The issue of collaboration in medical education is becoming prominent. Some faculty development programs have suggested an approach for promoting collaboration on a global level. However, non-English-speaking developing countries in Asia, especially in Southeast Asia, do not take advantage of them due to their unique context, such as language and culture. To address these issues, Seoul National University College of Medicine initiated a 6-week international faculty development program called the “Seoul Intensive Course for Medical Educators” for 16 fellows from five Asian countries . The aim of this study is to report the evaluation results of the outcome of the program and discuss better ways of collaborating with developing countries.Three levels of collaboration—intraorganizational, intranational, and international—were central initiatives of the program. Prior to setting up the program details, we first established four design principles, following which the contents, materials, and facilitators were determined to maintain consistency with the design principles. The evaluation of the program was done with Kirkpatrick’s four-level model. Most of the evaluation data for level 1 were collected by two questionnaires, the post-module survey and the post-program survey. Portfolios and progress reports were mainly used to collect outcome data for levels 2 and 3, respectively.The reaction was generally positive throughout the program and there was a significant correlation between satisfaction and relevance to one’s job or needs. Despite the fellows’ propensity for overestimating themselves, both the evaluators and fellows reported that there was significant improvement in learning. Opinions on the impact or urgency of the topics were slightly different from country to country; however, the answers regarding feasibility were fairly similar. Moreover, we could observe from the post-program progress reports that the transfer of learning was actively in progress, mainly for topics that were highly feasible.These results show that the program was successful in terms of its effectiveness. Consistent and timely support is essential for the sustainable development of the medical education systems in these countries. Further understanding of the underlying factors on transfer (level 3) could improve the effectiveness of faculty development programs for developing countries. The issue of collaboration in medical education is becoming prominent . The speDespite growing trends for international collaboration, developing countries are still experiencing hardships, not only in recruiting human resources for medical schools but also in making opportunities for academic education . Their eWhen focusing on a Southeast Asian context, there are region-specific issues to consider. First, Southeast Asia is one of the regions with the smallest number of medical schools per million population . The resAfter recognizing these challenges and disadvantages that non-English-speaking Asian developing countries face, Seoul National University College of Medicine (SNUMC) initiated an international FDP called the Seoul Intensive Course for Medical Educators (SICME). The Department of Medical Education (DME) and two affiliated institutions of SNUMC, the JW Lee Center for Global Medicine (CGM) and the National Teacher Training Center for Health Personnel (NTTC), had pivotal roles in planning and implementing the program. The primary and immediate goal of the SICME was to educate and prepare fellows as medical educators who would have a broad and general competency in the field. In the long term, we expect them to form a critical mass of leaders in medical education, and to drive educational reform in their own institutions and countries.In total, 16 fellows from five Asian developing countries were invited to SNUMC for the program. Four countries—Cambodia, Laos, Myanmar, and Vietnam—belonged to Southeast Asia and one country, Mongolia, to East Asia. Mongolia was the only country located in a different geographic region, but WHO classified it in the Western Pacific Region, together with Cambodia, Laos, and Vietnam. Indeed, they share common problems in human resources for healthcare  as well This study has two aims. The first one is to describe the key features of the program and to examine the evaluation results based on Kirkpatrick’s four-level training evaluation model to understand the effects and limitations of the program. The second aim is to discuss better ways to collaborate with developing countries in faculty development and education to overcome the challenges facing them. Even though the participants of the SICME are mainly from Southeast Asian countries, we also discuss the relevant implications that would be applicable to other non-English-speaking developing countries, especially those countries who have been marginalized from existing international collaboration due to language barriers.Three levels of collaboration were central initiatives of the program. One level was intraorganizational collaboration inside the host institution—DME, CGM, and NTTC—as mentioned above. Another level included two types of intranational collaboration—one among fellows from the same countries and the other among facilitators from various medical schools in South Korea. The last one was at the international level, which included collaboration among fellows from different countries and continuing international collaboration among institutions participating in the SICME.To promote the fellows’ ownership of the program, every component of the SICME must be organized based on the careful consideration of the needs of the fellows, their institutions, and their countries.To enhance the application and transfer of learning after the program, the contents must be adaptable in resource-limited settings. Additionally, every piece of educational material should be provided in both hard copy and soft copy formats, unless there are any copyright issues.To facilitate learning, participatory and learner-centered pedagogical methods rather than teacher-centered ones must be prioritized and maximized throughout all courses.For continuous improvement, evaluation of the program must be conducted based on Kirkpatrick’s four-level model and feedback from all participants must be considered.Prior to determining the detailed curriculum of SICME, the Planning Committee, consisting of ten faculty members from eight medical schools, reached a consensus on four overarching design principles of the program.Another major task of the Planning Committee was to determine the topics for the 6 week program. Because the NTTC possesses its own source of education programs for health professionals which have been developed, revised, and used for over 35 years since its inception, module topics and their contents and relative lengths were determined primarily based on the previous education experience of the NTTC. After developing the broad outlines of the program, the Planning Committee thoroughly examined the educational backgrounds, professional experiences, stated needs and interests of each participant in his/her application form for fine adjustments to the program contents. All the members of the Planning Committee had iterative meetings to reach a consensus on the final structure and detailed contents of the program. Finally, one week was allotted for modules 1, 2, 3, 4, and 5. Modules 6, 7, and 8 were given one-third each of week 6  and 5 (Expert/Mastery) referring to two widely used competency level frameworks suggested by Dreyfus H  and MillBecause it is recommended to do the level 3 evaluation 3 to 6 months after training, we requested that the fellows report their actual progress 3–4 months after they completed the SICME. Moreover, we had designed part of the PPS with the purpose to predict the transferability of their learning by asking about the anticipated impact (PP 7), urgency (PP 8), and feasibility (PP 9) of the topics in the 8 modules.t-test and Spearman’s correlation analysis were used to analyze the quantitative data obtained during the evaluation process.To ensure content validity, all the instruments for data collection were designed and developed with reference to the book by Kirkpatrick DL , the desFor this study, exemption from ethical review was approved by the Institutional Review Board (IRB) of Seoul National University College of Medicine. Before conducting the surveys, we obtained oral informed consent from all the fellows, and the IRB waived the documentation of informed consent later in the ethical review process.Table Two items, one from the PMS and the other from the PPS, showed statistically significant correlations with the level of satisfaction for each module. One was ‘PM 9’ which asked how much a fellow thinks the module will help him/her do his/her job better Table , and the“It is not easy to translate my impression into a quantitative measure. However, what I’ve found out during the SICME is that their (fellows’) way of thinking changed substantially and was constantly maturing as the SICME progressed. At week 6, the level of discussion and their attitudes as a medical educator were totally different from what I saw in the first week.”In the PMS, we asked the fellows to self-assess their improvement in knowledge, skills, and attitudes. One noticeable finding was that they assessed their improvement in attitude higher than that in knowledge or skills. Although the difference was not statistically significant, the trend was consistent throughout the program, except for module eight Table . This reTo evaluate learning, four evaluators independently assessed the portfolios of the fellows, and the fellows also self-assessed their own overall competencies Fig. . StatistBecause one of our major goals was to train trainers who can then facilitate educational reform at their own institutions, the fellows were expected to disseminate what they learned during the SICME after going back to their countries. Therefore, not only improvement in knowledge, skills, and attitudes but also the development of actual capability as a workshop facilitator who can train trainers is important. In this regard, in PP 6, we asked fellows to choose all the module topics for which they could run a workshop on by themselves after going back to their home institutions. Meanwhile, evaluators also evaluated the suitability of each fellow as a workshop facilitator based on his/her portfolio. The results from the fellows and the evaluators were in agreement in that the fellows are the most capable for facilitating workshops for modules 1 and 3, and the least capable for modules 7 and 8. The correlation between the evaluation results of the evaluators and the fellows also showed statistical significance Table .Table 5EPrior to collecting actual data on transfer (level 3), we tried to examine how fellows perceived each module topic in terms of its impact, urgency and feasibility in the PPS Fig. . As the The interim progress report for each country shows that fellows were actively sharing and transferring their experience from the SICME Table . There wNot long after the submission of the progress report, three of the five countries—Laos, Mongolia and Myanmar—requested that SNUMC provide further support and consultation as an external expert body. Hence, SNUMC organized three separate teams according to the topics and types of projects for which they requested support. Faculty members of SNUMC who participated in the SICME as facilitators took charge of each team as core members. In Myanmar, DME and CGM provided a three-day workshop in July 2014 on ‘Curriculum Development in Line with Accreditation’ to heads, directors, administrators from key organizations in Myanmar who have a major influence on medical education in that country including major medical schools, Myanmar Medical Council, and Myanmar Medical Association. In Laos, CGM, in collaboration with the Western Pacific Regional Office of WHO and University of the Philippines Manila, provided three one-week workshops that cover general topics of medical education to faculty members of the University of Health Sciences, the only medical school in Laos. Lastly, to support the Mongolian fellows, DME acquired funding for a three-year project from the Korea International Cooperation Agency (KOICA) which aims to strengthen the educational capacity of Mongolian health professionals. For this project, DME organized a joint team with experts in organization development who joined the SICME as facilitators in Module 5 and with Raphael International, a medical nonprofit organization whose primary activity is to provide medical aid to impoverished people, which has more than 8 years of experience in medical service provision in Mongolia.In this study, we organized an international FDP for Asian developing countries, based on four design principles using multi-level collaboration. The results show that it is was successfully implemented with fellows who had limited training opportunities to address their own needs. The training was also effective in terms of the first (reaction), second (learning) and third (transfer) levels of Kirkpatrick’s model. Despite the effectiveness of the program, further studies are needed on each level and on how the collaboration actually worked.First, for level 1 (reaction), the fellows showed generally high levels of satisfaction for the various aspects of the program. Although high satisfaction itself does not guarantee learning, this is important because participation might decline unless the fellows perceive that the time and effort they invested is meaningful. Thus, as we expected from our first design principle, it is important to consider the personal and professional needs of participants to motivate their participation , 25. ActRegarding level 2 learning, one of the most interest findings was that a larger increase in attitude, which is particularly important in adult learning, was more significant than that of knowledge or skills. The third design principle of the SICME, which emphasized facilitating learning through learner-centered teaching methods and teacher-centered lectures, seems to have contributed to this result. Based on this principle, we reduced the proportion of lectures, to as low as 30% and tried to maximize learner-centered methodologies, such as small- and large-group discussions, role-playing, and participatory workshops. Through those learner-centered activities, what we tried to achieve was to provide fellows from five different countries with the opportunity to rethink their attitude as medical educators while encountering the ideals and reality of other countries, finding similarities and differences with each other, and arguing for and against something. Through these experiences, they exhaustively reflected on themselves and their situations and thought about their future direction. Previous research showing that active learning and student-centered approaches foster positive attitudes towards the subject  further Although the portfolio evaluation results showed significant improvement in the overall competency of the fellows, we found a tendency for the fellows to overestimate their own competency in the self-assessment results. This is not unusual because prior research has shown that doctors have a weakness in evaluating their own abilities . HoweverLearning in a FDP is less meaningful unless it can then be applied to the workplace. Use of projects, in this regard, as an essential element for effective faculty development, is highly recommended , and manLooking at Fig. In addition to the four design principles, multi-level collaboration was another core strategy to overcome challenges that we are likely to face when attempting an international FDP, such as the SICME. First, there was an intraorganizational collaboration inside the host institution. Institutions that took initiative in the SICME have a distinct experience in educational development, either as a donor or as a recipient. In the 1950s, after the Korean War, there was tremendous financial and educational development aid from the U.S. provided to SNUMC in the form of the so-called Seoul National University Cooperative Project . A few dSecond, two types of intranational collaboration were key to organizing an English workshop with facilitators and fellows only from non-English-speaking countries. One form of the intranational collaboration was that of the facilitators. For most of the facilitators, who had experienced merely short-term training in a foreign country at most, preparing materials and running workshops in English was no small burden. We did, however, successfully lessen the burden of each facilitator by distributing that burden to more than 20 facilitators from 15 institutions while the module coordinators safeguarded the whole program keeping it aligned with the four design principles. The other was the collaboration among the fellows. The fellows were quite heterogeneous in terms of their English fluency, and sometimes, this was a barrier to delivering important concepts. To solve this problem, we encouraged active peer-tutoring and extensive discussions in their own language whenever they needed. The importance of this interaction is that our intended goal of collaboration among the fellows was not only a means to foster the learning of the educational contents during the SICME, but also a foundation for forming a ‘critical mass’ of leaders in medical education at their own institutions, and in their own regions beyond.The last one is characterized as continuous international collaboration which encompasses the whole process of the SICME—before, during, and after the program. Before the organization of the SICME, SNUMC and the partner institutions at the five participant countries already have been maintaining cooperative relationships. These relationships generated two main advantages. First, this allowed us to discern and select the most suitable fellows possessing an appropriate background, commitment to learning, and actual leadership to reach the long-term goals of the SICME. Second, it enabled us to develop the SICME program based on the up-to-date information of the participants which enabled us to address their needs more accurately. The positive impact created by the international collaboration among the participant countries did not end with the program. After completion of the program the fellows, rather than SNUMC, actively sought ways for further collaboration. They not only tried to transfer and share their learning through their own efforts, but also voluntarily looked for ways to utilize newly established international relationships by requesting the participation of SNUMC in their projects as an external expert group. There are two reasons that make this especially encouraging. First, projects initiated and led by the recipient side are likely to be more effective than donor-led projects in that they can target the needs and interest of the recipients accurately. Second, from the donors’ side, the fact that a project is proposed by a recipient institution that calls for external support would more strongly justify the necessity of the project and make it easier to prepare budgets for aid.The evaluation results for levels 1, 2, and 3 showed that we successfully overcame the major inherent challenges of this program through elaborated collaboration. However, there are still some limitations that need consideration. First, our strategy for inviting fellows to South Korea was effective in achieving high satisfaction and active participation in the program, but it places financial restrictions on any major increase in the number of fellows in the following years. More importantly, considering the current positions of the fellows at their institutions, leaving their positions for more than a month or two at a time is also demanding on them. Consequentially, it limits the length, timing, and frequency of the FDP. Ultimately, these limitations might restrict the formation of sufficient’critical masses’ in recipient institutions. Continuing the education of subsequent batches of fellows is important not only because most of the fellows in this study asked for it but also because one-time, short-training courses are at risk of having little or no effect without any further supports . Second,In this study, we implemented a FDP with the aim to help overcome problems in Asian developing countries, especially non-English-speaking countries, and those who are marginalized and only have had scarce opportunities in the area of faculty development. According to the evaluation results, fellows were highly satisfied with the program, and their learning significantly improved after every module. Moreover, there was active transfer of learning, mainly with topics that were highly feasible, depending on their current situation. Even though the format, content, and evaluations have limitations, the overall direction of the observed changes was in line with the initial purpose of the SICME. The foremost task in overcoming the current limitations is supporting current fellows by providing timely feedback at the individual level and establishing cooperative relationships for continuous support at the organizational level in the long term. Future research needs to examine the underlying factors of transfer in various contextual aspects, such as organizational structure, culture, and leadership. These could contribute to further improving the effectiveness of FDPs for developing countries.


Several studies describing the ultrastructure and extracellular matrix (ECM) of intervertebral discs (IVDs) involve animal models and specimens obtained from symptomatic individuals during surgery for degenerative disease or scoliosis, which may not necessarily correlate to changes secondary to normal aging in humans. These changes may also be segment-specific based on different load patterns throughout life. Our objective was to describe the ECM and collagen profile of cervical IVDs in young (G1 - <35 years) and elderly (G2 - >65 years) presumably-asymptomatic individuals. Thirty cervical discs per group were obtained during autopsies of presumably-asymptomatic individuals. IVDs were analyzed with MRI, a morphological grading scale, light microscopy, scanning electron microscopy (SEM) and immunohistochemistry (IHC) for collagen types I, II, III, IV, V, VI, IX and X. Macroscopic degenerative features such as loss of annulus-nucleus distinction and fissures were found in both groups and significantly more severe in G2 as expected. MRI could not detect all morphological changes when compared even with simple morphological inspection. The loose fibrocartilaginous G1 matrix was replaced by a denser ECM in G2 with predominantly cartilaginous characteristics, chondrocyte clusters and absent elastic fibers. SEM demonstrated persistence of an identifiable nucleus and Sharpey-type insertion of cervical annulus fibers even in highly-degenerated G2 specimens. All collagen types were detected in every disc sector except for collagen X, with the largest area stained by collagens II and IV. Collagen detection was significantly decreased in G2: although significant intradiscal differences were rare, changes may occur faster or earlier in the posterior annulus. These results demonstrate an extensive modification of the ECM with maintenance of basic ultrastructural features despite severe macroscopic degeneration. Collagen analysis supports there is not a “pathologic” collagen type and changes are generally similar throughout the disc. Understanding the collagen and ultrastructural substrate of degenerative changes in the human disc is an essential step in planning restorative therapies. The basic structure of the human intervertebral disc (IVD) has been known since at least 1858, while the first studies concerning the morphological changes secondary to aging  date from the 1920s [Countless subsequent studies have analyzed different microscopic and molecular aspects of disc degeneration but a relatively small number focused on the primary constituent of the IVD, i.e., the extracellular matrix and its collagen content. Several concerns exist over the direct application of these results to cervical discs—extrapolation of lumbar results, utilization of surrogates for normal human discs , age heterogeneity, undisclosed disc region  and analytical problems resulting from the use of “semi-quantitative” methods are just some of them –6. ThereG1) included 15 cadavers younger than 35 years old and Group 2 G2), 15 cadavers aged 65 or older  cadavers at the SVOC-USP. This study was reviewed and approved by the ICB-USP IRB 811/2007). Next of kin provided consent and were interviewed to exclude cadavers with known history of neck or back pain, neoplasms or rheumatological conditions as previously described [. Next ofor older . ThroughG1 and G2 each. MR parameters were adapted to our specimens to replicate a T2 sequence . Specimens were placed in a tray, surrounded by air and scanned at room temperature (20–23 degrees Celsius). Discs were analyzed semi-quantitatively with a modified Okada grading system: individual scores  were added and resulted in a final grade 0 (least) to 6 (most degenerated)[G1 and G2 results were compared with the Mann-Whitney test . A significance level of .05 was utilized throughout the study.The IFUSP 1.5T MR scanner  was employed to obtain T2 mid-sagittal and 2-mm axial images through the level of the C4-5 and C5-6 discs of five cadavers (ten discs) from enerated). G1 and G1versusG2 comparison made with the Mann-Whitney rank-order test.Following fixation in 4% formaldehyde for six months, all specimens were sectioned in the mid-sagittal plane and graded semi-qualitatively with the Thompson scale . Degeneranterior and posterior. The NP was not visible to the naked eye in most cases. Fragments were frozen-sectioned on a sagittal (20 discs/group) or coronal (10 discs/group) orientation. Semi-serial, 8 μm sections stained according to hematoxylin-eosin (HE), Sirius Red (SR), Verhoeff’s iron-hematoxylin (mature elastic fibers) and Weigert’s resorcin-fuchsin (elastic and elaunin fibers) techniques [Discs and their intact endplates were decalcified in 0.25M EDTA for 30 days, followed by 1M EDTA for 5 days immediately before processing. Cervical discs were divided in the axial plane at their mid-point in two sectors, chniques . PhotomiG1 and G2 each were randomly selected for SEM. Following decalcification and sectioning as described, the clean-cut mid-point surface of each specimen was attached, face-up, to an SEM stub [Six discs from SEM stub . AnterioG1 and G2 each were randomly selected for this experiment. A commercially-available ABC kit was utilized . Eight μm-thick sections of each disc sector (anterior and posterior) were sequentially prepared according to manufacturer’s instructions—protease-based antigen unmasking , blockage of non-specific sites , incubation with primary  and secondary antibodies  and avidin-peroxidase conjugate . DAB chromogen was allowed to react for 3 minutes and slides assembled in usual manner [Six discs from l manner . Each stpost-hoc Tukey tests to determine if it was significantly different than background or non-specific binding. Comparisons between disc regions (anterior versus posterior) and groups (G1versusG2) were performed with T test. Staining unable to be differentiated from artifact was only included in the G1 versus G2 comparison and excluded from sector and segment analyses. No adjustments were made for multiple comparisons as all modifications in collagen staining were considered part of the same pathophysiological process and analytical priority was given to the general picture over any individual comparison [Primary antibodies against human collagen types I, II, III, IV, V, VI, IX and X were utilized. Single- (no primary antibody) and double-negative (no antibody) controls were included. Quantification was performed with an area-based method as previously described and expressed as a percentage of total area . Ten ranmparison .G1 were not devoid of degenerative findings, though these were generally incipient  and non-existent in G2 (G2 (3/30). Advanced degeneration in G1 was usually due to small osteophytes and fissures but not complete ankylosis—accordingly, 7 of 30 discs were graded Th4 but only 1 received a Th5 grade. Tears could also affect the two graded discs of the same cadaver differently as seen in G1 to G2 was also confirmed through semi-quantitative grading (p < .001 - Although Thompson grades 1 through 5 (Th1 –Th5) were represented in our samples, Th1 discs were rare in nt in G2 . Since iG1, a central area of discernible loose connective tissue was seen in only 2/30 cervical discs; the usual finding was a central area of denser fibrous tissue with chondrocyte clusters in its interior. Under polarized light, the AF lamellae can be seen to firmly insert themselves into the adjacent endplates in the manner of Sharpey’s fibers—regardless of how degenerated the disc was, the central area never exhibited these insertions. Elastic fibers were found aligned with the connective tissue lamellae in the AF and staining was concordant between the Verhoeff and Weigert techniques, suggesting these fibers are of the mature elastic type. Elastic fibers were found in smaller quantities in more degenerated G1 specimens but were still present.A morphologically “young” fibrocartilaginous phenotype consisted of an anterior AF (aAF) with dense alternating lamellae, predominantly longitudinal in more superficial areas and oblique in deeper sectors, and a thinner posterior AF (pAF) with predominantly longitudinal fibers . Even inG2 discs included marked disruption of the lamellar structure, endplate hypertrophy and more numerous and larger chondrocyte clusters within the disc, while SR staining revealed a substitution of green-refringent fibers for opaque material. With the exception of a single cervical disc, G2 specimens uniformly lacked elastic fibers regardless of Thompson score.A morphologically “elderly” phenotype seen in most G1 lamellae. Endplate insertion was perpendicular in the anterior AF and obtuse in the posterior AF. SEM was the only method that could visualize the NP as a separate structure in all specimens due to its lack of lamellar organization and endplate insertion and greater retraction due to higher water content than the AF, regardless of the extent of degeneration. In G2 specimens, the AF matrix was far denser resulting in little space between lamellae, with preserved endplate insertion.The superficial layers of the anterior and posterior AF were indistinct from the anterior (ALL) or posterior (PLL) longitudinal ligaments, while the pattern of intertwined lamellae predominates in deeper areas . A fine G1 and G2 with the exception of collagen X  were rare and usually small; in G1, collagen V was seen in a larger area in the anterior disc while in G2 the expression of collagens III, IV and IX was higher in the anterior disc as well.Overall, collagen reactivity in The morphological and collagen profile modifications described above are the phenotypical and ultrastructural manifestations of a multifactorial process generically described as intervertebral disc degeneration. Based on the observation that endplate vascular channels close in the first two decades of life, a very early theory was conceived in that IVD degeneration was secondary to decreased availability of oxygen and nutrients to the cells of the adult disc, further substantiated by description of biochemical pathways that mimic changes in the proteoglycan structure of the disc ,14–18. Het al. demonstrated in the early 1990s that disc degeneration may be seen in MRs of approximately 60% of asymptomatic subjects in their 60s; these numbers have increased into the 85–90% range as MR technology improved. Asymptomatic progression of these changes over a long period has also been demonstrated in upwards of 80% of individuals from a Japanese cohort [et al. have already shown that MR vastly underestimates the extent of degenerative alterations in cervical discs. This is corroborated by our findings regarding the cervical NP, which through SEM was demonstrated to persist in older discs as a separate structure although a clear boundary was not seen through MR or light microscopy [Our morphological, MR and histology data largely confirms literature data that degenerative findings can be found in young individuals and are significantly increased in older, asymptomatic individuals. Boden e cohort . These ncroscopy . It is rcroscopy .et al. have demonstrated it in the anterior part of cervical discs [Light microscopy results demonstrate the loss of the loose lamellar arrangement in the AF and substitution by a more compact arrangement with numerous chondrocyte clusters. Although these are findings described a long time ago in the lumbar spine, only recently Sitte al discs . The ShaG2 but in the aAF only types II and VI reached statistical significance, while in the pAF types I, II, IV, VI and IX were significantly decreased. A single regional difference was seen in G1 (collagen V) but in G2 those types that did not yet reach a significant reduction in the aAF  accounted for the significant regional differences between aAF and pAF. Rather than demonstrate a different degeneration pattern, these results probably reflect the same process occurring faster in the pAF than in the aAF. It further suggests that the load each disc sector is subjected to alters its collagen content, as suggested by Brickley-Parsons et al. in young scoliotic spines [Collagen profiling revealed that type II collagen is the most common in the cervical disc, followed by collagen IV. Detection of all collagen types was decreased in c spines .et al. had suggested expression could happen in advanced degeneration [et al.[Regarding the contribution of each collagen type to disc structure, there is no comparable data for human cervical discs in the literature; lumbar data utilizing semi-quantitative or chromatography methods pointed towards a predominance of collagen II in the interior of the lumbar disc with less significant components of collagens III (in the AF), V, VI and IX (diffusely),27,28. Cneration . Severaln [et al.,31,19.There are a number of limitations to our study. Firstly, despite the screening interview, there is always a possibility the studied individuals were indeed symptomatic. The rarity of adequate human material is the biggest impediment to properly study morphological alterations in asymptomatic individuals and there is no truly equivalent bipedal animal model ,33. ThisThe results presented here are relevant to dispel the notion of a “pathologic” collagen marker within cervical discs and to delineate a structure which is not only at the center of a common health problem but is also the object of number of restorative strategies ,36,37,38


In recent years, jurisdictions have recognized the strain placed on limited existing resources by criminal offenders with mental illness who frequently cycle through local jail facilities. In response, many locales have developed and implemented specialized programs to more effectively and efficiently manage these offenders, particularly the process of assigning defense attorneys to these often indigent defendants.The current study examined the impact of an Indigent Defense Counsel (IDC) program designed to provide specially trained defense attorneys, and enhanced case management services to 257 indigent jail inmates with a qualifying, major mental health diagnosis . These offenders were compared to 117 similar offenders who did not receive these services, on both their length of stay in the jail, and their likelihood of recidivism after release to the community.Survival analyses revealed that program participants spent about 17 fewer days in jail; however, recidivism rates between groups, measured as return to the same county jail or as statewide re-arrest, did not differ.These results suggest that defendants with mental illness can potentially be managed effectively in the community, with little added risk to public safety and at potential savings in jail bed days/costs. Implications for the processing of indigent criminal defendants with mental illness are presented. Individuals with mental illness are over-represented in the U.S. criminal justice system. In local jail facilities, they are estimated to comprise anywhere from 14 to 16 % of jail inmates  program. Here, we examine the program’s impact on length of stay in jail and subsequent recidivism (return to this jail and re-arrest anywhere in the state), in comparison to a group of similar indigent, mentally ill inmates who were not provided a specially-trained defense attorney, nor did they receive enhanced case management services.Not every jurisdiction may have the financial and organizational resources to field more comprehensive, and costly mental health court program. In light of this, it is important to consider whether more limited interventions such as this can yield positive results  that would support the movement of mentally ill, indigent defendants out of jail while they await the disposition of their case. Doing so has a number of potential benefits, including reducing jail crowding and expenses related to housing mentally ill pretrial defendants, providing needed community-based treatment to these defendants, and breaking the cycle of repeated incarceration of defendants whose mental health issues go unremediated.Research shows that mental illness may act as a significant mediator in the pathway to offending when coupled with other environmental or genetic risk factors, such as prior victimization or pre-existing behavioral disorders , program components and implementation can vary greatly. A typical mental health court utilizes a non-adversarial team approach where criminal justice and mental health stakeholders work together to develop individualized plans for mentally ill offenders. Often, mental health courts include treatment programs, meetings with mental health professionals, drug screenings and regular appearances in front of the judge  or specialized caseloads for mentally ill offenders that are smaller in size and have a primary focus of responding to mental health issues  in 2000. IDS focused on enhancing the quality and uniformity in indigent defense services, and prioritized adequate data entry and the production of reliable data as a core part of their mission Laurin . StudiesSimilarly, Texas introduced the Texas Indigent Defense Commission (TIDC) in 2001 with the goal of developing standards for indigent defense practices, in addition to a research base to identify and guide the implementation of evidence based practices Laurin . The MenThough there has been an increase in data collection and empirical analysis of the efficacy of various indigent defense systems, there is still relatively little empirical evaluation on the impacts of indigent defense, especially in regards to services for those with mentally illness. Given the high likelihood of indigence among the mentally ill offender population, it is possible that court-based programs could be more effective if specially trained legal counsel were part of a broader program of support, however it is not clear that even attorneys trained in mental health issues have the skill or time to engage in adequate case management for their clients. As such, more rigorous evaluations of indigent defense programs are warranted, especially as applied to this population of defendants with mental illness.Court-based programs for mentally ill and/or indigent offenders are a relatively new practice. The primary goal for many of these new approaches is improved identification and assessment of those with mental illness, more efficient case management, enhanced quality of associated services, and reduction in subsequent recidivism levels. Unfortunately, little research exists on court-based models of support for mentally ill individuals , and program evaluations are sparse, often yielding equivocal results. Quantitative reviews of the existing literature demonstrate the wide variation in both implementation and outcomes associated with programs for mentally ill offenders, and consistently emphasize the need for rigorous program evaluations of existing and future programs Edgely .As such, the current study is timely in that it examines the combined impact of legal counsel and additional case management services on length of jail stay and recidivism outcomes for mentally ill, indigent defendants. Importantly, this program is less resource-intensive than a formal mental health court and while those comprehensive programs may produce positive results, their costs and resource requirements may limit the ability of smaller jurisdictions to implement such programs. The current IDC intervention on the other hand, involves only a small number of attorneys and case workers, such that if the results show even modest effects it might provide a response to the issues posed by defendants with mental health issues in jails that is more feasible for some agencies. Specifically, this paper presents the results from an evaluation of a program targeting indigent jail inmates who are diagnosed with one of three serious mental illnesses and compares them to similar offenders who receive representation by regular indigent defense attorneys  and no case management services. Outcomes examined in this study include the length of time in jail, as well as several measures of recidivism, including return to the same county jail and re-arrest anywhere in the state.The broader IDC program identifies offenders in county jail who have had prior mental health treatment and if indigent, provides those individuals with the opportunity to participate in a program that includes the appointment of one of twelve indigent defense attorneys, who have received specialized training in mental health issues. Defendants who have one of three qualifying major mental health diagnoses  also received the services of program caseworkers who provided screening and referral to relevant, existing community-based treatment and other social service programs. Indigent defendants with some other diagnosis can still be assigned a specially trained IDC attorney, but do not receive enhanced case management services from the program and these defendants are not included in the current evaluation. The treatment group  was compared to a group of similar offenders, also with one of the three qualifying diagnoses, who did not participate in the program . The comparison group received the standard treatment for indigent offenders, which included assignment to a defense attorney who has not received specialized mental health training. Defense attorneys assigned to defendants in the comparison group volunteer their services and were compensated with a flat fee paid by the court. Specifically, we examine the impact of this program on the length of stay in the local jail, and the likelihood of recidivism after program participation.The IDC program is located in a suburban county in a large southwestern state and provides services to only defendants deemed indigent by the local county court system’s indigent defense office, after considering the defendant’s net household income and assets . Defendants are screened for potential eligibility at the time of their booking into the local jail by jail staff who check a state-level database of records of those who have ever received mental health treatment. Individuals who do not appear in this database, but present at the jail with evidence of current mental health issues may also be referred to the program. IDC program caseworkers receive a list of all such potential participants from the booking officer each week day and then contact potential participants to screen them for mental illness and explain the program and give them the opportunity to participate. In terms of current offense types, all defendants except those charged with capital murder are eligible to participate in the IDC.If the individual is diagnosed with major depression, bipolar disorder and/or schizophrenia they are eligible for enhanced case management services as part of the IDC program, and the appointment of a specially trained defense attorney. For those defendants who receive IDC case management services, the program social workers assess the person’s mental health needs and social functioning and attempt to match them to available clinical services that exist within the local community, as well as any other types of social services  that may be needed. If the caseworker determines that the individual has some other kind of mental health issue, the defendant can still partially participate in the program—that is, by being assigned a specially trained defense attorney, but they will not receive the enhanced case management services. These individuals are not included in this study as part of either the treatment or comparison groups because they differ from these groups in their mental health issue diagnoses, and are thus not comparable to either group examined here.n = 257), relative to other indigent defendants who have one of these same three diagnoses, but chose not to participate in the IDC .Defendants who do not choose to participate in the IDC program at all follow normal court procedures for the assignment of an indigent defense attorney  and receive no enhanced case management services (no other program in this county’s court system offers such services). The current study thus examines those individuals appointed an IDC defense attorney, who had one of the three diagnoses that qualify them for the enhanced case management services  per IDC participant, and 2.0 mental health service referrals specifically per IDC participant. In addition to the enhanced case management services, a group of twelve attorneys volunteered to be part of the IDC program, and each received several hours of specialized training in mental health issues  from the IDC program social work staff. For instance, these attorneys take part in training which focuses on the symptoms of mental illness, the impact of such symptoms on their client’s social functioning and legal culpability, and the role of these symptoms as potential mitigating factors. Training also covers the possible side effects of medications used to treat such mental illnesses and how those side effects may also impact criminal culpability.Unlike a more comprehensive Mental Health Court model, the IDC program does not include any enhanced judicial supervision (they must appear in court for scheduled hearings as any defendant would). In addition, any conditions of pre-trial release are monitored only by a bail bonds person , not by a probation or pretrial release  authority. Participants in our comparison sample, likewise do not receive any particular judicial or pretrial supervision, other than that they must also appear in court for relevant hearings and may be monitored by a bail bonds person if they were released on a financial bond. The IDC program aims to quickly remove eligible program participants from the jail environment, so that their mental health needs may be more effectively addressed in community-based programs. Participation in the IDC program does not guarantee early release from the jail, as that decision still remains with the presiding judge, including whether to allow a personal recognizance bond, to set a financial bond amount, and any other conditions of release. If they are released from the jail (about 87 % of IDC participants were), IDC program participants meet with a program caseworker for additional assessment of social and clinical service needs , provision of relevant referrals for service, and regular meetings to monitor the individual’s progress while in the program. Because the IDC program includes several components  it is not possible to determine which component may account for any significant program effects relative to the comparison group, who received neither the case management, nor legal defense enhancements.IDC program staff collected quantitative data related to IDC participants and the comparison group cases directly from various computerized county court record systems from January 1, 2012 through March 30, 2013. Information on defendant’s dates of entry and release from jail, their current offense date and type, prior criminality , as well as various demographic factors  was collected. In addition, recidivism data was collected from the state’s criminal records system, reflecting the date and type of any re-arrests in the state after release from jail. Recidivism information was collected for a minimum of 12 months post-release from jail (time-at-risk in the community) for both the IDC and comparison group.During the 15-month evaluation period, the IDC program provided enhanced case management services and assigned specially trained defense attorneys for 257 indigent defendants who had a diagnosis of bipolar disorder, major depression, or schizophrenia-type disorders. This represents 68.7 % of those identified with a qualifying diagnosis over this time period. During the same time period, another 117 indigent individuals with similar diagnoses were booked in the local county jail; however, these individuals chose not to participate in the IDC program. While both groups are comprised of indigent defendants with similar mental illness diagnoses, those who volunteered to enter the IDC program may differ from those in the comparison group who chose not to participate , thus, multivariate analyses were used to control for criminogenic factors that could be related to the individual’s decision to participate in the IDC program and their risk of recidivism, including criminal history and current offense type.χ2 = 0.419, n.s.), followed by major depression  and schizophrenia . As indicated in Table The IDC and comparison groups are largely similar in terms of age, racial/ethnic composition, and current criminal offense. Recall also that all participants in each sample had been classified by the court system as indigent, and had been diagnosed with a qualifying disorder . The groups were generally similar in the distribution of these diagnoses as well. For instance, bipolar disorder was the largest proportion of each sample  than did the IDC group, this difference appears to be a function of the somewhat higher average age of the comparison group. For instance, IDC participants had prior arrests at a rate of .150 per year, while comparison group participants prior arrest rate was .177 per year . Overall, despite the potential for self-selection bias in these samples, there seem to be few significant differences in a number of criminogenic factors between these two groups. Subsequent multivariate analyses, described below control for these factors.The comparison group had slightly more male defendants, and defendants with a felony charge compared to the IDC group, but these differences were not statistically significant. Both groups were equally likely to have defendants with a violent, property, or drug/alcohol-related offense (including DUI) as the most serious current charge. While the comparison group had about one more prior arrest  subsequent to release from the jail. Time-at-risk for each of these three variables was measured from the date of release from jail through either the date of first re-offense, or the end of the data collection period (when a 12-month check of their arrest records was conducted) if recidivism did not occur. Recall that recidivism outcomes were generated based on records showing that the person returned to the local county jail , and a check of the state police department’s criminal record database, indicating the person had been re-arrested somewhere in the state. These comparisons include only those individuals in each group who had in fact been released from the local jail and thus has some period of time at risk in the community during which to potentially recidivate.Results presented below include simple bivariate comparisons of each group’s likelihood of being released from the jail to demonstrate the possible benefit of the IDC program in helping to remove indigent, mentally ill offenders from the jail sooner than they would otherwise be released. In addition, we present bivariate comparisons of each of our three recidivism measures between the two groups, as well as a series of multivariate models for each of the three outcome measures. Specifically, a series of Cox regression survival analyses depict whether there are differences in the recidivism rates  of indigent, mentally ill offenders who received enhanced case management, and legal services (IDC group) compared to those who did not, while controlling for other factors such as offender demographics and offense information. These multivariate Cox regression models are “time-to-event” comparisons that determine the probability of recidivism, while controlling for time until that event, as well as the covariates just described .χ2 = 8.296, p < .01; Cohen’s d = .30). Cohen’s (d) suggests that a d value over 0.2 would be considered at least a small effect, with a d over 0.5 being considered a moderate effect . While community release is not guaranteed as a part of IDC participation, and IDC staff have no direct influence on the release decisions of judges or bail bonds personnel, it is possible that these decision-makers perceive defendants who have agreed to engage in the IDC program to be more suitable candidates for release than defendants who chose to not participate in the program. For instance, participating in IDC means the defendants have an additional person  involved in monitoring their status in the community (Table Participation in the IDC program did not guarantee that the offender would be released from the jail (that remains at the discretion of the judge), yet a higher percentage of IDC program participants 87.2 %) were released from the jail during the study period than similar offenders who chose not to participate in the IDC . On average, this is a sizable and statistically significant difference of 25 days. The average cost to house an inmate with a diagnosed mental illness in a county jail in this state during the study period was $137 per day (per the state’s Legislative Budget Board). If the average number of days in jail for 257 IDC program participants is 25 days fewer than it otherwise would have been, the cost savings realized was approximately $880,000 over the course of the 15 months of this study.Not only are IDC participants more likely to be released from the jail than those in the comparison group, but IDC participants are released more quickly  than those in the comparison group  to return to jail for any reason . In addition, among offenders who returned to the county’s jail, only 52.7 % of the IDC group returned due to a new criminal charge. Although, this rate of return was less that the comparison group (69 %), it was not a statistically significant difference . In terms of statewide re-arrest rates, bivariate analysis showed no significant difference between the groups, although IDC participants were slightly higher than comparison group participants .We next turn to an examination of the recidivism risk for IDC program participants as compared to similar offenders who chose not to participate in the program. Specifically, this section examines the impact of the additional indigent defense and case management services on recidivism for defendants with a diagnosis of bipolar disorder, major depression, or schizophrenia-related disorders , relative to similar offenders who chose not to participate in the program. An examination of bivariate statistics indicates that IDC participants (31.6 %) were no more likely than their non-IDC counterparts  and to account for varying times at risk (from release until re-arrest or the end of the follow-up period), a multivariate survival analysis  was utilized. This multivariate model includes controls for age, gender , race (non-White = 1), Hispanic ethnicity (yes = 1), total number of prior arrests, current offense level (felony = 1), violent current offense (yes = 1), drug/alcohol-related current offense (yes = 1) and property current offense (yes = 1), number of days the individual had spent in jail prior to being released, as well as IDC program participation (IDC = 1).The magnitude and significance of each predictor variables’ effect on the likelihood of re-incarceration and/or re-arrest is indicated by the likelihood coefficients shown in Table any reason reveal that participation in the IDC program  did not significantly impact the probability of this outcome (see Table p < .01), as did non-White relative to White defendants ; while felony level defendants  and those with more prior arrests had a significantly higher likelihood of return to jail . Finally, regardless of whether the individual was in the IDC or comparison sample, those who spent days in jail prior to release had a significantly lower probability of return to the jail for any reason . Several other variables were marginally related to increased odds of return to jail for any reason, including Hispanic ethnicity and having been charged with a violent crime, while older individuals were marginally less likely to be re-incarcerated. Figure Results for the model predicting return to jail for new crime, IDC program participation was again not a statistically significant predictor of this outcome . Defendants facing a felony charge were less likely to return to jail for a new crime , while those with higher numbers of prior arrests were more likely to return to jail for a new crime . No other variables were found to be significant predictors of the probability of returning to this particular jail for a new criminal charge.In the model examining return to the jail for a p < .01), and was significantly lower for those with current felony offenses  and older offenders . Offenders charged with a current drug crime were also marginally less likely to be re-arrested , IDC program participation did not affect this outcome . The likelihood of re-arrest was significantly higher for offenders with a greater number of prior arrests  were not significantly different from those who did not receive the program’s services. That said, these IDC participants were released from the local jail nearly one month sooner than similar indigent offenders with mental illness who did not enroll in the program, and yet they appear to have posed no increased risk to public safety because of it. While the data do not support the conclusion that IDC participation improved recidivism risk, they do suggest that early release of these kinds of indigent, mentally defendants, coupled with enhanced case management and legal services can generate some positive outcomes  for the local jail, and county without posing an additional public safety risk.While significant reductions in the likelihood of these recidivism measures among IDC participants was a program goal, which was not met, it is important to note that IDC offenders were also no guarantee early release from jail as a program component, not only did this study find IDC participants were significantly more likely to be released from the jail, they were released on average 25 days earlier. IDC participants were also more likely than the comparison group to be released on a bond . Given that judicial discretion and bond requirements were retained, it can be inferred that criminal justice decision-makers may view IDC program participants as more viable candidates for early release from jail.Specialized services for the mentally ill criminal population have emerged over time as policymakers continually explore ways to respond to the needs of this population. Recent efforts have focused on improving timely and accurate clinical assessments, matching of appropriate services with treatment needs, increasing access to appropriate services, and improving the continuum of care, while attempting to maintain public safety and offender accountability. Many jurisdictions have implemented specialized mental health courts, which typically combine treatment and surveillance components, to allow for the delivery of treatment services in a community setting , nor to be re-arrested elsewhere in the state. Thus, while the IDC program decreased the average length of jail stay and associated costs, and facilitated the ability of indigent offenders with mental illness to retain appropriate community based treatment services this did not reduce re-offense risk. On the positive side, these individuals were not found to pose an reductions in recidivism, whereas this IDC program did not. Thus, it may be that while this sort of less intensive IDC program could help reduce jail crowding and promote access to needed services in the community, the additional supervision and coerced treatment aspects of the Mental Health court model are needed to produce more substantial improvements in recidivism.Programmatically, it is important to note that this IDC program lacked a number of the components that would typically be found in a Mental Health Court program, most notably mandated mental health treatment participation, on-going judicial interactions, and enhanced community supervision. Mental Health Court program evaluations have demonstrated significant In terms of the research design itself, limitations of the current study include the use of a quasi-experimental design, and in particular a lack of controls for self-selection into the IDC. While our multivariate models include a number of important control variables, it is not possible to rule out potential self-selection effects . It may be for instance that individuals who volunteered for the IDC were also better able to effectively present themselves to the judge/bonds-person at the time of pretrial release decision-making, and it was this fact, rather than IDC participation per se that accounted for higher rates of release for IDC participants. While the IDC and comparison groups were largely similar in terms of the proportions exhibiting each of the qualifying diagnoses for the IDC program , data was not available on the severity of symptoms experienced by each defendant, for instance. Had this data been available it might have been possible to determine the severity of each individual’s mental illness at the time of incarceration and better control for such potential confounds. At the same time, we believe the inclusion of important criminogenic control variables in the multivariate analysis should have helped to reduce this potential bias. Likewise, individuals in this study were followed for only one year after program participation, and only in terms of their recidivism outcomes. It is possible that the lack of significant differences in recidivism risk could eventually emerge over the longer-term, and that the program had beneficial effects in other areas, such as obtaining more stable housing, improved employment, or better psychological functioning, which were not measured in the current study.Finally, no information was available on the types and amounts of services that individuals in the comparison group may have received. While data on the number and type of clinical and other social services that IDC participants were referred to was available to the researchers, similar data on the comparison groups was not available specifically because they did not participate in any known programming that would have made (and recorded) such referrals. At the same time, if these defendants did receive types and levels of services that were comparable to those provided to IDC participants, any potential differences in recidivism outcomes between the two groups would be moderated.It is possible that a singular and limited approach to the complex mental health and social service needs of this population is not enough. Other researchers have noted that effective treatment should be supplemented with integrated services that address a range of psychosocial factors, as many of these offenders face a challenging array of problems Edgely . FurtherThe IDC program was successful at selecting appropriate, amenable candidates for enhanced case management and legal services. Most of these individuals were then granted early release from jail and generally had no increased risk of recidivating at the one-year follow-up. These results suggest that with some minimal case-management service provision and attorney training, it is possible to manage this kind of offender in the community, with little apparent increased risk to public safety. In addition, the program potentially generated cost savings for the local jail, or at least allowed for the reallocation of beds that would normally be used to house defendants with mental illness for use with other, higher risk offenders. In jurisdictions where the implementation of a full-fledged Mental Health Court program is not possible, for practical or political reasons, the implementation of similar IDC programs targeting defendants with mental illness might be a useful step in dealing with the many problems these individuals pose for local court and correctional systems, and for improving their own quality of life by providing needed services in a less restrictive and detrimental environment than that of the local jail.


Sarcophilus harrisii) of which 9 where affected by Devil Facial Tumour Disease (DFTD). DFTD is clonally transmissible cancer that has caused massive declines in devil numbers. Our analyses revealed that IgM and IgG expression levels as well as IgM/IgG ratios decreased with increasing devil age. Neither age, sex, IgM nor IgG expression levels affected devil DFTD status in our analyses. However, devils with increased IgM relative to IgG expression levels had significantly lower DFTD prevalence. Our results therefore suggest that IgM/IgG ratios may play an important role in determining devil susceptibility to DFTD. We consequently propose that our findings warrant further studies to elucidate the underpinning(s) of devil IgM/IgG ratios and DFTD status.Immunoglobulins such as IgG and IgM have been shown to induce anti-tumour cytotoxic activity. In the present study we therefore explore total serum IgG and IgM expression dynamics in 23 known-aged Tasmanian devils ( Sarcophilus harrisii), hence questioning the long-term survival of this iconic speciesSince its first sighting in 1996, the Tasmanian Devil Facial Tumour Disease (DFTD) has caused massive (>85%) population declines of Tasmanian devils  were blood sampled (500 μl/sample) in March and May 2012 at “West Pencil Pine”, 15 km to the west of Cradle Mountain National Park in north-west Tasmania. Devil age was determined by using 20RNA was extracted from blood samples using the RNeasy Protect Animal Blood Kit . Genomic DNA was removed from the RNA samples by the DNAse I AMPD1 kit  and cDNA was synthesized with the QuantiTect Reverse Transcription Kit .KU664590, Saha-RPS29: KU664591 and Saha-IgM: KU664592. Additionally melt curve analyses were conducted to confirm the lack of genomic DNA and primer dimers in the reaction ; IgG primers: qIgG-F: 5′-CAG GTG ATC AGC ACT CTC TCT G-3′, qIgG-R: 5′-GGA TGT GGG GC AAG ACA TA-3′, IgM primers: qIgHM-F: 5′-TTT GAT ATC TGG GGC AAA GG-3′, qIgHM-R: 5′-ACA GCA AAG GAG GCA TCT TC-3′. To control for the potential of cell-type specific gene expression of reference genes three housekeeping genes were tested, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), ornithine decarboxylase antizyme (OAZ) and 40S ribosomal protein S29 (RPS29) by using the software package BestKeeperSpecific IgG and IgM primers were designed using the Primer3Plus website (2 > 0.99) contained five dilutions from the dilution series with a linear dynamic range of at least 3 orders of magnitude. PCR efficiencies ranged between 0.94 and 1.07 . All samples were run in quadruplicate, and all Cq values for unknowns fell within the linear quantifiable range of the appropriate standard curves. Controls containing no reverse transcriptase enzymes, and controls containing no cDNA samples were run alongside the reactions to confirm that no genomic DNA was amplified, and the lack of primer dimers in the reactions, respectively : RPS29-F: 5′-ATG GGT CAT CAG CAG CTC TAC-3′, RPS29-R: 5′-AGG CCG TAT TTG CGG ATT AG-3′). Quantitative RT-PCR was conducted on the RotorGene6000 . Standard curves . Sci. Rep. 6, 25093; doi: 10.1038/srep25093 (2016).


Anopheles salivary gSG6-P1 peptide antibody responses in measuring exposure to Anopheles bites during early infancy has been assessed.The estimates of risk of malaria in early childhood are imprecise given the current entomologic and parasitological tools. Thus, the utility of anti-Anti-gSG6-P1 IgG and IgM levels were evaluated in 133 infants (in Benin) at three (M3), six (M6), nine (M9) and 12 (M12) months of age. Specific IgG levels were also assessed in their respective umbilical cord blood (IUCB) and maternal blood (MPB).Plasmodium falciparum infection intensity (p = 0.006 and 0.003), and inversely with the use of insecticide-treated bed nets (p = 0.003 and 0.3). Levels of specific IgG in the MPB were positively correlated to those in the IUCB  and those at M3 .At M3, 93.98 and 41.35% of infants had anti-gSG6-P1 IgG and IgM Ab, respectively. Specific median IgG and IgM levels gradually increased between M3 and M6 (p < 0.0001 and p < 0.001), M6–M9 (p < 0.0001 and p = 0.085) and M9–M12 (p = 0.002 and p = 0.03). These levels were positively associated with the Anopheles bites, and then the risk of malaria infection, can be evaluated in young infants by assessing anti-gSG6-P1 IgM and IgG responses before and after 6-months of age, respectively. This tool can be useful in epidemiological evaluation and surveillance of malaria risk during the first year of life.The exposure level to  In the absence of effective vaccines, malaria control and prevention strategies are primarily based on the widespread use of effective drugs and vector control by insecticide-treated bed nets (ITNs) and indoor residual sprays –3. Such Naïve newborns are at increased risk of malaria infection during the first year of life in endemic areas –10. NewbAnopheles interactions can potentially provide a promising alternative . Importantly, these levels of IgG and IgM gradually increased from M3 to M12 (MIgG = 0.721 and MIgM = 0.352), with intermediate values at M6 (MIgG = 0.527 and MIgM = 0.288) and M9 (MIgG = 0.646 and MIgM = 0.326). The increase of specific IgG levels , levels of specific gSG6-P1 IgG  were not significant, unlike that observed for anti-gSG6-P1 Ab levels.Interestingly, as observed for anti-gSG6-P1 IgG and IgM, the intensity of The percentages of IgG and IgM responders were calculated for the four time-sampling dates Table . ResultsAssuming that each pregnant woman delivered her baby at the closest maternity hospital, Immunological data were analysed based on the hospital of delivery. Avame, Gare and Cada received pregnant women from three , two (Dohinoko and Gbetaga) and four villages , respectively. The M3 levels of IgG and IgM Figure  and the The profile of median of specific Ab levels during the first life year was similar in the three MHs: a gradual increase from M3 to M12 . In contrast, anti-gSG6-P1 IgG responses significantly decreased with the use of vector control (ITNs) (RE = 0.47 and p = 0.0037). Finally, no significant variation of specific gSG6-P1 IgG or IgM levels was observed according to seasonality, the predictive risk of exposure to malaria or the prevalence of infection with P. falciparum , both individual IgG and IgM responses to gSG6-P1 were 20 and 8% higher at M6 (regression coefficient (RE) = 1.20 and p < 0.0001, RE = 1.08 and p = 0.0117, respectively), 34 and 12% at M9  and 39 and 16% at M12  compared to M3 , and considerably higher (p < 0.0001) than that of anti-gSG6-P1 IgM responders (41.35%). In addition, a positive association was observed between specific IgG levels in the MPB and the IUCB  and IgM . These ‘low’ endogenous M3-levels of plasma specific antibodies were not surprising, in that the newborn immune system is relatively considered as immature during early infancy [Anopheles bites, their salivary antigens, and eventually the Plasmodium spp. they carry [P. falciparum and the entomological risk of infant exposure to Anopheles bites [In the study, anti-gSG6-P1 IgG and IgM Ab were detected in respectively 93.98 and 41.35% of infants at 3 months (M3) of age.  infancy –41. In eey carry . This ises bites , 28, 33.Anopheles contact levels. Infants in the Avame area had lower specific IgG and IgM responses and presumably a lower contact level with Anopheles during their first year of life. This can be linked to a likely lower aggressiveness of Anopheles in this area, a higher protection level against vectors or different household characteristics  [Specific IgG and IgM levels significantly differed based on the location of residence, suggesting spatial differences in human-windows) –33, 38. windows) , 43, 44.Anopheles bites. Despite this positive association, maternal levels of specific IgG transfer could not accurately predict the level of infant specific IgG. In addition, such transfer also depends on the placental integrity, IgG subclass and nature of antigen [Maternal IgG is provided to the infant by transplacental transport , 45. Thi antigen , 46. UnfAnopheles contact level by using anti-gSG6-P1 IgG, the proportion contributed from the mother must be considered. The linear regression analysis has estimated about 52 and 21% of the maternal gSG6-P1-specific IgG found in blood of newborns just after delivery and at 3 months of life, respectively, indicating a rapid decline of maternally transferred IgG [Anopheles bites and the risk of malaria transmission. One hypothesis is that, depending on the level of exposure to mosquito bites, the initial anti-Anopheles saliva IgM response may have failed to switch to IgG after several weeks or months as has been shown previously for responses to P. falciparum antigens [For a reliable evaluation of the young infant-rred IgG , 48. It rred IgG , but sucrred IgG , 50. Intantigens . NeverthAnopheles mosquito bites and therefore the risk for malaria transmission in early infancy has been described in a malaria-endemic area of Benin. Moreover, because of transfer of IgG specific to salivary gSG6-P1 Anopheles peptide from mother to infant there may be an overestimation of the utility of such a ‘biomarker’ early in infancy (less than 3 months). To overcome that potential challenge, specific IgM and IgG isotypes may be assayed for in infants younger and older than 6 months, respectively.In summary, individual exposure levels to


Maintaining intervention fidelity should be part of any programmatic quality assurance (QA) plan and is often a licensure requirement. However, fidelity checklists designed by original program developers are often lengthy, which makes compliance difficult once programs become widely disseminated in the field. As a case example, we used Stanford’s original Chronic Disease Self-Management Program (CDSMP) fidelity checklist of 157 items to demonstrate heuristic procedures for generating shorter fidelity checklists. Using an expert consensus approach, we sought feedback from active master trainers registered with the Stanford University Patient Education Research Center about which items were most essential to, and also feasible for, assessing fidelity. We conducted three sequential surveys and one expert group-teleconference call. Three versions of the fidelity checklist were created using different statistical and methodological criteria. In a final group-teleconference call with seven national experts, there was unanimous agreement that all three final versions  should be made available because the purpose and resources for administering a checklist might vary from one setting to another. This study highlights the methodology used to generate shorter versions of a fidelity checklist, which has potential to inform future QA efforts for this and other evidence-based programs (EBP) for older adults delivered in community settings. With CDSMP and other EBP, it is important to differentiate between program fidelity as mandated by program developers for licensure, and intervention fidelity tools for providing an “at-a-glance” snapshot of the level of compliance to selected program indicators. Chronic conditions have received nationwide attention because of their adverse impact on individuals’ daily functioning, social interaction, and self-reported quality of life  as well Evidence-based programs such as the Chronic Disease Self-Management Program (CDSMP) have gained national and international recognition for helping people with chronic conditions learn self-management skills , 7. WhilThe U.S. Administration on Aging (AoA) Evidence-Based Disease Prevention Grant Programs, initiated in 2003, have stimulated the development and implementation of evidence-based programs (EBP) for seniors, which dispel earlier myths that health promotion efforts were futile in older populations . With thYet, the translation of scientifically tested research findings to community-based programs is often slow, fragmented, and subject to speculation by the practitioner community . As moreThe RE-AIM framework contains the following five key elements: reach, effectiveness, adoption, implementation, and maintenance , 23. SomAs EBP become widely disseminated, there has been growing attention to program fidelity in implementation science . In termWhile maintaining fidelity during program implementation is essential, ensuring the feasibility of monitoring fidelity is also important, especially for organizations with relatively limited capacity to administer the intervention . FidelitProgrammatic adherence to implementation aspects of CDSMP is supported by a centralized training and certification system that provides for scripted small-group and participatory workshops (2.5 h a week for 6 consecutive weeks) focused on self-management strategies that provide medical, emotional, and role management skills . In regahttp://patienteducation.stanford.edu/licensing/Fidelity_ToolKit2010.pdf. This fidelity checklist as part of the Toolkit is called “Must Do’s Fidelity Checklist” and provides guidance for personnel with regard to the implementation of CDSMP . Personnel are advised to go through the list and check “Yes” for all the items they are currently doing, and are encouraged to incorporate these items with their fidelity plan for the future if they are not able to implement the entire fidelity task right away. These 157 items are chronologically categorized under 7 headings (16 subheadings or blocks): (1) personnel; (2) delivery before training; (3) fidelity during training; (4) fidelity after training; (5) fidelity during workshops; (6) fidelity for leaders and master trainer retention; and (7) fidelity after workshops. Each heading was further divided into a couple of subheadings.A standardized resource material   helps prImplementing EBP can require detailed monitoring and tracking information, placing substantial administrative burdens on program coordinators . As suchThe expert consensus method refers to a multi-phase approach for statistically analyzing pooled opinions that minimizes biases inherent in other systems of summarizing expert viewpoints , 35. We As the credentialing unit, the Stanford University Patient Education Research Center compiles a list of all CDSMP master trainers and manages a listserv for exchange of information. Using this distribution list, we invited all active master trainers in 2010 to participate in our study. In Round One, we collected 119 responses , where 5 responses were eliminated from the final analysis since they were not master trainers. Twenty-six out of 114 were both master trainers and program coordinators. Out of these 114 master trainers, 47 agreed to participate in the second survey. In Round Two, 24 out of 47 master trainers responded to the survey (51% response rate). From this group, nine master trainers were willing to respond to the third survey. In Round Three, seven out of nine master trainers responded to the third survey (78% response rate). In Round Four, eight out of nine master trainers from Round Three agreed to participate in a telephone conference to obtain feedback, advice, and concerns from their experiences delivering and overseeing programs. In this last round, seven of out of eight experts were able to join the group-teleconference call with the study team. Each of the four rounds to streamline the CDSMP fidelity checklist contained multiple steps as shown below.n = 114) who identified through the Stanford CDSMP master trainer listserv. These experts helped us identify the items in the original 157-item CDSMP fidelity checklist, which they believed to be most important to ensuring the overall fidelity of the program. Participants were asked to rank statements on a scale of one (least important) to five (most important). During this initial step, we eliminated 8 items related to master trainer training and another item referring to language literacy, which resulted in an initial portfolio of 148 unique items to consider. To obtain the most relevant information from participants, the survey included skip patterns that presented participants with a list of items most appropriate to them based on their roles . Because of their universal relevance, some items were presented to every group.The survey in Round One was conducted in November and December 2010 with master trainers  to avoid the risk of Type I error . Second,The second survey was conducted in June 2011. In this round, we solicited the opinions of the 47 master trainers who agreed to participate after Round One. Round Two involved asking participants to provide feedback via a two-step process that assessed both “feasibility” and “endorsement.” The first step asked master trainers to rank how feasible they think it is to monitor each fidelity checklist item. Feasibility response categories included “not at all,” “somewhat,” and “very high.” Based on the items identified as having “very high” feasibility in the first step, the master trainers were then asked to select a predetermined number of items  from each question block that they would endorse for inclusion in the final, shorter fidelity checklist versions. We had 24 master trainers respond to our second survey, resulting in a 51% response rate.Employing the practical methodology based on the feasibility and endorsement responses, we were able to generate a shorter Fidelity-12 checklist (12 items), a medium-length Fidelity-20 checklist (20 items), and a longer version Fidelity-34 checklist (34 items). First, we calculated the percent of participants who endorsed each item relative to the total number of endorsements received for each question block . We also calculated the percent of participants who endorsed each item received relative to the total number of feasibility ratings of “very high” . The aggregate of this process was assessed on a combined scale of 0–200%. Fidelity-34 included 34 items that received the highest aggregate numbers of each question block . Due to our desire to streamline the checklist further, we selected only items with scores of 90 and 100 as cut-points on the combined 0–200 scale. Fidelity-20 (90 as a cut-off) included 20 items while Fidelity-12 (100 as a cut-off) included 12 items. At the conclusion of Round Two, 9 out of 24 master trainers agreed to participate in the survey in Round Three.We surveyed nine experts to review the three shortened versions of the fidelity checklist and to help us address some remaining questions related to their perceptions about the most critical items for assessing intervention fidelity using Fidelity-34 as the referent. We had seven experts respond to the short survey, and the response rate was 78%. A report of findings was prepared indicating that Fidelity-34 was the one that experts felt best balanced the inclusion of key fidelity items with the feasibility of administration.We held a telephone conference with seven experts identified in Round Three to report on our findings and solicit expert opinion regarding the use of fidelity checklists. This conference call was critically important for obtaining feedback and advice from those with experience in delivering and overseeing programs. The experts confirmed a preference for Fidelity-34, but felt that the other two shorter versions should be available since the purpose and resources for administering the fidelity checklist might vary from one setting to another.Table Using the original CDSMP fidelity checklist as a case example, this research provides a methodology for streamlining fidelity checklists that have many unique items, making field implementation resource-intensive and challenging. We see the methodology described in this paper as our key contribution, which can be applied to different EBPs. It should be noted that these shortened checklists are for research only and require further field-testing before specific endorsements can be made. The CDSMP fidelity checklist has been updated since the time of this study, and a new fidelity manual was developed that stresses the importance of setting intervention fidelity within an overall fidelity plan. These updated materials also distinguish “must do” fidelity strategies from those that are “nice to do” to strengthen program fidelity . For theApplying the expert consensus technique, we consolidated the 157-item CDSMP fidelity checklist into three abbreviated versions without sacrificing fidelity items deemed essential by master trainers. Due to its overall length, the original Stanford checklist was often used more as a self-assessment reminder rather than an actual fidelity checklist. Given the importance of program implementation as a core component of program evaluation , 23, we Though the abbreviated checklists are likely less time-consuming than the original version, further improvements may be needed. First, any checklist should be seen as just one element in an overall QA plan . AdditioIn addition to generating three abbreviated versions of CDSMP fidelity checklist, this study also demonstrated an effective use of expert consensus method for generating consensus from a broad field of CDSMP experts with varying experience and perspectives. When dealing with a diversity of opinions, problems may arise due to conflicting viewpoints, self-censorship due to lack of anonymity, incomplete feedback loops or poor communication, or lack of defined statistical methods for attributing quantitative values to subjective factors. Many of these potential pitfalls were avoided by using three iterative rounds of online surveys. Because respondents did not communicate directly, they were free to express their opinions. Statistical and practical methods were used to give each respondent’s perspective equal weight in reaching consensus. In the Round Four telephone conference, expert participants did directly communicate, but because much of the work related to consolidating the list was already concluded, the participants were able to reach consensus easily.At the end of the process, we were able to identify the most relevant and applicable items and garner experts’ endorsement of the abbreviated checklists as useful. The methods employed in this study could be used as a model for administrators of other EBP aiming to reduce the length of a fidelity checklist for program monitoring. However, it is important to note that CDSMP sites must comply with licensure requirements and be familiar with the official CDSMP Implementation and Fidelity Manuals, which will need to be updated on a regular basis, if programmatic or licensure requirements change.n = 114) in Round One survey, and multiple rounds of survey, and a final telephone conference with content experts. Second, our study is potentially limited by focusing on one major stakeholder group, i.e., master trainers. The inclusion of various opinions from CDSMP completers, lay leaders, T-trainers, program developers, and researchers in academia in the Round Three survey could have ensured better representation by various CDSMP implementers and stakeholders. Third, the CDSMP program was revamped after the initiation of this study. While some aspects of the program have been improved upon, we believe the basic elements have remained consistent to ensuring fundamental intervention fidelity based on what is needed before, during, and after workshop delivery. Hence, the need for shortened fidelity checklists is still relevant. Fourth, the study was conducted within a specific time period when federal funding was available for CDSMP implementation. Such changes in the availability of resources and program demands may influence, which fidelity checklist items are most feasible to monitor. However, the ever-changing context and limited funding resources might make three short versions of the CDSMP fidelity checklist helpful and valuable. Fifth, there were noticeable dropouts between streamlining rounds. Since data were not collected from the purposive list of participants, it was not possible to make real comparisons between responders and non-responders. Sixth, we note that generating one intervention fidelity tool may not be the most effective or efficient way to capture all aspects of fidelity, which could be implementation fidelity for leaders or program fidelity for program coordinators and agency administrators. Last, we do not know the level of expertise and knowledge among participated master trainers since we did not collect this information. Nevertheless, we strongly believe master trainers are appropriate experts given the required level of training and experience with delivering CDSMP. To retain their certificates, master trainers are required to conduct 4-day Leader training within 18 months of original training and conduct either a 4-day Leader Training, a 6-week series of community workshops, or a Leader cross training  can be used for efficient data collection, analyses, and tracking of participant response with built-in reminder systems. Third, it is important to have input from stakeholders with various roles to have a comprehensive picture of intervention fidelity. We encourage researchers to apply this expert consensus model to other EBP, and to conduct further study of the reliability, validity, and practicability of fidelity checklists.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.This paper is included in the Research Topic, “Evidence-Based Programming for Older Adults.” This Research Topic received partial funding from multiple government and private organizations/agencies; however, the views, findings, and conclusions in these articles are those of the authors and do not necessarily represent the official position of these organizations/agencies. All papers published in the Research Topic received peer review from members of the Frontiers in Public Health  panel of Review Editors. Because this Research Topic represents work closely associated with a nationwide evidence-based movement in the US, many of the authors and/or Review Editors may have worked together previously in some fashion. Review Editors were purposively selected based on their expertise with evaluation and/or evidence-based programming for older adults. Review Editors were independent of named authors on any given article published in this volume.