ARID1A is a tumour suppressor gene that is frequently mutated in clear cell and endometrioid carcinomas of the ovary and endometrium and is an important clinical biomarker for novel treatment approaches for patients with ARID1A defects. However, the accuracy of ARID1A immunohistochemistry (IHC) as a surrogate for mutation status has not fully been established for patient stratification in clinical trials. Here we tested whether ARID1A IHC could reliably predict ARID1A mutations identified by next‐generation sequencing. Three commercially available antibodies – EPR13501 (Abcam), D2A8U , and HPA005456 (Sigma) – were optimised for IHC using cell line models and human tissue, and screened across a cohort of 45 gynaecological tumours. IHC was scored independently by three pathologists using an immunoreactive score. ARID1A mutation status was assessed using two independent sequencing platforms and the concordance between ARID1A mutation and protein expression was evaluated using Receiver Operating Characteristic statistics. Overall, 21 ARID1A mutations were identified in 14/43 assessable tumours (33%), the majority of which were predicted to be deleterious. Mutations were identified in 6/17 (35%) ovarian clear cell carcinomas, 5/8 (63%) ovarian endometrioid carcinomas, 2/5 (40%) endometrial carcinomas, and 1/7 (14%) carcinosarcomas. ROC analysis identified greater than 95% concordance between mutation status and IHC using a modified immunoreactive score for all three antibodies allowing a definitive cut‐point for ARID1A mutant status to be calculated. Comprehensive assessment of concordance of ARID1A IHC and mutation status identified EPR13501 as an optimal antibody, with 100% concordance between ARID1A mutation status and protein expression, across different gynaecological histological subtypes. It delivered the best inter‐rater agreement between all pathologists, as well as a clear cost‐benefit advantage. This could allow patients to be accurately stratified based on their ARID1A IHC status into early phase clinical trials. ARID1A underpin 57% of ovarian clear cell carcinomas (OCCC) TP53 mutations, where p53 immunohistochemistry (IHC) is routinely used in clinical practice to aid diagnosis TP53 mutations are uncommon in OCCC; these differences in driver mutational profiles highlight the distinct aetiology of the two diseases. Moreover, the presence of ARID1A missense mutations may not alter ARID1A protein expression, unlike TP53 missense mutations. Loss or significant reduction of ARID1A protein expression is associated with heterozygous ARID1A mutations ARID1A alterations that led to tumour formation with loss of ARID1A protein expression observed by IHC. The first was an ovarian endometrioid tumour with co‐existent PTEN loss ARID1A loss and a PIK3CA (H1047R) mutation promoted ovarian clear‐cell tumourigenesis ARID1A mutations are also detected at high frequencies in other solid tumours including 23% of pancreatic ductal adenocarcinoma, 23% of advanced urothelial carcinomas, 18% hepatocellular carcinomas, and 6% of metastatic castrate‐resistant prostate cancers Recent studies have highlighted that somatic loss of function mutations in the tumour suppressor gene ARID1A mutations have focused largely on using synthetic‐lethal approaches. Bitler et al highlighted the potential of targeting the antagonistic activity between SWI/SNF and EZH2 methyltransferase with the EZH2 small molecule inhibitor GSK126, which triggered apoptosis in ARID1A mutated cells PIK3IP1, a direct target of EZH2, and selectivity was further enhanced upon inhibition of PI3K‐AKT signalling et al has shown that ARID1A‐mutated ovarian cancers are selectively dependent on HDAC6 activity, due to HDAC6 upregulation in ARID1A mutant cells that mechanistically inactivates the apoptosis‐promoting function of TP53 due to deacetylation of histone lysine 120 [22]. The work showed that treating ARID1A‐mutated tumours with the small molecule HDAC6 inhibitor, ACY1215, showed a survival benefit in vivo. Additional approaches identified reliance on the ARID1A paralogue ARID1B in mutant cells ARID1A defective OCCC tumours can be targeted with the multikinase inhibitor dasatinib, mediated through addiction to the dasatinib target YES1 [9] and more recently a profound sensitivity to inhibition of the DNA repair kinase ATR, leading to premature mitotic entry, genomic instability, and apoptosis et al have additionally shown that loss of ARID1A leads to impaired G2‐M DNA damage checkpoint activation and repair of DNA double strand breaks (DSB), causing sensitivity to DSB inducing treatments such as the Poly (ADP‐ribose) polymerase (PARP) inhibitor talozaparib, both in vitro and in vivoARID1A mutations, such as OCCC.Novel ways of treating patients with ARID1A mutational status. However, there are three early phase trials investigating ARID1A mutational status and response to therapy, the first of which allocates treatment to patients whose biopsies are sequenced as part of on‐going clinical sequencing programmes outside of the remit of the clinical trial PIK3CA, AKT, or ARID1A mutations will receive olaparib with the AKT inhibitor AZD5363 [26]. A second is a randomised phase II study of nintedanib  compared to chemotherapy in patients with clear cell carcinoma of the ovary or endometrium, which will assess ARID1A mutational status retrospectively and correlate with outcome ARID1A mutational status is potentially cost‐prohibitive and the turn‐around time can make it difficult for trial recruitment. Therefore, a surrogate biomarker of mutational status such as IHC is needed.Currently there are no clinical trials recruiting patients that prospectively assess ARID1A mutations, rapid sequencing is not widely available. Hence, IHC would be the commonest method to infer mutational status, highlighted by the fact that a number of open clinical trials are performing retrospective ARID1A mutational assessment. Studies that have so far assessed the correlation between ARID1A mutational status and IHC have demonstrated a good concordance ARID1A mutation in ovarian carcinoma has not been precisely defined as there is no uniform scoring system or specific antibody that is recommended for clinical IHC use. In the largest concordance study to date, Wiegand et al assessed ARID1A in 182 gynaecological tumours, defining positive staining as definitive nuclear staining and negative as no immunoreactivity ARID1A mutational status in both OCCC and endometrioid carcinomas ARID1A mutation showed loss of ARID1A expression. However, 11% of OCCC (4/36 cases) with no ARID1A mutation also showed loss of ARID1A protein expression Despite the clinical importance of ARID1A mutational status in gynaecological tumours. In particular, we sought to compare the concordance of a number of commercially available antibodies using a standardised scoring system and identify the most optimal assay for clinical assessment of mutation status.Here our aims were to develop ARID1A IHC as a surrogate predictive biomarker for diagnostic assessment of 2. Cell lines were tested to confirm no mycoplasma infection using Mycoalert™ Mycoplasma Detection Kit as per manufacturer's instructions . Cell line identity was confirmed with short tandem repeat typing using the Promega GenePrint®10 system . Cell pellets were formalin fixed and paraffin‐wax embedded (FFPE) for antibody optimisation.Cell lines ES2 and TOV21G were obtained from the American Type Tissue Collection (ATCC). HCT116 isogenic ARID1A (Q456*/Q456*) and parental lines were purchased from Horizon Discovery . These were developed by knock‐in of a premature stop codon (Q456*). Cell lines were cultured in a humidified 37 °C incubator with 5% COAll patients gave written consent for the use of material for research purposes and tissue samples were obtained with appropriate ethical approval under the Royal Marsden Hospital (RMH) NHS Foundation Trust study: CCR3705 “Analysis of tumour specimens for biomarkers in gynaecological cancers” Table . All patDNA extraction and NGS took place in Good Clinical Laboratory Practice (GCLP)‐accredited laboratories at The Centre for Molecular Pathology, The Royal Marsden NHS Foundation Trust, Sutton. Genomic DNA from FFPE tissue sections was extracted using QIAamp FFPE Tissue Kit  according to the manufacturer's instructions for both tumour and non‐malignant content. Genomic DNA from blood was extracted using the QIAamp Blood mini kit  or QIAsymphony DNA Midi Kit (automated) (Qiagen) according to the manufacturer's instructions. DNA quality was assessed on the Agilent 2200 Tapestation  and the Qubit Fluorometer .ARID1A mutations were identified using a targeted capture panel , designed to target 59 genes for the FOrMAT clinical trial . The panel typically covers ARID1A at 99% >250X , ARID1A/BAF250A, rabbit monoclonal 1:250, D2A8U , and anti‐ARID1A, rabbit polyclonal 1:400, HPA005456 , using the Dako‐Autostainer Link 48 with the EnVision FLEX kit as per manufacturer's instructions . Human breast, prostate, and kidney tissues were used as positive controls and xenograft models were obtained as previously described Cases were independently scored using an immunoreactive scoring system ARID1A isogenic (mutant and wild‐type) cell lines, ES2 (ARID1A wild‐type), TOV21G (ARID1A mutant) ovarian clear cell carcinoma cell lines, and in HCT116 ARID1A isogenic xenograft models  , 11 and 12 (D2A8U) and 6 and 12 (HPA005456) , 100% D2A8U, and 97% (HPA005456). The histograms for all antibodies show that overall there is a clear bimodal distribution in immunoreactive scores between the mutant and wild‐type cases. This is best exemplified with EPR13501 and D2A8U, with HPA005456 showing the greatest variation, perhaps due to the polyclonal nature of the antibody, whereas the D2A8U and EPR13501 are monoclonal. For instance, comparing OCCC cases alone, our concordance was 100% with all antibodies, compared to 73% (27/37 samples) as reported by Wiegand 501, 100%ARID1A mutation occurring after the ARID1A epitope sites and hence the detection of the truncated residual protein. We observed one endometrioid ovarian adenocarcinoma with a small area of subclonal loss . The patient did not have an identifiable ARID1A mutation and their tumour had an ARID1A IHC score of 12 (>80% of tumour staining strongly). How such patients respond to targeted therapy will only be evaluable in the context of a clinical trial. Of note, we did not identify any somatic in‐frame deletions. However, given reports that such mutations affect the subcellular distribution of ARID1A One of the limitations of this study is that even though we identified 45 patient samples initially, we were only able to assess 43 cases. However, the rarity of these tumours in general renders larger series challenging. In order to correct for this, we were stringent with our analysis of the sequencing data, including only cases where mutations were identified by both sequencing platforms. Thus, we could be confident with the mutation calls that we made. Overall, we have shown that IHC is generally concordant with mutational status; we did observe some variation in the carcinosarcoma cases, which may, in itself, reflect the heterogeneity of these tumours and the limitations of using an immunoreactive score. For example, in case 3705‐0500, this may be explained by the et al analysed archival tissue by IHC and mutational status as part of a 40‐patient phase II clinical trial in OCCC with ENMD‐2076, an oral multitargeted kinase inhibitor ARID1A mutant cases and 13 wild‐type cases, where the concordance of the mutational status with IHC was only 69%. Furthermore, the antibody and specific scoring details and nature of mutations were not detailed. Guan et al compared ARID1A IHC and mutational status in uterine carcinomas using the polyclonal HPA005456 antibody (targeting amino acids 1266–1370), with negativity defined as absence of nuclear staining, and identified that only 50% (5/10) of cases with deleterious mutations showed complete lack of ARID1A expression. Our study only included gynaecological tumours and would need to be extended to other tumour types to ascertain its general applicability.Although a number of smaller studies have assessed concordance between ARID1A IHC and mutational status in gynaecological carcinomas, the concordance rates are lower than we report here and the antibody details and scoring systems used are not fully reported ARID1A mutations in deep infiltrating endometriosis, with loss of ARID1A immunoreactivity serving as a surrogate for ARID1A inactivating mutations using the HPA005456 antibody A recent sequencing study identified cancer‐associated inactivating ARID1A status with a cut‐off of <8 using our optimised scoring system. This will be useful for recruiting patients for clinical trials based on ARID1A mutational status. An international academic trial of ATR inhibition in combination with a PARP inhibitor in ARID1A‐stratified gynaecological cancers that utilises our findings is planned to open in 2018 using this approach, allowing validation and evaluation of the IHC scoring system in the context of a prospective clinical trial.In conclusion, we have systematically assessed a number of commercially available antibodies and identified EPR13501 as a robust biomarker of RN, CJL, and SB conceived and designed the study. SK, KN, AA, DK, FD, AL, TJ, MH, KF, and NM carried out the experiments and undertook IHC scoring. JC, TJ, MH, AGR, and RN performed the bioinformatics analysis. SK, KN, AA, DK, FD, CJL, and SB discussed and interpreted the results. SK, CJL, SB, and RN wrote the first draft. All authors read and approved the final manuscript.SUPPLEMENTARY MATERIAL ONLINEFigure S1. ARID1A status of OCCC cell lines. Western blot of ARID1A protein expression in ES2 (OCCC ARID1A wild‐type cell line) and TOV21G (OCCC ARID1A mutant cell line) using the EPR13501, D2A8U, and HPA005456 antibodies. ARID1A (250 kDa fragment), loading control β‐Actin (42 kDa)Click here for additional data file.Figure S2. Subclonal expression in a Grade 2 endometrioid adenocarcinoma of the ovary (case 3705‐0482). Images of an area of subclonal expression with IHC scores and sequencing results. Top Row: Low power magnification, arrow shows area of absent protein expression surrounded by area of positive expression with all three antibodies . Bottom Row: High power magnification, arrow shows area of absent protein expression surrounded by area of positive expression with all three antibodies Click here for additional data file.Table S1. Extended table of clinicopathological features of the patient cohortClick here for additional data file.Table S2. Summary of ARID1A sequencing metrics from the targeted capture panelClick here for additional data file.Table S3. Summary of individual and combined scores for ARID1A IHCClick here for additional data file.Table S4. Inter‐pathologist concordance metricsClick here for additional data file.Table S5. Summary of ARID1A mutations identified and their validationClick here for additional data file.


The Enhanced Recovery After Surgery (ERAS) program hastens recovery from colorectal cancer by shortening the treatment period and enabling a return to normal activities. However, patients with colorectal cancer treated under the ERAS program have fewer opportunities to consult with medical staff and receive education regarding self-care and experience more affective stress and anxiety.This study aimed to develop and assess an educational program for patients with colorectal cancer treated under the ERAS program, considering affective aspects.n = 118) who underwent open colon surgery under the ERAS program were assigned alternately in the order of admission on a 1:1 basis to a treatment group (n = 59) and conventional care group (n = 59). The treatment group received a two-week mobile-based intervention, whereas the control group received conventional care. Quality of life, self-efficacy, anxiety, and depression were compared between the two groups.Patients with colorectal cancer (The mobile web-based educational program significantly reduced the negative impact of surgery on the quality of life in the treatment group, compared with the conventional care group, and triggered a noticeable decline in anxiety and depression and increase in self-efficacy.The developed mobile web-based educational program effectively enhanced self-efficacy, positively impacted the quality of life, and reduced anxiety and depression. The program could have a positive effect on the quality of life of patients with colorectal cancer treated under the ERAS program. Depresset al.  showed tTo improve the effectiveness of treatment in patients with colorectal cancer, it is important for them to actively engage in treatment and nursing to cope with the illness more aggressively. Furthermore, their experience greatly contributes to the planning and provision of nursing . AlthougAdditionally, patients with colorectal cancer undergoing surgery who are treated under the ERAS program require an easily accessible educational program with accurate information. An educational program intended to help patients both during hospitalization and after discharge should be designed to offer this information. Therefore, there is an urgent need for a reliable and easily accessible educational program that is linked to the treatment received at the hospital and can be provided to patients who leave the hospital during the early post-surgery stage. Patients and their caregivers often find it difficult to participate in offline educational programs, which are provided by a few medical staff members for a limited time. To address such limitations, computer technology, auditory and visual media, and supplementary materials, such as leaflets, have been utilized in tandem . Advancevia telephone two weeks after discharge, albeit without a structured approach [The current study established a theoretical framework for an educational program for colorectal cancer patients undergoing surgery under the ERAS program. The framework is based on Bandura’s theory of self-efficacy  and aimsapproach . However22.1A quasi-experimental design and comparative study was conducted among patients with colorectal cancer undergoing surgery treated with the ERAS program at Seoul National University (SNU) hospital in Korea between March 2016 and March 2017. The treatment group received a two-week mobile web-based intervention, whereas the control group only received conventional care. Changes in the primary  and secondary outcomes  between the treatment and conventional care groups were compared.2.22.2.1The inclusion criteria were as follows:aged 18 years or older and scheduled to undergo colorectal cancer surgery at SNU hospital;no impairment in mental or cognitive ability;no difficulty reading, speaking, and writing in Korean to communicate with others;able to use a smartphone and other mobile devices; andunderstood the purpose of this study and provided written informed consent to participate in a mobile web-based educational program.Exclusion criteria comprised the following:already taking part in other educational programs;unable to communicate in Korean;diagnosed with psychiatric conditions such as depression or with a prior record of cognitive disorders;suffering from a complex illness in addition to colon cancer;expected to undergo surgery again in the near future;developed fever before the surgery;had pneumonia, ileus, or complications around the surgical wound area; orhad undergone an emergency surgery.2.2.2The quality of life score, the primary endpoint of this study, was utilized to determine the necessary sample size. A two-tailed t-test, which was conducted using the software G*Power (v3.1) with a significance level of 0.05, a group number of 2, an effect size of 0.5, and a power of 0.8, showed that a total of 128 subjects (64 in each group) were needed for this study . Data we2.3This study developed and offered an educational program to improve the quality of life of patients with colorectal cancer undergoing surgery under the ERAS program by reducing negative feelings, such as anxiety and depression, while enhancing self-efficacy. Some previous studies used a telephone-based program  but wereBased on Bandura’s theory of self-efficacy , the pro2.42.4.1via mobile devices. Each member of the treatment group was granted an individual ID through which they could join the program. In addition to individual education, feedback, and support from a health professional, participants were encouraged to participate in mobile education via short text messages (during the first and second weeks) and telephone counseling (during the second week) three times during the two weeks after discharge. During the initial introduction to the program, the authors provided supplementary materials: manuals that explained how to use the program and a simple booklet that was produced by referring to the learning content index in the program (Appendices B and C). Participation in the education program and learning progress were checked through the website and via short text messages three times over the two weeks [The educational program delivered content through a website accessible wo weeks .2.4.2Patients who were assigned to the conventional care group were not allowed to take part in the mobile web-based educational program. Instead, they were given booklets and received the conventional education program that consisted of physician- and nurse-led protocol-based individual education and group education with a question and answer session, when applicable. After the experiment concluded, the conventional care group was introduced to the mobile web-based program so that they could use it if they desired.2.52.5.1et al. [r = 0.85) with Functional Living Index-Cancer (FLIC) scores. Furthermore, previous research by Ward et al. [r = 0.74). In the current study, Cronbach’s α reliability coefficients for the physical, social/family, emotional, and functional well-being domains were 0.85, 0.83, 0.82, and 0.88, respectively, and that of the FACIT-C subscale was 0.90.Quality of life was measured using the Functional Assessment of Cancer-Colorectal survey (FACIT-C v 4) developed by Ward et al. . In addiet al.  examinedd et al.  observedTo measure anxiety and depression, this study adopted the Hospital Anxiety Depression Scale, which Zigmond and Snaith  developeet al. [Self-efficacy was examined using a Korean version of the Hospital Anxiety Depression Scale comprising 17 questions developed by Sherer et al.  and modiet al. . In the Finally, resilience was examined using a Korean version of the 25 questions developed by Wagnild and Young . Cronbac2.5.2SD), while non-normally distributed data are reported as the median (range) and categorical data are reported as the number and frequency. To test for differences in demographic characteristics, an independent t-test was performed on normally distributed continuous data and the Wilcoxon rank-sum test was performed on continuous data without a normal distribution. For categorical data, the chi-squared test or Fisher’s exact test was conducted as appropriate. As age, education, employment, and pre-test scores were significantly different between the two groups (p < 0.05), an analysis of covariance was used to determine intergroup differences, using these variables as covariates. All statistical analyses were performed using SAS 9.3 .The normality of variables was assessed using the Shapiro-Wilk test. Normally distributed data are reported as the mean ± the standard deviation  and 61% were men and 39% were women; most participants were married (94.9%) and employed (53.4%). Fifty percent of participants had cancer of Stage 3 or higher, and most did not have an intestinal stoma (95.7%). There were differences between the treatment and conventional care groups in terms of age, education, and employment. Table 1.Of the 139 patients who met the inclusion criteria, eight refused to participate and 13 withdrew. Finally, 118 patients were recruited. The participants in this study had a mean age of 61 years (3.2SD = 17.71) before receiving the education and 93.69 (SD = 12.46) afterwards. In contrast, the conventional care group showed a decline from 87.76 (SD = 18.56) before the program to 82.73 (SD = 19.57) after four weeks. The analysis of covariance demonstrated a significant gap between the groups in the changes they made after the program . In particular, the mean scores of the affective status in the treatment group increased from 15.98 (SD = 4.3) to 18.31 (SD = 3.2) after the mobile web-based educational program was offered, while the conventional care group’s score was 15.29 (SD = 4.9) before the program and 15.88 (SD = 5.05) four weeks later. The analysis of covariance also demonstrated a markedly significant difference  in these scores of affective status. Table 2.In terms of quality of life, the mean scores of the treatment group were 94.32 (SD = 4.07) for anxiety before receiving the education and 3.61 (SD = 2.48) afterwards. In contrast, the conventional care group showed a decline in anxiety score from 6.24 (SD = 4.62) before the program to 6.14 (SD = 4.54) after four weeks. The analysis of covariance revealed a significant gap between the groups in the changes demonstrated after the program . Similarly, the mean depression scores in the treatment group declined from 7.37 (SD = 5.06) to 5.85 (SD = 3.5) after the mobile web-based educational program was offered, while the conventional care group’s score increased from 8.76 (SD = 4.3) before the program to 9.36 (SD = 4.7) four weeks later. Analysis of covariance for this metric demonstrated a significant intergroup difference . The educational program was effective at increasing the treatment group’s self-efficacy, with an increase in mean score from 46.81 (SD = 10.29) to 51.34 (SD = 8.83), while the conventional care group’s score decreased from 48.8 (SD = 9.67) before the program to 47.63 (SD = 10.8) four weeks later. The analysis of covariance also demonstrated a significant intergroup difference in this case . Table 3.Furthermore, the mobile web-based educational program significantly improved patients’ anxiety, depression, and self-efficacy. More specifically, the treatment group scored 5.54 (SD = 31.46) to 137.19 (SD = 29.98) after the mobile web-based educational program was offered, while the scores of the control group showed a moderate rise from 124.92 (SD = 31.16) before the program to 125.75 (SD = 31.3) four weeks later.In addition, the mean scores of the treatment group’s resilience increased from 129.15 (4Colorectal cancer is a traumatic and chronic illness that affects an increasing number of individuals due to the world’s aging population and an improved survival rate. Patients with colorectal cancer undergo serious hardship at every stage, including diagnosis, surgery, treatment, and after discharge. As patients with colorectal cancer undergoing surgery with the ERAS program have a shorter hospital stay and less contact with medical professionals, they face various issues, such as the lack of information concerning self-care after leaving the hospital, neglected psychological needs, and insufficient self-efficacy. The resulting distress can lead to other problems, including depression and anxiety  and can This study reports the role of a web-based mobile platform in addressing the post-surgical and post-discharge needs of patients with colorectal cancer treated under ERAS. Furthermore, the findings show that the program significantly reduced the negative effects of surgery on the quality of life of those in the treatment group compared to the conventional care group and triggered a sharp improvement in the emotional status of the treatment group. The effect of the program may have been further amplified by the multidimensional system of emotional support involving a tripartite participation of the patient, family members, and medical teams, ensuring mutual and active communication.This study examined the effect of the platform on patients with colorectal cancer, 50% of whom had cancer at Stage 3 or above and had undergone open surgery under the ERAS program. It is worth noting that, after receiving the mobile web-based educational intervention, the treatment group experienced a positive effect on their quality of life within a short period after hospital treatment. This is further supported by the fact that some patients had a marked improvement in their quality of life within the first month, indicating the necessity of measuring patients’ quality of life during the early post-surgery stages . The quaIn addition, this study demonstrated that the educational program significantly reduced patients’ anxiety and depression and increased their self-efficacy. The significant improvement in self-efficacy and the positive effect on quality of life after participation in the program may be attributable to active engagement in self-care, supporting previous findings . PatientIn the educational program used in this study, patients established their health goals by considering their own disease status. To achieve their goals, patients used a checklist to share their progress in mobile self-learning and understanding at every session and were given rewards by a medical professional.Medical professionals reviewed the patients’ degree of accomplishment by acquiring information on the need for self-care, the reliability of information provided, and the scope of support, and provided patients with assistance and feedback.via chat rooms in the “colorectal cancer patient community.” In addition, affective arousal can be achieved with education on how to cope with stress and negative feelings. These procedures became feasible using a mobile web-based educational program that the patients could use individually whenever and wherever after discharge. This supports a previous study that found that a mobile-based system can assist cancer patients in more effectively managing their illness by allowing them to interact with medical staff. This approach may also reduce complications by educating patients on how to prevent complications, curb medical costs incurred by long-term hospitalization, and result in better quality of life among patients with colorectal cancer treated under the ERAS program.Moreover, the alleviation of affective arousal may be made possible by the vicarious experience of sharing instructional materials and the sharing of disease experiences by patients with colorectal cancer and their families These patients have mostly depended on the Internet for information but often find inaccurate information and are left in doubt, leading to feelings of insecurity. Moreover, most caregivers have only focused on the post-surgery and transitional periods between the hospital and the home . AccordiWith the increasing pressure on the healthcare system, integrating health care services with mobile computing could enhance the emotional well-being and self-efficacy of patients with colorectal cancer by incorporating home care processes into the system . This coIt is also worth noting that in this study, nurses communicated with patients regarding concerns and addressed health status improvement by checking each patient’s learning performance for each item. Self-efficacy increased through verbal persuasion by nurses.Although this mobile web-based educational program was verified to be useful and effective for patients, some older patients might feel that it is difficult to work with the mobile equipment. Older patients in the treatment group withdrew more often, and it seemed that they were unfamiliar with and unskilled in the use of mobile web-based programs. As such a possibility may produce a biased result, we attempted to minimize any effect of the differently distributed variables between the two groups by including them as covariates in the analysis. After reviewing all 131 patients assigned equally between the two groups, we found that all variables except education were balanced between the two groups. Consistent with the findings of a previous study, we did not observe any correlation between quality of life and age, education, marital status, or income , or any Resources for self-efficacy enhancement, such as those suggested in the current study, can aid patients with colorectal cancer treated under the ERAS program to better deal with negative feelings and to have a greater sense of self-efficacy regarding caregiving. Furthermore, the present study provided the program in a timely manner, thus helping address patient concerns that had been unaddressed due to early discharge. This lowered anxiety and depression and enhanced self-efficacy ultimately lead to a better quality of life among the patients.In this study, a mobile web-based educational program was developed and used with patients with colorectal cancer who underwent surgery under the ERAS program and had been discharged. Compared to those undergoing the conventional program, patients receiving the educational program experienced a significant decline in anxiety and depression levels and a significant improvement in their self-efficacy, positively impacting their quality of life. The mobile web-based educational program can make education more convenient and reduce complications and expenses incurred from long-term hospitalization and conventional education. In addition, the program can lower distress, anxiety, and depression while enhancing self-efficacy, thereby positively affecting the quality of life of patients treated under the ERAS program.An important issue for further research is whether the findings and implications of this single-center study can be replicated with other cancers, at other hospitals, or even in other regions. Moreover, the mobile web-based intervention was conducted within two weeks of discharge. Given that some studies indicate that patients complain of anxiety and depression at various times during hospitalization or after discharge, further investigation is required to explore whether there are time-specific differences in program effectiveness. In addition, while our analysis was adjusted for covariance between unequal variables, the possibility of further differences between the groups calls for careful interpretation and generalization of the findings of this study. Further research conducted on a larger sample size and including follow-up to examine the substantive effects of the intervention over a longer time period is recommended.


Oasis Senior Supportive Living (Oasis) is an active aging-in-place model created by older adults in a naturally occurring retirement community, such as an apartment building. The program is member-driven so that participating older residents determine the programming and services that best address their needs. The first Oasis program was established in an apartment building in Kingston, Canada and has been running for more than ten years. Preliminary evaluations of the Oasis program demonstrate that its members report feeling more socially connected, are more physically active, and have increased nutrition as a result of participation. In-depth interviews were conducted with Oasis members and key program stakeholders to identify the core dimensions of the Oasis program that has led to its success in supporting active aging in place. Interviews were audio-recorded and transcribed verbatim. Thematic analysis was used to identify, analyze and report themes. Four themes emerged: (1) nutrition, social and physical activities as critical programming pillars; (2) the importance of active member participation and decision-making; (3) the need for onsite support to facilitate programming; and (4) Oasis as a family. These findings highlight the need for programming that is designed for and by older adults. Supporting older adults to come together and form community is key to healthy and active aging. Identification of these elements is critical to modelling Oasis in other community contexts. Oasis is currently being expanded to seven new communities across Ontario using a participatory action research approach.


This presentation will review the design, methods, and early lessons learned from the Making Engagement Meaningful through Organized Routine Interaction (MEMORI) Corps trial recently funded by NIA. This trial is evaluating the feasibility and efficacy of the MEMORI Corps program, a novel 12-week activity-based companion care model designed to mobilize and equip senior volunteers to deliver individualized, evidence-based activity programming to persons with dementia PWD living at home and offer family CGs needed respite. The intervention synthesizes and adapts prior evidence-based work from the Tailored Activities Program® (an activity-based intervention persons with dementia), Experience Corps® , and MIND at Home® (a home-based dementia care coordination program) to simultaneously address unmet respite care needs of family CGs, provide PWD structured meaningful activities and social engagement, and provide meaningful engagement and peer support opportunities for senior volunteers.


The “Strengthen Your Ankle” neuromuscular training program has been thoroughly studied over the past 8 years. This process evaluation is a part of a randomized controlled trial that examined both the short- and long-term effectiveness of this particular program. Although it was shown previously that the program, available both in a printed booklet and as a mobile app, is able to effectively reduce the number of recurrent ankle sprains, participants’ compliance with the program is an ongoing challenge.This process evaluation explored participants’ opinions regarding both the methods of delivery, using RE-AIM (Reach Effectiveness Adoption Implementation Maintenance) Framework to identify barriers and challenges to program compliance. Although Reach, Effectiveness, and Adaptation were the focus of a previous study, this paper focuses on the implementation and maintenance phases.t tests assessed between-group differences in quantitative survey responses. Interviews were assessed by thematic analysis to identify key themes.Semistructured interviews and online questionnaires were analyzed using qualitative content analysis. Fisher exact, chi-square, and P=.006).While there were no significant differences in the perceived simplicity, usefulness, and liking of the exercise during the 8 weeks of the neuromuscular training program, semistructured interviews showed that 14 of 16 participants agreed that an app would be of additional benefits over a booklet. After the 12-month follow-up, when asked how they evaluated the overall use of the app or the booklet, the users of the app gave a mean score of 7.7 (SD 0.99) versus a mean score 7.1 (SD 1.23) for the users of the booklet. This difference in mean score was significant  Injuries, due to participation in sports and physical activities, are prevalent. Internationally, ankle sprains are one of the most common musculoskeletal injuries . In partOne of the many available interventions that has been shown to be effective in reducing the risk of recurrent ankle sprains, as well as protecting against secondary complaints, is neuromuscular training (NMT) -5. MultiAs with other preventive interventions, the translation of the evidence on ankle sprain prevention through NMT to the real-world context of sports remains a challenge, by which effective ankle sprain prevention in the community is lagging . The sucAlthough developed for use in health care settings, the RE-AIM framework has been previously used to evaluate the success of introducing strategies for sports injury prevention within a practical sports context ,18. ConsThe full details of the “Strengthen Your Ankle” study have been described elsewhere ,4,13. InThe RE-AIM framework describes five dimensions to evaluate the practical feasibility of an intervention: “Reach,” “Effectiveness,” “Adoption,” “Implementation,” and “Maintenance” . The dimThe “Effectiveness” dimension describes the clinical impact of the studied intervention. The short- and long-term effectiveness of the app compared with the booklet for preventing ankle sprain recurrences were assessed in a RCT. The full methods and results of this trial have been published elsewhere ,4,13. InImplementation concerns the participants’ use of the intervention strategies. In this study, we quantified use as compliance with the 8-week NMT program in each of the study groups, measured as a percentage of the total program completed. In addition, the participants’ attitudes and perceptions toward the delivery of the NMT programs were assessed.During the 8 weeks of the NMT program, participants received a weekly online questionnaire. The questionnaire registered what percentage of the program was executed during the week, the amount of difficulty that was experienced while conducting each of the exercises, and the reason for a possible lack of compliance. For each of the 6 different exercises, participants indicated what percentage of the exercises they performed each week. Additionally, using a 5-point Likert scale, participants were asked how they perceived the exercises. When participants failed to complete the questionnaire, reminders were sent by email. The details on the questionnaire have been published previously .t test was performed to examine the difference in scores between the two groups.After the 8-week training period, a more extensive evaluation questionnaire was completed, including closed and free-text questions on the subjectively-experienced value of the NMT program delivery mode, a subjective evaluation of the program, and the perceived disadvantages and advantages of the allocated intervention delivery mode. To measure satisfaction, all remaining participants (75 in the app group and 88 in the booklet group) were asked to give a 0-10 score for the app or booklet. An unpaired “Maintenance” describes the long-term effectiveness of the intervention strategies. For this study, this dimension was defined as the percentage of participants still conducting the NMT program combined with the advantages the participants perceived related to the app or paper booklet use for intervention delivery.After 12 months, semistructured interviews were conducted with individual participants to assess the perceived advantages of using the app over the paper booklet. All study participants were asked if they were willing to participate in a semistructured interview concerning the NMT program; 27% (32/119) of the remaining participants, evenly divided over the two study groups, responded positively. The interviews were structured using a preselected topic list on the individual experiences with the NMT program either through the booklet or app. All interviews were conducted and transcribed by one researcher (MA). Interviews were conducted via telephone until saturation was reached, that is, when interviews did not lead to new themes or information, within both study groups, resulting in 16 semistructured interviews with 8 randomly selected participants in the booklet group and 8 randomly selected participants in the app group. t tests with assumed equal variances were conducted to assess for differences in the average Likert responses between the two study groups. The significance level was evaluated at P=.05. SPSS (version 22.0) and was used for all statistical analyses.Due to dropout during follow-up (n=57 after 8 weeks and a further n=44 after 12 months), sample sizes differed between questionnaires. The reasons for dropout were unknown. The participants’ answers on the 5-point Likert scales regarding attitudes and perceptions toward the program, as registered during the 8-week program, were averaged for each participant over the available follow-up moments. Independent sample All semistructured interviews were audiorecorded and transcribed verbatim. In transcriptions, any personal information or information that was deducible to an individual was anonymized. Verbatim-transcribed interviews were thematically analyzed and fragmented on the basis of topical similarity using Atlas.ti . Open, iPrevious studies that looked at the effectiveness of the “Strengthen Your Ankle” program provided further details on the (cost)-effectiveness of the program in the short and long term ,4. In shDuring the 12-month follow-up, there were 139 recurrent ankle injuries, resulting in injury incidence densities of 15.59 per 1000 hours of sport (95% CI 11.94 to 19.24) in the app group and 15.84 (95% 12.10 to 19.58) in the booklet group. Over the long term, this difference in injury density was not significant  [The first study in this larger research project looked at compliance during the 8 weeks of the NMT intervention. It was shown that the average compliance to the exercise scheme was 73.3% (95% CI 67.7% to 78.1%) in the app group and 76.7% (95% CI 71.9 to 82.3%) in the booklet group. No significant difference in compliance was found between the groups [The weekly questionnaires  showed tAfter the 8-week intervention period, 35 participants using the app and 22 participants using the booklet discontinued the study for unknown reasons. The remaining 75 users of the app found this method of NMT program delivery more user friendly, easier, fun to use, and less annoying and thought that the videos were more helpful than the booklet . The latt test showed that the users of the app were significantly more satisfied with the app  compared with booklet users; 7.7 (SD 0.99) versus 7.1 (SD 1.23) P=.006.Therefore, the answers of 53 of the booklet users were “neutral” when asked if the online videos were of help; this was in comparison with 5% (4/75) in the app group. Some participants failed to answer all the questions, the number of missing responses can be found in At the end of the 12-month follow-up period, an additional 44 participants discontinued the study. These participants were asked if they were still doing (part of the) NMT program. Only 23% (28/122) of all participants still in the study responded affirmatively. We did not ask what amount of the program they were still doing.Two main themes arose from the semistructured interviews that related to the design of the app and possible additional benefits of the app. Fourteen out of 16 participants stated that an app would provide an additional benefit compared with a booklet. The main reasons given were that most of the participants always had their mobile phones with them and that the app provided visual support and had a reminder function. The two participants who did not feel that the app offered any benefit found the exercises too easy, which made the app redundant.Errors in navigation and explanation, the lack of feedback and music, and lack of explanation of the purpose of the exercises were the main disadvantages experienced by the app users. The greatest perceived disadvantages of the booklet were the big size when folded out, small font, lack of robustness, and errors in explanation. Previous studies ,4 have sInterventions for preventing sport injuries require high participant compliance  ThereforOver the years, compliance with the “Strengthen Your Ankle” program in RCTs has steadily increased from 23%  to 45%  and 75% This study aimed to explore user experiences with the NMT program, as well as with the app and booklet as delivery methods, by means of semistructured interviews. The information gathered can be used to further improve the methods of delivery and, thus, increase future reach and compliance. The interviews and questionnaires showed that the app and booklet can be successfully used to prevent recurrent ankle sprains and that both show high user satisfaction. Future updates may include options for feedback or postponement of exercises, an explanation of the use of specific exercises, and possibly music; these additions could further improve user perceptions of the program and hence increase compliance.A limitation of this study, and that of previous studies on the “Strengthen Your Ankle” program, is the mismatch between compliance and adherence. Although both constructs have been used interchangeably, they are not synonymous. Adherence refers to a situation where a clinician or researcher develops a program in cooperation with the participant. The participant attempts to follow the program as best as possible, taking personal preferences and constraints into consideration. Adherence can be seen as what happens in real-life conditions when individuals with an ankle sprain try to follow the program; compliance is studied in clinical settings. The extent to which the participant obeys the program instructions is measured by compliance rates ,24. ReseA further limitation of this study is the possibility of selection bias for the semistructured interviews. It is possible that only those participants that carried a strong negative or positive view of the program agreed to participate because the invitation for the interviews was made only after termination of the 12-month follow-up. Additionally, the (single) interviewer did not structure the interviews and continued to question the participants when needed. This may have affected the validity of the data analyses. However, it is recognized that this characteristic is inherent to the flexible nature of thematic analysis and does not threaten the depth of analysis .With the use of semistructured interviews and online questionnaires, we were able to evaluate users’ opinions on both the app and booklet. The users of the app were significantly more satisfied with the app although there was no significant difference in the perceived simplicity, usefulness, and liking of the exercise during the 8 weeks of the NMT program. In the interviews, users acknowledged the need for improvements. Future updates should take the users’ suggestions into account because adherence with the NMT program remains an ongoing challenge.


The aim of the current study was to investigate the feasibility of a Web-based program that promotes behavior change for stress-related problems in terms of the program’s acceptability, practicability, and any possible effects. In addition, the aim was also to study how appropriate and realistic the study’s process and resource management would be for conducting a randomized controlled trial. A convenience sample consisting of 14 individuals was recruited from a university in Sweden. The participants had access to the program for a duration of 9 weeks. Questionnaires were answered before accessing, during use of, and after completing the program. Both qualitative and quantitative data were collected and analyzed. The program was considered acceptable and practically feasible, though small adjustments have to be made. The program was considered time-consuming, extensive, and in need of some clarifications. Regarding process and resource management, the study participants required minimum support. It was difficult to identify the time point when to send out the process measures because the participants worked at their own pace. Also, one of the process measurements, the motivation to change, remained stable. With some adjustments to the instructions to the study participants and minor changes in the program, the intervention and study’s procedure were considered as feasible and can be carried out in a randomized controlled trial. Recently, supporting the management of mental health problems through Web-based programs has become a more researched topic. Web-based self-management programs have shown to be effective in supporting individuals to change different health-related behaviors  was developed. The program was built using evidence from multiple fields, such as behavior change, stress management, and information design. MSC is a multi-tracked, tailored, and interactive platform that includes effective behavior change techniques and stress-management strategies. Information is delivered in several ways: texts, videos, and audio recordings. The interactivity is at a high level and includes assessments and assignments that contribute to the tailoring of and further advancement within the program.When conducting a feasibility investigation, the important parameters for a planned, randomized controlled trial (RCT) can be identified, adjusted, and further developed to improve the chances of success in a larger, more costly study. Feasibility studies can help to identify what needs to be modified regarding the intervention as well as regarding the research methodology : The PSS : The CSS : The MCQ : The QPS for psychological and social factors at work contains 37 items that are divided into 23 subscales and single questions. All the items are scored using a 5-point Likert scale : The UWES is a nine-item scale that measures a person’s engagement in his or her work. All items are scored using a 7-point Likert scale. The means for each subscale, as well as the mean for the total scale, are calculated. The UWES has three subscales  and a total score ranging between 0 and 6  by one participant.Fourteen participants completed the first round of measures. Ten participants completed the second round. Eight participants completed the third round. See Table The main reason for dropping out of the study was a perceived shortage of time (four people). One study participant ended the study participation because of sick leave caused by depression and anxiety. One person did not send in the third round of measures and did not provide any reason for this.Concerning the acceptability of the program, the results for the statements assessing the participants’ opinions and experiences of the content, tailoring, feedback, to conduct an own behavioral analysis, setting goals, graphic and pedagogical design, and how the information was perceived are summarized in Table Six participants answered the question regarding the time spent for going through the program. The reported time ranged from 1 h to 7 weeks. The total amount of time spent on questionnaires for the pre, process, and post measures were answered by seven persons. The average time spent were 80 min, ranging from 60 to 120 min.Regarding the open-ended answers on the acceptability questionnaire and the e-mail correspondence, six categories were identified regarding acceptability and practicability: extensiveness, interference, clarity, flexibility, insights, and need for reminders.The participants expressed that the program was more extensive than they first thought and that there was “too much” material to be filled in for the assignments on the stress-management strategies. It was suggested to make the assignments shorter. The program was perceived as time-consuming. One study participant described it as paradoxical: it is hard to take time for stress management when you already are stressed.Some factors that interfered with using the platform were identified. One bug that locked further progress was found. Also, two of the audio recordings had low quality, and some of the videos lagged for one user. The video platform YouTube was used for embedding videos on MSC. However, it was perceived as confusing the way in which YouTube suggested other videos after the embedded video played. It was not clear for the users if these videos were included in the program or not.The need for clarifying some parts were identified. Here, the comments ranged from clarification of how items on the questionnaires were formulated to how the platform was constructed. The comments on the structure of the platform mainly concerned how easy or difficult it was to find a way through the program and how the program and platform signaled what was already completed and what was next. The small notifications when different sections of the MSC were completed were appreciated. The voices and pictures in the videos were perceived as suitable. Two study participants commented on the voices, which they liked. One voice was described as “kind, trustworthy, and supportive.” Suggestions on how to clarify progression through MSC by including instructions for navigation were provided. There was also conflicting information: in one part, MSC stated after a video to click on the “first activity,” and then beside the same activity, MSC stated “next activity.” Thus, more consistent use of commands was proposed to enhance clarity. One user wanted to look around at the platform before starting and was confused when it was impossible to reach the locked areas that would be unlocked later on. After watching the first video, the button “I have seen this film” was hidden by the scroll bar function, and the user did not understand that this button must be clicked to access the next task. One study participant noticed and liked the pop-up feedback saying that recommended stress-management strategies were available.To enhance flexibility, participants suggested MSC should be delivered as a mobile application. MSC’s structure forces users to go through all the assignments in a predetermined order, and this was perceived as a barrier for using. One of the participants expressed that the individualization was not relevant. One of the participants with low stress levels expressed that for a person with a low stress level, it was difficult to stay motivated to go through such an extensive program.The study participants described the insights they discovered regarding what stress really is for them and how their stress could be handled. Mainly, the insights were about becoming aware of their stress and how stress can be different for everyone. How to prevent stress and plan for recovery were also insights that the study participants shared.The study participants expressed that they often forgot to log in to the program, and one participant suggested to add in reminders that could pop up on the screen.The descriptive statistics (medians and range) for pre, process, and post measures for all the participants in all measures are presented in Table p < 0.05: the coping strategy “acceptance.” However, when correcting for multiple tests according to Bonferroni, a significant p value for the variable “acceptance” should have been < 0.003. See Table There were no significant differences between pre and post measures, save for one variable with There were some issues in determining the appropriate time to send out the process measures because the users worked at their own pace. Because of this, an overview function in the administration tool for MSC was developed during the current study, allowing the first author to see when the users had completed the recommended stress-management strategies and started the lifestyle-related strategies for stress management .The study participants required minimum support while using the program.Of the three process measures  included in the study, the MCQ was stable according to the median values . The reason behind these low scores on MSC’s ambivalence module could be because only two participants took the ambivalence module and hence were the only ones who answered this question. After analyzing the questionnaire regarding MSC’s practicability and acceptability, there was a difference regarding the scores for two types of items: the questions related to issues that could be easily recognized earlier on, such as how easy the program was to navigate, how the program was individually tailored, and how the symptoms of stress survey caught the user’s stress-related symptoms, received higher scores. Questions regarding issues that would have required the user to work with the program longer, such as fulfilling goals and trying a new behavior in different situations, received lower scores. This could be because of the users’ shorter time with the program compared to what MSC was developed for and maybe because users were not expected to have enough time to fulfill their goals, hence not having time to try their new behavior in the situations described in their ABC model. Also, regarding the program’s acceptability, one participant scored above the cutoff score on HADS and excluded. However, the text with further instructions to contact other healthcare providers after being denied access was judged as fair and “okay” by that user.The time spent going through the program varied a lot. The data provided by the study participants were difficult to decipher since it seems that the participants’ interpretation of the question was not clear. While one person may have answered how long time was spent on the Web-based platform, others seem to have answered how long time it took from first login, going through assignments provided by MSC until reaching the last module. How the question was formulated is probably a limitation in this study.The current feasibility study was theoretically based on a model for developing and evaluating Web-based behavior change interventions  even though the study population consisted of only a few people (n = 22)  and had a college education. This is considered as limitation regarding generalizability of the acceptability and feasibility to different populations. This must be considered when recruiting for the RCT.According to the predetermined cutoff scores, the current study shows that MSC is feasible for a RCT. However, to enhance the chance for success, some modifications need to be made before conducting the RCT.


BCR-ABL1. Allogeneic stem cell transplantation  was considered the first-line treatment for CML, before the introduction of tyrosine kinase inhibitors (TKIs). However, patients are at risk for relapse years after transplantation. We present a patient who relapsed 25 years after allo-SCT for chronic phase CML. Polymerase chain reaction (PCR) detected gradually evaluated levels of BCR-ABL1 transcripts, eventually leading to the diagnosis of relapsed disease. Additional mutational analyses did not reveal mutations in the BCR-ABL1 gene, or other cooperating mutations. The patient was successfully treated with imatinib 400 mg daily, leading to new molecular remission. The case presentation emphasizes the need for long-term follow-up of such patients and the potential benefit of initiating TKI treatment with early signs of relapse.Chronic myeloid leukemia (CML) is a myeloproliferative disorder in which neoplastic cells exhibit the Philadelphia chromosome and the related oncoprotein  ABL1) oncogene with the breakpoint cluster region (BCR) gene. The malignant transformation is hence caused by the acquisition of the constitutively active tyrosine kinase BCR-ABL1 in a hematopoietic stem cell, transforming it into a leukemic stem cell (LSC) that self-renews, proliferates, and differentiates to give rise to a myeloproliferative neoplastic disease [Nearly 1.5 million people worldwide suffer from chronic myeloid leukemia (CML), which is morphologically characterized by an accumulation of myeloid precursor cells in the peripheral blood and bone marrow. Philadelphia chromosome-positive CML is identified by the genetic translocation t9;22)q34;q11.2) [2, targeting the kinase activity of patients . Howeverpatients , althougpatients –9. Here,9/L  together with increased serum concentration of lactate dehydrogenase (LDH) 969 U/L (200–450 U/l) and cobalamin 2834 pmol/L (150–840 pmol/L). A blood smear demonstrated dominance of myeloid precursor with increased metamyelocytes and rods. CML was confirmed by identification of the Philadelphia chromosome t by using conventional G-banding analyses.A previously healthy 41-year-old woman was diagnosed with CML, after presentation of symptoms caused by hypersplenism with gravity sensation under the right costal margin. Initial blood tests demonstrated severe leukocytosis 227 × 10Treatment was initiated with hydroxyurea combined with interferon, and the patient reached morphological remission, then proceeded to allo-SCT for consolidation treatment. The transplantation was performed by a myeloablative condition (MAC) regime with busulphan 1 mg/kg for four days followed by cyclophosphamide 60 mg/kg for two days, followed by bone marrow-derived stem cell from her human leukocyte antigen- (HLA-) matched sister. Standard graft versus host disease (GVHD) prophylaxis by using cyclosporine A and methotrexate on day 1, 3, 6, and 11 after transplant was given . No seveBCR-ABL1 transcripts [BCR-ABL1 was detected by nested PCR. She was therefore controlled twice yearly, without signs of progression judged from karyotyping and interphase fluorescence in situ hybridization (FISH) of 200 interphases with probes against BCR and ABL1 in the bone marrow. By standardization of quantitative real-time (RT) PCR, yearly analyses were performed [After the development of polymerase chain reaction (PCR) analysis for nscripts , this tenscripts . Six yeaerformed , and lowBCR-ABL1 of 245 interphases by FISH using dual fusion probes, and this was regarded as insignificant. The bone marrow smear was hypercellular with increased myeloid precursors and megakaryocytes, although without evidence of increased myeloblasts. Hence, we maintained the diagnosis of CML with molecular relapse appearing 25 years after initial allo-SCT. The patient was screened for other mutations commonly occurring in myeloid malignancies, including mutations in BCR-ABL1, but no additional mutations were detected. Donor chimerism status revealed that the majority of myeloid cells (99%) were of donor origin. We thought that her relapsed disease was likely to be sensitive to treatment with first-generation TKI, and she was given imatinib 400 mg daily. She tolerated the treatment well without major side effects; after three months, she obtained MR4 status  is not uncommon neither for allografted patients nor for patients treated with TKIs [BCR-ABL1 transcripts is believed to be caused by the persistence of an LSC pool in CML patients [The present patient was allografted before the introduction of TKIs. She was given induction therapy with hydroxyurea and interferon, considered as the standard treatment at that time . After rrecently ; hence,  relapse . Howeverith TKIs . The detpatients . HoweverBCR-ABL1 expression in the hematopoietic stem cell compartment seem to have inferior survival irrespective of the disease status [BCR-ABL1 transcript level and probability of relapse seem apparent [Studies have demonstrated that patients with e status . The quaapparent .In the 1990s, donor lymphocyte infusion (DLI) was the mainstay of treatment for posttransplant CML relapse , 21. DLIBCR-ABL1 kinase domain point mutations are detectable in approximately 50% of patients with treatment failure and progression on TKIs, although the incidence of BCR-ABL1 mutations in patients relapsing after allo-SCT remains uncertain. Although our patient had not been exposed to TKIs previously, we considered this as a relapsed disease. We therefore investigated her for BCR-ABL1 mutations, but this could not be detected. Hence, treatment with imatinib was initiated. No clinical studies comparing different TKIs in CML relapse after allo-SCT exist, and the choice of TKI should in our opinion be based on risk for potential side effects, patient age, previous exposure to TKI, and potential BCR-ABL1 mutations.The use of maintenance TKI treatment after allo-SCT has also been investigated –33 and sBCR-ABL1 transcripts over years, relapse can still occur. Early diagnostics and introduction of TKI therapy are crucial to avoid transformation to more advanced stage of CML.To conclude, our case report emphasizes the need for long-time follow-up for allo-transplanted CML patients. Despite stable levels of


DMHN1, which allows DCNP to become fully traceable in a sensitive, selective, and responsive manner. This is the first fluorescent turn-on probe within the dipolar naphthalene platform induced by ESIPT (excited state intramolecular proton transfer) suppression that allows us to sense DCNP without any disturbance by other similar G-series chemical weapons. The successful demonstrations of practical applications, such as in vitro analysis, soil analysis, and the development of an on-site real-time prototype sensing kit, encourage further applications in a variety of fields.Diethylcyanophosphonate (DCNP) is a simulant of Tabun (GA) which is an extremely toxic chemical substance and is used as a chemical warfare (CW) nerve agent. Due to its toxic properties, monitoring methods have been constantly come under the spotlight. What we are proposing within this report is a next-generation fluorescent probe,  Among ttrations a 2]. G-. G-1O toward DCNP  and selectivity (only DCNP), fast-response time (<3 min), and wide practical applicability, such as in real-time monitoring of DCNP in soil samples.Recently, we have focused on the development of naphthalene-based electron donor (D)-bridge-acceptor (A)-type dipolar fluorophore and its applications as molecular probes ,16,17,18ard DCNP c. The ESP  and soils  were purchased for applications. Commercially accessible reagents and anhydrous solvents were used without further purification. Chemical reactions were carried out under argon atmosphere. Thin-layer chromatography (TLC) was performed using pre-coated silica gel 60F-254 glass plates .The chemical reagents were purchased from Aldrich , TCI , Alfa Aesar , and Acros Organics . Species used to perform the screening of nerve agent simulants: DCNP, DCP, DMMP, TPP, TEP, CHDMHN1 was synthesized by following the reported method by our group (see 1H NMR data of synthesized DMHN1 was compared with the reported result. Important points: (i) Slowly and dropwise add t-BuLi (1 drop every 5 s). Fast t-BuLi adding generates the isomer and dimer of formylated products which are difficult to separate in column chromatography. (ii) Fresh t-BuLi and DMF should be used. (iii) Add t-BuLi at a temperature of –20 °C. Caution: t-BuLi is very reactive and fragile. Keep the appropriate PPE .roup see  20]. Th. ThDMHN1DMHN1 in acetonitrile  at 25 °C. Solvent screening was conducted within acetonitrile (ACN), ethanol, isopropanol, dimethylformamide (iPA), dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), ethyl acetate (EtOAc), deionized water (DI H2O), and dichloromethane  in CH3CN (1% Et3N) for 60 min at 25 °C. During the light exposure, UV/Vis absorption and fluorescence change spectra were recorded according to the given time lapse . The maximum absorption wavelength was used for the emission spectra acquirement. High-resolution mass spectra were obtained by a JEOL JMS-700 spectrometer  at the Korea Basic Science Center, Kyung-Pook National University, and the values are reported in units of mass to charge (m/z).UV/Vis absorption and fluorescence spectra were acquired by a spectrophotometer  and spectro-fluorophotometer  with a 1 cm standard quartz cell , 108-F-10-40 (10 × 4 mm); Hellma Analytics, Müllheim, Germany) each. The absorption and fluorescence spectra were recorded at the following condition; 10 μM of ane DCM, . PhotostDMHN1 solution (10 μM) in CH3CN (1% Et3N). The fluorescence changes of the solution were investigated for 0–120 min by a digital camera  under UV light (365 nm). The relative fluorescence intensity and standard deviation were calculated by Image-J software  in the specific fluorescence signal region.A spoon of each soil  was transferred to an aluminum dish . Two milliliters of DCNP solution (100 mM) in acetonitrile was poured into an aluminum dish under room temperature (25 °C). Soils were incubated for 2 min at 25 °C. After incubation, each soil sample was transferred into 3 mL of DMHN1 solution , 1 mL) was placed in a screw-cap HPLC vial  as a prototype sensing kit. A drop of the original DCNP solution was collected and transferred to the vial by using a capillary tube . The fluorescence changes of the kit were monitored for ~40 s with a digital camera  under UV light (365 nm). The relative intensity and standard deviation were calculated by Image-J software  in the fluorescence signal region from video.DMHN1 in sensing media  exhibited weak fluorescence due to the ESIPT quenching. However, after being treated with DCNP, it showed significant fluorescence enhancement at an emission maximum of 485 nm  significant fluorescence recovery (>20-fold) after reaction with DCNP , but the signal was not high enough to detect it, compared with the acetonitrile condition , represent the absorption of DMHN1 in the short wavelength region, and they are corresponding to the experimental results of UV/Vis absorbance; absorption maximum around 350–400 nm , DMMP (dimethyl methylphosphonate), TPP (tripropyl phosphate), TEP (triethyl phosphate), and acid (acetic acid in this study) was then evaluated  and 31P NMR. What we mainly observed was the only phosphorylation production  for the detection of DCNP, because chemical warfare nerve gas is usually sprayed on the field during wartime or a terrorist attack. The protocol: step 1, put 1 g of each soil  into an aluminum dish; step 2, treat the DCNP solution (100 mM in CH3CN); step 3, pour DCNP-pretreated soils (1 g) into the solution of DMHN1 ; and step 4, monitor fluorescence changes at the ambient temperature (25 °C) (DMHN1 (10 μM) represented the detection limits as 3.125 mM for sand soil and 6.25 mM for the other soils  a,b. With (25 °C) , and the (25 °C) d–f. The er soils . These dDMHN1, we prepared a prototype DCNP sensing kit for real-time on-site application. Prior to the kit development, a high photostability of DMHN1 was verified under strong light irradiation  , (ii) DCNP crude solution for positive control, and (iii) capillary (diameter: 1.2 mm) for the liquid sample collection ) (DMHN1 solution using the capillary (approximately 20 μL) and analyzed the fluorescence responses. Surprisingly, the bright blue fluorescence was monitored from 9 s and it became saturated within 21 s  . The com (lit.)) a. The pr (lit.)) b. In ordhin 21 s . With thDMHN1, that allows the tracing of DCNP, a simulant of GA nerve gas. As a next-generation fluorescence probe, DMHN1 showed superior sensing ability of DCNP with high selectivity and sensitivity (8.16 ppm) and fast response time (<3 min), and it can be used in a real-time on-site situation. The sensing application of DMHN1 in the DCNP-moistened soils and the development of a proto-type sensing kit proved its potential for further studies. Within this study, the first new sensing approach was disclosed; fluorescent turn-on by reaction-based suppression of ESIPT fluorescence quenching in the intramolecular H-bonding containing D-A-type fluorophore. The fast and selective sensing abilities of DMHN1 encourage further applications in basic science as well as at war zone and crime scenes.In conclusion, we developed a selective fluorescence turn-on probe,


An economic crisis in Zimbabwe from 1999–2009 resulted in a shortage of faculty at the University of Zimbabwe College of Health Sciences (UZCHS) and declining enrollment and graduation rates. To improve proficiency and retention of graduates, the college sought to develop a competency-based curriculum using evidence-based educational methodologies. Achievement of this goal required a cadre of highly qualified educators to lead the curriculum review and innovation processes. The Health Education Advanced Leadership for Zimbabwe (HEALZ) program was established in 2012 to rapidly develop the needed faculty leadership. HEALZ is a one-year program of rigorous coursework delivered face-to-face in three intensive one-week sessions. Between sessions, scholars engage with mentors to conduct a needs assessment and to develop, implement, and evaluate a competency-based curriculum. Forty scholars completed training from 2012–15. All participants reported they were satisfied or extremely satisfied with the training after each week. Pre-post surveys identified significant knowledge gains in all key content domains. The program garnered significant organizational support. Scholars showed significant variation in progress toward implementing and evaluating their curricula as well as the quality of the work demonstrated by program end. Interviews of scholars and UZCHS leaders revealed important impacts of the program on the quality and culture of medical education at the college. An economic crisis in Zimbabwe from 1999–2009 had far-reaching negative effects on medical education at the country’s primary health professions school, University of Zimbabwe College of Health Sciences (UZCHS). During this period, many UZCHS faculty emigrated to pursue careers outside Zimbabwe, and it was difficult to recruit and retain new junior faculty. Support for medical education deteriorated, and there was minimal investment in new infrastructure.By 2010, 192 of 314 (61%) faculty positions at UZCHS were unfilled, and UZCHS was forced to decrease student enrollment by 49% (from 204 in 2006 to 105 in 2009) despite an abundance of qualified applicants [The Novel Education Clinical Trainees and Researchers (NECTAR) grant funded by the Medical Education Partner Initiative (MEPI) was developed to disrupt the cycle of declining medical practitioner capacity in Zimbabwe. NECTAR was a consortium of faculty with a long history of strong and productive collaborations in education and research that included UZCHS, Stanford University, University of Colorado School of Medicine (UCSOM), and The Evaluation Center at the University of Colorado Denver (UCD). The goals of NECTAR were to (1) increase the number and proficiency of UZCHS graduates, (2) improve retention of UZCHS graduates in Zimbabwe, and (3) transform the UZCHS academic environment, creating new and sustainable educational and clinical partnerships and increasing research opportunities.To improve the proficiency of graduates, NECTAR sought to develop a competency-based curriculum at UZCHS. Initially, we aimed to develop this curriculum with a focus on HIV, TB, and malaria 4. CurricNeeds assessments performed by UCD and NECTAR evaluation teams indicated that investments in faculty leadership development were needed for successful implementation of the curriculum revisions. In surveys of UZCHS faculty, 100% agreed or strongly agreed that continued exposure to faculty development was necessary for their personal professional growth. Evaluation results also indicated a need for more in-depth training in curriculum development, educational scholarship, and change management. UZCHS faculty felt curriculum change was the responsibility of all faculty members and that a majority would need training to participate meaningfully in this change. UZCHS leaders believed the training should occur in person and in country, rather than occurring online or abroad, because of ongoing issues with internet bandwidth, faculty shortage, and limited funding. Based on these needs, a program for advanced training in education leadership was developed. In this paper we describe the development and evaluation of the Health Education Advanced Leadership for Zimbabwe (HEALZ).Our working group  designed the HEALZ Program in 2012. The goal was to rapidly develop a cadre of highly qualified medical educators to lead the curriculum review and innovation processes. Specifically, the aim was to enhance the educational capacity of UZCHS by developing skills in curriculum development, program evaluation, and educational leadership for faculty interested in pursuing advanced training in medical education. In addition, we sought to build a cohesive community of successful health professions educators. To achieve these goals, we designed a one-year program of rigorous coursework delivered face-to-face in three intensive one-week sessions Table https://evaaagaard1206.wixsite.com/website). Scholars are then expected to implement their curriculum through appropriate processes within the health sciences campus and their respective departments and assess its effectiveness and acceptability.The HEALZ curriculum was designed to be taught using a combination of experiential and small group strategies. The curriculum is spiral and iterative, and it incorporates both constructivist and social learning theories . ContentIn addition, HEALZ includes activities designed to develop peer-mentoring relationships between scholars through daily small group interaction and team building exercises 8. DuringAs one indicator of the implementation of HEALZ, we documented participation and completion rates.To measure the value of the program, we adapted Guskey’s five-level model of evaluation of professional development to collect data on (1) participants’ reactions, (2) perceptions of learning, (3) evidence of organizational support, (4) use of new knowledge and skills, and (5) evidence of impact on medical education in this setting .To assess participants’ reactions and learning, we distributed exit surveys following each training week. Participants rated their overall satisfaction on a 5-point scale . To collect data on participant learning, we asked scholars to self-assess their knowledge and skills in key content areas. Using a 5-point scale , participants rated their competence both retrospectively (“before this workshop”) and post-workshop (“now”). We combined results for cohorts One and Two for each of the three weeks. We analyzed differences in the knowledge self-ratings using Wilcoxon signed-ranks tests and calculated effect sizes. Exit surveys included open response questions to collect additional reactions from participants.In 2013, independent evaluation team members who were not otherwise involved with HEALZ conducted interviews with scholars (n = 5) to collect further information about participants’ reactions, use of new knowledge, organizational support, and program impact. In 2014, interviews with scholars (n = 10) were conducted again to further examine the program’s impact on individuals. Interviews were audio recorded and transcribed. All interviews were analyzed using a grounded theory approach. Results were triangulated with other evaluation data.https://evaaagaard1206.wixsite.com/website) includes a 4-point scale  in eight categories designed to assess scholars’ preliminary curriculum descriptions. HEALZ faculty other than an individual’s mentors reviewed each curriculum summary and shared scores and comments with the scholars. Results were analyzed using descriptive statistics.To provide the scholars with feedback on their progress, we developed rubrics for scoring the curriculum project. The curriculum summary rubric  in cohorts One through Three reported they were “satisfied” or “extremely satisfied” with their professional development after each training week. The satisfaction increased over time with 87% of respondents reporting they were “extremely satisfied” following cohort One’s third week. All respondents also indicated they were confident in their ability to complete their projects and reported they planned to use their learning in other aspects of their professional work. Responses were consistent across cohorts.We found statistically significant differences between the pre and post scores in all HEALZ content areas; respondents as a group believed they increased in knowledge and skills in key content. While some individuals reported no change in some areas, the majority of respondents reported increased competence in all areas Table . Effect In addition, survey respondents also reported gaining competence in leadership and interpersonal skills, such as enhanced communication and improved interactions with colleagues in other disciplines.HEALZ benefitted from early and active support from the UZCHS dean who participated in program design and recruitment and selection of scholars. This support was essential to the program’s successful inauguration. Support for the HEALZ program was also evident at the broader university level. In October 2013, the vice chancellor of the University of Zimbabwe delivered the keynote address at the first HEALZ graduation, an important marker of institutional support. In February 2013, he also established a Department of Health Professions Education within the university structure, which will oversee future faculty development efforts and serve as an academic home for programs like HEALZ. Representatives of the chancellor presented at the graduation ceremonies for the two subsequent cohorts as well.HEALZ graduates co-facilitated the program beginning with cohort Three and assumed full responsibility for facilitating all sessions for cohort Four, as further evidence of organizational support and capacity.Despite the institutional support described above, scholars also identified gaps. Specifically, interviewees reported a need for protected time to engage in coursework and project development, for funding to support project development, and for support in obtaining human subjects approval. Interviewees requested guidance from university leaders to support the implementation of their curricula.HEALZ scholars provided evidence of their ability to apply new knowledge by preparing a curriculum summary, a written description of their project to facilitate implementation and to prepare the scholar for publishing their curricular work. The ratings of the projects for cohorts Two and Three show the areas of relative strength and weakness across projects Table . For botIn interviews, scholars reported they were applying their knowledge and skills in their role as medical educators. For example, one scholar said, “I changed my course curriculum, and it is now team-based learning. I cover it in an amazingly short period of time, and the students benefit more.” Another scholar explained:In my daily work, like teaching, almost everything that I learned … I want to apply it in a deliberate sense. Maybe previously I did things with no background and with no real understanding of what I was doing. For example, when I am preparing lectures or when I am giving the lectures, I feel I am qualified to actually assess myself and I can identify where I think I could do better.As of April 2016, 17 of the 34 curriculum projects Table  developeIn interviews, scholars and UZCHS leaders reported HEALZ had contributed to the quality of medical education at the college. One specific theme of improvement was that HEALZ participation had increased interaction across departments. One scholar explained, “I was able to interact with medical people, with laboratory people, under one roof, over a long period of time. From there, we developed relationships that will last a lifetime because I can actually communicate with them without barriers.”Another impact described by scholars was a shift in the culture within the college to a more student-centered approach. One scholar said, “I think one of the biggest things that I have learned and I think my colleagues have also learned is to appreciate the role of the students in their learning experience.” Scholars explained this shift was evident in the increased use of interactive teaching methods, the dissemination of explicit objectives, and the greater use of valid and fair assessment methods.Other impacts on medical education noted by scholars were the renewed commitment to improving the curriculum both within and across departments and the implementation of new teaching methods. While HEALZ was not intentionally designed to improve teaching skills, scholars reported they learned new skills by adopting teaching methods used in the HEALZ program. One scholar described this process:Observing teaching methods … I actually translated that into my teaching. … That was like a hidden curriculum for me because I used some of the methods that she was using, and I just copied it, and it is tremendous in terms of the impact it has made to my students.UZCHS leaders also expressed the belief that HEALZ scholars were important assets for the curriculum review process both at the department and college level. One interviewee summarized the high expectations for the role of the HEALZ scholars stating, “We can now ensure that each department is equipped with resource persons with skills and knowledge for curriculum design, innovation, evaluation, teaching methods, and teaching assessment methods.”https://evaaagaard1206.wixsite.com/website) for completion after each session. The snapshot guides the scholars through the tasks to be completed between weeks and is sent to both the program leadership and the mentoring team for feedback.Our program evaluation suggested very high levels of satisfaction and self-perceived gains in knowledge and skills. In addition, the program has garnered significant organizational support that has continued even after the completion of MEPI funding. Early on, scholars showed wide variation in progress toward implementing their curricula. We believe this reflected a need for additional infrastructure and organizational support to ensure project completion. To address this for cohort Two, we enhanced the mentoring structure by providing training on working with mentors and explicitly setting expectations for activities to be conducted between sessions, including regular virtual meetings. Each scholar was also assigned a near peer mentor, a recent HEALZ graduate who provided on-the-ground assistance. In addition, the group elected a team leader charged with scheduling regular meetings for the cohort to provide additional opportunities for collaboration and problem solving. To hold scholars accountable, we assigned a structured project snapshot , annual postgraduate enrollment increased by 61% (75 to 121), and medical student enrollment increased by 70% (123 to 210). Interviews of faculty and trainees suggest that HEALZ was a significant contributor to these results  in Zimbabwe: Outcomes and Challenges.” Accepted for Publication in Global Health: Science and Practice, Dec. 2017 estimated publication date) . OngoingThe additional files for this article can be found as follows:10.29024/aogh.19.s1Appendix 1.https://evaaagaard1206.wixsite.com/website).Curriculum Overview (10.29024/aogh.19.s2Appendix 2.https://evaaagaard1206.wixsite.com/website).Curriculum Project Rubric (10.29024/aogh.19.s3Appendix 3.https://evaaagaard1206.wixsite.com/website).HEALZ Project Snapshot Week 1 (