Results showed that the program was well received by participants and positively impacted the intended outcomes. Overall, the data presented in this Proof-of-Concept evaluation was deemed to support the development and implementation of the full-scale 1616 Program for a more comprehensive evaluation.The 1616 Program is a newly developed and evidence-informed story-based positive youth development (PYD) program for young ice hockey players (10–12 years of age) in North America. The program uses elite ice hockey players as role models—through story-telling—to serve as inspirational figures to engage youth athletes and important social agents  with evidence-informed PYD concepts. The objective of this study was to use a Proof-of-Concept evaluation to assess whether the 1616 Program ‘worked’ in enhancing PYD outcomes and to determine if the concepts were engaging and enjoyable for youth, their parents, and coaches. The 5 week Proof-of-Concept evaluation was conducted with 11 ice hockey teams ( Extensive evidence supports the positive outcomes of sport participation for youth . UnfortuGiven that youth sport programs serve as a viable avenue to promote PYD, sporting organizations have sought to develop programming that can assist in ensuring that involvement-related benefits are realized . The LadA team of researchers was asked to assist with developing the program to ensure that the program content was evidence-informed and aligned with the sporting context. Since the primary delivery mechanism was storytelling, various other organizations specializing in educational material and digital and video content creation were engaged in the partnership . For a more detailed description of partnership development, please see Martin et al. . The conThrough the 1616 Program, the Ladd Foundation sought to promote healthy sport experiences by capitalizing on inspirational stories from elite athletes without over-structuring or detracting from physical practice and playing time for youth. Their initial objective was to ensure that an intervention with youth ice hockey players did not impose additional requirements  on already busy parents and coaches and, perhaps most importantly, was free for any interested teams/organizations. They grounded the 1616 Program in PYD and coaching literature, specifically the sport-based Personal Assets Framework (PAF) ,13. SpecIt is important to recognize that developing and evaluating novel sport interventions should not be seen as separate processes. For instance, recent systematic reviews and meta-analyses emphasize that, although there is some evidence for the effectiveness of sport-based PYD interventions, the quality of evaluations and transparency of the research process are lacking ,15. In rGiven the extensive personnel, time, and financial resources dedicated to the development of the 1616 Program , it was Two primary research objectives were determined through several PoC collaborative planning meetings with the Ladd Foundation, Impact Society, and the research group. Objective 1 (OB1) was to evaluate whether the 1616 Program ‘worked’ in enhancing PYD-related outcomes in youth. Objective 2 (OB2) was to determine if the concepts were engaging and enjoyable for youth, their parents, and coaches. More specifically, we were interested in knowing if representative weeks from the proposed program could positively impact youth competence, confidence, connection, and character  and whether the program’s PYD concepts and story-based structure were feasible and acceptable—that is, appropriate, delivered effectively and engagingly, and whether participants were satisfied with the quality . Ultimately, this study’s objective was to gather information from the participants that would help inform further decisions about full-scale program development and implementation.For each week during the 5 week PoC evaluation, new material was introduced to youth, parents, and coaches on a selected topic from existing sport and PYD literature . The primary (and unique) content delivery mechanism involved a ~5 min edited video of a professional  or international  ice hockey player telling their personal story concerning a particular PYD concept. As an overview of the PoC content, week 1 involved a program introduction focused on the concept of commitment/engagement. Weeks 2–4 involved the concepts of morality/integrity, psychological safety, and self-efficacy, followed by a consolidation and program conclusion in week 5. Throughout the program, participants were given access to online videos/stories in addition to reflection and action-based activities  each week. The videos/stories, and additional activities were narrated and introduced by an animated buffalo named ‘Buffalou’. The program’s content was tailored for relevance to young ice hockey players aged 10–12 years.In addition to the content provided to youth, parents were sent resources each week to support their child through the sport experience . Importantly, these resources were informed by current youth sports literature about parent education, communication, and reflective practice ,24,25. SThe PoC was conducted with a convenience sample comparable to previously completed mixed-methods PoC studies exploring novel behavioral interventions . Samplesone posttest time point, rate items based on their recall of two specific instances: ‘now’ and ‘before’  resource…overall just such a positive experience for everyone’ . Coaches also commented on how the program enhanced their motivation to support their athletes: ‘The videos really spoke a lot to me as a coach. I want to make that difference now. I don’t want a player to have success in spite of me’ .Weekly Youth Process Questionnaires. As shown in Post-Program Process Questionnaires. Follow-up Focus Group Interviews. Overall, there was a sense of engagement with the stories being told, and athletes could relate to the messages delivered by the players. For instance, they described their excitement with the way the reports were delivered: ‘It was fun to see different players and the stories that they’ve been through’  and ‘…it felt like you actually knew them personally’ . However, focus groups also highlighted the need for content to be age appropriate. Similar to the results presented above, older athletes were not as engaged with certain aspects, such as the buffalo mascot for the program, ‘I didn’t like the buffalo in the first two videos. He was a little much’ . Conversely, younger athletes found the pace and some of the content difficult to follow. For instance, although athletes described enjoying the stories and self-reflection questions, one athlete discussed needing more clarity on the weekly messages, ‘Just the way it’s said could be a little better… I guess [the message] just has to be a little clearer’ . Additionally, another player discussed the fast pace of the weekly content, ‘Maybe give us more time to talk about [the content of] each week’ .Post-Program Process Questionnaires. strongly disagree) to 7 (strongly agree), 100% of parents selected a response of five or higher when describing the program as aligning with their beliefs and values, as useful, credible, and a positive experience, as well-structured and organized, and as effective. Areas of improvement marked by parents for the Ladd Foundation to consider were observed in relation to effectiveness over other resources (82%), the available evidence of the impact of the program (91%), and time requirements (91%).Follow-up Focus Group Interviews. During interviews, parents expanded their appreciation for the resources shared through the program. One parent elaborated: ‘The ‘Chats with Brandy’ videos where you can see them talking to their kids and how they’re relaying the same weekly messages to them in their own day-to-day life…that gave us more to talk about than just the normal ‘How was your day?’ The way that it tied a lot of things together was really beneficial.’ (U10 Parent).Parents also highlighted several challenges/barriers they experienced with the program, including the frequency of messaging they were receiving and the speed at which new content was being presented: ‘I feel like it was a lot of texts and emails. I would say ask people what they prefer and then just get that one [form of communication] rather than both’ (U10 Parent). Another parent recommended spacing out the delivery of the content to allow for more time to digest the messaging: ‘We were talking about spreading the [content] out… then they really get to dive a little bit deeper into each one of them’ (U10 Parent).Post-Program Process Questionnaires. strongly disagree) to 7 (strongly agree), 100% of coaches selected a response of five or higher to describe the program as aligning with their beliefs and values, as useful, credible, and a positive experience, as well-structured and organized, and as effective. Whereas all items were rated highly, areas to consider for improvement could be demonstrating effectiveness over other resources (82% five or higher), available evidence of the impact of the program (91% five or higher), and time requirements (91% five or higher).Follow-up Focus Group Interviews. Coaches provided contextualizing feedback during the follow-up interviews: ‘The 4 Cs…that’s the stuff that carries on and off the ice, and if hockey becomes a teaching tool for that, great. That’s where the strength of the program is, the culture. The 4 Cs did resonate with the [athletes]’ . Coaches also discussed witnessing the program’s positive impact on their athletes: ‘It’s a positive experience for the kids. They really start to learn about overcoming adversity, struggling, and character building, and it’s presented in a great way’ .The purpose of this article was to describe the evaluation of a PoC trial involving the 1616 Program. The two overarching objectives for the 5 week PoC were to evaluate whether the 1616 Program ‘worked’ in enhancing PYD-related outcomes, validate the story-based intervention approach , and explore participant process-related experiences . In doing so, we would determine whether full-scale development was warranted and what changes needed to be made before rolling out the complete program. Within the following sections, we summarize the findings, discuss implications as they pertain to the literature, and conclude by describing the next steps for continued development and refinement of the program.There are relevant outcome-related findings for youth, parents, and coaches. Concerning youth, the RPP evaluations demonstrated that every week, the youth felt that they improved in relation to the topic introduced. Given that the eventual 1616 Program will aim to include a weekly message over 16 weeks, this is a promising finding. In other words, an introductory video/story, accompanied by a reflection question and ‘Live It Out’ activity, represents a format whereby youth feel like they learn and improve with a particular PYD topic. Although the theoretical and conceptual foundation and rationale for the program structure are described elsewhere , we expeInterestingly, the only significant finding concerning the pretest-posttest questionnaires involved mental toughness . AlthougRegarding parents, results suggested favorable outcomes. For instance, in comparison to before the program, they believed their children improved across the 4Cs. Further, the quality of the sport environment is critical for healthy development , and parOur results suggested that the program was also effective from the coach’s perspective. For instance, they felt that their athletes improved for the 4Cs. Similarly, they felt that their capability and motivation to support their athletes improved, in addition to their awareness of opportunities to do so . It is wThe second aim of the PoC evaluation was to explore participant experiences with the program. Our findings suggest that the overarching idea and messaging of the 1616 Program were well received by all participants. For example, focus group discussions with each of the stakeholders revealed that the ‘Buffalo Mindset’ and 4Cs resonated and aligned with participants’ sport values. For the youth specifically, almost all reported engaging with the content, and the mean responses were all above four on a 5-point Likert scale when asked if they were enjoyable, if they improved understanding, and if they were worthwhile see . SimilarThe coaches and parents appreciated the common language that the program provided and how it was applicable to other contexts, providing them with a language/vocabulary to communicate with their athletes and children. Suggestions for improvement from these participants mainly focused on program delivery rather than the content itself. For instance, they indicated that the content and messaging were being sent too frequently. As such, in subsequent conversations with the program partners, the quality and intentionality of content delivery will be prioritized for the proposed 16 week program. This will allow time for content to be absorbed by participants and provide opportunities for greater engagement in activities. Notably, the lowest responses from coach and parent feedback were their perceptions that (a) the 1616 Program was more effective than other programs, (b) evidence of its potential impact was available, and (c) time requirements were appropriate see . This fiThis article described the initial evaluation of a 5 week PoC test of the 1616 Program. This was an important first step in program development and represented a novel attempt to evaluate an initial program originating from an iKT approach in sport. Indeed, recent reviews highlight the limitations of PYD interventions in sports . Thus, t


Eremosparton songoricum (Litv.) Vass. is a rare and extremely drought-tolerant legume shrub that is distributed in Central Asia. E. songoricum naturally grows on bare sand and can tolerate multiple extreme environmental conditions. It is a valuable and important plant resource for desertification prevention and environmental protection, as well as a good material for the exploration of stress tolerance mechanisms and excellent tolerant gene mining. However, the regeneration system for E. songoricum has not yet been established, which markedly limits the conservation and utilization of this endangered and valuable desert legume. Assimilated branches derived from seedlings were cultured on several MS mediums supplemented with various concentrations of TDZ or 6-BA in different combinations with NAA. The results showed that the most efficient multiplication medium was MS medium supplemented with 0.4 mg/L 6-BA and 0.1 mg/L NAA. The most efficient rooting medium was WPM + 25 g/L sucrose. The highest survival rate (77.8%) of transplantation was achieved when the ratio of sand to vermiculite was 1:1. In addition, the optimal callus induction medium was MS + 30 g/L sucrose + 2 mg/L TDZ + 0.5 mg/L NAA in darkness. The E. songoricum callus treated with 100 mM NaCl and 300 mM mannitol on MS medium could be used in proper salt and drought stress treatments in subsequent gene function tests. A rapid and efficient regeneration system for E. songoricum that allowed regeneration within 3 months was developed. The protocol will contribute to the conservation and utilization of this rare and endangered desert stress-tolerant species and also provide a fundamental basis for gene functional analysis in E. songoricum. Eremosparton songoricum (Litv.) Vass. is a leafless legume shrub distributed in Central Asia, with a fragmented distribution in the mobile sand dunes of the Gurbantunggut Desert of Xinjiang [E. songoricum is the only species of the genus in China, and is also a Grade II endangered plant in Xinjiang [E. songoricum is a promising plant for desertification control and environmental protection. The majority of studies on E. songoricum were focused on the ecology adaptation mechanisms at morphological [EsDREB2B [Xinjiang . E. songXinjiang . As a tyXinjiang . In the Xinjiang . This spXinjiang . Meanwhiological , physiolological , and bioological . Recentlological , isolatiEsDREB2B , the obtEsDREB2B .Populus tomentosa Carr. [Bixa Orellana L. [Toona ciliate Roem. [Betula platyphylla Suk. [Malus sieversii (Ledeb.) M. Roem. [Tamarix elongate Ledeb. [Glycine max (L.) Merr. [Medicago sativa L. [Medicago truncatula Gaertn. [Vigna unguiculata L. Walp. [Robinia pseudoacacia L. [Pongamia pinnata (L.) Merr. [Cajanus cajan (L.) Millsp. [Faidherbia albida (Del.) A. Chev. [Mucuna pruriens (L.) DC. [Robinia pseudoacacia L. [Plant tissue culture, also known as in vitro culture or sterile culture, is an important technology for plant regeneration, conservation, and genetic transformation ,8. Theresa Carr. , Bixa Orllana L. , Toona cte Roem. , Betula lla Suk. , Malus sM. Roem. , and Tame Ledeb. . Current.) Merr. , Medicagativa L. , Medicag Gaertn. ,20, VignL. Walp. , and Robcacia L. , and onlcacia L.  such as .) Merr. , Cajanus Millsp. , FaidherA. Chev. , Mucuna (L.) DC. , and Robcacia L.  have estE. songoricum is a good material for excellent gene mining and has great potential in being a model desert legume plant for stress tolerant mechanism study [E. songoricum markedly limits further mechanism exploration and gene function analysis. Meanwhile, considering the aggravation of global climate change and human activity disturbances, the protection of this important, rare, and endangered species is urgent. Therefore, the establishment of an effective regeneration system in E. songoricum is urgently required for germplasm conservation, the establishment of a transformation system, and the discovery and utilization of gene resources. The current study focused on the establishment of an efficient in vitro regeneration protocol for E. songoricum using an assimilated branches regeneration system. Different mediums with different plant hormones for assimilated branch proliferation, rooting, and transplantation were systemically investigated, and callus induction and abiotic stress treatments on callus were also evaluated. This study will provide technical support for the establishment of a rapid regeneration system for E. songoricum for the conservation and utilization of this endangered and extremely stress-tolerant species, as well as laying the foundation for further function analyses of stress tolerance genes in E. songoricum.sm study ,3,4. HowE. songoricum seedlings.Growth regulators have different effects on somatic embryogenesis and axillary shoot regeneration. The regeneration rate of assimilated branch explants was dependent on the auxin/cytokinin ratio. We selected NAA and 6-BA at different ratios for shoot regeneration. After cultivation on the shoot regeneration MS medium, the new lateral shoots were observed with the different growth phenotypes. The formation of fewer dwarf shoots and vitrified callus were observed with the addition of NAA (0.1 mg/L) at different 6-BA concentrations (0.2 mg/L and 0.6 mg/L) into the shoot regeneration medium. The 6-BA at concentrations of 0.3 and 0.5 mg/L was able to induce regeneration shoots, which were separate for dwarf shoots with vitrified calluses and had less shooting with vitrified calluses. In contrast to these, regenerated shoots were vigorous, and calluses formed when the 6-BA concentration was 0.4 mg/L . The 6-BE. songoricum, the growth factors NAA and IBA were selected for root induction (To obtain complete plantlets of nduction . Growth nduction A. Collecnduction B. The renduction C. Therefv/v) exhibited vitality and health phenotypes. However, the seedlings showed a wilting and whitish phenotype both on the matrices of soil–perlite–vermiculite  and with pure sand (v/v). The survival rate of seedlings was the lowest at 22.2% in the matrix of soil–perlite–vermiculite . The survival rate of seedlings was slightly higher on the matrix of pure sand than on the matrix of soil–perlite–vermiculite  .For improved hydroponics, the regenerated seedling with roots were exposed to the air of the greenhouse for 7 days. Then, the seedlings were transplanted into three kinds of matrixes. After fifteen days’ transplant and cultivation, the survival rates were analyzed. At 1 day from transplant, the seedlings on the three kinds of matrix showed a green and vibrant appearance. At 15 days from transplant, the seedlings planted on the matrix of sand and vermiculite  B. Taken E. songoricum were used as explants to initiate callus induction. To identify the most efficient medium composition for callus induction from explants, different hormone ratios of concentrations were examined (Thirty-day-old in vitro assimilated branches of examined . Most of2), the average area of the calluses under NaCl treatment was significantly reduced, at 16.43 ± 0.715 cm2 and 16.2 ± 1.56 cm2 under 50 and 75 mM NaCl stress, respectively. Under 100 mM NaCl treatment, the average area of the callus was 14.42 ± 1.145 cm2  grew well, with a yellowish phenotype and soft texture. The callus treated with NaCl showed a brownish-red callus, and the texture became compact; similarly, the calluses on the MS medium supplemented with mannitol were yellow, poorly grown and hard A. Compar.145 cm2 B. ThrougS medium C. ComparS medium D. The weS medium E. Moreovstresses . The genntensity A,B. Whenol/gprot A. When tol/gprot B. Additiol/gprot C. When tol/gprot D. CollecE. songoricum are too short, the leaves and hypocotyls of E. songoricum were not selected as explants in this study. We selected assimilated branches as explants, mainly because they are abundant, easy to obtain, and fast-growing. Based on our results, one seed can produce about fifty assimilated branches after 40 days of culture, each of which can expand to four branches, and finally one seed can produce 200 regenerated plants over a three-month cycle, which proved that assimilated branches are a good and efficient explant choice. This may be due to the strong clonal regeneration ability of assimilated branches, which ensures the possibility of more rapid and efficient regeneration.Explants used in different species with success in the regeneration of plants are diverse, and include the leaf, shoot tip, root, seed, embryonic axes, epicotyl, and protoplast ,22,26,28Aeschynanthus pulcher (Blume) G. Don. [Sinningia Hybrida Voss. [Salvia plebeia R. Br. [Bougainvillea buttiana [Plants have different responses to plant growth regulator induction. Research shows that the appropriate combination of cytokinin and auxin is conducive to providing a higher regeneration rate . A combi G. Don. , Sinningda Voss. , and Sala R. Br. . Similarbuttiana . Our datE. songoricum. Plant culturing normally requires sucrose as the carbon source for cell proliferation and development, and the availability of sucrose in the culture medium has been found to affect somatic embryogenesis in many plant species [Acacia species [E. songoricum.Many studies have shown that WPM has higher rooting rate for woody plants compared with MS medium ,36, and  species ,38,39. S species ; for exa species . SimilarAcacia mangium Willd. [E. songoricum was 0.5 mg/L NAA + 2 mg/L TDZ. Previous studies suggested that 2,4-D was not conducive to subsequent callus differentiation and explant status [E. songoricum.The effect of different plant growth regulators on callus induction was dependent on plant growth regulator type and concentration. Studies show that 2,4-D and NAA are commonly used auxins for inducing calluses ,43,44. Mm Willd. . Similart status ,48, and t status ,49,50. TE. songoricum (Litv.) Vass. seeds were harvested from the Gurbantunggut Desert Xinjiang province, p. R. China  [v/v) sulfuric acid for 4 to 5 min to break physical dormancy [−2 s−1 light intensity and 45% relative humidity. Plants were maintained through regular subculturing at monthly intervals to provide fresh media with the same composition. The cotyledons of E. songoricum were grown after 5-day seed germination, and assimilated branches started to grow at 12 days. The 40-day assimilated branches chosen as explants were cut into 1 cm segments.Seeds were soaked in 98%  basal medium supplemented with different concentrations of NAA and IBA (Indole-3-butyric acid) to initiate root formation. A range of sucrose concentrations  were added to the MS basal medium. Two kinds of auxin were added to the MS and WPM medium for the root inducement.There were three auxin concentration treatments: (1) a concentration of NAA 0.1 mg/L; (2) a concentration of IBA 0.1 mg/L; (3) MS/WPM mediums with neither NAA nor IBA, which served as the control. . The incE. songoricum seedlings were first hardened by opening the tissue culture bottles for 7 days. The acclimatized seedlings were then removed from the medium and washed carefully with sterilized distilled water to remove the adhered agar. They were immediately transferred to pots containing three kinds of substrates: a mix of autoclaved soil, perlite, and vermiculite ; autoclaved pure sand from the desert habitat of E. songoricum; and a mix of autoclaved sand and vermiculite  (25 explants for each of the three different substrates). The pots with plantlets were covered with cling film to maintain a high moisture level. The growth conditions were consistent with the explant culture conditions. After 7 days, the film was partially removed. After 10 days, the film was completely removed and the plantlets were watered once every 5 days.Sixty-day-old rooted E. songoricum were used to initiate callus induction and implement abiotic stress treatments. The assimilated branches were cut into 1-cm-long branch segments with wounds at both ends. The branch segments were placed in a callus induction medium . To determine which cytokinin is suitable for callus induction, the medium contained various concentrations of thidiazuron (TDZ) or 6-BA in different combinations. A range of TDZ or 6-BA concentrations  were added to the MS basal medium. Somatic embryos were also obtained through culturing friable calluses in a liquid medium containing a certain mixing ratio of auxin and cytokine [Thirty-day-old assimilated branches of cytokine . In ordeE. songoricum is an extremely drought-tolerant woody plant. The long growth cycle limits the obtention of transgenic plants and a rapid functional evaluation of resistance genes. Therefore, testing the stress tolerance of E. songoricum using calluses will contribute to the establishment of a rapid screen system for abiotic stress resistance genes. Fifteen-day-old calluses were placed in different abiotic-stress mediums, which were callus induced MS mediums containing NaCl and mannitol. For salinity treatment, 50, 75, and 100 mM NaCl were added to the callus-induced MS medium. For drought treatment, 100, 200, and 300 mM mannitol were added to the callus-induced MS medium. Ten pieces of callus were placed in each Petri dish (90 mm in diameter), containing approx. 25 mL medium for salinity and drought treatments. The culture conditions were the same as above.2O2 and proline (PRO) contents were measured using detection assay kits , according to the manufacturer’s instructions.The Hp < 0.05 significance level.Statistical analysis was performed using SPSS 26.0  software. Three independent biological replicates were performed to ensure the accuracy of the analyses. The data were analyzed using Duncan’s multiple range test followed by one-way ANOVA at the E. songoricum was established, as well as a successful induction and stress tolerance evaluation of callus tissues. To our knowledge, this is the first report on the successful establishment of a rapid (from seed to rooting plants within 3 months) and efficient (one seed could produce at least 200 rooting plants after one cycle of regeneration) regeneration system for desert woody legumes via assimilated branches. The details of the regeneration process of E. songoricum are summarized as follows (v/v) for natural growth. For the callus induction, the optimal medium was the MS medium with 2 mg/L TDZ, 0.5 mg/L NAA, and 30 g/L sucrose. Our evaluation concluded that the suitable salt and osmotic stress concentrations for calluses were 100 mM NaCl and 300 mM mannitol, respectively.In this study, a rapid and efficient regeneration system of  follows : the ste


The Deadly Liver Mob (DLM) is a peer-delivered incentivised health promotion program by and for Aboriginal and Torres Strait Islander Australians, and was introduced in response to the disproportionate number of Aboriginal and Torres Strait Islander Australians who are impacted by blood borne viruses (BBVs) and sexually transmitted infections (STIs). The goal of the program is to increase access to BBV and STI education, screening, treatment, and vaccination in recognition and response to the systemic barriers that Aboriginal and Torres Strait Islander peoples face in accessing health care. This commentary introduces a series of papers that report on various aspects of the evaluation of the Deadly Liver Mob (DLM) program. In this paper, we explain what DLM is and how we constructed an evaluation framework for this complex health promotion intervention. This commentary is the first in a series of papers that report on various components of the evaluation of a complex health promotion program aiming to increase access to screening and treatment for blood borne viruses (BBVs) and sexually transmitted infections (STIs) among Aboriginal and Torres Strait Islander Australians. The Deadly Liver Mob (DLM) program ran in several sites in New South Wales, Australia from 2013 to 2020. In this paper, we explain what DLM is and how we constructed an evaluation framework using the RE-AIM framework .In this paper we respectfully use Aboriginal and Torres Strait Islander to refer to the First Nations peoples of Australia. We use the term First Nations to refer to Indigenous peoples around the world.It is well known that mainstream health services are, typically, not set up to serve the needs of First Nations people and can fail to attract and retain First Nations people in care. It is important that any analysis of barriers to health care is framed within a strengths-based approach which foregrounds social relations and collective practices and identities  and avoiAboriginal and Torres Strait Islander Australians make up just 3.2% of the total Australian population , yet areDLM was designed to better support Aboriginal and Torres Strait Islander people to manage HCV, with recognition that offering effective testing and treatment is central to disease control . The enaRaise awareness about HCV, including transmission risk factors and treatment options;Increase access to BBV and STI testing and treatment by Aboriginal and Torres Strait Islander people; andProvide a point of entry to other health services for Aboriginal and Torres Strait Islander people.Deadly Liver Mob (DLM) is a peer-driven, incentivized health promotion program that provides a culturally safe, sensitive, and appropriate way to increase access to testing and treatment of BBVs and STIs among Aboriginal and Torres Strait Islander Australians. It is important to note that the word “deadly” is used by Aboriginal and Torres Strait Islander Australians to indicate something that is very good or excellent . The aimA further goal of this project centered on establishing DLM as a sustainable program in routine operations of a health service. This is important as the cycle of piloting programs for First Nations people and then removing them can be dispiriting for communities .DLM began as a trial program in one site in metropolitan Sydney in 2013. This expanded to a second site in the pilot phase. Results from this pilot have been published , 18. On DLM uses a peer-driven intervention that asks Aboriginal and Torres Strait Islander community members to attend for education about viral hepatitis with an Aboriginal and/or Torres Strait Islander health worker, be screened for BBVs and STIs, return for their results, and receive any required treatment or vaccination. Clients are also asked to pass on their learnings to family and friends, and to encourage them to attend DLM. Each contact with the health service entitles a DLM client to an incentive payment in the form of a voucher. These contacts include: education, recruitment of others, attendance for screening, returning for results, and additional sexual health treatment or vaccination for hepatitis A or B (HBV) (if required) . Given tDLM is modelled on the Safe Injecting CWIZ (SIC) project that was conducted by the architects of DLM in 1998–2002 and targeted people under the age of 25 years who injected drugs , 22. TheThe DLM program was designed to meet the needs of the community and to ensure that messages were culturally appropriate. Aboriginal and Torres Strait Islander cultures share stories through yarning, an Indigenous style of conversation and telling and sharing stories and information , 29. TheThe education is guided by visual aids and conversational chunks of information such as: what is HCV?; how do I get it?; how do I avoid it?; what can I do if I have it? The education session is designed to be easily accessible for clients with low literacy. Yarning between the Aboriginal and Torres Strait Islander staff member and the DLM clint in HCV education sessions monitor the quality of peer messages and build on the client’s knowledge while dispelling any myths. Yarning takes possible negative experiences of education into account by taking a non-authoritative approach to knowledge building.Following education, the DLM worker offered clients the opportunity for testing. The Aboriginal and/or Torres Strait Islander DLM worker accompanied the client to screening to introduce sexual health workers  who manage the clinical aspects of DLM including screening, delivery of results, and provision of treatment such as for HBV (vaccination or treatment), HCV, HIV, and STIs (if required) as per standard care. When initially introduced in two pilot sites in 2013 and 2015, direct-acting antiviral treatments for HCV had not yet been introduced, thus treatment available for HCV consisted of combination pegylated interferon-alpha with ribavirin. In March 2016, the Australian Government began subsidizing access to direct-acting antiviral treatments, which became the treatment available for HCV across existing and subsequent DLM sites. The DLM Aboriginal and Torres Strait Islanders workers were involved, if needed, in re-contacting DLM participants to ensure that test results could be delivered by clinical staff.Robust and high-quality evaluation frameworks are built upon and examine the causal assumptions of the intervention , 30. FigIn designing the DLM evaluation framework, we used insights from the RE-AIM model  and fromMoore et al.  define cThe research funds from the NHMRC enabled the establishment of an independent evaluation team based at the Centre for Social Research in Health at UNSW Sydney. As Moore and colleagues note , there iDLM operated as a network with governance and processes established to guide both implementation and evaluation. A particular issue in governance processes was the involvement of Aboriginal and Torres Strait Islander people to meet the expectations of community control in delivery and in evaluation of the DLM program. The governance policies emphasised the need for Aboriginal and Torres Strait Islander people to be involved in all aspects of the program in implementation, evaluation, and in public presentation of the DLM program.The nine sites involved in the DLM program committed to regular teleconference meetings for management and for catch-up with sites and an annual face-to-face meeting, which included opportunities for the Aboriginal and Torres Strait Islander workers to meet. These processes enabled the staff at each site to share information about the ways in which they had solved implementation issues at their site and for the evaluation team to monitor and record these issues. These meetings provided the opportunity for the evaluation team to identify instances where data were recorded in different ways in some sites and to harmonise these in a timely way.www.deadlylivermob.org). The next section illustrates how the evaluation framework was designed using the RE-AIM framework to examine the causal assumptions of the DLM program (as illustrated in the program logic).The plan for the evaluation design included qualitative data , quantitative data (routinely collected data from NSP services) and data linkage . In addThe five dimensions of the RE-AIM framework were designed to guide more comprehensive evaluations of public health programs designed for wide-scale and real-world implementation, such as in busy services operating without the support of a research infrastructure. Part of the vision of RE-AIM is to move beyond individually focused outcome measures, to those which reach into organisational levels. That is, RE-AIM guides evaluations to consider factors beyond only efficacy, and to incorporate measures and evaluation designs that broaden the range of factors beyond clinical measures only. In this case, the acceptability of the DLM to clients and staff was also a key aspect of evaluation. The sections below map out the key evaluation aims of each element of RE-AIM and then how the DLM evaluation framework was designed to examine these.In this element of the framework, evaluations should consider the individual characteristics of DLM participants in comparison with the broader target population. The target population for DLM included Aboriginal and Torres Strait Islander people living, working, or visiting the area around the DLM program and those who had ever or currently injected drugs, or were classified as “at risk” of injecting drug use and/or BBVs and/or STIs . DLM sites were established in areas where significant numbers of Aboriginal and Torres Strait Islander people were known to live. Many DLM sites established outreach work where they would conduct the DLM program in other services which potential DLM participants were already accessing . The provision of incentives included the rationale that this small amount of money could support the attendance of people who might not otherwise have the means to attend, including covering transport costs.In a commitment to low threshold access to DLM, minimal data about DLM participants was collected directly. We were able to use data routinely collected by the service on participants’ engagement in the various stages of the program, which also included peer referral or how many DLM participants recruited others to the program. If DLM participants accessed clinical services, we were able to use data linkage to explore additional demographic and clinical variables. Qualitative research  explored issues around reach, including barriers to engagement and participation.This is the second individual level dimension of the RE-AIM framework and is focused on determining whether the program achieved its aims. The authors of the RE-AIM framework also point to the need to consider not just biological but also behavioural  and participant-centred indicators of program impact (such as broader indicators of well-being and satisfaction with the program). Evaluation of efficacy should also focus on positive and negative outcomes including unexpected pathways and consequences .The outcomes within the DLM program logic model include increased awareness of HCV and decreased burden of HCV among Aboriginal and Torres Strait Islander communities via linkage to testing and treatment. It was considered that assessment of knowledge of HCV via survey of DLM participants was not appropriate. For example, a survey of DLM participants prior to engagement in DLM (and with associated informed consent procedures) would have presented an unacceptable and unethical barrier to service access. Further a survey of knowledge would risk being considered by clients as researchers working within a deficits-based approach  rather than framing the project as considering how health services could more effectively communicate health information to Aboriginal and Torres Strait Islander clients. In qualitative interviews, we explored what DLM clients valued about the program including what knowledge was gained and whether being a part of DLM affected their engagement with HCV and other health services. These interviews were conducted by Aboriginal researchers from the evaluation team and not involved in DLM operations or clinical care. Similarly, in qualitative interviews with DLM staff, we explored their perceptions of the impact of DLM on clients’ health care access, as well as their perspectives of offering the DLM program (and associated services) including implementation and adaptation issues. Using data linkage, we planned to explore clinical outcomes relevant to DLM efficacy including proportion of new diagnoses, treatments provided in the local region. In addition, we planned to establish whether a DLM participant had either accessed sexual health services prior to DLM, and whether they returned for additional care following engagement in DLM.As an organisational-level RE-AIM dimension, adoption refers to the proportion and representativeness of settings that have adopted the program. Which settings have adopted the program can be observed.www.deadlylivermob.org).At full operation, DLM was operating in nine sites across the state of NSW  which were situated in seven of 15 LHDs in the state. To further promulgate the DLM method and provide resources for additional sites, we have developed an online toolkit for implementation  with the expectation that a significant amount of time was required for a program of this type to become institutionalised as routine programming and supported by management.While DLM was supported for a three-year evaluation, there were factors that significantly impacted operations. Data collected in team meetings and via the issues register were used to map interruptions to service . We used these data to populate ‘trouble shooting’ sections of the implementation toolkit to guide future sites in strategising solutions to maintain effective connection with Aboriginal and Torres Strait Islander communities. The final period of DLM evaluation overlapped with the start of the COVID-19 pandemic. Given the vulnerabilities of Aboriginal and Torres Strait Islander communities to COVID-19 , many noEvaluation of real-world programs which are designed to improve the health of marginalised groups requires a careful design with a sensitive and flexible research apparatus. The main goal of the evaluation design was not to interfere with the program’s efforts to engage Aboriginal and Torres Strait Islander people in health care. This meant, for example, negotiating a waiver of consent to use routinely collected data that can be messy and vary across settings, using qualitative data to explore the detail of program delivery and acceptability, and using linked data to explore clinical outcomes of the program . This evaluation design also necessitated close engagement between researchers and those involved in program delivery as we sought to understand the various ways in which sites implemented DLM. However, this engagement brings a richness to the evaluation process and its outputs, particularly in the design of a toolkit to enable others to implement this program as efforts to improve the health of Aboriginal and Torres Strait Islander people must continue, and critically engage with the key barriers that have produced such stark inequities in health over centuries of colonisation.


In recent years, novel teaching methodologies have been emerging with the aim of improving student learning. One of them is known as Blended Learning. BL allows educators to integrate elements of traditional face-to-face teaching with tailored online learning modalities, integrating the distinct strengths of both methodologies.To determine the effectiveness of a heart disease blended learning program in undergraduate physiotherapy students.124 participants  performed an 8-week heart disease blended learning program that included face-to-face classes and online resources. Knowledge was assessed at baseline, at 4, 8, 12 and 20 weeks. Motivation and engagement were assessed at 4 and 8 weeks. Design of the instructions and learning behaviors were measured at 8 weeks. Finally, 108 subjects completed the studyp = 0.02), at the end of the program (p < 0.001), at 12 weeks (p < 0.001) and 20 weeks (p = 0.001). After the intervention, a high intrinsic motivation was shown (5.60 ± 0.80)) over 7), whilst extrinsic motivation scored 4.24 ± 0.97 over 7.Finally, engagement (3.98 ± 0.52) over 5), design of the instructions (4.15 ± 0.62) over 5) and learning behaviors (70.51 ± 36.08) downloads, 28.97 ± 16.09) topics visited, and online questionnaires scored 7.67 ± 1.60) over 10) reported adequate scores.Knowledge significantly increased mid-program (This program seems to be an appropriate methodology in future physiotherapists, since it improved knowledge and participants exhibited a high motivation and an adequate engagement, design of the program instructions and learning behaviors. The rapid technological evolution experienced recently has meant significant progress, resulting in greater accessibility to knowledge generating changes in the needs of society . In the One of the principles that should pursue education is to attempt to improve knowledge acquisition. A recent meta-analysis by Li et al.  demonstrMotivating future healthcare professionals is necessary to improve the acquisition of knowledge. Previous studies have strongly suggested that BL promotes such motivation , 9. SpecConcerning the different dimensions engagement involves, it seems that social presence, described as the online student's sense of being and belonging in a course, maybe one of the reasons behind the success of BL . In addiFinally, the design of the program instructions comprises those dimensions related to interaction in online environments that can help analyse the educational processes generated in institutions that use this educational modality .BL is an effective method within the health professions , 10. ResThe spectrum of cardiac diseases is vast, and to effectively fulfil their responsibilities, physiotherapists must receive specialized and appropriate training for a comprehensive understanding of cardiac pathology. This knowledge equips them to make informed decisions, tailor rehabilitation programs to individual needs, and support patients recovering from various cardiac conditions. The knowledge, skills, and practices acquired through blended learning can serve as a bridge, addressing the existing educational gap and equipping physiotherapists with the expertise they require in this field of healthcare .In this context, our study aims to assess the effectiveness of a meticulously designed blended learning program tailored to address cardiac pathology. Our focus includes evaluating knowledge acquisition, motivation, engagement, program instructions, and learning behaviours among undergraduate physiotherapy students. Our ultimate goal is to contribute to the comprehensive training of future physiotherapists, subsequently enhancing the quality of cardiac rehabilitation for patients across a broad spectrum of cardiac diseases.n = 17). The study was carried out at the authors' institution.124 undergraduate physiotherapy students  were recruited from January 2021 to February 2021. Criteria for participant inclusion were to be studying second year of the Physiotherapy Degree at the aforementioned University and to be willing to participate. Participants with previous heart disease training were excluded to prevent the bias of prior knowledge, as they may have preexisting expectations or biases that could influence their perception or response. From a total of 141 individuals who fulfilled the inclusion criteria, 124 took part in the study. The main reason for exclusion was unwillingness to participate . The principles of voluntariness, confidentiality and anonymity were respected during the research process. No incentives were provided for participation. The study was registered in Clinicaltrials.gov (NCT05645159) on 25/11/2022.Participants provided demographic information, including age, gender, occupational status, years of previous computer experience, years of previous internet experience and years of previous online learning experience.•Knowledge acquisition of cardiovascular risk factors and cardiovascular disease, measured with two questionnaires: (i) “Coronary Artery Disease Education Questionnaire” (CADEQ) ( (CADEQ) ; and (ii (CADEQ) . CADEQ i (CADEQ) . EMDADER (CADEQ) . Student•Motivation, using the Academic Motivation Scale and Attributional Styles Questionnaire . The questionnaire is divided into five dimensions: Intellectual Capabilities (items 1–10), Working Together (items 11–16), Teaching (items 17–25), Teacher-student Relationship (items 26–29), and Student-student Relationship (items 30–35). The maximum score of the questionnaire is 5. Cronbach's alpha ranges from 0.75 to 0.89  that includes three dimensions: (i) Cognitive Presence (items 1–13), related to the degree to which participants are able to construct meaning and knowledge through continuous communication, reflection, and discussion; (ii) Social Presence (items 14–22), related to the ability of participants to identify with the community, communicating and developing interpersonal relationships; (iii) Teaching Presence (items 23–34), referring to the design, guidance and direction, on the part of teachers, of cognitive and social processes with the purpose of achieving the result of meaningful learning in students. The maximum score of the questionnaire is 5. Questionnaire validation shows satisfactory results  (y Survey . A 34-itmension) .•Learning behaviours, including number of downloads, topics visited and total score of questionnaires were retrieved and collected from the institution's Moodle platform Virtual ClassroomTM, through class progress (progress . StudentKnowledge was assessed at baseline (T1), at week 4 (T2), at the end of the intervention [week 8 (T3)], and at two follow-up time points (follow-up at 12 weeks (T4) and follow-up at 20 weeks (T5)). Motivation and engagement were assessed at T2 and at T3, whilst design of the program instructions and learning behaviours were measured at the end of the program (T3).We excluded participants with prior training in heart disease to maintain uniformity in our study and ensure that the results accurately reflect the impact of the intervention on people with no prior expertise. Assessments were conducted by a teacher with more than 10 years of experience. The outcomes were as follows:A health allied teacher with over 10 years’ experience in teaching heart disease performed the 8-week BL program. The BL program combined asynchronous online learning modules and scheduled online activities with face-to-face lectures offered at set points during the semester. Participants had autonomy and flexibility for accessing online course content, except for the seven scheduled face-to-face classes. Moodle platform was utilized as a virtual communication platform, including breaking news, access to the teaching guide, or as a means to solve doubts through discussion forums; (ii) An online syllabus about heart disease composed of seven themes developed from the knowledge considered as basic for health allied students, including topics such as anatomy and physiology of the heart, arrhythmias, hypertension, coronary artery disease, heart failure, shock, endocarditis, myocarditis and pericarditis; (iii) Online videos of international and national scientific societies were used, which aimed at improving the knowledge regarding heart disease, and reinforcing the concepts of heart disease, arrhythmias, nerve conduction, hypertension, angina pain pattern, left ventricular ejection fraction, fluid accumulation in heart failure, cardiogenic shock, etc., In addition, one-minute bullet-point videos were developed by the research team; (iv) Links to websites of international and national scientific societies were used, such as the American Heart Association, the European Society of Cardiology or the Spanish Heart Foundation/World Heart Federation, aimed at reinforcing knowledge acquisition and the concepts of hypertension, coronary artery disease, heart failure, shock, or guidelines for the diagnosis of pericarditis; (v) Podcasts of international and national scientific societies such as the Spanish Cardiac Society or the Spanish Heart Foundation were presented; vi) Online multiple-choice questionnaires were created and personalised comments about the activities were reported by the teachers to give feedback to the students; vii) Mobile apps were used  to improve knowledge on heart anatomy, or to prevent cardiovascular risk and locate nearby defibrillators; viii) Forums, emails and online tutoring were delivered, by means of an online communication platform (Blackboard Collaborate), which is a simple and reliable virtual classroom solution to power online teaching needs. It is a browser-based web conferencing with easy access and high-definition audio and video that enables the students to participate remotely. The tool has been shown to be an efficient means in healthcare and academic environments (The online resources used were as follows: (i) A ronments , 10.α level was set at <0.05 for all tests. For the effect size of the continuous variables, Cohen's d was computed, whereby the effect size was rated as follows: small (0.20–0.50), medium (0.50–0.80), or large (>0.80).Statistical analyses were performed using SPSS v. 24 . Descriptive statistics were performed. Continuous variables are shown as mean , and categorical variables as absolute frequency (percentage). Additionally, the inferential analyses of the data were conducted using a one-factor mixed multivariate analysis of variance (MANOVA) having a within-subject factor “time measurements” with five categories  for knowledge variables. Post-hoc analyses were requested using the Bonferroni correction. Homoscedasticity and sphericity were evaluated using Levene's test and Mauchly's test, respectively. A paired t test was used to investigate motivation changes between T2 and T3, while a Chi-squared test was used to analyse engagement differences between T2 and T3. Furthermore, the correlations between knowledge, motivation, engagement, and design of the program instructions were statistically evaluated using Pearson's correlation coefficient. The The study included 124 participants, of whom 108 (87.10%) completed the study . The meaF = 11.63, p < 0.001, η2 = 42.92]. A gradual and significant increase of knowledge with respect to T1 was observed in pairwise comparisons in the T2 assessments (mean difference = −0.87 ± 0.26), p = 0.02, Cohen's d = −0.19), in T3 (mean difference = −1.296 ± 0.29), p < 0.001, Cohen's d = −0.54), in T4 (mean difference = −1.659 ± 0.25), p < 0.001, Cohen's d = −0.66) and T5 (mean difference = −1.13 ± 0.285), p = 0.001, Cohen's d = −0.48). Furthermore, a higher score was observed after one-month follow-up than mid-program (mean difference = −0.78 ± 0.23), p = 0.01, Cohen's d = −0.41).Regarding CADEQ scores , there wF  = 13.88, p < 0.001, η2 = 55.51]. In addition, the knowledge gained increased significantly with respect to T1 in all subsequent assessments: T2 (mean difference = −0.89 ± 0.19), p < 0.001, Cohen's d = −0.75), T3 (mean difference = −0.56 ± 0.16), p = 0.01, Cohen's d = −0.53), T4 (mean difference = −1.10 ± 0.20), p < 0.001, Cohen's d = −0.94) and T5 (mean difference = −1.05 ± 0.17), p < 0.001, Cohen's d = −0.90). Significant differences were further observed between T3 and T4 measurements (mean difference = −0.54 ± 0.17), p = 0.02, Cohen's d = −0.50) and T5 (mean difference = −0.49 ± 0.14), p = 0.01, Cohen's d = −0.51)  .p > 0.05).At the end of the program, the Intrinsic Motivation dimension had the best scores (5.60 out of 7 points), followed by the Extrinsic Motivation (4.24 out of 7 points), and, lastly, Performance Motivation (3.96 out of 7 points). As shown in p > 0.05)  out of 5). Scores at the end of the program were similar to those obtained mid-program ( > 0.05) .Regarding Teaching Presence, more than 95% of the responses indicated "neutral" and above with a mean score of 4.15 ± 0.62. In relation to Social Presence, more than 81.38% of the responses indicated "neutral" and above with a mean score of 3.56 ± 0.8. Finally, with regard to Cognitive Presence, more than 89.66% of the responses indicated "neutral" and above with a mean score of 3.77 ± 0.79 (Data shown in r) = 0.18; p = 0.04], Performance Motivation , Engagement , Cognitive Presence , Social Presence  and Teaching Presence ; as well as a significant negative relationship with Extrinsic Motivation . In addition, there was a strong correlation between the Engagement and Design of the instructions domains: Cognitive Presence (r = 0.71), Social Presence (r = 0.65) and Teaching Presence (r = 0.70) . There was also a low-moderate correlation between Performance Motivation and Social Presence  and Teaching Presence , as well as between Knowledge and Cognitive Presence  (We observed a significant positive relationship between Intrinsic Motivation and the following variables: Knowledge [Pearson's Correlation ( = 0.04) .To the best of our knowledge, this is the first study that evaluates the effect of a heart disease BL program on knowledge, motivation, engagement, design of the program instructions and learning behaviours in future physiotherapists. The proposed BL program is effective in acquiring knowledge about risk factors and cardiovascular disease in the short term (at mid-intervention and at the end of the intervention) and medium term (at 12 and 20 weeks after the start of the intervention). In addition, participants showed a high motivation, engagement, evaluation of the design of the program instructions and learning behaviours. Interestingly, it was observed that the greater the intrinsic motivation, the greater the performance motivation, knowledge, engagement and evaluation of the design of the program instructions.Regarding the acquisition of knowledge on cardiovascular risk factors and cardiovascular disease, the BL program is effective in the assimilation of theoretical concepts regarding heart disease. These results are consistent with previous studies which concluded that BL is an appropriate learning methodology, equally , 23–25 oIt has further been described that BL has a high impact on motivation . In factIn terms of engagement, most of our participants stated that BL is a method that stimulates intellectual skills . A possible reason is that, in BL, the participant acquires an active role and seems to be more involved in the learning process due to the autonomous monitoring of online resources, which in turn allows in-depth review of the subject, enabling participants to interact with the teacher and their peers more effectively . This isIt is interesting to assess the design of program instructions as it guides teachers towards creating a useful/meaningful learning experience . Our finThis study presents a number of limitations that should be taken into account for future research. First, the sample consisted of future physiotherapists from only one institution, which prevents extrapolating the results to other institutions and other health allied professionals. Second, it would have been interesting to compare the results of the BL program against a control group following a traditional learning method, or with an e-learning program. Third, the possibility of assessing motivation, engagement and design of the instructions at the beginning of the intervention and after a follow-up period of could be considered.Despite the limitations, the present study has several strengths that should be highlighted. On the one hand, studies on BL in higher education are scarce despite its importance based on current technological progress. In fact, to date, this is the first study that addresses a heart disease BL program in future physiotherapists and evaluates the knowledge not only after the intervention, but also mid-program and at two follow-up times in order to determine if the knowledge persists over time. On the other hand, it is highly interesting to evaluate the motivation and engagement, as well as the design of the program instructions, since that in turn favours knowledge acquisition. We further highlight the fact that the BL program carried out has a large amount of online material that is rarely included or scarcely detailed in previous studies.The BL program was effective for acquiring knowledge about risk factors and cardiovascular disease. In addition, participants presented high levels of motivation, engagement, evaluation of the design of the program instructions and learning behaviours. Therefore, BL seems to be an effective method for future physiotherapists and may be considered a teaching-learning strategy of choice to be implemented in health allied professions.


Longer central line (CL) dwell times are associated with increased risk of central line associated blood stream infections (CLABSIs). Removal of invasive devices when they are no longer clinically indicated is key to CLABSI prevention.Table 1Comparison of the Device Review Programs Impact on Central Line Utilization Rates and CLABSI RatesOur health system designed two quality improvement initiatives intended to serve as external review and feedback processes on the necessity of invasive devices. Line Stewardship (LS) was initiated March 2022 in Hospital A and later implemented in 6 acute care facilities. A team consisting of infection preventionists (IP), vascular access nurses and nurse leaders performed chart reviews to determine if CLs met institutional criteria for necessity. If no indication for the device was found, the clinical team was contacted to recommend removal. The second program was called Infection Prevention Integration Program (IPIP), which had a stepwise rollout throughout 2022 in 5 acute care facilities. This program involved IPs joining multi-disciplinary rounds to make recommendations on device removals.Hospital A piloted the LS program in 8 units and during the first year, removed 398 CLs, and saw a reduction in the CLABSI rate compared to the year prior (Table 1). Similarly, implementation of IPIP led to a reduction in the CLABSI rate. Both non-LS and non-IPIP units reported an increase in CLABSI rates during the intervention period compared to baseline (Table 1).Both programs saw improvements in CLABSI rates, achieving the goal of reducing infections. IPIP units saw a larger decrease in the utilization rate compared to LS units. This may be due to differences in the criteria used to determine eligibility for line review. Also, there were differences in unit selection; general wards were selected in LS facilities and intensive care units in IPIP facilities. Both LS and IPIP teams noted benefits of the program beyond line removal in improved attention of staff to overall infection prevention practices. Given the increases seen on non-LS and non-IPIP units, it is important to ensure resources aren’t being diverted away from non-intervention units. While both interventions are time and resource intensive, they led to a reduction in CLABSI burden justifying the necessary institutional support.All Authors: No reported disclosures


Effective response strategies to earthquake disasters are crucial for disaster management in smart cities. However, in regions where earthquakes do not occur frequently, model construction may be difficult due to a lack of training data. To address this issue, there is a need for technology that can generate earthquake scenarios for response training at any location. We proposed a model for generating earthquake scenarios using an auxiliary classifier Generative Adversarial Network (AC-GAN)-based data synthesis. The proposed ACGAN model generates various earthquake scenarios by incorporating an auxiliary classifier learning process into the discriminator of GAN. Our results at borehole sensors showed that the seismic data generated by the proposed model had similar characteristics to actual data. To further validate our results, we compared the generated IM  with Ground Motion Prediction Equations (GMPE). Furthermore, we evaluated the potential of using the generated scenarios for earthquake early warning training. The proposed model and algorithm have significant potential in advancing seismic analysis and detection management systems, and also contribute to disaster management. Advancements in digital conversion and storage technology for earthquake records have prompted an upsurge in the utilization of artificial intelligence (AI) for earthquake analysis. A range of AI-driven models demonstrates high performance in analytics within their trained parameters. However, accurately analyzing the non-stationary seismogram for earthquakes remains a challenge. Even for earthquakes with similar magnitudes and epicenters, there is a difference in the wave time series of each event . TherefoRecently, many researchers have swiftly developed AI models focused on the detection and analysis of seismic data. It’s recognized that AI methodologies are more efficient than traditional empirical analysis methods conducted by humans . This fiGenerative Adversarial Networks (GANs) that can generate data have been used as a solution to data shortages ,14,15. GThe waveforms allow us to infer a multitude of characteristics associated with seismic activity processes. These waveforms provide critical information for estimating aspects such as the energy level of the source , the hypocenter , and geological effects  ,23,24,25In addressing the question of whether we can produce artificial waves by incorporating various physical factors inherent in seismograms, this study navigates through two primary limitations: (1) the complexity of the geological conditions that pose challenges in labeling , and (2)In this study, we pursued a method for generating artificial seismic waves based on a minimal set of seismic features, with the primary considerations being the source and the path. We tried to produce an artificial wave for the epicenter distance that mimics the arrival time of the Phase and the attenuation of amplitude. Our aims were to develop earthquake scenarios that could contribute to effective disaster management . To achi= 1 for actual data Generative Adversarial Networks (GANs) are a deep learning model composed of two opposing networks—a generator and a discriminator—that is used for unsupervised learning . In the Although GANs have the ability to generate realistic samples, we cannot control which samples are created . ConditiLM, and epicenter distance R). Thus, {Auxiliary classifier GAN (ACGAN) is a variant of CGAN that incorporates random noise and class label information, where the discriminator is composed of two classifiers that classify real/fake and class . ACGAN iThe digitally recorded earthquake data could be utilized for conducting earthquake hazard assessments based on statistical and probabilistic estimates. A prime example is Ground Motion Prediction Equations (GMPEs). GMPEs offering empirically simple solutions predict ground motion based on statistical and probabilistic methods ,38. EmpiThis study considers the foundational theory of the GMPE. The GMPE identifies three primary effects: (1) source effects, which are related to the characteristics of the earthquake’s energy and origin ; (2) path effects, which concerns the seismic wave’s path from the earthquake source to the observation site ; (3) site effects, which are linked to the unique conditions of the location where the ground motion is predicted . Of these, the attenuation of seismic waves is determined by the amount of energy released at the epicenter distance . For sitBased on these physical features, we proposed the concept illustrated in https://www.kyoshin.bosai.go.jp, accessed on 30 July 2020) and Korea Meteorological Administration (KMA) data  as its basic dataset. The seismic records used in this study were collected only at borehole sensors from 1997 to 2021. This study utilizes kik-net data (LM) and Epicenter distance . The data contains source information  and Station information . Therefore, we were able to configure labeling when applying GAN. In this study, we grouped the data based on the important functions of local magnitude  seismogram based on the set magnitude and target separation distance. The generating data format is mini-SEED. However, our program can only generate less than 120 km from the epicenter due to the training data set.Additionally, we designed a program to generate artificial seismic waves based on the KMA borehole-type seismic network. The verification for the final version focused on the attenuation of seismic waves, which was based on actual earthquake locations. The objective of this study, using ACGAN, was to create earthquake scenarios in areas of low seismicity. So, we verified possible the simulation of early warnings utilizing the proposed program. For our simulations, we used ElarmS 3.0 , which hThe magnitude error was found to be up to 0.67, which is an acceptable range of error given the range of magnitudes labeled during fine-grained training. The location error was up to 3.7 km, and the time error was up to 1.41 s. The error in the analysis with artificial seismic waves was not significant, and it was confirmed that the P-S time was well simulated. Therefore, it is confirmed that our model can be used for the verification of early earthquake warnings based on the attenuation characteristics of P-wave and maximum acceleration, and a good simulation of P-S arrival time.LM < 6.0) were considered, with amplitude attenuation trends confirmed. The site effect was not trained, and for estimating IM at a specific site surface, passive methods such as transfer functions or one-dimensional ground response analysis  should Manual preprocessing for seismic training and validation is complex and requires global, unified rules. The number of AI-generated seismic data for each seismic event is still limited, and more data for comparison/validation is needed for greater statistical reliability. The variance (regression error) of AI-generated earthquakes can be useful for handling outlier data, whereas a smaller variance is beneficial for generating data that better simulates amplitude decay. The optimized loss function of the GAN model can partially control this variance. Finally, GAN models are technically challenging to train in AI, requiring significant computational resources and expertise.In conclusion, this study has successfully utilized AC-GAN, an advanced artificial intelligence technology, to generate virtual earthquake data for the Korean Peninsula. The model used was an improved version of GAN that accurately reflects the characteristics of real seismic waves and was trained with a large amount of seismic observation records. The generated earthquake data was undistorted and responded appropriately to changes in input samples and epicenter distance. By inputting the virtual earthquake data into the ElarmS earthquake early warning system, the time, location, and magnitude of the earthquake source were simulated with high accuracy. This technology can be utilized for virtual earthquake simulation exercises specific to the Korean Peninsula and can supplement actual earthquake history by creating scenarios of earthquakes that can potentially occur in the region. This study could use important technology for earthquake preparedness and risk management in the Korean Peninsula.Given the specific nature of the data used to train our GAN models, their applicability may not extend to all scenarios. Therefore, it is essential to integrate them with traditional interpretation methods for predicting seismicity that reaches the surface. Through refining and effectively combining these learning methods, we can enhance our ability to predict the impact of various earthquakes. Additionally, although the characteristics of the earthquakes we have analyzed primarily focus on the P-S phase , it is crucial to also consider a broader range of factors, such as stress drop, wave tails, and the clustering features of seismic waves. Developing a GAN model that can accurately simulate these aspects will further advance our earthquake analysis capabilities.


The 7.8 magnitude earthquake that occurred in southern Turkey on February 6, 2023, has resulted in over 40,000 and 5,000 confirmed deaths in Turkey and Syria, respectively, including substantial infrastructure damage. While Turkey has received assistance from various countries and international organizations, the level of support Syria has received remains unclear. The Assad regime has demanded that aid be sent to the capital Damascus, but this may hinder the delivery of assistance to the areas most severely affected by the earthquake because the affected regions were mainly controlled by rebel forces.One of the biggest challenges in providing aid is accessing the affected region, as the earthquake occurred close to the border between Syria and Turkey, where roads and other infrastructure are poorly constructed. Furthermore, the northwest area of Syria shelters many internally displaced people, and more than 50% of medical facilities are not functioning due to the ongoing conflict, making the situation more hazardous.In light of the experience of the Great East Japan Earthquake, securing direct support routes and dispatching medical personnel to the affected areas is crucial for a gradual recovery from the disaster. Therefore, it is essential for the international community, including Japan, to negotiate with the Assad regime to expand direct support routes and provide support for the dispatch of medical personnel who will remain and work in the affected areas. Humanitarian assistance and political issues should be kept separate to avoid further hindrances to aid delivery. In this context, the magnitude 7.8 Turkey-Syria earthquake occurred on February 6, 2023. More than 40,000 people in Turkey and 5,000 in Syria have been confirmed dead. Although Turkey has received assistance from 70 countries, such as the United States, the United Kingdom, and Russia, including 14 international organizations, the situation of support for Syria from the international community is unclear.The need for international cooperation, regardless of the underlying political issues, to save the local people from disasters in countries experiencing internal conflicts is currently being emphasized (2). Furthermore, in Syria, more than 50% of medical facilities are reportedly dysfunctional due to the prolonged internal conflict (3), and the Syrian people are desperate to recover from the disaster on their own. As for international assistance for the earthquake, the Assad regime has demanded that all aid be sent to Damascus’s capital, including aid to areas outside their control. So far, Iran, Egypt, India, and some other countries have sent aid supplies directly to airports under the Assad regime’s control.This is mainly due to the internal conflict within Syria that began in 2011, which has divided the country into several ruling groups and resulted in a lack of domestic coordination. The Assad regime has been internationally criticized and isolated for its thorough suppression of rebel forces and is under severe sanctions. Consequently, the current report revealed that more than 80% of the Syrian people live in poverty, less than US$2 per day and more than 9 million people live in food scarcity (3), thus making the situation much more hazardous.However, some areas most severely affected by the earthquake were regions controlled by rebel forces. Although international aid should be provided based on formal requests from the affected country’s government to protect its sovereignty, delivering aid to the Assad regime by air may prevent timely assistance to victims in rebel-controlled areas, making it increasingly important to provide direct local assistance from abroad. Therefore, access to the area for humanitarian activities has become one of the major challenges since the earthquake occurred near the border between Syria and Turkey, where roads and other infrastructure are not well-developed. Indeed, before the earthquake, only one road in this area could carry supplies directly from Turkey to Syria, as rebel forces controlled this area. This is also an area where many internally displaced people, mainly women and children, have taken shelter from the internal conflict (4). This enabled the direct provision of necessary support and the dispatch of medical professionals from other prefectures, which considerably contributed to promptly improving the health of the affected areas. Despite different backgrounds, it is essential to recover from the disaster to prepare support routes as quickly as possible and to dispatch researchers and medical personnel to the affected areas so that the medical system can be set up promptly (4).Considering the experience of the Great East Japan Earthquake, one of the most critical initial responses was to secure 16 emergency routes to the affected areas by removing obstacles and opening access roads, known as the "teeth of a comb strategy," resulting in 97% of them being passable within one week (5). Thus, considering that the fundamental cause of the difficulty in providing international aid to Syria stems from the ongoing civil war, which has made it challenging to trust the current regime, it is crucial to undertake efforts to dispel tensions between the Assad regime and the international community by continuously implementing peacekeeping activities and long-term support, rather than solely focusing on short-term assistance in the aftermath of an earthquake. We look forward to establishing an international cooperative framework between Turkey and Syria and hope for a rapid reconstruction of both countries.In this context, the continued failure to secure support routes to Syria could lead to more deaths and injuries in the affected areas. Despite the differences in social stability, political, and cultural backgrounds between the current earthquake and the Great East Japan Earthquake, regardless of the political issues, it is crucial for the international community, including Japan, to negotiate with the Assad regime to expand direct support routes and to assist dispatching the medical personnel who will remain and work in the affected areas. Additionally, the purposes of the World Health Organization Emergency Medical Team Initiative include simultaneously enhancing the timeliness and quality of medical services through collaboration among domestic and international emergency medical teams, promoting rapid response capabilities in the immediate aftermath of disasters, outbreaks, and other emergencies, and strengthening the capacity of national health systems to lead coordination efforts NoneConception, designing of the study, and writing this paper; Kaneda YCritical revision of the paper; Akashima SAll authors have read the final draft and approved the submission.


Two different isoforms of Kv4.3 are present in the human ventricle and exhibit differential remodeling in heart failure (HF). Cardioselective betablockers are a cornerstone of HF with reduced ejection fraction therapy as well as ventricular arrhythmia treatment. In this study we examined pharmacological effects of betablockers on both Kv4.3 isoforms to explore their potential for isoform-specific therapy. Kv4.3 isoforms were expressed in Xenopus laevis oocytes and incubated with the respective betablockers. Dose-dependency and biophysical characteristics were examined. HEK 293T-cells were transfected with the two Kv4.3 isoforms and analyzed with Western blots. Carvedilol (100 µM) blocked Kv4.3 L by 77 ± 2% and Kv4.3 S by 67 ± 6%, respectively. Metoprolol (100 µM) was less effective with inhibition of 37 ± 3% (Kv4.3 L) and 35 ± 4% (Kv4.3 S). Bisoprolol showed no inhibitory effect. Current reduction was not caused by changes in Kv4.3 protein expression. Carvedilol inhibited Kv4.3 channels at physiologically relevant concentrations, affecting both isoforms. Metoprolol showed a weaker blocking effect and bisoprolol did not exert an effect on Kv4.3. Blockade of repolarizing Kv4.3 channels by carvedilol and metoprolol extend their pharmacological mechanism of action, potentially contributing beneficial antiarrhythmic effects in normal and failing hearts.Cardiac K There are two different isoforms that result from the alternative splicing of exon 6. The longer Kv4.3 L variant and the shorter isoform Kv4.3 S differ in a 19 amino acid long sequence at the intracellular C-terminus [v4.3, isoforms are differentially expressed: Kv4.3 L is upregulated, whereas Kv4.3 S is downregulated. As a result, the long isoform is predominantly expressed in the insufficient heart [The cardiac Kotential . Changesure (HF) ,3,4. A cure (HF) ,6. In anobserved ,9,10,11.terminus ,13. In p+ channels and two-pore-domain potassium channels (K2P) [Betablockers constitute a cornerstone of pharmacological HF therapy . Metoprols (K2P) ,20,21,22v4.3 isoforms to provide the basis for isoform-specific HF drug therapy.The aim of this study was to examine differential effects of carvedilol, bisoprolol, and metoprolol on Kv4.3 peak current. Both isoforms were similarly affected. Maximum inhibitory effects observed after 50 min yielded a current block of 76.6 ± 2.0%  and 67.1 ± 5.7% . Kv4.3 currents before and after application of carvedilol, as well as the development of the block, are shown in Carvedilol caused time-dependent inhibition of the Kv4.3 L and Kv4.3 S currents was partially reversible. The peak current returned to 33.8 ± 2.6% for the L isoform, and 49.1 ± 6.8% for the S isoform after 30 min wash out. Blockade was concentration dependent with IC50 values of 57.1 ± 12.6 µM  and 58.2 ± 6.2 µM  (The inhibition of K = 8–13) E,F. Activation and inactivation kinetics were assessed by applying depolarizing steps from −100 mV to +50 mV  from a holding potential of −80 mV. There was a return pulse to +50 mV after the first voltage step. The double-step voltage protocol as well as typical current traces in the absence and the presence of 100 µM carvedilol are depicted in v4.3 channel activation, peak currents measured during the first part of the voltage protocol were normalized to the peak current of the last trace and then plotted against the test pulse voltage. Application of carvedilol led to a shift of the half-maximal activation voltages of both Kv4.3 isoforms towards more positive voltages. The half-maximal activation voltage in the presence of carvedilol  differed significantly from the measurements under control conditions  (To examine the effects of carvedilol on K n = 11) C,D. v4.3 isoforms was analyzed by plotting the peak current during the second step of the voltage protocol against the respective test pulse potential. Half-maximal inactivation voltages after application of 100 µM carvedilol were numerically more positive compared to control conditions without reaching statistical significance. Kv4.3 L half-maximal inactivation voltage was −39.5 ± 1.3 mV under control conditions and −38.3 ± 1.3 mV after incubation with carvedilol , whereas values obtained with Kv4.3 S yielded −40.2 ± 2.1 mV under control conditions and −39.5 ± 1.6 mV after carvedilol administration  (The current peak evoked by the second voltage step reflects channel inactivation. Inactivation of the two K= 0.398) E,F.v4.3 L: V1/2 = 25.1 ± 2.1 mV, Kv4.3 S: V1/2 = 24.6 ± 2.8 mV) and after 50 min incubation with 100 µM carvedilol  (v4.3 was −22.5 ± 1.6 mV (control) and −21.7 ± 1.2 mV after incubation with carvedilol . For Kv4.3 S, values of −23.6 ± 3.1 mV under control conditions and −22.7 ± 1.7 mV after treatment with carvedilol  were calculated  C,D. Furtlculated E,F. v4.3 inactivation was assessed using a multistep protocol. After a depolarization step from a holding potential of −80 mV to +50 mV for 500 ms, a return pulse to the −80 mV holding potential was applied with durations ranging from 10 to 200 ms in 10 ms increments. The variable duration allowed the channel to recover from inactivation and was then followed by a 250 ms long depolarizing step from −80 mV to +50 mV. The peak currents recorded during the final variable voltage step were normalized to the highest peak current and then plotted against the respective duration of the preceding step. Representative traces are depicted in n = 10, p = 0.002) were observed with Kv4.3 L. For Kv4.3 S, the increase of the time constant was not significant. Time constants of 229.1 ± 45.3 ms under control conditions and 295.9 ± 20.2 ms in the presence of carvedilol were obtained .Next, the recovery from Kn = 11, p < 0.001)  C,D.v4.3 isoforms was analyzed as described earlier using a single step depolarizing voltage protocol. Example traces are depicted in v4.3 L nor Kv4.3 S current amplitudes  or Kv4.3 S   C,D. v4.3 isoforms were similarly assessed. Kv4.3 L currents were blocked 36.5 ± 2.8% , and Kv4.3 S 35.3 ± 3.9%  during metoprolol application    for Kv4.3 L and 49.8 ± 0.7 µM for Kv4.3 S (n = 9–11), respectively  D. No app, n = 9) C. IC50 vectively E,F. v4.3 L and Kv4.3 S whole cell protein was not significantly reduced after incubation with betablockers bisoprolol, carvedilol, or metoprolol, respectively , 64.0 ± 7.8% for carvedilol  and 71.2 ± 6.6% for metoprolol  for Kv4.3 L without reaching statistical significance. For the Kv4.3 S isoform, protein expression relative to control yielded 85.1 ± 7.6% for bisoprolol , 77.0 ± 6.1% for carvedilol , and 94.2 ± 14.2% for metoprolol  without reaching statistical significance. To study the effects of the betablockers on the expression of Kv4.3 protein, both isoforms were individually expressed in HEK-293T cells A,B. Exprectively C,D. Protv4.3 channels isoforms that contribute to repolarization of the cardiac action potential. By contrast, bisoprolol did not affect Kv4.3 currents, indicating drug-specific actions of carvedilol and metoprolol. Carvedilol and metoprolol significantly blocked two cardiac Kv4.3 isoforms as the primary molecular mechanism of action. This assumption is reinforced by changes in biophysical characteristics of the Kv4.3 current after application of carvedilol. It has been shown that pre-pulse duration affects Kv4.3 inactivation kinetics [v4.3 L and Kv4.3 S isoforms by carvedilol. The rapid development of the block after application of metoprolol and carvedilol indicates a direct interaction between the drug molecules and the respective Kkinetics . Thus, wv4.3 L is upregulated and Kv4.3 S is downregulated in HF [to-targeting antiarrhythmic drug therapy should ideally target the Kv4.3 L isoform. There were no pronounced differences between the effects on Kv4.3 L and Kv4.3 S currents for any of the studied betablockers and biophysical parameters. We conclude from these findings that metoprolol and carvedilol cause Kv4.3 current inhibition of both isoforms via the same molecular mechanism(s). The Kv4.3 L type isoform differs from the S isoform in a 19 amino acid long sequence at the C-terminal, intracellular end of the channel [v4.3 isoforms via adrenergic signaling pathways under adrenergic stimulation that are beyond scope of this study. K channel ,13. Thisv4.3 expression and the concomitant reduction of Ito in different HF animal models [v4.3 isoforms. It should be noted that HEK-293T cells endogenously express alpha-1 adrenoreceptors [Bisoprolol and metoprolol counteracted the decreased Kl models ,25. In oeceptors , and eveBetablockers bisoprolol, carvedilol, and metoprolol exert a class effect during treatment of HF patients with reduced ejection fraction, with no apparent evidence for the superiority of any single agent over the others ,27. Howev4.3 channels by carvedilol or to lesser extent metoprolol could thus exert beneficial antiarrhythmic effects. The drug concentrations used in our study are apparently higher when compared to the maximum therapeutic plasma concentrations: IC50 values of 57.1 ± 12.6 µM (L isoform) and 58.2 ± 6.2 µM (S isoform) were obtained for carvedilol. During therapeutic application of carvedilol, maximum plasma concentrations ranging from 0.1–0.6 µM were measured [laevis oocytes tend to be about 5 to 10 times higher [Inhibition of Kmeasured   and performed as previously reported [Animal studies were performed in compliance with the Guide for the Care and Use of Laboratory Animals, as approved and published by the U.S. National Institutes of Health  as well as the current version of the German Law on the Protection of Animals. The investigation conforms to the Directive 2010/63/EU of the European parliament. Surgical procedures on female Xenopus reported .v4.3 isoforms L and S were introduced into DH5-α bacteria with the help of the plasmid vector pMAX−. Plasmid DNA was then isolated using the QIAprep Spin Miniprep Kit  and linearized using PmeI. Next, the DNA was transcribed using T7 DNA polymerase and the mMessage mMachine Kit . The concentration of the transcribed RNA was determined using NanoDrop 2000 . The RNA was then injected into stages V and VI defolliculated Xenopus laevis oocytes using a Nanoinjector . The injected volume was 46 nl and the concentration of injected cRNA was 10 ng. The electrophysiological measurements were carried out 2–3 days after the injection. DNA encoding K2. HEK cells were transfected with the 1 µg DNA of Kv4.3 L and S per well using the Lipofectamine TM3000 Transfection reagent . Twenty-four hours after transfection, the cells were incubated with 10 µM of the different betablockers for another 24 h. Human embryonic kidney (HEK-293T) cells were cultured at 37 °C with 5% CO2, 1 mM MgCl2 und 5 mM HEPES and was adjusted to pH 7.4 with NaOH. Before the measurements, the oocytes were preincubated in this solution for at least 20 min. The experiments were carried out under steady gravity-driven perfusion at room temperature. Two to three days after RNA injection, the electrophysiological measurements were performed using the two-voltage electrode clamp technique as described before . Currentv4.3 currents were induced with a single depolarizing voltage step from a holding potential of −80 mV to +50 mV for 250 ms. To evaluate the effect of 100 µM carvedilol on Kv4.3 current, oocytes were first treated with the betablocker for 50 min, followed by washout with a 4 mM K+ solution to assess reversibility. Values of measured peak amplitudes were normalized to the value of the peak amplitude obtained during the last measurement prior to drug application. K3VO4, 1 mM NaF and inhibitors proteases . Those lysed cells were incubated on ice for 20 min and then centrifugated for 30 min at 14,000× g and 4 °C. The supernatants were then collected, and the protein concentration was determined using the bicinchoninic acid (BCA) protein assay . The proteins were then diluted to equal concentrations with water. Next, equal amounts of proteins were separated on a 10% SDS polyacrylamide gel and then transferred onto polyvinylidene difluoride membranes . After being blocked with 5% milk in PBST for 2 h at room temperature, those membranes were incubated with primary antibodies directed against Kv4.3  at 4 °C overnight. As a control, the respective control peptides for Kv4.3, supplied by the company, were used . A secondary antibody donkey-anti-rabbit  was used. Signals were developed using the Azure 600 Ultimate Western Imaging  and ECLTM Select Western Blotting Detection Reagent . After removal of the primary and secondary antibodies , the membranes were incubated in anti-GAPDH primary antibodies  and the corresponding secondary donkey-anti-rabbit antibody . Optical density was quantified using ImageJ 1.50i Software . For Western Blot studies, HEK cells were lysed in a radioimmunoprecipitation (RIPA) buffer consisting of 20 mM Tris-HCl, 0.5% NP-40, 0.5% sodium-deoxycholate, 150 nM NaCl, 1 mM EDTA, 1 mM Nan)/(kn + xn)). Curves for activation and inactivation were fitted with a Boltzmann function (y = A2 + (A1 − A2)/(1 + exp((x − x0)/dx))). Current traces for the deactivation measurements were fitted with a one-phase exponential decay function with time constant parameter (ExpDec1) (y = y0 + Ae−x/t). Curves for the recovery measurements were fitted with a one-phase exponential association equation (ExpAssoc1) (y = Yb + A × (1 − e−(x−TD)/Tau)). Kolmogorov–Smirnov tests were used to confirm normal distribution of the data. To test the statistical significance, paired Student´s t-tests were applied for all the electrophysiological measurements. For the statistical analysis of the Western Blots, ANOVA tests were used. p < 0.05 was considered statistically significant. Data was analyzed using Origin2022 software  and Microsoft Excel software 2021 . Data are expressed as mean ± standard error of the mean (SEM). The concentration response curve was fitted with a Hill1 function (y = START + ((END − START) xv4.3 channels underlying the Ito current. Carvedilol has a strong inhibitory effect on the Kv4.3 isoforms, whereas metoprolol was less effective. Concentrations required for blockade were within upper physiological ranges. Bisoprolol did not have any effect on Kv4.3 currents. Specific electropharmacological actions of carvedilol and metoprolol may be considered when choosing betablockers for HF therapy. Widely used cardioselective betablockers exert differential effects on cardiac repolarizing K