There is a paucity of long-term prospective disaster studies of the psychological sequelae among survivors.At 1½ and 25 years after the Spitak earthquake, 142 early adolescents from two cities were assessed: Gumri (moderate–severe exposure) and Spitak (very severe exposure). The Gumri group included treated and not-treated subjects, while the Spitak group included not-treated subjects. Instruments included: DSM-III-R PTSD-Reaction Index (PTSD-RI); DSM-5 PTSD-Checklist (PCL); Depression Self-Rating Scale (DSRS); and Center for Epidemiological Studies-Depression Scale (CES-D).p < 0.001) and DSRS scores (p < 0.001) compared to the Gumri-not-treated group. At 25 years, the Spitak group that had experienced fewer post-earthquake adversities (p < 0.03), had a greater decrease in PTSD-RI scores (p < 0.02), and lower CES-D scores (p < 0.01). (3) Before treatment, PTSD-RI and DSRS scores did not differ between the Gumri-treated and not-treated groups. At 25-years, the Gumri-treated group showed a greater decrease in PTSD-RI scores (p < 0.03), and lower mean PTSD-RI (p < 0.02), PCL (p < 0.02), and CES-D (p < 0.01) scores. (4) Predictors of PTSD symptom severity at 25-years included: home destruction, treatment, social support, post-earthquake adversities, and chronic medical illnesses.(1) Between 1½ and 25 years, PTSD rates and mean scores decreased significantly in the three groups (over 50%). However, at 25 years 9.1–22.4% met DSM-5 PTSD criteria. (2) At 1½ years, the Spitak group had higher PTSD-RI (Post-disaster PTSD and depressive symptoms can persist for decades. Trauma-focused treatment, alleviation of post-disaster adversities, improving the social ecology, and monitoring for chronic medical illnesses are essential components of recovery programs. The field of Disaster Psychiatry has become well-established and is anchored in numerous studies of the psychological sequelae among survivors of various types of natural and man-made disasters. The majority of disaster studies conducted among children and adolescent do not extend past 12 months , the intensity of the earthquake was rated X (‘Devastating’) on the Medvedev–Sponheuer–Karnik-64 (MSK-64) scale, with a death toll of 5000. In Gumri, located 16.8 miles from the epicenter (population 250 000), the intensity of the earthquake was rated IX (‘Destructive’), with a death toll of 17 000  and Spitak (N = 70) were evaluated for PTSD, depression, and separation anxiety disorder. Information on these subjects has been reported previously  had not received mental health treatment up to the time of the follow-up. In Spitak, 67 of the original 70 subjects were located and completed the study. None of these subjects had received mental health treatment since the earthquake. Two of the original group had died, and the third was lost to follow-up. The total number of participants in 2014 was 142 . The high rate of capturing subjects at follow-up was because many of the original participants had remained in the city they lived in at the time of the earthquake, were cooperative in helping to locate their peers from the original cohort, and were positive about participating.Data for the current study were collected in 2014, 25-years post-earthquake. Seventy-six of the original 94 participants from Gumri were located, with only one refused to participate. Three of the original group had died, and the rest were lost to follow-up. Of these 75 participants, 33 were among the group of 36 students who were provided treatment at 1½ years shortly after the baseline assessments. The rest , the study subjects were given a full description of the study, including potential risks and benefits. Written informed consent was obtained from all participants.The treatment provided at 1½ years post-earthquake, after the baseline data were collected, has been detailed previously , and unemployed. Education was dichotomized: ⩽high school (reference group), and >high school education. Marital status was dichotomized: married (reference group), and separated, divorced, single, widowed.Demographic information collected at 25 years  and 2 inUCLA Exposure Questionnaire was used , and severe damage beyond repair. Nuclear Family Deaths related to the earthquake was dichotomized as none (reference group), and ⩾1. Earthquake-related Serious Injuries  were dichotomized: none, mild (reference group), and ⩾1 serious injury. Subjective Experiences (i.e. scared during the earthquake), was rated on a 5-point scale: 0 = none, 1 = a little, 2 = moderate, 3 = a lot, and 4 = very much. These scores were dichotomized: none, a little, moderate (reference group), and a lot, very much. Exposure to Pre- and Post-Earthquake Traumatic Experiences  were dichotomized absent = none, mild (reference group), and present = moderate to extremely stressful.City-wide official measures of exposure included the intensity of the earthquake and the death toll attributed to the earthquake. At 25-year follow-up the Post-earthquake Adversities were derived by comparing post-earthquake to pre-earthquake conditions . Responses were dichotomized into no difference, better (reference group), and worse. Change of Socioeconomic Status (SES) for the 10 years post-earthquake compared to pre-earthquake was dichotomized: no difference, better (reference group), and worse. Post-earthquake Chronic Illnesses were self-reported based on the information provided to the subjects at the polyclinics where they were enrolled. The illnesses included hypertension, myocardial infarction, stroke, asthma, and other respiratory illnesses, autoimmune illnesses, chronic genitourinary and digestive tract disease, diabetes, arthritis, musculoskeletal disorders, migraine, and cancer. The total number of illnesses (range: 0–13) for each participant was used for the analysis. Perceived Current Social Support by family and friends was assessed using the Duke-UNC Functional Social Support Questionnaire  and at 25 years. Psychometric properties of the instrument have been reported elsewhere  based on DSM-5 criteria  designed for use in children and adolescents  were conducted with two-tailed significance (p ⩽ 0.05). Post-hoc analyses were conducted using Tukey's HSD, and Scheffe's as well as Tamhane's T2 where issues of heterogeneity were present.Data were analyzed using Statistical Package for the Social Sciences (SPSS) software (Version 22). Significance was calculated at Home Destruction, Subjective Experience (scared during the earthquake), Socioeconomic Status, Lifetime Traumatic Events, and Post-earthquake Adversities, were dichotomized for use as dummy variables in the multiple regression analyses instead of creating dummy variables for each ordinal category which would have proliferated the variables in the models given and reduced the already limited sample sizes. Numerical variables, including Nuclear Family Death(s) and Serious Injuries, were also dichotomized due to the severely restricted range, as there were only a few subjects with multiple deaths and serious injuries. It was deemed more important to explore differences in qualitative dimensions (e.g. deaths v. no deaths) rather than highly skewed and limited continuous distributions.Different variables were dichotomized for different reasons. Ordinal variables, including Sex, Education, Home Destruction, Nuclear Family Deaths, Earthquake-related Serious Injury, Post-earthquake Adversities, Treatment after Baseline, Post-earthquake Traumatic Events, PTSD-RI, DSRS, and SAD scores at 1½ years, Post-earthquake Chronic Illnesses, and Current Social Support. Since the risks-based regression coefficients in the final stepwise model err on the high side, the full model results are also reported to provide parameter estimates of all variables considered.For this exploratory study, stepwise backward multiple regression analysis was used as it is more inclusive and allows variables that are marginally significant individually but work synergistically as a set, to be explored with the targeted dependent variables. The pre-, peri-, and post-earthquake variables were explored as potential predictors of PTSD-RI, PCL, and CES-D scores at 25 years. Limited sample size precluded assessing all variables of interest in the same model. The variables used included: Regarding missing subjects at 25-year follow-up, comparisons of the 1½ year data across the two key outcome variables, PTSD-RI and DSRS scores for those who did not participate in the 25-year follow-up with the data for those who completed the 25-year study yielded no significant differences. This was the case for the Gumri groups combined and the Spitak group, the Gumri-treated and Gumri-not-treated groups, and the Gumri-not-treated and Spitak-not-treated groups. The lack of significant differences at any level supported the decision to drop the missing subjects from the analyses.The data were checked for completeness. At the 25-year follow-up, there were no missing data. For outcome questionnaires at 1½ years, those missing <10% of the responses, mean values were added in place of the missing data. For those with ⩾10% missing values, the subject questionnaire was excluded from the analysis. For the 1½ year study, a total of six participants had ⩾10% missing data. Four of the six participants had their DSRS and SAD responses excluded. Of the other two, one's DSRS, and another's SAD were excluded.Home Destruction, Earthquake-related Serious Injuries, and Post-earthquake Adversities.2 = 9.94, p < 0.002), and the Gumri-not-treated group .p < 0.05). At 25 years, the rate was higher for the Spitak group (28.3%) compared to the Gumri-not-treated group (14.3%), but the difference was not significant (p < 0.09). Likewise, at 25 years, there was no significant difference between DSM-5 PCL-based PTSD rates.Between-group comparisons of PTSD-RI-based PTSD rates at 1½ years showed a significantly higher rate for Spitak  was significantly higher than that of the Gumri-not-treated group  . However, at 25 years, the mean PTSD-RI scores did not differ significantly between the two groups: Spitak-not-treated group  v. Gumri-not-treated group  . The mean delta PTSD-RI score for the Spitak-not-treated group  was significantly greater than for the Gumri-not-treated group  . At 25 years, there was no significant difference between the mean DSM-5 PCL score for the Spitak-not-treated group and the Gumri-not-treated group . However, at 25 years, the pattern reversed, where the mean CES-D score was less for the Spitak-not-treated group compared to the Gumi-not-treated group (p < 0.01).v. 38 years respectively). While age was statistically significant between the two Gumri groups, the difference was minimal, and during the initial analyses, age consistently failed to be a significant covariate. Thus, to preserve degrees of freedom, age was not included in subsequent analyses as a covariate.2 = 4.22, p < 0.04), and the Gumri-not-treated group: 35.7% to 14.3% . Between-group comparison of PTSD, rates did not differ significantly at 1½ and 25-years post-earthquake.M = 44.0, s.d. = 9.9) and the Gumri-not-treated group  . However, at 25 years, the mean PTSD-RI score of the Gumri-treated group  was significantly lower than the Gumri-not-treated group  . Within-group by time (between 1½ and 25 years) comparisons of PTSD-RI scores showed a significant decrease (p < 0.001) for both groups. The mean delta PTSD-RI score of the Gumri-treated group  was significantly greater than the mean delta score for the Gumri-not-treated group  . Also, at 25 years, mean DSM-5 PCL score was less for the Gumri-treated group compared to the Gumri-not-treated group  ( < 0.02) .v. 20.7; p < 0.01). At 25 years, the mean DSM-5 PCL score was lower for the Gumri-treated group compared to the Gumri-not-treated group .R2 = 36%); (2) for PCL scores at 25 years, higher social support scores and treatment were also predictive of lower PCL scores, while higher number of chronic illnesses and worsening adversities were predictive of higher PCL scores (R2 = 33%); and (3) for CES-D scores at 25 years, higher social support was predictive of lower depression, while home destruction, worsening adversities, higher number of chronic illnesses, higher SAD symptom count at 1½ years were predictive of higher CES-D score (R2 = 40%).To our knowledge, this is the first long-term (past 5 years) prospective study examining the 25-year status of PTSD and depressive symptoms, risk and protective factors, and treatment outcome among adults who experienced a catastrophic earthquake as early adolescents. This study culminates a 30-year series of initial and follow-up studies among children, adolescents, adults, and older adults emanating from a major post-disaster mental health outreach, recovery, and research program implemented in the aftermath of the catastrophic 1988 Spitak earthquake in Armenia. The clinical findings of importance include the chronicity of PTSD and depressive symptoms 25 years after the disaster among a substantial portion of the exposed population, and the suggested long-term benefits of trauma-focused therapy for early adolescents. Of note, the school-based intervention used at 1½ years post-earthquake was a precursor of the UCLA Trauma Psychiatry Program trauma/grief intervention that has evolved into Trauma and Grief Component Therapy for Adolescents . The regression analysis indicated that adversities were risk factors for both the PCL and PTSD-RI scores. The post-earthquake adversities were significantly less for the Spitak group (p < 0.03). This was consistent with citywide faster recovery in Spitak (e.g. more reconstruction), with lower rates of poverty (36% Spitak v. 44% Gumri), and lower unemployment (37% Spitak v. 47% Gumri) , morbidity , and home destruction . At 25-year follow-up, rates of PTSD and mean severity scores subsided significantly in both groups, with the Spitak group manifesting a greater decrease in PTSD-RI scores  compared to those who were adults at the time of exposure  (p < 0.01 for both cites) suggesting that adolescents may be more vulnerable than adults to developing chronic PTSD symptoms and should be prioritized for early risk screening and treatment. The age effect of trauma on long-term sequelae needs further investigation.The differential effect of trauma on adults p < 0.03), the mean CES-D score was lower than that of Gumri-not-treated group. Similar to PTSD, fewer adversities experienced and the more favorable recovery environment, including more rebuilding, employment, and less poverty in Spitak may have contributed to the faster recovery of depression symptoms.Regarding depression, at 1½-years, the DSRS score for the Spitak-not-treated group was significantly higher compared to the Gumri-not-treated group. However, at 25-years these scores were reversed. For the Spitak-not-treated group, with fewer post-earthquake adversities (v. 16%). The treatment effect was consistent with the regression analyses showing that treatment at baseline was predictive of lower PTSD symptom severity at follow-up.At 1½ years, there were no significant differences in pre-, peri-, and post-earthquake variables, including PTSD-RI severity scores and PTSD rates between the Gumri-treated and Gumri-not-treated groups. A treatment effect was evident at 25-years post-earthquake, with the mean PTSD-RI and PCL scores for the Gumri-treated group being significantly lower than the Gumri-not-treated group. PTSD-RI scores had decreased in both groups at follow-up; however, the decrease was significantly greater for the Gumri-treated group , and two protective factors  contributing to the variance in PTSD-RI, PCL, and CES-D scores at 25 years. The present findings extend shorter-term findings after disasters, indicating that adversities constitute a risk factor in adults for PTSD  indicating pleiotropy (shared genetic vulnerability) (Goenjian et al., SAD symptoms at baseline also predicted depression at 25 years. Many of the early adolescents in the aftermath of the earthquake were fearful of something bad happening again or to their caretakers and avoided separation from them by refusing to go to school (Goenjian et al., Strengths of the study included the extensive long-term follow-up of exposed preadolescents with 87% of the original cohort retrieved at follow-up, exposure of all of the subjects to the trauma contemporaneously, and the inclusion of treated and not-treated subjects. Additionally, we used the same instrument, the DSM-III-R based PTSD-RI scale, to measure symptom severity at 1½ and 25-year follow-up to reduce discrepancies introduced by using different measures at different time points. Finally, we used the PCL to estimate current rates of PTSD based on DSM-5 criteria.The response to some of the questions dating back 25 years, such as the distress experienced during the earthquake and post-earthquake adversities may have been subject to recall bias. Given that children were not randomly assigned to treatment, confidence in the outcome findings must be qualified in that there may have been unknown differences in the comparison groups.Despite the decline, a sub-group of the population in both cities continued to experience substantial levels of PTSD and depressive symptoms. This represents a public mental health problem for the region. In addressing chronic cases, mental health programs should include ongoing surveillance for PTSD and depression, as well as the post-earthquake onset of traumatic experiences. Public health programs should also strive to mitigate ongoing post-disaster adversities.The association of persistent PTSD and depression with chronic medical illnesses point to the need for targeted outreach services across physical and behavioral health systems. Finally, the enduring impact of treatment provided at 1½ years post-earthquake reinforces the benefit of implementing school-based trauma-grief focused interventions that may benefit a generation of adolescents as they transition to adulthood.


BET: 1009.94 m2/g, pore size <2.21 nm). Then PEIs@TA-CMS was employed as nimodipine (NMP) carrier and compared with the drug carry ability of MCM41. After drug loading, NMP was effectively transformed from the crystalline state to an amorphous state due to the space confinement in mesopores. As expected, PEIs@TA-CMS had superiority in both drug loading and drug release compared to MCM41. It could incorporate NMP with high efficiency, and the dissolution-promoting effect of PEIs@TA-CMS was more obvious because of the unique interconnected curved pore channels. Meanwhile, PEIs@TA-CMS could significantly improve the oral adsorption of NMP to a satisfactory level, which showed approximately 3.26-fold higher in bioavailability, and could effectively prolong the survival time of mice on cerebral anoxia from 10.98 to 17.33 min.The aim of this study was to build up a novel chiral mesoporous silica called PEIs@TA-CMS through a facile biomimetic strategy and to explore its potential to serve as a drug carrier for improving the delivery efficiency of poorly water-soluble drug. PEIs@TA-CMS was synthesized by using a chiral crystalline complex associated of tartaric acid and polyethyleneimine (PEIs) as templates, scaffolds and catalysts. The structural features including morphology, size, pore structure and texture properties were systematacially studied. The results showed that PEIs@TA-CMS was monodispersed spherical nanoparticles in a uniformed diameter of 120–130 nm with well-developed pore structure (S The structural features of PEIs@TA-CMS were characterized by using Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), transmission electron microscope (TEM), and nitrogen adsorption and desorption tests. In order to improve the drug dissolution and oral bioavailability, NMP was selected as the model drug and was incorporated into PEIs@TA-CMS according to the organic solvent drying method. FTIR, differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) analysis were conducted to confirm the physicochemical properties of samples before and after drug loading. The drug loading amount and 2.2.1.Tetraethoxysilane (TEOS) was obtained from Aladdin . Linear polyethyleneimines and L-tartaric acid (L-TA) was provided by Chengdu Xiya Chemical Technology Co., Ltd. . Nimodipine was obtained from Wuhan Fungzhilin Chemical Co., Ltd. . MCM41  was purchased from Suzhou Jiedi Nano Technology Co., Ltd., . Double deionized water was prepared by using ion exchange method. All other chemicals were of reagent grade and used without any further purification.2.2.As described in 2.3.For the first time, a new type of chiral mesoporous silica named as PEIs@TA-CMS was synthesized by using the chiral crystalline complex PEIs@TA formed from chiral tartaric acid and PEIs as catalysts, scaffolds and templates. In a typical run, the obtained PEIs@TA was dispersed into 30 mL deionized water under vigorous stirring. After that, 6 mL TEOS was immediately added to the system, stirred continuously for 24 h, and statically treated for another 24 h. The product was collected by centrifugation, washed by ethanol and water for several times, and dried thoroughly. Finally, the dried sample was exposed to thermal treatment at 550 °C for 6 h with a slow heating rate to get PEIs@TA-CMS.2.4.−1. KBr pellet method was used in this study; samples were carefully mixed with dried KBr and were compressed into tablets before analyzing.To confirm the successful synthesis of PEIs@TA and PEIs@TA-CMS, FTIR study was carried out by Spectrum 1000 spectrometer  over the spectral region of 400–4000 cmThe morphology and mesoscopic structure of PEIs@TA-CMS and MCM41 was observed using a TEM instrument  and a SEM instrument . The TEM samples were prepared by dispersing the sample in ethanol through sonication. Subsequently, one drop of the solution was deposited on a carbon-copper grid and the sample was dried for 10 min under an infrared lamp. Before the SEM examination, samples were attached on the double side adhesive carbon tape, and then gold-coated under vacuum condition. Meanwhile, the particle size distributions were accounted according to the SEM images  The size distribution was further studied using a Zeta-Potential/Particle Sizer  and the value was the average of three consecutive measurements.BET) of the sample was calculated on the base of the Brunauer–Emmett–Teller (BET) method, while the pore volume and pore size distribution were acquired by using the Barrett–Joyner–Halenda (BJH) method derived from the desorption branches of the isotherms.Nitrogen desorption/adsorption tests were performed on a V-Sorb 2800 P adsorption analyzer  to give information on the texture properties and pore structure of PEIs@TA-CMS and MCM41. Prior to the testing, the sample was degassed at 120 °C for at least 6 h. The specific surface area (S2.5.The poorly water-soluble drug nimodipine (classified as BCS II) was selected as a model drug, and was loaded into PEIs@TA-CMS according to solvent deposition method, which had been proved to effective method for the preparation of drug loaded samples. This method involves two stages, including an initial adsorption equilibrium step and a solvent evaporation step. The high-concentration NMP ethanol solution was prepared by dissolving 20 mg of NMP into 2 mL ethanol. A series of NMP loaded PEIs@TA-CMS samples (NMP/PEIs@TA-CMSs) was achieved by adding PEIs@TA-CMS to the ethanol solution of NMP at the drug: carrier ratio of 1:1, 1:2 and 1:3 (w/w), respectively. Then the system was sealed and stirred for 24 h to assure the maximum drug loading and dried under vacuum to remove the organic solvent. Afterwards, NMP/PEIs@TA-CMSs was washed using a small volume of ethanol (2 mL) to remove the drug adsorbed on the surface of carrier, and thoroughly dried subsequently. Samples were named as NMP/PEIs@TA-CMS (1:1), NMP/PEIs@TA-CMS (1:2) and NMP/PEIs@TA-CMS, respectively. NMP/MCM41 sample was acquired by the same method at the drug/carrier ratio of 1:3 (w/w). Meanwhile, physical mixtures of NMP with PEIs@TA-CMS and MCM41 were prepared through a simple mixing process of drug and carriers  and regarded as references.To measure the drug loading content, an accurately weighed quantity of NMP/PEIs@TA-CMSs was dispersed in 100 mL ethanol, and extracted completely under ultrasound. After passing through the 0.22 μm polytetrafluoroethylene (PTFE) membrane filter, the drug concentration was determined by ultraviolet (UV) spectroscopy  at a wavelength of 238 nm.2.6.−1. Moreover, XRD measurement was carried out on an X-ray diffractometer  to analyze the typical changes in physical state of samples before and after NMP loading. The data was scanned at the diffraction angle range of 5° to 40° (2θ) with a scanning speed of 0.05°. DSC test of NMP, carriers, physical mixtures, and drug loaded samples was conducted on a thermal analyzer  by heating samples from 25 to 200 °C under a N2 flow at the step of 10 °C/min.To analyze the interactions between drug and carrier, FTIR study of NMP, PEIs@TA-CMS, MCM41, physical mixtures, NMP/PEIs@TA-CMS and NMP/MCM41 was carried out by Spectrum 1000 spectrometer  over the spectral region of 400–4000 cm2.7.in vitro release behavior of samples was assessed by a USP II paddle method on a dissolution apparatus . Prewarmed medium of 0.5% (w/v) sodium dodecyl sulfate (SDS) solution  was added to the dissolution cup with a stirrer rotation speed of 50 rpm. 10 mg NMP, NMP/MCM41 and NMP/PEIs@TA-CMSs samples containing 10 mg of NMP were suspended in the release medium. 5 mL of aliquots were collected and replaced by an equal volume of fresh isothermal supplement at predetermined time intervals, After filtering through a 0.22 μm membrane filter, the drug release amounts were tested by UV spectroscopy  at 238 nm. All in vitro release studies were repeated three times.The 2.8.Animal experiments were approved by the Institutional Animal Care and Use Committee at China Medical University. All rats were maintained complied with guidelines for the Care and Use of Laboratory.n = 4): NMP group, NMP/PEIs@TA-CMS group and NMP/MCM41 group. Prior to the experiment, animals were fasted overnight with free access to water. The animals were orally administered the water suspensions of NMP, NMP/PEIs@TA-CMS and NMP/MCM4 with a drug dose of 2.5 mg. At appropriate sampling times, aliquot blood sample (about 0.6 mL) was withdrawn via the retro-orbital venous sinus, centrifuged to separate the plasma, and stored at −20 °C.Twelve male Sprague-Dawley rats  were randomly divided into three groups  method. The separation procedure was performed on a Kromasil ODS-2C18 column  equipped with a JanuSep C18 pre-column , and the column temperature was kept at 25 °C. The UV detector was set at 240 nm. The mixture of methanol, acetonitrile and water  was selected as the optimized mobile phase with a flow rate of 1 mL/min. The NMP content was calculated according to internal standard method, and the main pharmacokinetic parameters were obtained using the software of DAS 2.0.In the pretreatment procedure, 20 μL of internal standard solution  was added into 200 μL plasma sample and vortexed for 1 min. Afterwards, 100 μL NaOH (0.01 mol/L) was uniformly mixed with the system and vortexed for 1 min. The drug was extracted by 2.5 mL diethyl ether, vortexed for 5 min, and centrifugated for 12 min to separate the organic layer (2 mL). The organic layer (2 mL) was then transferred to a new tube and evaporated to dryness under a gentle stream of N2.9.n = 6): Normal saline group, NMP group, NMP/PEIs@TA-CMS (low dose) group, NMP/PEIs@TA-CMS (middle dose) group, NMP/PEIs@TA-CMS (high dose) group and NMP/MCM41 group. Before dosing, animals were fasted overnight with free access to water. Animals in the Normal Saline group were received oral treatment of 0.5 mL normal saline, and were considered as negative control. While for NMP group which severed as positive control, 0.5 mg pure NMP was suspended in 0.5 mL normal saline and was imposed to animals. Normal saline suspensions of NMP/PEIs@TA-CMS and NMP/MCM41 containing 0.5 mg NMP were also oral administrated to mice. Meanwhile, half and twice of the dose in NMP/PEIs@TA-CMS (middle dose) group, which were respectively in doses equivalent to 0.25 mg and 1 mg NMP, were given to mice to further study the influence of dose. To make sure that NMP had been circulated in the body to exert an effect on cerebral vasospasm, the cerebral anoxia of mice was established by intraperitoneal injection of NaNO2  90 min post oral administration. Then the clinic manifestation and survival time of mice was recorded to study the protective effect of NMP formulations on mice cerebral anoxia.The pharmacodynamics study was performed to further evaluating the effect of PEIs@TA-CMS on improving the oral adsorption of NMP. 36 SPF-grade Kunming mice (18–22 g body weight) were assigned into six groups, randomly  could be obtained by cooling the mixture to induce crystallization, and then functioned as templates to direct the structure of PEIs@TA-CMS. It should be mentioned that, the synergistic effect from the association of carboxyl groups with amine groups was reported to facilitate the silica condensation , indicating the connection of PEIs with L-tartaric acid. After silica deposition, PEIs@TA-CMS were successfully build up evidenced by characteristic absorption of MSNs, including the antisymmetric stretching vibration of Si–OH at 3452.1 cm−1, antisymmetric stretching vibration of Si–O–Si at 1080.3 cm−1, symmetric stretching vibration of Si–O–Si at 801.9 cm−1, and the bending vibration of Si–O–Si at 464.0 cm−1  was also employed as drug carrier and regard as a reference. It was well-formed spherical nanoparticles with a diameter of 240–260 nm see . As disp2/g .3.3.2 nitrogen adsorption–desorption, the texture parameters  of NMP/PEIs@TA-CMS and NMP/MCM41 were decrease sharply to lower values , mostly reasoned by the poorly water solubility. To solve this problem, NMP was incorporated into PEIs@TA-CMS by the solvent deposition method. As indicated by the Nr values . It provThe drug loading content was determined by UV-vis analysis, and the results were summarized in 3.4.−1 corresponded to the stretching vibration of the –NH group, band at 1694.9 cm−1 relative to the stretching vibration of carbonyl group, band at 1523.2 cm−1 refer to the –NO2 stretching, and band at 1308.8 cm−1 relative to the C–N stretching vibration , 1084.6 cm−1 (Si–O–Si antisymmetric stretching vibration), 801.7 cm−1 (Si–O–Si antisymmetric stretching vibration) and 465.3 cm−1 (Si–O–Si bending vibration) , suggesting the absence of chemical interactions or non-covalent weak transitions. After drug loading, both NMP/PEIs@TA-CMS and NMP/MCM41 presented characteristic adsorption of the silica carriers with the disappearance of most of the NMP bands, demonstrating the successful loading of NMP into the nanospace in silica carriers.As presented in 3.5.θ range of 15.8°, 17.9°, 20.1°, 20.7°, etc., while PEIs@TA-CMS and MCM41 showed broad bands between the 2θ range of 5° and 40°, suggested that they were kinds of amorphous materials. Observably, The XRD patterns exhibited very different diffractograms between drug loaded samples and physical mixtures. When drug molecules were physically mixed with PEIs@TA-CMS or MCM41, the crystallization diffraction peaks of the drug were still remained  with reduction of intensity. After completion of the drug loading, the XRD patterns of NMP/PEIs@TA-CMS and NMP/MCM41 showed the absence of distinctive peaks. Instead of existing in the original crystalline state, NMP loaded into PEIs@TA-CMS underwent an amorphization process, because the nanopores of mesoporous materials prevented the drug in the noncrystalline state by space confinement.The XRD analysis of the drug loaded samples was used to determine the transformation of the crystalline state. As collected in The crystalline properties were also evaluated by DSC test, in which the melting point is a standard mean to determine the present of crystals. The characteristic melting peaks of pure NMP were observed at 114.4 °C, which was in accordance with the intrinsic melting point . NMP/PEIs@TA-CMS could release 70.03% of NMP within 240 min, while NMP/MCM41 could release 53.6% within 240 min. To be specific, the drug release amount of NMP/PEIs@TA-CMS and NMP/MCM41 reached 57.31% and 38.42% within 60 min, which was respectively 1.83-fold higher and 1.31-fold higher than pure NMP. The improvement in drug release was the combined effect of at least two factors: the limitation of drug size and the amorphization of drug molecules  of 0.10 μg/mL. Double peaks appeared at 0.5 h (Tmax) and 8 h post administration, strongly suggested the existence of enterohepatic circulation. Compared to pure NMP, NMP/MCM41 and NMP/PEIs@TA-CMS showed clear differences in the shape of the curves, in which only one main peak was found in each curve, and the Tmax reached later. For both drug loaded samples, the plasma concentration of NMP gradually increased up to the maximum concentration at 4 h (Tmax), and then the value started to decline. The Cmax values were raised to 0.35 μg/mL and 0.26 μg/mL for NMP/PEIs@TA-CMS and NMP/MCM41, which were 3.68-fold and 2.72-fold higher than that of pure NMP, respectively. Furthermore, as shown in in vivo.To evaluate the performance of PEIs@TA-CMS on promoting the drug absorption, Cmax then NMP/MCM41, in vitro release results. In vivo pharmacodynamics study illustrated that PEIs@TA-CMS exhibited great potential for release and delivery of NMP.Among them, the PEIs@TA-CMS presented beneficial oral absorption with higher bioavailability and higher maximum drug concentration  was intraperitoneal injected to induce cerebral anoxia. As indicated in 2 was found to be 10.98 min, suggesting the successfully establishment of mice cerebral anoxia model. In NMP group, the administration of NMP motivated the oxygen utilization coefficient and enabled the oxygen supply in blood, and the survival time of mice was prolonged to 14.33 min. Besides, owing to the enhanced bioavailability, the survival period of NMP/PEIs@TA-CMS (middle dose) and NMP/MCM41 underwent a further prolongation to 17.33 min and 15.26 min. Compared to NMP and NMP/MCM41, NMP/PEIs@TA-CMS was found to be more powerful in treatment of cerebral anoxia under the same dose. The order of survival time was NMP/PEIs@TA-CMS (middle dose) > NMP/MCM41 > pure NMP, which was in accord with the order of bioavailability. Moreover, with the aim of exploring the effect of dose, mice in NMP/PEIs@TA-CMS (low dose) group and NMP/PEIs@TA-CMS (high dose) group were orally administered half and twice of the dose in NMP/PEIs@TA-CMS (middle dose) group, respectively. The results revealed that NMP/PEIs@TA-CMS also significantly and dose-dependently postponed the coming of death to 14.34 min and 18.83 min, respectively. All these results provided adequate evidence and convincing confirmed the superior of PEIs@TA-CMS in improving the oral adsorption of poorly water-soluble.As a dihydropyridine calcium channel blocker, NMP was globally used to treat resultant ischemia and cerebral vasospasm. To further probe the function of NMP/PEIs@TA-CMS and NMP/MCM41, pharmacodynamics study was carried out. In this experiment, NMP, NMP/PEIs@TA-CMS (middle dose) and NMP/MCM41 were administered orally to animals at the dose of 0.5 mg; 0.4 mL NaNO4.The present study reported a novel drug delivery system established by PEIs@TA-CMS with chiral structure and sphere appearance. For the first time, chiral mesoporous silica nanoparticle named PEIs@TA-CMS was developed through a facile and controllable strategy by using a chiral crystalline complex as templates, scaffolds and catalysts. PEIs@TA-CMS was well-formed spherical nanoparticles in a uniformed diameter of 120–130 nm with curved nanopores. Then crystal NMP was effectively loaded into PEIs@TA-CMS and transformed to an amorphous state due to the space confinement. After that, both the drug release rate and amount was significantly improved, and best result came from NMP/PEIs@TA-CMS sample (at drug: carrier weight ratio of 1:3), in which 70.03% of NMP could release within 240 min. Notably, PEIs@TA-CMS was a drug delivery platform to realize the efficiency delivery of NMP with satisfactory relative bioavailability (up to 326.2%) and pharmacodynamics effects. Compared to MCM41, it had superiority in improving the oral adsorption of poorly water-soluble drug to a satisfactory level. Undoubtedly this study will be of great significant in the rational and flexible design of drug carriers.


My Strengths Training for Life™ (MST4Life™) is a positive youth development program for improving wellbeing and social inclusion in young people experiencing homelessness. MST4Life™ addresses a gap in strengths-based programs aimed at promoting healthy and optimal development in vulnerable older adolescents/emerging adults. The program was co-developed with a UK housing service as part of a long-term (>8 years) community–academic partnership. This mixed-methods study describes a key step in developing and evaluating the program: exploring its feasibility and acceptability with 15 homeless young people . Participants experienced 8 weekly sessions within their local community, followed by a 4-day/3-night residential outdoor adventure trip. In addition to their attendance records, the viewpoints of the participants and their support workers were obtained using diary rooms and focus groups. Feasibility was indicated via the themes of attendance, engagement, and reaction. The findings suggested that young people enjoyed and perceived a need for the program, that they considered the program and its evaluation methods to be acceptable, and that both the community-based and outdoor adventure residential phases could be implemented as planned. Minor modifications are needed to recruitment strategies before it is more widely rolled out and evaluated. Homelessness is a global public health problem that comes with high social and economic costs for many communities ,2. It isPast research highlights the need for interventions that enable young people to develop their strengths while also acquiring skills to manage their emotions and build positive relationships ,7. StrenInspired by the mental skills training interventions that are typically used in sports settings , the MyIn sport, a mental skill is defined as a regulatory capacity to maintain or develop a psychological outcome . Many oMST4Life™ is an experiential and strengths-based psychoeducational program intended to promote the use of mental skills in young people, to enable them to build resilience by better self-regulating their thoughts, feelings, and behaviors, and transferring the use of these skills to other life domains . The long-term outcomes of participating in the program are predicted to be: (a) reducing the likelihood that a young person will present as homeless; (b) improving mental, social, and physical health over the course of their life; and (c) lowering rates of mental illness and mortality .In adopting a strengths-based approach, MST4Life™ capitalizes upon positive youth development  as the As a means of facilitating positive relationships between facilitators and young people, MST4Life™ is additionally framed by self-determination theory ; a theoMST4Life™ was iteratively developed, delivered, and evaluated through action research cycles . This stThe present study is part of a large community-based participatory research (CPBR) project . As MST4Recruitment to pilot the MST4Life™ program was carried out by two support workers, who approached young people directly and invited them to take part. The support workers also encouraged young people’s participation throughout the program by reminding them about sessions and arranging transportation when needed. Young people were invited to participate in the pilot MST4Life™ program if they: (a) were experiencing homelessness; (b) lived in one of the housing services’ long-term supported accommodation sites ; and (c) were referred by their support worker due to their limited engagement with education, employment, or training opportunities  and/or perceived lack of mental skills .The pilot MST4Life™ program was delivered face-to-face to participants in groups over two phases: (1) 8 weekly sessions of 1.5 to 4 h in length (April–June 2014); and (2) a short (4-day/3-night) residential course at an outdoor pursuits center in the Lake District, UK (September 2014). A residential course is defined as one when participants stay in a residence during the course; in this case, the outdoor pursuits center provided participants with accommodation . The first phase (community-based) targeted the initial development of both existing and new mental skills  .The weekly sessions in this phase were jointly led by two researchers with experience in delivering either mental skills training programs in sports settings or experiential learning in outdoor pursuits settings. Facilitators focused on promoting a relaxed and needs-supportive environment aligned with SDT . Young pThe second phase of MST4Life™ was a residential trip to the University of Birmingham’s outdoor adventure center. This center, located in the Lake District, UK, was chosen owing to its connections with the university and the broad range of facilities offered. Its location was crucial to the undertaking of Phase 2; this trip away from the young people’s normal urban environment aimed to promote and further develop their mental skills in a novel, fun, and challenging setting for the transfer of learning . The actThe young people who took part in the pilot MST4Life™ program received no external incentive for their involvement in the program or its evaluation. However, refreshments were provided during sessions.The feasibility study followed a non-randomized design consisting of a single group of participants at two different intervention sites in Phase 1 and a combined group in Phase 2 at a single intervention site. In Phase 1, data was collected both during and six weeks after the program finished; in Phase 2, data were collected on the first three days . For theTwo different sites were chosen by the housing service to host the pilot MST4Life™ program because they accommodate and support the highest number of young people classified as NEET and those with the most complex needs, thereby providing a realistic test of whether it was possible to engage young people experiencing homelessness with MST4Life™ in this setting. Young people were permitted to join the program after it had begun.Data for the study was obtained via attendance records and qualitative methods during and after each phase of MST4Life™ .A semi-structured video diary room was employed to gain reflections from the young people. A semi-structured diary room can aid participants’ learning as a self-reflection tool. The diary room provided participants with a private yet engaging means to reflect and give feedback on the MST4Life™ program content and delivery . The appMost participants provided individual video-recorded entries, but they could also do so in pairs and/or audio-record if they felt more comfortable with that. Entries were recorded using a Canon 60D camera, with questions provided on cards. In Phase 1, young people were invited to give diary-room entries at two time points . Four young people volunteered to participate (44.44%), with reasons for non-participation being due to non-attendance at the session where the diary room was present, or young people expressing that they were not comfortable with having their views recorded. During the residential trip in Phase 2, the diary room was more readily available  and was participated in by 9 young people (90%). Diary-room entries ranged from 1 min 26 s to 10 min 49 s (Mean = 4 min 49 s).Three focus groups were held 6 weeks after Phase 1 of MST4Life™, with separate discussions for young people  and support workers (2 participants). The semi-structured topic guide was phrased in the form of open questions, allowing for both positive and negative experiences to be discussed, and participants were encouraged to be as honest as possible. The facilitator also welcomed negative feedback about the program and explained that it was an opportunity for the young people to influence its future improvement. The focus groups lasted an average of 46.33 min and were audio-recorded and transcribed verbatim.We (the researchers) locate the overall MST4Life™ project within a pragmatist paradigm, with explicit reference to Dewey’s  philosopAnalysis of the verbatim transcripts stemming from diary-room entries and focus group discussions was conducted using NVivo (Version 10.2) and followed the six-phase process outlined by Clarke et al.  for inteWithin Deweyan pragmatism, a broad view of credibility is adopted that extends beyond methodological rigor to emphasize the role of reflection in gaining a new understanding of beliefs, problems, and prior knowledge . In thisTarget recruitment size was between 6 and 12 participants per group, so as to be maximally engaging for young people. Of the 78 potential participants living at the two supported accommodation sites, 15 people  enrolled in at least one intervention phase , representing a reach of 19.2% of potential participants. Due to the dynamic nature of supported accommodation, four young people had successfully moved into independent accommodation by Phase 2 and were either unable to attend the residential course due to new education, employment, and training (EET) commitments or were no longer in contact with their support worker. For this reason, an additional 6 participants were recruited for Phase 2. At the time of their participation, the young people had lived in supported accommodation for an average of 1.6 years (SD = 1.0) and 67% were NEET. Participants were of various ethnicities and 27% spoke English as a second language .A high level of commitment was required from the support staff during recruitment and throughout the program to support attendance. Young people appreciated the role played by support workers in making them aware of the program. However, they believed that improvements could be made to the recruitment plan by advertising the program via posters, timetables, and leaflets. One young person believed that better advertising would lead to more young people taking part: “If they advertised it a lot more then people would attend. I reckon they would, man [believe they would]. You need to get the advertising across”.Young people displayed an initial reluctance to be involved in qualitative data collection, suggesting that more time was required to establish trust and rapport. The more confident young people gave short diary-room entries in Phase 1, and five participated in the focus group discussions that took place between phases. By Phase 2, nearly all participants had completed a diary-room entry, including those who had not participated in Phase 1. The young people appeared more relaxed and gave longer and more in-depth entries later in the program. The average diary-room entry was 2 min 36 s in Session 4 of Phase 1 (Mean = 26 s per question) and lengthened to 6 min 43 s by Day 3 of the residential course in Phase 2 (Mean = 45 s per question).Another notable feature was that the diary room served to encourage young people to engage in reflective learning and provided meaningful opportunities for developing communication skills. For example, one participant described how they would previously have been hesitant and unsure of what to say when being filmed, “Like, just me now speaking to the camera, before I know I would have been like, ‘if’ing’ and ‘er’ing’ [describing themselves as being unsure of what to say], don’t know what to say, this and that, but it’s become a lot better, I think”. On occasions, however, some of the young people found it hard to describe their experiences, with another participant saying, “I just feel some changes in me, I can’t really explain how I feel, it’s kind of hard as well, but I just feel something in me has changed, I don’t know what”.Young people’s pattern of attendance throughout the program indicated that one session per week over 8 weeks in Phase 1 and 4 days/3 nights of residential course in Phase 2 was appropriate, in terms of both structure and length. Of the 9 young people who participated in Phase 1, the attendance rate for each session was 75% see . All 10 The high level of attendance in Phase 1 for a weekly program was considered an important feature to the young people because it meant, as one young person put it, that “there was a lot of people you could, like, connect with and talk to”. Reasons for non-attendance included attending a job interview, visiting family in another city, and a dispute occurring between two members of the group outside of MST4Life™, which led to one participant declining further involvement beyond Week 7. The level of attendance was deemed highly successful by the support workers, who commented: “To have a program running for 8 weeks and have them engaged right the way through, you gotta [have to] be doing something right”. Indeed, young people expressed their willingness to engage with an even longer Phase 1 and/or repeated sessions to enable their further development. A young person explained: “It’s good when you do things more than once because you just feel greater and greater every time you do it”.Staff favorably compared attendance at MST4Life™ to other training courses offered by the housing service. A support worker explained: “They don’t turn up for nothing. Even a 2-week course they’d probably do half of the first week. But they’ve shown that they can be quite consistent [with MST4Life™]”. A staff member also described: “What was interesting was that the only incentive, right, was for their personal development”.As is mainly relevant in Phase 1, contextual features, such as the support workers and the location of the sessions, contributed to ongoing attendance. The support workers initially provided encouragement to the young people. They noticed, however, a decreased need to prompt young people to attend each session as the program progressed, indicating improved self-motivation through the program, with one explaining how they would initially have to knock on the door of each young person:At the start it was a constant—’bam, bam, bam’ [knock on the door], until it got to the stage where I would remind them [the day before] and give them a knock in the morning. Simple as that. Some of them I wouldn’t even have to, they’d be ready.”“The proximity of sessions to the young people’s accommodation was also considered to be vital for maximizing attendance in Phase 1. A young person described how convenient it was to attend sessions by saying: “We live in the same place … you’re not going to miss nothing innit [are you], so if you miss something then it’s your fault”. Similarly, possessing an initial level of confidence was also deemed important. A young person explained:They [young people] need the mentality and the confidence as well, like if you ain’t [are not] confident to do it [take part in MST4Life™] there’s no point, like, setting yourself up and looking like an idiot. So yeah, a lot of people need to be a little more confident when they are doing this.”“Engagement during sessions was evident by the young people having fun while still learning. A young person described how they felt drawn into MST4Life™ from the outset of the program and the enjoyment that they experienced during the sessions helped to maintain their engagement:Just from that one week it drawed [sic] me in anyway. It drawed me [describing themselves being attracted to the program] in for the rest of the weeks because I had a good time and it was fun. And I was learning as well as having fun. I loved it.”“Indeed, the participants would become engrossed in learning, with one young person saying that learning occurred “without even realizing it”. Others explained that during the sessions, they often didn’t “pay attention to the time length” of the sessions, and instead they focused on “just getting the job done”. A support worker explained how MST4Life™ “didn’t overdo the paperwork side of things, you tried to keep it as practical as possible, it kept them fully focused and engaged with what’s coming, ‘what’s next?’”. In turn, the participants appreciated the relaxed nature of the program; as one young person put it: “It’s not too pushy and it’s not too planned. So you just go with the flow. When there’s things that are planned, there’s not really that much fun”.When reflecting on their experiences, many of the young people expressed surprise at their initial low expectations of the program having been surpassed. They felt a sense of pride over what they had achieved. A young person explained how they had no preconceived expectations of how they would benefit from taking part: “We never actually thought we would gain nothing from the course. But as the course went through … we started to realize the changes … I’m just proud of it”. They did not want the program to end and expressed gratitude for having had the opportunity to take part. They also commented on how beneficial it would be for other young people. As another young person observed:Not a lot of people can do this [MST4Life™ program] but now maybe the way this group that we’ve got now can improve and get better and make doors open for other people that want to go on it.”“Similar positive reactions were additionally expressed for the approach taken by the facilitators. Few direct references were made to autonomy-supportive strategies  but young people conveyed acceptance of the structure . The interpersonal involvement provided by facilitators was also appealing; they were described by the young people as “upfront and straight”, “respectful and genuine”, “really friendly”, and “attentive and supportive”. It was evident that young people perceived themselves as having a great rapport with the facilitators. Examples of the positive feedback included statements such as “you’re doing a really good job for everyone” and “I love the staff”. The support staff also agreed: “The young people took to you guys very well”, which in part was due to the facilitators being young-person-led. One support worker explained:You’ve met them, met them on their terms… And if ever there was a week where someone felt they wasn’t [sic] feeling it this week you wasn’t in their head saying ‘Come on, come on!’… You were like ‘No problem, do what you’re doing’, and I think that worked for them.”“The aim of this study was to report on the feasibility of a PYD program for young people experiencing homelessness, MST4Life™, as determined by participant attendance, engagement, and reaction. Following the recommendations of Bowen et al.  and OrsmMST4Life™ addresses a gap in strengths-based psychoeducational programs aimed at promoting healthy and optimal development towards independence and adulthood in vulnerable older adolescents/emerging adults. The program was developed in collaboration with the staff and service users of the housing service. Together, we worked in partnership to identify the specific program goals and priorities, the nature of the activities, and the intended atmosphere of the program. It is likely that having this input from the outset contributed to the necessary “buy-in” from staff that led them to encourage young people to take part, thereby leading to those young people perceiving the content of the program to be enjoyable, relevant, and meaningful to them. In the future, the recruitment plan will combine this approach with other methods for advertising the program, based on the young people’s suggestions. That it was the young people who identified a need for better advertising reinforces the benefit of the collaborative approach in this study. In planned future collaborative research around MST4Life™, it will be possible to explore the ways in which essential stakeholder feedback can be integrated into the program.Aligning with the researchers’ methodological position of Dewey pragmatism, the program was refined through continual reflections on whether the data collection methods  were enabling the researchers to: (a) understand what made MST4Life™ acceptable and attractive to its participants; (b) test these assumptions with the stakeholders by including both staff and young people in the evaluation; and (c) be critical about what areas could be changed to improve program uptake and adherence. The results suggest that major changes to the evaluation model were not needed prior to larger-scale implementation; however, further improvements were planned. For example, alternative methods of collecting information at baseline were considered to accommodate young people who are not comfortable with being audio- or video-recorded . A reluctance to engage in qualitative research without first having established trust in and rapport with the researchers is consistent with findings from other studies ,45.Using questionnaires in the future may help to overcome problems with personal expression as part of a flexible strategy for data collection, thereby avoiding the exclusion of young people from the evaluation due to its methods and ensuring that the findings are more representative of the participants . AdoptinAttendance indicated feasibility within the present study and the 75% attendance in Phase 1 was favorably compared by staff from the supported housing service to other programs. Variation in attendance was previously noted as an issue in a review of interventions for homeless children and young people that were similarly aimed at promoting inclusion and reintegration . HoweverThe lack of external incentives in MST4Life™ indicated that attendance was intrinsically motivated. In contrast, staff reported lower uptake by young people in the present study to other initiatives that offered financial rewards for participation. Rotheram-Borus et al.  similarlThe finding of staff support as important for program uptake is consistent with PYD research. Newman et al.  found thTrust is related to the third factor affecting program uptake and attendance, namely, the characteristics of the young people. Introducing a new program into the supported accommodation site brought what staff described as a “fear factor” about what participation would involve. The program seemed to attract those individuals who had enough confidence and enthusiasm to overcome this initial fear: a finding that suggests baseline differences may exist between those who agree to participate in MST4Life™ and those who decline . In thisReflecting the dynamic nature of supported accommodation, only four out of 15 young people participated in both phases of the program. Rather than viewing this as a limitation, a pragmatic decision was made to use this unexpected opportunity to explore whether Phase 1 was a necessary pre-requisite for Phase 2 . FacilitExperiential learning, as the chosen pedagogical approach, was a key contributing factor to engagement in the program . In keepA rich array of positive reactions to the program was evident within the data, which suggested that MST4Life™ was both acceptable to the participants and fulfilling a need among young people in their situation. In line with the expressions of gratitude from young people in this study, it will be necessary to explore the ways in which the program could be scaled up and out, so that others may be offered access to the same potential benefits by involving key stakeholders of staff and young people in a process of collaborative knowledge translation research. This will be important not only in supporting young people more fully, in addition to “wrap-around” support, but also, crucially, in terms of supporting individuals to go on to lead independent adult lives beyond housing support.The main limitations of this study were the small sample size and the use of a cohort design rather than randomization into intervention vs. standard care/wait-list control groups. Two main reasons guided the design choice: (a) the co-produced nature of the program, and (b) the desire to test the intervention in the real world under the practical constraints of that setting . While tThis study has demonstrated the need within housing services for a strengths-based psychoeducation program that is community-informed and framed by a PYD approach. MST4Life™ uniquely extends the reach of mental skills training beyond a sport psychology context, to support young people who are homeless and moving toward education, employment, and training. It additionally meets the long-standing call for programs within this population to take a strengths-based approach, enabling young people experiencing homelessness to recognize and build upon their existing assets and resources, as opposed to focusing on their deficits and problems. Moreover, the content and delivery of this program are distinctive because of its explicit links to both psychological  and pedagogical  theories. That is, the program is designed to encourage young people to reflect upon and learn from the fun and meaningful experiences offered across the two phases of the program, in a way that facilitates their basic psychological needs for autonomy, competence, and relatedness as well as to transfer this learning to other life domains. By doing so, MST4Life™ offers the potential for a new model of intervention for services that support young people experiencing homelessness or those at risk. This study and the extant literature on MST4Life™ ,27,51,52


Mw ≥ 7.3) subduction earthquakes struck Central America within a period of 10 weeks; subsequently, some volcanoes in the region erupted a few days after, while others took months or even years to erupt. Here, we show that these three earthquakes contributed to the increase in the number of volcanic eruptions during the 7 years that followed these seismic events. We found that only those volcanoes that were already in a critical state of unrest eventually erupted, which indicates that the earthquakes only prompted the eruptions. Therefore, we recommend the permanent monitoring of active volcanoes to reveal which are more susceptible to culminate into eruption in the aftermath of the next large-magnitude earthquake hits a region.Understanding the relationship cause/effect between tectonic earthquakes and volcanic eruptions is a striking topic in Earth Sciences. Volcanoes erupt with variable reaction times as a consequence of the impact of seismic waves (i.e. dynamic stress) and changes in the stress field (i.e. static stress). In 2012, three large ( Based on this observation, he proposed the possibility of a relation between earthquakes and volcanic eruptions. Observed cases of volcanic eruptions supposedly caused by tectonic earthquakes have been reported in different tectonic settings. For example, the Plinian eruption of Mt. Fuji (an arc volcano situation on the Japanese subduction front), was preceded by a gigantic megathrust earthquake Mw = 8.7 (Hoei earthquake in 1707), 49 days before2. In the extension zone of Iceland occurred an increment in the volcanic eruptions after the earthquakes sequence of 1618 and 17893. In the case of a hot spot volcano, the Mw = 7.7 Kalapana earthquake (Hawaii) in 1975 promoted rift-zone intrusions in Kilauea volcano and unleashed the 1977 eruption4. Nonetheless, some research has examined this question from an opposite standpoint and focusses instead on how volcanic activity increases seismicity6.“Was the volcanic eruption triggered by the earthquake?” The answer to this question is usually “maybe” or “it could be a coincidence”. These ambiguous answers are due to the lack of observational data and/or clear scientific evidence relating these two processes. Darwin10. Other manifestations related to seismic events observed in volcanoes include variations in deformation rates12, degassing and heat flux15, and phreatic activity19.Alterations in volcanic activity are observed after an increase in seismicity at both short (< 100 km) and long (> 500 km) distances from the epicenter20. These reactions are assumed to be triggered by the dynamic stress caused by the seismic waves transmitted through the volcanic system16.Some studies suggest that volcanoes can react to a tectonic earthquake very quickly, in just a few hours or days23. These longer reaction times can be explained by (1) the co-seismic pressure change in the stress field around the volcano or in the magma system, known as static stress9 and/or in the case of giant megathrust earthquakes in convergent tectonic systems by (2) the viscoelastic relaxation of the mantle and its effect on the magmatic system. An example of these long reaction times is the increase in the number of eruptions per year in the Cascades (western North America), for over a century after the Mw = 9.0 giant earthquake that hit the region in 1700 AD7. Recently, studies have suggested that giant earthquakes can create subsidence, which instigates the horizontal movement of magma bodies and hydrothermal systems; an example of such a process would be the Mw = 8.8 Maule (Chile) and Mw = 9.0 Tohoku (Japan) earthquakes in 2010 and 2011, respectively12.Other studies discussed that volcanoes will tend to erupt in the medium-to-long term, that is, months, years or even decades after the earthquakes25.Yet, it is not clear why some volcanoes change their behavior after a tectonic earthquake, although the majority of them do not. Recent research has proposed that an earthquake alone is not enough to trigger an eruption, if the magmatic system is not ready to eruptMw = 7.3; September 5, Costa Rica, Mw = 7.6; November 7, Guatemala, Mw = 7.4) and how these earthquakes affected the state of unrest or eruption in the volcanoes of the region. Here, we conduct a statistical analysis (Monte Carlo approach26) and numerical modelling of the stress regime of selected volcanoes that erupted after this series of earthquakes and demonstrate that only those that were in a clear state of unrest before the arrival of the seismic waves actually ended up erupting.This study investigates the unique occurrence of three major earthquakes in Central America, generated by the subduction of the Cocos plate beneath the Caribbean plate, over a period of just 72 days in 2012 , Mw = 7.6 (September 5) and Mw = 7.4 (November 7) struck El Salvador, Costa Rica, and Guatemala, respectively, within a period of just 10 weeks  the number of eruptions and explosivity increased after these three earthquakes. Notably, the number of paroxysmal explosions in Fuego increased drastically after the 2012 earthquakes .Nevertheless, for the last two decades, the available data set for the region is complete because each country  has its own seismic and volcano observatory agencies and offices of Civil Protection. Seismic and volcanism programs and data-bases now exist globally, and social networks help to spread the news and other information exceedingly quickly. With this in mind, our study is anchored in 2012, the year in which three large earthquakes of magnitudes In the following years, other volcanoes increased their levels of unrest, which in some cases culminated in large volcanic eruptions . Some volcanoes, which passed through decades of volcanic quiescence, resumed their magmatic activity after the earthquakes series: San Miguel, Momotombo, Rincón de la Vieja, Poás, and Turrialba erupted after 37, 110, 18, 62 and 148 years of volcanic quiescence, respectively.The aim of our present research was to investigate whether or not the three large earthquakes in 2012 promoted the increase in volcanic activity in Central America in the short- and/or long-terms. Here, we considered the characteristics of the earthquakes and the pattern of activity in each one volcano prior to the series of earthquakes as key parameters for unravelling why some volcanoes erupted and others did not.30 (VEI) ≥ 2 occurred in Central America, of which 21 were from before the three large 2012 earthquakes and 30 were afterwards  using the seismic waveform and the static stress differential (σsdiff), maximum (σsmax) and minimum (σsmin) in each analyzed volcano in response to the three large earthquakes . This volcano also underwent the most significant change in its static stress with a σMw = 9.3 Andaman-Sumatra earthquake , where there was a fourfold increase in the eruption rate in the region, due mainly to the expansion in the volcanic system22. However, after the 2012 Central America earthquakes, the volcanic eruptions occurred diachronously: some volcanic eruptions occurred shortly afterwards (within a matter of days), and other months or even years after the earthquakes. Nevertheless, no migration of the volcanic eruption based on the location and time was obvious, except for two volcanic eruptions clustered temporally (weeks to months after the earthquakes) and spatially close to each other. This is the case for the volcanic eruptions series of Fuego and Pacaya volcanoes and San Cristóbal, Telica and Momotombo volcanoes  was 11.8 km and had low high-frequency (HF) energy radiation and a long period, which are typical characteristics of “tsunamigenic earthquakes”35. Nine days later, the Costa Rica earthquake  struck with moderate HF energy radiation and with a hypocenter depth of 15.8 km35. The hypocenter depth of the Guatemala earthquake  was 24 km, where conditionally stable areas surround small patches in the slab that, at failure, produced a moderate slip and high HF radiation35.The three large earthquakes occurred within 10 weeks of each other, almost equidistantly (420–450 km), but at different hypocenter depths Fig. . The hyp36  as well of the volcanic edifice37, in order to evaluate whether or not Fuego and San Cristóbal volcanoes could have entered into resonance and squeezed out magma after crack opening. We calculated the resonance frequency of theoretical magma-filled conduits, i.e., dykes (frd) with hypothetical widths of 100 m and 10 m to be 0.09 and 0.28 Hz, respectively. The resonance frequency of the volcanic edifices calculated (frv) for Fuego volcano is around 0.16 Hz and for San Cristóbal volcano is around 0.27 Hz , at the same continuous frequency as well as the corresponding, continuous dynamic stress. This could have caused the sloshing mechanism in the hydrothermal and/or magmatic plumbing system38.Dynamic stress is generally considered for time intervals of just a few seconds. However, in the case of the El Salvador earthquake, Telica volcano experienced stress lasting around 120 s  and 73.5 MPa (magma chamber depth: 3000 m of Fuego volcano), respectively  43, and Merapi (Indonesia)44, three of the world’s most frequently erupting volcanoes. Geological evidence from the 2006 Merapi eruption, shows that on the preceding May 26, 2006 the Yogyakarta earthquake (Mw = 6.4) added xenoliths from the carbonate basement to the magma chamber, thereby causing an internal pressure increase generated by CO2, which eventually culminated in an eruption45.Regarding the role of the static stress, the respective alignment system could be crucialsdiff was from 5 kPa for Turrialba to 55 kPa for Rincón de la Vieja. The σsdiff in the November 7 Guatemala earthquake ranged from 12 kPa for Pacaya to 0.1 MPa for Santa María. The static stress in Karymsky volcano  produced by a tectonic earthquake (Mw = 7.1) that led to dyke intrusion and triggered the 1996 eruption was 0.2 MPa46, which means that it is difficult to explain with our results alone how static stress could have opened cracks and generated a dyke intrusion. Quantifying the stress regime around each volcano is a necessary constraint for determining whether the static stress reduces or increases the country-rock strength. An example of how the static stress changes according to the alignment is provided by Rincón de la Vieja volcano; where the stress regime had at least three directions . The largest σsdiff (55 kPa) occurred in the deepest part of the magma chamber with a W–E alignment. This differential pressure could cause magma to rise towards the shallow reservoir, thereby leading to overpressure and the superheating of the shallow magma chamber. Another factor that could be related to the crack propagation and/or dyke intrusion is the increase in the temperature which reduces the frictional coefficient along the fractures41. After the 2012 earthquakes, the temperature of fumaroles and/or acid lakes on Telica, Rincón de la Vieja, Poás and Turrialba volcanoes, increased; these volcanoes erupted years later, which indicates how magmatic intrusion can occur over an extended period of time.For the August 27 El Salvador earthquake, the static stress applied was low, in the order of ± 2 kPa in three volcanoes . In the case of the September 5, Costa Rica earthquake, the σ48. In addition, the presence of a mush zone, part of which could be an eruptible melt at crustal depth, a seismic event or some other process, such as the addition of a mafic melt, can trigger eruptions years later (e.g. the deadly phreatic eruption of Ontake volcano in 201449).The possible responses of volcanoes in the long term (months to years) to earthquakes depend on the degree of the critical stage of each volcano, which explains why some of the studied volcanoes that received more stress (dynamic and static) than others responded later, or not at all. For example, Rincón de la Vieja and Poás volcanoes erupted in 2017 and underwent more stress change than Turrialba volcano, which had already erupted in 2014. Volcanic processes such as magma migration from the mantle to the crust or magma mixing, can occur on various time scales, from months to years or even centuries51. A good example is provided by San Miguel volcano, which erupted in December 2013, after 37 years of quiescence. According to GPS data, the horizontal displacement by the co-seismic slip at San Miguel volcano was around 1.2 cm50. Nevertheless, almost one year after the three earthquakes, the horizontal displacement reached 2 cm due to the post-seismic slip50.Another hypothesis regarding the increase in the number of eruptions even years after the 2012 earthquakes, is the post-seismic activity in Central America. The region is well known for the occurrence of post-seismic slow-slip earthquakes, as was the case of the El Salvador and Costa Rica 2012 earthquakes19, a Mw = 6.2 tectonic event with an epicenter 10 km from Poás and also after the 2012 earthquakes. On April 10, 2014, a Mw = 6.1 tectonic earthquake hit near Momotombo volcano (Nicaragua), triggered seismic swarms52 and resumed explosive activity in December 2015. We cannot rule out the possibility that other strong earthquakes such as the 2014 Nicaragua earthquakes or even the Chiapas earthquake  have affected the volcanic system. Indeed, the “cocktail” of earthquakes could provide extra stress (dynamic and static) in volcanoes that were at the point of erupting. The most impressive change in the increase in the number of eruptions took place on Fuego volcano: in just three years (2015–2018), 50 paroxysmal eruptions occurred, including the deadly eruption of June 3, 2018, which is far more than the 21 paroxysmal eruptions that occurred in 1999–201229 .Although some of the 19 studied volcanoes had already erupted prior to the 2012 earthquakes, the number of eruptions increased after the earthquakes. For Poás volcano, the number and magnitude of phreatic explosions increased after the January 8, 2009 Cinchona earthquake56. Our research categorized the information available on volcanic activity into three different “degrees of unrest”, determined by the energy released of volcanoes57 and running in a range from the lowest degree (unrest 1), through intermediate degree (unrest 2), to the highest degree (unrest 3) degree. These degrees of unrest can be described thus: Unrest 1 = increase in the seismicity of the volcanic system  sometimes escalates into volcanic eruptions or triggers other hazard eventse unrest , throughr 2 Fig. . A possi59. (3) large eruption occurred on Cerro Negro in August 1999 and unrest degree 1 was reached on June 4, 2013. The behavior from these eight volcanoes indicate that the earthquakes themselves were insufficient to trigger volcanic eruptions, despite the fact that the earthquakes caused an increase in the degree of unrest in some cases. However, the same seismic energy transmitted to the other volcanoes that were already in an advanced state of unrest was sufficient to trigger a new eruption. In consequence, we postulate that, in view of the data presented and the obtained results, the dormant volcanoes or volcanoes with low activity levels did not change their states to any significant degree simply as a result of the effects of the shaking generated by the earthquake, or the change in the stress field regime. The earthquakes were not able by themselves to bring the volcanoes from equilibrium to eruption.Despite decades without any magmatic eruptions, some of the other volcanoes already had unrest degrees of 1 or 2 . Other earthquake characteristics in addition to magnitude and location  may also play a role in explaining how tectonic earthquakes contribute to volcanic eruptions. Nevertheless, this external energy supply, regardless of the distance between the earthquake epicenter and the volcano and the magnitude of the event, is not sufficient to raise the state of a volcano from quiescence directly into eruption. Our results confirm the need to monitor all active volcanoes as a means of establishing their degree of unrest at any particular time and hence prior to the next large earthquake, as well as the need to determine future scenarios for possible increased volcanic activity and eventually for volcanic eruption in the short (days) or long (years) terms. This kind of surveillance is a key forecasting tool for future eruptions, and will help Civil Protection authorities and other decision-makers to adopt appropriate strategies to disaster risk reduction at the regional or local scales.26  when 21 out of 51 volcanic eruptions had already occurred; and (c) 30 out of 51 eruptions occurred after the second earthquake . We ran 10,000 simulations, following the law of large number and found that only 0.12% of these simulations satisfies the testing hypothesis. Our results show that it is likely that the observed acceleration in the number of volcanic eruptions is not due to chance, but represents, instead, a significant change induced by the earthquake.The question discussed in this paper stems from the fact that there is that it seems to have been an acceleration in the number of eruptions after the large earthquakes of 2012 . This can be calculated using the Eq. (60:PGV is the peak ground velocity of the seismic wave (km/s), G is the shear modulus with a value of 30 GPa for the region32 and Vph is the velocity phase of the wave (km/s). The dynamic stress considers the maximum peak-to-peak velocity of the waveform ::3):2\doc30 (VEI) ≥ 2, and reported with its day, month, and year of occurrence from January 1, 2000 to December 31, 2019. In the case of phreatic explosions, the lack of volcanic deposits and the existence of confusing reports are typical and so we only took into account the eruptions with a well-defined VEI, despite the occurrence of phreatic eruptions at some volcanoes in the region  during the study period.We recognized volcanic eruptions occurring in the Central American region with a Volcanic Explosive Index9 for determining whether or not the earthquakes that occurred in 2012 increased volcanic unrest. The catalog compiled for the states of volcanic unrest of the 19 volcanoes included information from internal reports by local observatories, scientific papers, and personal data in addition to the weekly report from the Global Volcanism Program (GVP)27.This research delimited a period of 5 years before and 5 years after the earthquakesSupplementary Information.


The findings indicate that the “High-Up” program can enhance the nurse management competency of experienced nurses who need to prepare for nurse manager roles, and that it can also positively influence the performance of nursing organizations. However, it can be difficult to comprehensively enhance nursing management competency in a short period of time, meaning continuous education is required.The aim of this study was to develop an educational program to strengthen the nursing management competency of experienced nurses who are prospective nurse managers and then determine the effectiveness of the program. This quasi-experimental study was conducted from January to April 2021. A total of 22 nurses were assigned to the experiment group , and 20 were assigned to the control group . The program, known as the “High-Up” program, comprised problem-based learning (PBL) and video lectures. In the experiment group, nurses discussed PBL cases through video conferences and applied problem-solving methods. The collected data were analyzed using the Friedman test and Wilcoxon rank-sum test (administered through SPSS). At four weeks after the intervention, the experiment group showed higher critical thinking tendency scores than the control group (pre-intervention score: 3.48 ± 0.36; post-intervention score: 3.71 ± 0.49; Z = −1.99,  Between 2008 and 2018, the number of nurses in South Korea increased by approximately 150,000  [Systematic education and training programs for nursing managers are important to strengthen nursing managers’ management competency and, consequently, improve nurses’ job performance and benefit nursing organizations . Korean In contrast, in the US, the Fundamental Skills for Nurse Managers (FSNM) course has been developed to help foster competent nurse managers . This isTo strengthen prospective nurse managers’ ability to solve novel, complex organizational management problems, they should be exposed to various teaching and learning methods centered on actual cases. Problem-based learning (PBL) is a self-directed learning strategy that provides learners with enhanced responsibility and autonomy and asks them to solve problems through small group cooperation .Blended learning concerns combining two or more teaching techniques or delivery methods to enhance learning content and learners’ learning experiences . Such leSeveral previous studies have focused on creating educational programs for nurse managers. For instance, Abraham  developeThe present research aimed to develop an educational program for strengthening the nursing management competency of experienced nurses who are prospective nurse managers and to evaluate the program’s effectiveness, particularly in regard to communication ability, critical thinking tendency, and problem-solving ability. This program, named “High-Up,” integrates nursing management core competencies (identified through a systematic literature review), uses the FSNM as a theoretical framework, and features blended e-PBL.The FSNM is an educational program that provides guidelines for nurse managers. It was developed by the American Organization for Nursing Leadership and focuses on mid-careerists. The FSNM provides learners with the confidence and knowledge to grow from general nurses to nurse managers by emphasizing five core competencies: getting started as a new nurse manager, human resource management, financial management, quality and safety, and leadership . The FSNShen et al.  used theThe FSNM characteristics and aims accord with the purpose of this study; therefore, the FSNM was used as a theoretical framework for the “High-Up” program.To identify and confirm the nursing management competency concepts that would form the basis of the “High-Up“ program, a systematic literature review was conducted, focusing on academic literature published in the last 10 years, from January 2010 to April 2020. The searched databases included Ovid-EMBASE and Ovid-MEDLINE, as well as South Korea-based academic databases, such as RISS, NDSL, and KISS. The search was performed by combining keywords such as “nurses”, “management competency” , “program”, “empowerment” , “development”, and “advancement” (“improvement”).The population, intervention, comparator, and outcomes (commonly known as “PICO”) approach was used for literature extraction; the population was nurses, the intervention was a nursing management competency program, and the comparator and outcomes were not limited. The PICO strategy can be used to construct several types of research questions originating from clinical practice . The incThe search returned 38,535 articles, including 28,489 from Medline, 13,559 from Embase, 141 from RISS, 8 from NDSL, and 2 from KISS. First, 34,882 duplicate articles were excluded. Second, after removing duplicate articles, 3653 full texts and abstracts were confirmed. Third, 3344 articles deemed not to be related to nursing management competency programs for nurses were excluded. The inter-rater agreement for this decision was 0.92 (kappa coefficient). Fourth, from the remaining 309 documents, 284 were excluded. The reasons for the exclusion were as follows: 2 studies not targeting hospital nurses, 7 studies where the original text could not be obtained, 257 studies that did not apply intervention, and 18 studies that were not appropriate to be included in the content analysis. Twenty-five articles were left for extraction. The agreement between evaluators at this stage was 0.91. Finally, the remaining 25 articles were evaluated for quality using the methodological checklist version 2.0 of the Scottish Intergroup Guidance Network (SIGN) [For the final extracted literature sample, content analysis was conducted on participant numbers, program contents, major measurement variables, program operation methods and time periods, pre- and post-program scores, and evaluation methods. The core elements of the “High-Up” program were selected by combining the results of this analysis with the FSNM framework. The overall research process for this study is summarized in The following hypotheses were set for this study:Hypothesis 1: The experiment group, which is the group that participates in the “High-Up” program, will show significantly higher communication ability scores at the first post-test (T1), the second post-test (T2), and the third post-test (T3) when compared to the control group, which does not participate in the program.Hypothesis 2: The experiment group will show significantly higher critical thinking tendency scores at T1, T2, and T3 when compared to the control group.Hypothesis 3: The experiment group will show significantly higher problem-solving ability scores at T1, T2, and T3 when compared to the control group.This was a quasi-experimental study with a repeated-measures design, a non-equivalent control group, and pre- and post-tests. The aim was to develop a nursing management competency-strengthening program for nurse managers named “High-Up” and to analyze its effectiveness after administering the program for five weeks to experienced nurses working in hospitals.The participants were experienced nurses working in small- and medium-sized hospitals with less than 500 beds, where systematic education programs for career nurses were scarce. The sample size was calculated using G*Power 3.1.9.2. To afford repeated-measures analysis of variance (ANOVA) of an experiment and control group, the power was set to 0.90, the significance level to 0.05, the effect size to 0.5, the number of groups to two, and the number of repeated measurements to four. Additionally, to afford within–between interaction analysis and difference analysis between the two groups, a calculation was performed with a power of 0.80, a significance level of 0.05, and an effect size of 0.5 . To estiThe inclusion criteria for participation were nurses who (1) worked in small- or medium-sized hospitals or general hospitals with 101–499 beds; (2) had 3–5 years of experience , a consortium of major professional associations in the fields of nursing and medicine, was used to select content topics for the “High-Up” program. Specifically, the five-session program was constructed based on the sub-domains of the HLA model: communication and relationships, knowledge of the health-care environment, leadership, business skills and principles, and professionalism.The “High-Up” program was online-based and provided PBL through video conferences and lectures. The video conferences lasted 120 min each week, and concerned PBL cases were selected to represent each targeted topic. Following the PBL procedure, the program proceeded in the order of team building, presenting problems, identifying problems, writing a study plan, self-directed learning and team activities, completing and reviewing solutions, and presenting, evaluating, and reflecting on solutions .The PBL cases used in the lectures were examples of practical cases that commonly occur in clinical settings; these were chosen to strengthen the nurses’ nursing management competency. Additionally, for effective discussion in the e-PBL classes, participants were assigned the roles of moderator, logicist, idea person, intuitionist, optimist, and pessimist throughout the entire discussion, which encouraged the learners to be actively engaged. Six colored hats, one of the creative thinking techniques, were used . The rolThe construct and content validities of the “High-Up” program were evaluated by a panel of 15 experts, which included nursing professors and nurse managers. Content validity was evaluated using the content validity index (CVI) , with onThe “High-Up” program was applied over five weeks, from January 18 to 21 February 2021. Educational materials and online training videos were provided to the experiment group at the beginning of the program, and each week, they were asked to participate in the real-time online learning (e-PBL) after performing advanced self-learning of the content to be discussed that week. The e-PBL was conducted for two hours each week, with the same content being provided on three different days ; this allowed the participants to choose a day that suited their work schedule, thereby facilitating participation. Additionally, to encourage self-directed learning, participants were asked to log the completion of each video lesson on social media, with these learning progress reports being checked regularly. Similar to the experiment group, the control group was provided with the “High-Up” program textbook, which allowed them to engage in self-directed learning over five weeks; only the experiment group received the intervention.Communication ability was measured using a scale developed by Lee et al. . This scThe participants’ critical thinking tendency was measured using a scale developed by Yoon . This scProblem-solving ability was measured using a scale developed by Lee et al. . This scData were collected from 11 January to 18 April 2021. The questionnaire used for data collection was administered at the pre-test, which was held two weeks prior to the start of the program (T0); at the first post-test, which was held on the same day as the completion of the program (T1); at the second post-test, which was held four weeks after the completion of the program (T2); and at the third post-test, which was held eight weeks after the completion of the program (T3).p-value.Data analysis was performed using IBM SPSS/WIN 26.0. Descriptive statistics were analyzed using frequencies, percentages, means, and standard deviations. Wilcoxon’s rank-sum test and Fisher’s exact test were used to test the homogeneity of the variables. The Kolmogorov–Smirnov test was used to test normality; this indicated that the communication ability, critical thinking tendency, and problem-solving ability variables did not follow normality. A non-parametric analysis was performed on these variables. The Friedman test was conducted on each group to verify the effectiveness of the program. Wilcoxon’s rank-sum test was used to examine the degree of change in the post-test values when compared to the pre-test. A two-sided cut-off of 0.05 was used for the This study was approved by the institutional review board of Inha University, Incheon, South Korea (200218-1AR). After obtaining the prior consent of the hospital’s nursing department, the recruitment notice was uploaded to the nursing department social network systems or ward bulletin boards. Nurses who wished to participate were given an explanation of the purpose of the study, the data collection method, and their right to choose not to participate and to withdraw consent at any time during the study. Only individuals who provided written consent to participate were included in the sample. To remove the risk of influence from the authors on the program’s intervention effect, a separate trained research assistant was in charge of administering the curriculum.p = 0.010); specifically, a statistically significant intergroup difference was identified when comparing T1 and T0 scores for critical thinking tendency, partially supporting Hypothesis 2 . In contrast, the intergroup differences associated with Hypothesis 1 and Hypothesis 3 were not statistically significant  was 3.80 ± 0.37 in the experiment group and 3.59 ± 0.29 in the control group, showing no statistically significant intergroup difference. However, when compared to the pre-test, the control group’s score had increased by 0.07 ± 0.06, while the experiment group’s score had increased by much more, 0.14 ± 0.12. This result is partially consistent with that of Jang et al. , who argRegarding problem-solving ability, both groups showed changes in average scores across the time points. Both groups showed an increase in scores at the third post-test. In particular, among the seven subareas of critical thinking tendency, including intellectual passion/curiosity, prudence, confidence, systematicity, intellectual fairness, sound skepticism, and objectivity, there was a significant difference between the groups in terms of intellectual fairness . The conRegarding limitations to this study, it is regrettable that the hypotheses were only supported with regard to critical thinking tendency. Nursing management competencies include abstract and complex concepts that are difficult to change in a short period of time. Therefore, the provision of a one-time, five-week intervention may have been insufficient to significantly impact communication ability and problem-solving ability. Thus, a future study that, after applying the program, features subsequent booster classes is required. This study was designed as a non-equivalent control group, and pre- and post-tests and random assignments were not carried out. Therefore, there will be limitations in the generalization of the research results.The “High-Up” program developed in this study showed a positive effect on the critical thinking tendency of prospective nurse managers. Furthermore, the fact that the content of the evidence-based program was constructed by combining the results of a systematic literature review and the FSNM framework indicates it can represent useful material for the development of follow-up education programs for strengthening nursing management capabilities. In terms of methodology, e-PBL, which combines self-learning, video education, and real-time online lectures, was applied to accommodate the need for online teaching and learning environments during the COVID-19 pandemic. In particular, e-PBL is a flexible educational resource that can be used regardless of time and place, overcoming the limitations of face-to-face education. This can be especially important in the nurse education context, as the nursing profession often involves three-shift rotation schedules, meaning nurses can have difficulty attending formally scheduled classes. Nursing management competency is a complex concept that is difficult to change in a short period of time. Therefore, the development of an education and training system that can provide continuous, boosting education is required. The “High-Up” program has been developed for experienced nurses who are prospective nurse managers; it will be necessary in the future to develop in-depth programs tailored to various other types of nurses with diverse clinical experience and prior knowledge.