a workplace-based assessment of nontechnical skills of surgeons including Situation Awareness, Decision Making Communication and Teamwork and Leadership.14Many of the residency training program directors believe that teaching the medical expert role is easier and less challenging than teaching the other roles of the framework.et al reported in a single institute study on 33 residency programs that little is known about teaching and evaluating the role of the Health Advocate.Discussions of professionalism, teaching of communication skills and collaboration with other healthcare workers and families are now included in the Canadian residency training programs as mandated by the RCPSC.The physician should remain updated through career development and self-promotion and teaching all health care professionals throughout his career.This study reveals GSRTP residents’ self-assessed satisfactory Clinical Leadership Skills. They also confirmed and embraced their acquisition of the CanMEDS competencies during their residency program implemented by SCFHS, including leadership competency, which will prepare them for leadership positions in the future. Still, more research is needed to assess objectively the residents’ leadership skills and evaluate deficiencies and difficulties in order to better apply this framework.Like many other studies, ours has its limitations, primarily being a self-reported study and in a single city. Further research is needed at a wider range by including other cities and to evaluate Program Director’s knowledge and insight about the CanMEDS application in residency training. Also, comparing the Program Directors’ evaluation for the residents with the residents’ self-assessment would not only be enriching and informative but also beneficial to avoid possible bias. As such, we strongly recommend more research to further investigate CanMEDS implementation and detect areas of improvement.