The glycoprotein (G) of rabies virus (RV) is required for binding to neuronal receptors and for viral entry. G-deleted RV vector is a powerful tool for investigating the organization and function of the neural circuits. It gives the investigator the ability to genetically target initial infection to particular neurons and to control trans-synaptic propagation. In this study we have quantitatively evaluated the effect of G gene deletion on the cytotoxicity and transgene expression level of the RV vector. We compared the characteristics of the propagation-competent RV vector (rHEP5.0-CVSG-mRFP) and the G-deleted RV vector (rHEP5.0-ΔG-mRFP), both of which are based on the attenuated HEP-Flury strain and express monomeric red fluorescent protein (mRFP) as a transgene. rHEP5.0-ΔG-mRFP showed lower cytotoxicity than rHEP5.0-CVSG-mRFP, and within 16 days of infection we found no change in the basic electrophysiological properties of neurons infected with the rHEP5.0-ΔG-mRFP. The mRFP expression level of rHEP5.0-ΔG-mRFP was much higher than that of rHEP5.0-CVSG-mRFP, and 3 days after infection the retrogradely infected neurons were clearly visualized by the expressed fluorescent protein without any staining. This may be due to the low cytotoxicity and/or the presumed change in the polymerase gene (L) expression level of the G-deleted RV vector. Although the mechanisms remains to be clarified, the results of this study indicate that deletion of the G gene greatly improves the usability of the RV vector for studying the organization and function of the neural circuits by decreasing the cytotoxicity and increasing the transgene expression level. Rabies virus (RV) selectively infects neurons and propagates between synaptically connected neurons in an exclusively retrograde direction -4. We haWickersham et al. ,10 have in vitro and in vivo. As we had expected, rHEP5.0-ΔG-mRFP did infect neurons retrogradely but did not propagate trans-synaptically. Furthermore, out of our expectation, the deletion of the G gene markedly affected aspects of the RV vector other than its infection properties such as the transgene expression level [To improve the infection features of our RV vector, we have generated a G-deleted RV vector (rHEP5.0-ΔG) by deleting the entire G gene from the genome of rHEP5.0-CVSG. A monomeric red fluorescent protein (mRFP) was inserted into each vector  was constructed by deleting the entire G gene from pHEP5.0-CVSG . A PCR fragment containing the sequence from the GCTAAGCAAAATCATGCAAGATGA-3’5’- CAA (the Blp I site is underlined)P-Blp-5: CGTACGAGAGGTGTTAATAGTTTTTTTCACATCCA -3’5’- AGT BsiWI-M-3: Blp I site and Bsi WI site was removed from pHEP5.0-CVSG and was replaced with the PCR fragment shown above. The resulting plasmid was designated pHEP5.0-ΔG. We have deposited the sequence of the full-length cDNA of pHEP5.0-ΔG in the DDBJ/GenBank/EMBL database . In this study we used RV vectors that express mRFP as a transgene. mRFP cDNA containing the Not I site, open reading frame, and the Sac II site was amplified and inserted into the additional transcription insertion unit between the N and P genes of pHEP5.0-CVSG and the pHEP5.0-ΔG. The resulting plasmids were designated pHEP5.0-CVSG-mRFP and pHEP5.0-ΔG–mRFP  as described previously . The res3. After the primary antibody was aspirated, cells were washed and permeabilized in PBS containing 0.1% Triton X-100 (PBT). Cells were then incubated for 2 hours at room temperature in Cy2-conjugated anti-rabbit goat IgG  and Hoechst 33258 solution  diluted in PBT. The cells were then washed 3 times with PBS, and coverslips were adhered to glass slides with mounting medium. Fluorescent labeling was assessed using the confocal laser-scanning microscope LSM 5 Exciter (Carl Zeiss). The fluorescence intensity of mRFP was quantified by measuring the average fluorescence intensity per pixel in the infected neurons with ImageJ software (http://rsb.info.nih.gov/ij). Since we measured the fluorescence intensity only from cells whose fluorescence was above the fixed threshold, apoptotic cells which hardly show fluorescence were not included in the analysis.NA cells were plated on glass coverslips in a 12-well plate and maintained at 37°C in minimum essential medium supplemented with 10% heat-inactivated fetal bovine serum (FBS). To evaluate the infection properties of rHEP5.0-CVSG-mRFP and rHEP5.0-ΔG-mRFP, each virus was applied to the dish at a multiplicity of infection (m.o.i) of 1. To evaluate the efficacy of mRFP expression of the two vectors, each of the two viruses was applied at a m.o.i of 15. One hour after infection the inoculum was replaced with fresh medium and cells were incubated at 34°C. The spread of the viruses and the fluorescence intensity of the mRFP were examined at different time points (1–9 days post-infection). Cells were fixed for 45 min at 4°C in phosphate buffered saline (PBS) containing 4% formaldehyde, washed with PBS three times, and then soaked for an hour at room temperature in PBS containing 5% goat serum and 0.1% Triton X-100. Cells were then incubated overnight at 4°C with monospecific rabbit anti-N antiserum  diluted 2, 1.3 mM MgCl2, 10 mM D-glucose, 10 mM HEPES, 0.1% BSA, adjusted to pH 7.4 with NaOH), and the dish was mounted on an inverted microscope . During recording, the bath solution was perfused with fresh extracellular solution at 34–37°C. Infected cells were detected by direct visual observation of mRFP fluorescence.NA cells were plated on a poly-D-Lysine coated 35-mm dish with a coverslip bottom, and the cells were infected with each virus as described in the preceding paragraph. Two to 6 days later the medium was replaced with extracellular solution . Whole-cell recordings were low-pass-filtered at 1 kHz and digitized at 10 kHz. Data were digitized with a digitizer  and fed into a computer for off-line analysis using AxoClamp 9.0 software . Patch-clamp recordings in the whole-cell mode were made using a patch-clamp amplifier with a capacitive headstage  using glass recording electrodes (3–5 MΩ) filled with intracellular solution  as humane endpoints, but since no rats showed any clinical signs of rabies, all rats were sacrificed with an overdose of sodium pentobarbital after a certain survival time according to the experimental schedule. All rats infected with the propagation-competent RV vector (rHEP5.0-CVSG-mRFP) were sacrificed at relatively short survival times (within 7 days), whereas some of the rats infected with the G-deleted RV vector (rHEP5.0-ΔG-mRFP) were sacrificed after a longer survival time (21 days) because this viral vector is known to be non-pathogenic and does not cause any detectable symptoms . All expRats were deeply anaesthetized with ketamine  and xylazine , and were mounted in the stereotaxic frame. The skull was exposed, and a small burr hole was drilled above the injection site. The injection was made by means of a glass micropipette (tip diameter = 30 μm) connected to a 1-μl Hamilton microsyringe.8 FFU/ml, n = 5) or rHEP5.0-ΔG-mRFP  was injected into the medial entorhinal cortex (MEC). Each virus was injected with 1% of pontamine sky blue so that the injection sites could be located. After the injection at 40 nl per minute, the pipette was left in place for an additional 15 minutes before it was withdrawn. The skin wound was sutured, and the animal was monitored for recovery from anesthesia and returned to its home cage. Throughout the survival times, the rats were kept inside a small safety cabinet. Either 800 nl of rHEP5.0-CVSG-mRFP  and were transcardially perfused and fixed with 10% sucrose in 0.1M phosphate buffer  followed by 4% paraformaldehyde in 0.1M PB. The brains were removed from the skulls, postfixed in the same fresh fixative for 4 hours at 4°C and then cryoprotected for at least 48 hours at 4°C in PB containing 30% sucrose. The brains were coronally sectioned at 50 μm on a freezing microtome. in vitro study was conducted to visualize RV-infected neurons. Fluorescent neurons were examined under a Zeiss Axiovert 200M, and imaged either with a laser scanning confocal unit  or with a digital camera (AxioCam MRm). An immunofluorescence procedure similar to that used for the To quantify the mRFP fluorescence intensity, the images of the infected cells were captured by using the laser scanning confocal microscope  under identical conditions. Since the ipsilateral hippocampal region contained numerous labeled neurons, the images were taken from the contralateral CA2, where only few rHEP5.0-ΔG-mRFP-infected neurons were observed in each slice. In the contralateral CA2 region of rHEP5.0-CVSG-mRFP-infected samples, there were many neurons labeled by the immunofluorescence of the N protein. Most of the infected neurons were considered to be trans-synaptically infected neurons because mRFP fluorescence was hardly observed in these neurons. In order not to underestimate the mRFP fluorescence intensity of the rHEP5.0-ΔG-mRFP-infected neurons, only few bright neurons in each slice, which were thought to be the initially infected neurons, were measured and used for quantitative analysis. Average intensity per pixel of mRFP fluorescence in the soma (arbitrary units) was measured using Zen software (Carl Zeiss). 8 FFU/ml, N=8) was injected into the lateral septum (LS) of the 21- to 28-day-old rats as described above, and 3–16 days later the rats were anaesthetized with isoflurane and decapitated. Horizontal hippocampus slices (400 μm thick) were prepared using a vibratome  in ice-cold sucrose artificial cerebrospinal fluid (s-ACSF). The s-ACSF (pH 7.4) was composed of 185 mM sucrose, 2.5 mM KCl, 0.5 mM CaCl2, 25 mM NaHCO3, 1.2 mM NaH2PO4, 10 mM MgSO4, and 25 mM D-glucose oxygenated with a mixture of 95% O2-5% CO2 and chilled to 4°C. Before the start of recording, slices were submerged (in an incubation chamber) in standard ACSF at room temperature (26–28°C) for 1 h. The standard ACSF used for incubation and recording consisted of 119 mM NaCl, 2.5 mM KCl, 2 mM CaCl2, 25 mM NaHCO3, 1.2 mM NaH2PO4, 2 mM MgSO4, and 12.5 mM D-glucose oxygenated with a mixture of 95% O2-5% CO2 (pH 7.4). 800 nl of rHEP5.0-ΔG-mRFP  mounted on an upright microscope . Infected cells were detected by direct visual observation of mRFP fluorescence. Patch-clamp recordings in the whole-cell mode were conducted as described above. Resting membrane potential was measured by taking the average voltage over 10 s in the absence of any current injection. Holding current maintaining the membrane potential at −80 mV was injected, and 500-ms current injections were used to elicit action potentials. Data shown in the Results section are expressed as mean values ± the SEM. The statistical significance of differences between means was evaluated by two-tailed Student’s t-testing and one-way ANOVA followed by Bonferroni’s post hoc test, both performed using Prism .The infection characteristics of rHEP5.0-ΔG-mRFP were examined in NA cells and compared with those of rHEP5.0-CVSG-mRFP. NA cells were infected with either rHEP5.0-ΔG-mRFP or rHEP5.0-CVSG-mRFP to achieve 1–5% infection at 24 hours after infection and were fixed at different time points (1–6 days post-infection (dpi)). The infected cells were visualized by the immunofluorescence of viral N protein . The number of cells infected with rHEP5.0-CVSG-mRFP increased significantly , and almost all cells were infected at 6 days post-infection . The numThe mRFP expression level of rHEP5.0-ΔG-mRFP and rHEP5.0-CVSG-mRFP were compared in NA cells. Cells were infected with either rHEP5.0-ΔG-mRFP or rHEP5.0-CVSG-mRFP to achieve 90–100% infection at 24 hours after infection, and the fluorescence intensity of mRFP was examined at different time points  did not differ significantly from that of the cells infected with rHEP5.0-ΔG-mRFP  or that of the cells infected with rHEP5.0-CVSG-mRFP  . Four days after infection, however, the resting membrane potential of the rHEP5.0-CVSG-mRFP-infected cells  was significantly higher than that the rHEP5.0-ΔG-mRFP-infected cells  and that of the uninfected control cells   of the rat. Ten rats received injections of rHEP5.0-ΔG-mRFP, and the intensity of mRFP fluorescence was examined at 3 dpi (n = 2), 5 dpi (n = 2), 7 dpi (n = 2), 14 dpi (n =2), and 21 dpi (n =2). Five rats received injections of rHEP5.0-CVSG-mRFP and were examined at 3 dpi (n = 2), 5 dpi (n = 1), and 7 dpi (n = 2).We next examined the mRFP expression level of rHEP5.0-ΔG-mRFP and rHEP5.0-CVSG-mRFP In all samples, many labeled neurons were observed in the subiculum, CA1, CA2, presubiculum, medial septum and the diagonal band, supramammillary nucleus, claustrum, midline dorsal thalamic nuclei, and lateral and anterior groups of the dorsal thalamus. These brain areas are all known to have direct projections to the MEC . In sampTo evaluate the ability of the viral vectors to express transgenes, we compared the native fluorescence of mRFP in the hippocampal region. Although 7 days after infection many CA1 neurons in both samples were infected , rHEP5.0To quantify the difference in the transgene expression level of the two vectors, we measured the mean native fluorescence intensity from the soma of the infected contralateral CA2 neurons . Three dTo test whether rHEP5.0-ΔG can be used for physiological studies, rHEP5.0-ΔG-mRFP was injected into the lateral septum of the rat, and 3–16 days later the electrophysiological properties of the infected neurons in hippocampal brain slices were examined using whole-cell patch-clamp recording.Many retrogradely labeled mRFP positive neurons were observed in the pyramidal cell layer of the CA1 and the subiculum. These fluorescent labeled neurons were compared with nonfluorescent control neurons in the pyramidal cell layer. Neither the input resistance nor the input capacitance differed significantly between the infected and non-infected neurons. Mean resting membrane potential was almost identical  and the G-deleted RV vector (rHEP5.0-ΔG-mRFP) and have demonstrated that the deletion of G gene not only affects the infection property but also markedly affects the transgene expression level and the cytotoxicity of the RV vector. The glycoprotein of RV forms spike-like projections on the virus particle that are required for attachment to neuronal receptors and for viral entry into the cells. It has been reported that cells infected with the G-deleted virus were unable to produce infectious virus particles  and thusntivirus ,26.in vivo that infection with rHEP5.0-ΔG-mRFP does not influence the basic physiological properties of the infected neurons for at least 16 days after infection  is different from SADΔG with respect to the RV strain and the position of the transgene insertion site .0-ΔG is ,9,10. In


Falls among older adults are a serious public health issue, and fear of falling can limit mobility, which in turn increases fall risk. A Matter of Balance/Volunteer Lay Leader Model is an evidence-based program designed to address fear of falling. The objective of this study was to describe implementation, dissemination, and outcomes of this program in 3 regions of South Carolina with a predominantly African American and largely underserved population.We developed partnerships throughout the state, organized master and lay leader trainings, and documented numbers of lay leaders, programs offered, demographic characteristics of participants, program fidelity, and attendance. Outcome measures were self-reported confidence to prevent and manage falls and a quantitative measure of functional mobility. Both measures were assessed at baseline and after program completion.Older adults (N = 235) attended 18 classes at 16 sites. Barriers to implementation were program teams' limited familiarity with the concept of evidence-based programs and the importance of adhering to program content. Facilitators were state-level leadership and a history of state, regional, and local groups collaborating successfully on other projects. Outcomes indicated greater confidence in managing falls and carrying out activities of daily living. Mobility improved significantly, suggesting a reduced risk for falls.Evidence-based programs such as A Matter of Balance/Volunteer Lay Leader Model can be successfully disseminated in underserved areas. Outcomes indicate that participation in fall prevention programs can benefit groups of predominantly African American older adults. Medscape, LLC is pleased to provide online continuing medical education (CME) for this journal article, allowing clinicians the opportunity to earn CME credit.This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and Preventing Chronic Disease. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians. AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.Medscape, LLC designates this Journal-based CME activity for a maximum of 1 www.medscape.org/journal/pcd (4) view/print certificate.All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 70% minimum passing score and complete the evaluation at Release date: May 23, 2012; Expiration date: May 23, 2013Upon completion of this activity, participants will be able to:Describe implementation of AMOB/VLL, an evidence-based program designed to address fear of fallingDescribe barriers and facilitators to implementation of AMOB/VLLDescribe outcomes of implementing AMOB/VLLCME EDITORPreventing Chronic Disease. Disclosure: Nancy Saltmarsh has disclosed no relevant financial relationships.Nancy Saltmarsh, Editor, CME AUTHORLaurie Barclay, MD. Freelance writer and reviewer, Medscape, LLC. Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships. AUTHORS AND CREDENTIALSDisclosures: Gerhild Ullmann, PhD; Harriet G. Williams, PhD; Cora F. Plass, MSW have disclosed no relevant financial relationships.Affiliations: Gerhild Ullmann, Clemson University, Clemson, South Carolina; Harriet G. Williams, University of South Carolina, Department of Exercise Science, Blatt Center, Columbia, South Carolina; Cora F. Plass, South Carolina Department of Health and Environmental Control, Columbia, South Carolina.Falls and fall-related injuries are a public health issue; they often have serious consequences for older adults and can lead to loss of independence. Every year, 36% to 40% of adults aged 65 or older fall at least once ,2; fallsFalls and fall-related injuries are not necessarily a result of aging. Environmental, physical, and behavioral factors contribute to increased fall risk. Fear of falling is an additional factor contributing to falls ,5; it caAs part of an Administration on Aging grant to mobilize states to implement evidence-based programs in local communities, we partnered with the Aging Network (Area Agencies on Aging and aging service providers), the Lieutenant Governor's Office on Aging (LGOA), the South Carolina Department of Health and Environmental Control (DHEC), and the University of South Carolina (USC) School of Public Health to implement a 3-year project in South Carolina (2006-2009). In year 2, we implemented A Matter of Balance/Volunteer Lay Leader (AMOB/VLL) Model ,11, an eThe study was a quasi-experimental design with pre-post assessments and no control group. The institutional review boards of DHEC and USC approved study procedures and protocols. All participants could withdraw from the study at any time and signed a written consent before programs and testing began.We disseminated AMOB/VLL in 3 regions of South Carolina: Appalachia, Pee Dee, and Trident (Lowcountry). The Appalachia region includes the urban areas Greenville, Spartanburg, and Anderson and surrounding rural areas in 6 counties. The Trident region includes Berkeley, Charleston, and Dorchester counties. Metropolitan Charleston is surrounded by rural, underserved, and geographically isolated areas. The Pee Dee region in northeastern South Carolina encompasses 6 counties and is a rural underserved area with a large African American population. Program sites included churches, hospitals, older-adult centers, and Council on Aging nutrition centers.AMOB/VLL uses a cognitive-behavioral approach that focuses on identifying and modifying fall risk factors , teaches that falls are not an inevitable consequence of aging, and uses theory to overcome misconceptions and raise confidence of participants -12. The We created a 3-tiered organizational structure consisting of an active, engaged, and interactive group of people and organizations. Tiers included a state-level team, a regional team, and local service providers to serve as implementation sites. The state team consisted of representatives from South Carolina DHEC , LGOA (State Aging Unit), and the USC School of Public Health. Key responsibilities of the state team were consulting with regional project teams and providing technical assistance to these teams in developing partnerships, implementing programs, and evaluating program delivery. The regional teams (1 for each area studied) included representatives from regional health departments, Area Agencies on Aging, and local County Councils on Aging. The third tier included local aging service provider organizations .Representatives from the state tier made up the core team, which provided overall leadership for the project. Major activities of the core team and regional teams are described in the box.Training staff to implement and conduct AMOB/VLL programs involved 2 phases: preparing master trainers and training lay leaders to lead classes.Regional teams identified candidates for master trainers. National trainers from the Maine Department of Health and Human Services, originator of AMOB/VLL, provided a master trainer session  in South Carolina at the outset of the project ,11. ReprRegional teams and service provider organizations identified potential lay leaders to implement local programs. Regional program coordinators and master trainers organized 2-day trainings (16 hours) for lay leaders, using the same format as for master trainings. Master trainers helped lay leaders throughout the implementation of programs in their areas.We used several strategies to recruit participants: enrolling participants from sites that served older adults, placing advertisements in local newspapers, attending health fairs, distributing fliers and brochures throughout the local community, and speaking at Council on Aging sites and to local faith-based groups for older adults. After several programs were completed, word of mouth became another recruiting tool.We used first and last session surveys and the attendance form designed for the project by states involved in the broader Agency on Aging initiative ,11. We aTo monitor implementation and dissemination of programs, teams met regularly to review and discuss ongoing activities and to document major barriers and facilitators through reports from site program coordinators and minutes of meetings. We tracked numbers of programs offered by region, lay leaders trained, total participants, and attendance. People who attended 5 or more of 8 AMOB/VLL sessions were considered to be completers and to gain benefits from the program . All proWe monitored program fidelity by using checklists designed to evaluate the degree to which content of AMOB/VLL programs was carried out according to program protocol. Fidelity checklists were developed for each session, including the introductory session, and highlighted the main topics of session content, provided a space to check whether that part of the session had been completed, and allowed for comments about deviations from session content. Lay leaders used fidelity checklists as a guide in carrying out each session's activities and completed them immediately after each session. Lay leaders' objectivity in using fidelity checklists was examined during implementation of the AMOB/VLL program in Lee County, South Carolina. In this instance, independent observers visited sessions periodically, reviewed activities, and completed checklists. Comparison of independent observers' checklists with those of lay leaders indicated 98% agreement.We measured outcomes with the Falls Management Scale (FMS) and Timed Up and Go (TUG), a quantitative assessment of mobility performance  ,12,15. BNot all sites provided complete data on all aspects of programs. We ascertained the number of attendees and degree of program completion by using attendance data. To assess barriers to program implementation, we reviewed reports from regional teams and notes from team meetings.To evaluate fidelity to program content, we examined fidelity checklists from all programs using these guidelines and reviewed and categorized written comments from lay leaders about omissions or deviations. We calculated the percentage of adherence to program content on the basis of checked items and summarized comments.P < .05. All models controlled for age.For analyses of intervention outcomes, we used only data from participants who completed both preassessments and postassessments and we applied mixed models for repeated measures to compare performances. All analyses were performed using SAS version 9.1 . Significance was set at We received demographic information on 150 participants from 13 programs in 2 regions. Demographic data from 5 programs were missing. Not all 150 participants completed all survey questions. Fifty-seven percent of participants were African American, 62% had an annual income of less than $15,000, and 69% had a high school education or less .Fifteen lay leaders conducted 18 AMOB/VLL classes in 3 regions at 16 sites . The 18 Major barriers included lack of awareness about the availability of programs, insufficient knowledge of the potential benefits of such programs, and lack of easy access to program sites. Barriers for program leaders were related to implementation of programs, such as lack of knowledge or skills regarding 1) evidence-based programs, 2) program fidelity and its importance, and 3) how to administer, collect, and record pre-post assessment data. Facilitating factors included the state-level leadership in guiding the project; the history of the state, regional, and local groups working successfully together on other projects; the structure of the Area Agencies on Aging; the recruitment of participants through these agencies; and the commitment of local groups to providing their facilities for use in delivering the program.We received fidelity checklists for 13 programs; 117 sessions were conducted (13 programs A- 9 sessions) and 116 fidelity checklists were completed. More than 80% of program content was delivered appropriately in all 13 programs. Nine programs covered more than 90% of program content.P < .001); TUG age-adjusted performance times decreased from a mean (SD) of 13.0 (0.47) seconds to 11.7 (0.47) seconds (P < .001).For the 108 FMS and 113 TUG participants for whom data were available, analyses showed significant improvement in self-reported falls management (FMS) and objectively measured mobility (TUG). Age-adjusted mean (standard deviation [SD]) scores on the FMS improved from 2.3 (0.07) at baseline to 1.8 (0.07) post-intervention . No demographic data were available from 5 programs; in addition, attendance forms were missing for 20 participants. Still, we had data on most participants who completed 13 programs. Deviation from delivery of prescribed program content was minimal and occurred most frequently in the final 2 sessions. This was due, in part, to the participation of guest health professionals in these sessions. AMOB/VLL content encourages the use of guest speakers, but often their participation took time away from other program content.Facilitating factors included the leadership provided by the state agencies in guiding area partners in planning and implementing programs and the structure of the Area Agencies on Aging for delivering services to older adults. These groups had a history of collaboration. Another factor was the decision to recruit participants from organizations that already served older adults. Commitment of partner groups to offer use of facilities as sites for program implementation was integral to project success. Such commitment facilitated participant recruitment and expedited program implementation.To our knowledge, this is the first time that AMOB/VLL program outcomes were evaluated by using a quantitative assessment of mobility. Although exercise was only 1 component of the AMOB/VLL program, we found a significant improvement in mobility. This outcome suggests that participation in even minimal physical activity may be enough to bring about small improvements in mobility; other intervention studies with older adults have reported similar findings ,19.This study had several limitations. Without a control group, outcomes must be interpreted with caution; because all participants were volunteers and not randomly selected, outcomes cannot be generalized to all older adults. Loss of data from 5 programs was greater than desired. Data from these programs were either not submitted or were lost. Future research should address the length and type of training needed to fully prepare lay leaders to conduct tests and gather and report outcome data appropriately.Before this study, AMOB/VLL programs had been implemented primarily among white populations ,13,17. A


Tobacco mosaic virus (TMV), a widespread plant pathogen, is found in tobacco (including cigarettes and smokeless tobacco) as well as in many other plants. Plant viruses do not replicate or cause infection in humans or other mammals. This study was done to determine whether exposure to tobacco products induces an immune response to TMV in humans. Using a sandwich ELISA assay, we detected serum anti-TMV antibodies  in all subjects enrolled in the study . Smokers had a higher level of serum anti-TMV IgG antibodies than non-smokers, while the serum level of anti-TMV IgA from smokeless tobacco users was lower than smokers and non-smokers. Using bioinformatics, we also found that the human protein TOMM40L  contains a strong homology of six contiguous amino acids to the TMV coat protein, and TOMM40L peptide exhibited cross-reactivity with anti-TMV antibodies. People who smoke cigarettes or other tobacco products experience a lower risk of developing Parkinson’s disease, but the mechanism by which this occurs is unclear. Our results showing molecular mimicry between TMV and human TOMM40L raise the question as to whether TMV has a potential role in smokers against Parkinson’s disease development. The potential mechanisms of molecular mimicry between plant viruses and human disease should be further explored. Tobacco mosaic virus (TMV), the first plant virus discovered, is a single stranded RNA virus. It is present worldwide and is known to infect over 150 different plants, including tobacco, tomatoes, peppers, and cucumbers Tobacco smoking has been shown to cause cancers The study protocol for the use of human subjects was approved by the Committee of the Institutional Review Board of the University of Louisville. Written informed consent was obtained from each subject prior to enrollment according to the Declaration of Helsinki guidelines.Table S1).Healthy male volunteers were recruited in this study: 20 non-users of tobacco products , 20 current users of smokeless tobacco , and 20 current smokers . Race/ethnicity data and tobacco use history of participants were obtained from direct interview  was immediately transferred into 1 ml aliquots and stored at –80°C until analysis.Tobacco mosaic virus common strain U1  was kindly provided by K. E. Palmer  and used to determine anti-TMV antibody levels in human serum by Enzyme-linked immunosorbent assay (ELISA). The translocase of outer mitochondrial membrane 40 homolog (yeast)–like (TOMM40L) peptide (a blocking control for specificity of TOMM40L antibody) was purchased from Fitzgerald Industries International .™Nunc Immuno maxiSorp plates were coated with 100 µl/well of murine TMV monoclonal antiserum  in coating buffer  at 4°C overnight. After blocking with 10% Fetal Bovine Serum (FBS), 100 µl per well of 2.5 µg/mL TMV U1 was added and incubated for 1 h at room temperature, then serum samples were added and incubated for 2 h at room temperature. Plates were then incubated for 1 h at room temperature with horseradish peroxidase (HRP)-conjugated goat anti-human IgG, IgG1, IgG2, IgG3, IgG4, IgA, IgD, IgE or IgM  , followed by color development with TMB  substrate. Results were expressed as optical density (O.D.) value at 450 nm  with double or triple wells per sample. Values obtained from serum dilution buffer were subtracted from those with subject samples.Serum anti-human TMV IgG antibodies and anti-human TMV IgA/D/E/M antibodies were detected by ELISA as described previously http://blast.ncbi.nih.gov/Blast.cgi) to search its sequence homology with any human proteins of our potential interests. The parameters for the searches were set for maximum target sequence at 1000, expect threshold at 1000, word size at 2, matrix at PAM30 (Point Accepted Mutation 30), and no adjustments or filters included.Using the TMV coat protein sequence, we performed a Basic Local Alignment Search Tool (BLAST) analysis at the National Center for Biotechnology Information (NCBI) website . 100 µl of TOMM40L peptide (10 µg/ml) or TMV U1  were added to an anti-TMV-coated 96-well microtiter plate and incubated for 2 h at room temperature. After washing, the plates were further incubated with alkaline phosphatase-conjugated enzyme for 2 h and then developed with p-Nitrophenyl (PNP) substrate. Results were expressed as O.D. at 405 nm.t test or Mann-Whitney U test was used for two group comparisons. One-way analysis of variance (ANOVA) with Tukey post-hoc test or Kruskal-Wallis nonparametric test with Dunn post-hoc test was used for multiple comparisons among groups. p <0.05 was considered statistically significant.Results are presented as means ± SE, and statistical analysis was done using GraphPad Prism software . An unpaired Student’s p < 0.01, t test). The levels of anti-TMV IgG did not differ between smokers and smokeless tobacco users and between smokeless tobacco users and non-users  named in order of their abundance in serum, TMV-specific IgG subclasses were analyzed. Anti-IgG1, 3, and 4 were all present in human sera whereas very low seropositivity was detected for serum anti-TMV IgG2. Anti-IgG1 was the predominant subclass and the only one that smokers had a significantly higher level than non-smokers Table 1.p < 0.05, t test), but not in the Caucasian smokers . For the Caucasian ethnic group, the serum level of anti-TMV IgG1 from smokers was marginally higher than non-smokers (Table S2). However, among the African-American group, the levels of anti-TMV IgG3 and IgG4, but not IgG1, were significantly higher in smokers than non-smokers (Table S3).To determine if ethnic differences among enrolled groups were associated with TMV immune responses, the 60 subjects was stratified into Asian, Black/African American and White/Caucasian ethnic groups. Asian male subjects were found only in the non-user group, thus we focused on African American and Caucasian groups in our subsequent analysis . Although it was also lower, it was not significantly different from non-smokers    showed significant sequence similarity to the TMV coat protein (-32L---36FQTQQA41-) with an overlap of 6 contiguous amino acids  have been mapped at the surface of TMV coat protein and their structure has been extensively studied Our data demonstrate that anti-TMV antibodies can cross-react with TOMM40L. These observations suggest molecular mimicry between TMV and human TOMM40L protein. Molecular mimicry is a concept by which autoimmune diseases may be caused by the structural similarity of antigenic determinants. For example, an immune response against a viral sequence shared by the host and the virus can evoke a tissue-specific immune response that is capable of eliciting cell and tissue destruction Parkinson’s disease is the second most common neurodegenerative disorder in the U.S. About 50,000 American are diagnosed with PD each year, with more than half a million Americans affected. Epidemiologic evidence has long suggested a negative association between smoking and the risk of PD. Statistics show that PD appears to affect men at a slightly higher rate than women and is less likely to affect African Americans or Asians than whites Molecular mimicry has been linked to a number of naturally occurring human diseases such as myasthenia gravis (the acetylcholine receptor AChRα-subunit amino acids 160–167 shows cross-reactivity with a shared homologous domain on herpes simplex virus glycoprotein D p286–293) Our study has a number of limitations. The study’s sample size is small, with only 20 people in each group, with uneven distribution of African American subjects. The measurement of anti-TMV antibody in serum by ELISA is semi-quantitative, and we were unable to quantitatively measure antibody levels. The study population included relatively young subjects and aged adults are at higher risk for PD, so we are unable to draw a firm conclusion regarding PD. Further studies are needed to evaluate the relationships among anti-TMV and anti-TOMM40L antibodies and the development of PD, and to determine the role of TOMM40L in pathogenesis of PD. Future study of the effects of TMV exposure on human health and disease may provide a possible therapeutic strategy against Parkinson’s disease. Finally, TMV is being used as a vector for antigen delivery in bioengineered vaccines Table S1History of Tobacco Use. Tobacco use history of participants was obtained from direct interview. NA indicates data Not Available, a mean ± SE, and b percentage.(DOCX)Click here for additional data file.Table S2Levels of Anti-TMV IgG Subclass in Human Serum (Caucasian). Sera were obtained from Caucasian study population of smokers and non-tobacco users. Serum anti-TMV IgG subclass levels were measured by a customized sandwich ELISA assay. The serum dilution factor for anti-TMV IgG1/ IgG3/IgG4 was 1∶100 and for anti-TMV-IgG2 was 1∶10. Data represent two to three independent experiments with double wells per subject. Results are expressed as O.D. values (mean ± SE); p-value, a Student’s t test, *p < 0.05.(DOCX)Click here for additional data file.Table S3Levels of Anti-TMV IgG Subclass in Human Serum (African American). Sera were obtained from African American study population of smokers and non-tobacco users. Serum anti-TMV IgG subclass levels were measured by a customized sandwich ELISA assay. The serum dilution factor for anti-TMV IgG1/ IgG3/IgG4 was 1∶100 and for anti-TMV-IgG2 was 1∶10. Data represent two to three independent experiments with double wells per subject. Results are expressed as O.D. values (mean ± SE); p-value, a Student’s t test, b Mann-Whitney U test, *p < 0.05.(DOCX)Click here for additional data file.


Obesity is on the rise in the United States and there has been a conscious effort on the part of the government and physicians to provide measures to counteract the epidemic. Diet is an important part of therapeutic lifestyle modification, but many physicians feel lacking in their ability to provide sound and adequate counseling. Our objective was to assess the main reasons why residents at Lenox Hill Hospital chose to enroll in a nutrition education program.Sixteen residents of varying specialties at Lenox Hill Hospital wrote essays to apply to a nutrition education program given by the hospital. A theme analysis was applied to assess common reasons why residents chose to apply to the program. Each theme was assigned a letter and the number of appearances of a theme was tabulated.There were seven main themes that were consistently present in the residents’ essays as to why they wanted to enroll in a nutrition education program: 56% alluded to a lack of nutrition education; 44% listed diseases with relation to diet; 44% wrote about a desire to make changes to their own lives; 31% spoke about improving patient health outcomes; 25% spoke about the obesity epidemic; 19% about wanting to “practice what they preach” in terms of nutrition; and 13% thought the program could help them field patients' questions about nutrition.Young physicians at Lenox Hill Hospital chose to apply to a nutrition education program because of a recognition of a disease epidemic related to diet, a desire to improve personal and patient education and outcomes, and above all, the perception that they lack sufficient nutrition education.


Human Cytomegalovirus (HCMV) is the most common cause of congenital infections. The maternal immune status plays a major role in the likelihood of congenital infection. The aim of this study is to shed light on the seroprevalence of HCMV in pregnant women, hospitalized children and newborns including cases of congenital infections in Palestine.We analyzed HCMV IgG and IgM test results that had been ordered for pregnant women, hospitalized children and newborns in the years 2006–2012 at Al-Makassed Islamic Charitable Hospital (MICH) in East Jerusalem. Furthermore, we reviewed the medical charts of newborns and HCMV IgM-positive children.HCMV IgG was positive in 96.6% of pregnant women, in 88% of hospitalized children and in 98.4% of hospitalized newborns. HCMV IgM was positive in 11.5% of pregnant women, in 11.7% of hospitalized children and in 2% of hospitalized newborns respectively. The HCMV avidity assay revealed that 95% of IgM-positive pregnant women had high avidity (>60%) indicating that most Palestinian women were undergoing a recurrent HCMV infection. Real time PCR on limited number of cases indicated that 62.5% of infants, mostly born to IgM-positive mothers and 83.3% of HCMV IgM-positive children had detectable HCMV DNA in their urine. Out of the 249 newborns tested during this study period, four (1.6%) were subjected to Gancyclovir treatment because of symptomatic congenital HCMV infection.This is the first report to provide an insight into HCMV seroprevalence in Palestine. Despite the high rate of seropositivity, the importance of HCMV testing during pregnancy should not be underestimated. A comprehensive study with a long term follow-up examination of offspring born to HCMV IgM-positive mothers would be required to provide estimates of an accurate percentage of symptomatic congenital HCMV infection in Palestine. Some of the most common infections associated with congenital anomalies are summarized in TORCH testing. TORCH includes Toxoplasmosis, Other , Rubella, Cytomegalovirus (CMV), and Herpesvirus infections. Most of the TORCH infections cause mild maternal morbidity. However, they may have very serious consequences in the fetus, with a high rate of congenital anomalies, mental retardation, and an increased incidence of stillbirths .Human cytomegalovirus (HCMV), HHV-5, belongs to the beta herpes family and is one of the most common causes of congenital viral infections. Congenital HCMV infection is associated with permanent hearing loss, vision loss and neurological impairment -5. MaterThe seroprevalence of HCMV is generally high in developing countries, and among those of lower socioeconomic status in developed countries . HCMV seIn this study, we analyzed the results of HCMV-specific IgG and IgM assays at Al-Makassed Islamic Charitable Hospital (MICH) in East Jerusalem, the referral hospital in Palestine, and from the limited number of HCMV viral load records maintained at the Virology Research Laboratory, Medical Research Center, Al-Quds University, East Jerusalem, Palestine. The data presented here shed light on the incidence of HCMV infection in pregnant Palestinian women, children and newborns.MICH is the referral hospital for Palestine and the main teaching hospital associated with Al-Quds University Medical School. Accordingly, patients visiting the hospital come from all over the West Bank, East Jerusalem and the Gaza strip. However, most pregnant women seeking consultation at MICH are predominantly residents of East Jerusalem district. The range of monthly deliveries at MICH is 180–200, most of which are not booked, i.e. they did not consult the MICH outpatient clinic during pregnancy. HCMV IgG and IgM tests were ordered routinely for pregnant women as part of TORCH surveillance. The age of pregnant women ranged from 17–45 years with the majority in their twenties and thirties. The TORCH test was ordered for children mainly if they presented with jaundice and/or prolonged fever of unknown origin. The age of children was between one month and 14 years. In case of newborns, HCMV IgG and IgM tests were ordered either as part of TORCH surveillance if any clinical manifestation suggestive of congenital infection was observed, or because they were offspring of HCMV IgM-positive mothers, even when signs of congenital infection were absent. Newborns were between one and 21 days old and were mainly tested using their mother’s name as identification as most of them had not yet been determined.Patients’ data and results were made available by the director of the MICH Central Laboratory and approved by the MICH Ethics Committee. Reviewing medical files was approved by the MICH Ethics Committee.IgG and IgM were tested from serum samples using AxSYM kits  on Abbott AxSYM machine according to the manufacturer instructions. Tests were performed at the MICH Central Laboratory. The laboratory participates regularly in internationally recognized external quality control  for HCMV serology three times annually.HCMV IgG avidity assay was performed on IgM-positive serum samples using Anti-CMV ELISA . HCMV IgG avidity assay had been introduced into the test list of the MICH Central Laboratory in January, 2012. The laboratory participates in internationally recognized external quality control  for HCMV IgG avidity once annually.AD169, quantitated DNA PCR control, cat# 08-925-000, Abionline, MD, USA) was used as a standard in all experiments. The standard was serially diluted in ultra pure water from 106 down to 101 copies/μl and dilutions were freshly prepared with each run.Real time PCR for HCMV was performed at the Virology Laboratory at Al-Quds University. DNA was isolated from urine or whole blood, serum or urine samples using the QIAamp DNA Blood Mini Kit . Real time PCR for viral load detection was performed using an ABI Real Time PCR 7500 . The reaction included TaqMan universal master mix (Applied Biosystems), CMV –gB-F: 5′-TGG GCG AGG ACA ACG AAA TC-3′, CMV –gB-R: 5′-TGA GGC TGG GAA GCT GAC AT-3′ as primer and 5′(FAM) -TGG GCA ACC ACC GCA CTG AGG – (BHQ) 3′ as probe , respecThe results were collected from an Access data base program designed by the director of MICH Central Laboratory and copied into Excel spread sheets for analysis. Clinical presentations, data for HCMV viral load and HCMV avidity were analyzed separately.In total, 1620 HCMV IgG and 1620 HCMV IgM tests performed for pregnant women, children, and newborns during the period from 2006–2012 were analyzed. In 1480 patients (91.4%) both IgG and IgM were tested simultaneously. In the remaining 8.6% of the patients, either IgG or IgM was tested. The following analysis was based only on those cases for which both tests were obtained simultaneously.556 37.6%) of analyzed records were those of pregnant women in their first trimester, 924 (62.4%) of children, 249 cases (26.9%) of which were newborns Table . HCMV Ig7.6% of aRegarding the IgM status of pregnant women, 84.7% were negative, 11.5% were positive and 3.8% were in the grey zone Figure .Among the children, 11.7% were IgM positive, 85.4% were negative and 2.9% had IgM values within the grey zone  were tested for HCMV IgG avidity. Twenty-six of these serum samples had been archived since 2010; the remaining 14 sample belonged to women who had tested positive for HCMV IgM in 2012. Thirty-nine women (97.5%) were positive for both IgG and IgM, while only one woman was IgG negative and IgM positive, for whom IgG avidity could not be tested. Another woman presented with 44% HCMV IgG avidity, which is in the grey zone according to the manufacturer of the kit. All the other 38 women (95%) presented with high HCMV IgG avidity (>60%).The urine of 10 (62.5%) out of 16 newborns (13 were born to IgM-positive mothers) tested positive for HCMV DNA. Viral load for two positive newborns was not tested at the Virology Research Laboratory. The urine of 15 (83.3%) out of 18 children  and 3 out of 4 children (IgM grey zone) tested positive for HCMV DNA.HCMV viral load was assayed in the whole blood of another 17 children between the ages of two months and 14 years. Eleven children were HCMV DNA viremic, six were HCMV IgM positive, while five were HCMV IgM negative.Sixteen of the women tested for HCMV avidity were also tested for HCMV DNA in their sera. While three women tested negative for HCMV DNA, 13 were viremic (including the one IgG negative and IgM-positive case).Medical charts of all 103 HCMV IgM-positive children, aged 23 days to 14 years, were reviewed and clinical presentations suggestive of HCMV infection were recorded. The major clinical presentations were hepatosplenomegaly or hepatomegaly (60%), followed by jaundice (30%). Prolonged fever or fever of unknown origin was recorded in 10% of the cases as one of the major clinical signs, while acute liver failure or fulminant liver failure presented in 8.7% of the cases. An ophthalmologic exam was ordered for 33 (32%) children, eight (24.2%) of whom were suffering from different eye findings, including chorioretinal spots, bilateral mild cataract, bilateral optic atrophy and bilateral choroidal coloboma. Hearing was impaired in one case. Nevertheless, out of all 103 children cases, only a single case, a two month-old child, suffering from progressive intrahepatic cholestasis was treated with Gancyclovir.Medical registers of all 249 newborns tested for HCMV serology were reviewed. Sixteen newborns were subjected to HCMV viral load testing in urine; thirteen were born to mothers with recurrent HCMV infection. The remaining three newborns were admitted to MICH following birth  and tested for HCMV because of symptomatic congenital infection. The only cases treated with Gancyclovir, because of symptomatic congenital HCMV infection, along with viral shedding in urine, were one newborn born at MICH to a mother with recurrent HCMV infection and the three newborns admitted following birth. The first case suffered from HCMV chorioretinitis, the one-day-old newborn presented with microcephaly and intracerebral calcification, the 10-day-old infant (HCMV IgM positive) suffered from hepatosplenomegaly and neonatal jaundice, while the 19-day-old infant (HCMV IgM positive) presented with cholestatic jaundice and neurological manifestation. Interestingly, two of the mothers, whose newborns were admitted, tested positive for HCMV IgM on the admission of their infants (1-day and 10-day-olds). Finally, all infants, born at MICH to HCMV IgM-positive mothers were discharged with recommendations to follow up with ophthalmic test and auditory brain stem evoked response (ABER) hearing test, even when HCMV DNA in their urine was negative and congenital symptoms were absent.The seroprevalence of HCMV IgG among pregnant Palestinian women and children as presented here is comparable to regional studies from Egypt , Qatar , TunisiaThe percentage of active infection (positive HCMV IgM) among pregnant Palestinian women is 3–5 times higher than that described in regional studies from Iran , Qatar , Sudan  and TurkThe percentage of positive HCMV IgM among hospitalized Palestinian children at MICH is also higher than percentages reported in a control group from Iraq  and QataSince vertical transmission of HCMV is 15-20% higher in primary infected women compared to women with recurrent infection ,11,12,52We have no records regarding the socioeconomic status (SES) of the women and children, whose results are presented here. Reports from various countries have shown that SES is proportional to the high rate of HCMV infection ,46,59,60Screening pregnant women for HCMV IgG and IgM is not performed routinely in Palestine; MICH policy is thereby an exception. The data provided here and that of other studies strongly encourage routine testing for HCMV IgG and IgM among pregnant women in Palestine. Finally, follow-up tests with offspring to HCMV IgM-positive mothers are essential, in order to detect the consequences of congenital infection and to allow treatment to occur as early as possible.The authors declare that they have no competing interests.TN, AQ, EA, FD and TN (Nusseibeh) performed the serology testing and samples’ archiving for DNA analysis. TN and AQ established and performed the Avidity testing. TN, AQ, EA and AA reviewed the patients’ files for clinical data. AA summarized the clinical findings and helped with literature review. NS and LQ performed the viral load testing. HK, MA and AA reviewed the newborns’ registers; HK reviewed the clinical observation summary presented here and approved it. TN and MA analyzed and verified the HCMV serology data. SB designed the program for data analysis, retrieved all serology tests and patients data available at the laboratory, verified and provided them for analysis. MA designed the study, summarized the data and wrote the paper. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/13/528/prepub


A total of 231 schools participated in the Project P.A.T.H.S. in 2009/2010 school year. After completion of the Tier 1 Program, subjective outcome evaluation data were collected from 3,259 program implementers. Based on the consolidated data with schools as units, results showed that participants had positive perceptions of the program, implementers, and benefits of the program. More than four-fifth of the implementers regarded the program as helpful to the program participants. Multiple regression analyses revealed that perceived qualities of the program and the program implementers predicted perceived effectiveness of the program. Similar to previous studies, compared to implementers' perception about their performance, the perceived program content appeared to be a stronger predictor of program success. The present study provides additional support for the effectiveness of the Tier 1 Program of the Project P.A.T.H.S. in Hong Kong. How to prevent adolescent risk behavior, such as delinquency, drug abuse, unprotected sexual behavior, and school failure, has been a challenging issue for psychologists, educators, policy makers, and other helping professionals –3. In reThe approach of positive youth development has been widely adopted in designing programs for adolescents in the west . HoweverAs the Project P.A.T.H.S. has been implemented in a large scale in Hong Kong adolescents, one important question that must be asked is how effective the project is. To answer this question, systematic evaluation of the program is necessary. Since the launch of the program, numerous evaluation studies have been carried out, with the use of a variety of evaluative strategies, including objective outcome evaluation, subjective outcome evaluation, focus group interview, case studies, direct observation, and a longitudinal randomized group controlled trial , 13. FinWhile objective outcome evaluation, particularly randomized controlled trial, is considered the “gold” standard for the assessment of program effectiveness, subjective outcome evaluation has several unique advantages in program evaluation –22. FirsAlthough very encouraging evaluation findings have been reported for the initial phase of the project, it is important to know whether similar positive findings could be found for the extension phase. Against this background, subjective outcome evaluation findings based on the perspectives of program workers who implemented the Tier 1 Program in the 2009/2010 school year were reported in this paper. In addition, instructors' perceptions about the program, their own performance, and the effectiveness of the project were contrasted among different grade levels to learn about whether program workers at different grades have different views about the program. Previous findings suggested that instructors who taught the curriculum in the lower forms had more positive perceptions than did instructors teaching the program in the higher forms. As such, it was hypothesized that similar pattern regarding the grade effect on program implementers' subjective evaluation would also be observed in the present sample. Besides, the relationships among program implementers' views towards the program, perceptions about the instructor, and the overall effectiveness of the program were examined to gain a further understanding of critical factors that influence perceived program effectiveness by program workers. Based on prior findings, it was hypothesized that program implementers' perceived program quality and their own performance would significantly predict their subjective evaluation on program effectiveness.A total of 231 schools joined the Project P.A.T.H.S. in the fourth year of the full implementation phase in the 2009/2010 school year , with 219, 185, and 173 schools in secondary 1, secondary 2 and secondary 3 levels, respectively. The mean number of students per school was 154.36 (ranged from 6 to 240 students), with an average of 4.50 classes per school (ranged from 1 to 12 classes). Among them, 32.24% of the respondent schools adopted the full program  whereas 67.76% of the respondent schools adopted the core program . The mean number of sessions used to implement the program was 28.54 (ranged from 2 to 48 sessions). While 47.31% of the respondent schools incorporated the program into the formal curriculum , 52.69% used other modes  to implement the program. The mean numbers of social workers and teachers implementing the program per school per form were 1.71 (ranged from 0 to 7) and 5.11 (ranged from 0 to 27), respectively.After the Tier 1 Program was completed, the implementers were invited to respond to a Subjective Outcome Evaluation Form (Form B) developed by the first author . In the The Subjective Outcome Evaluation Form (Form B) was used in the present study, including the following parts.Program implementers' perceptions of the program, such as program objectives, design, classroom atmosphere, interaction among the students, and the respondents' participation during class (10 items).Program implementers' perceptions of their own practice, including their understanding of the course, teaching skills, professional attitude, involvement, and interaction with the students (10 items).Implementers' perceptions of the effectiveness of the program on students, such as promotion of different psychosocial competencies, resilience, and overall personal development (16 items).The extent to which the implementers would recommend the program to other students with similar needs (1 item).The extent to which the implementers would teach similar programs in future (1 item).The extent to which the program implementation has helped the implementers' professional growth (1 item).Things that the implementers obtained from the program (open-ended question).Things that the implementers appreciated most (open-ended question).Difficulties encountered (open-ended question).Areas that require improvement (open-ended question).For the quantitative data, the program workers who collected the data were requested to input the data in an EXCEL file developed by the Research Team which would automatically compute the frequencies and percentages associated with the different ratings for an item. When the schools submitted the hard copy of the reports, they were also requested to submit the soft copy of the consolidated data sheets. After receiving the consolidated data by the funding body, the research team aggregated the data to “reconstruct” the overall profile based on the subjective outcome evaluation data. It should be noted that although both qualitative and quantitative data were collected, the present paper only focused on the quantitative reports. Qualitative findings are to be reported elsewhere.Percentage data were examined using descriptive statistics. A composite measure of each factor  was created based on the total scores of each scale divided by the number of items. Pearson correlation analysis was used to examine if the program content and program implementers were related to the program effectiveness. To compare program implementers' evaluation across different grades, several one-way ANOVAs were conducted with the three subscale scores as the dependent variables and grade as the independent variable. Hierarchical linear regression analyses were further performed to examine the relationship between different aspects of implementers' evaluation about the project and the program effectiveness. All analyses were performed by using the Statistical Package for Social Sciences Version 17.0.The quantitative findings based on the closed-ended questions are presented in this paper. Several observations can be highlighted from the findings. First, the participants generally had positive perceptions of the program , includiα = .95), 10 items related to the implementer (α = .94), 16 items related to the benefits (α = .98), and the overall 36 items measuring program effectiveness (α = .98). Results of correlation analyses showed that both program content  and program implementers  were strongly associated with program effectiveness.Reliability analysis with the schools as the unit of analyses showed that Form B was internally consistent : 10 itemF = 3.77, P = .02. Post hoc analysis using Tukey's procedure with Bonferroni adjustment  revealed that significant difference was found between secondary 1 (M = 4.47) and secondary 3 (M = 4.36) participants (P = .03), with the secondary 1 program perceived to be relatively more favorable than the Secondary 3 Program.To examine differences in the perceived variables  across grade levels, several one-way ANOVAs were performed with the perceived variables as dependent variables and grade level  as independent variable. Significant results were only found in program content, P < .01). The prediction of program effectiveness was stronger for perceptions of program (β = .70) than for views towards implementers (β = .13). The model explained 63% of the variance toward the prediction of program effectiveness. For participants in different grades, the pattern of relationships and the amount of variance in program effectiveness explained by the two predictors were very similar. While views towards program content consistently predicted program effectiveness across grades, the relationship between views towards implementers and program effectiveness was only significant for the analyses based on the secondary 2 participants.Multiple regression analyses were performed on both the whole sample and the responses of students in different grades separately. The present study investigated the subjective outcome evaluation by program workers who implemented the Tier 1 Program of the Project P.A.T.H.S. in the 2009/2010 academic year. The findings showed that program implementers generally held positive views towards the program and the instructors and perceived the program as effective to promote healthy development of the participants. Program implementers' perceptions about the program and instructor significantly predicted their subjective evaluation about the program effectiveness, with views towards program content being a stronger predictor than views towards instructors. Moreover, these findings were held true for participants from different grade levels. There are three unique features of this study. First, the sample size was quite large. Actually, it is very rare to see such a large number of program implementers participated in outcome evaluation in the literature. Second, a validated measure of subjective outcome evaluation was used. Third, as there are few studies on the evaluation of positive youth development programs in general, particularly in Chinese people, the present study is an important addition to the literature.Overall, more than 80% of the participated program implementers had positive evaluation about different aspects of the program content, including the good curriculum design, strong theoretical support, pleasant classroom atmosphere, and active participation of the students. In particular, more than 90% of the instructors agreed that the objectives of the curriculum were very clear and the activities were carefully planned. Explicit learning objectives with respect to the required skills and a variety of instructional activities to facilitate learning are two critical components in outcome-based education which embraces the notion that the learner is accountable for his or her own achievements and represents the most updated approach to nowadays education –28. The Program implementers also viewed their own performance in teaching the program favorably, in terms of mastery and preparedness of the curriculum, teaching skills and attitudes towards the course and students, personal gains, interaction with students, and general evaluation of oneself as an instructor of the program. While self-fulfilling prophecy may explain the findings, it is noteworthy that this observation is consistent with previous findings that the students also perceived the instructors in a favorable light , 29, henWith respect to the perceived effectiveness of the program, program implementers regarded the program as having promoted positive development in the participated students in multiple areas. For example, more than 90% of the instructors agreed that the project had enhanced students' bonding with others, resilience in adverse conditions, social competence, ability to make sensible and wise choices, and overall development. Students who attended the program were evaluated as having more life reflections and self-awareness. These findings are consistent with previous results based on other evaluation methods regarding the effectiveness of the Project P.A.T.H.S., such as the objective outcome evaluation and the subjective evaluation by students , 30.Program implementers' subjective outcome evaluation was also compared among different grades. No significant grade differences were detected in program implementers' views about their own performance and perceived effectiveness of the program, which suggests that program implementers from different grade levels had similar favorable views towards the instructor and the program effectiveness. However, it was found that program content was evaluated more positively by secondary 1 implementers than by secondary 3 implementers. Similar findings were also noted in previous studies. While the curriculum designed for different grades has different content including various activities and topics for discussion, the basic framework of the course that consists of eight core positive youth development constructs is the same across grade. Therefore, the secondary 1 program may be perceived as more fresh and attractive to teachers than secondary 3 program. Besides, students in junior grade may also show more interests and better involvement in the course than senior students who attended the program since they entered to the secondary school. This finding provides some insights for the curriculum design in the future. Perhaps more novel units and topics especially suitable for senior secondary students could be developed and incorporated into the curriculum. Despite the grade difference, program implementers in the secondary 3 grade still reported favorable views towards the curriculum, with more than three fourths of the participants having positive evaluation about different aspects of the program content, which suggests that the curriculum is generally well received by the instructors.Results of regression analyses suggest that for the whole sample of students, both perceived program and instructors significantly predicted the perceived effectiveness of the program, supporting the critical roles of program quality and implementers in program success. However, when data in different grades were analyzed separately, while program workers' subjective evaluation of the program quality consistently predicted perceived effectiveness of the program across grade, the effect of views about instructors' performance was only significant for secondary 2 participants. Apparently, program worker's evaluation about the program content appeared to be a stronger predictor than did their evaluation about instructors' performance. Similar findings were reported in Shek et al.'s paper . While aThere are several limitations of the present study that should be acknowledged. First, the data were collected in a self-reported manner, which may be biased by the implementers' personal attitudes and perceptions towards the program. To reduce the potential bias, several measures were taken. First, program implementers responded to the questionnaire anonymously, and the confidentiality was repeatedly assured. Second, in the questionnaire, no threatening questions were asked that might elicit the respondents' feelings of role conflict and social desirability. Third, participants were encouraged to candidly report their negative views or feelings in the survey, and open-ended questions were provided for the teachers to record their suggestions on how to improve the program. Despite of these measures, the present findings should be interpreted with cautions, and evaluative studies that use other approaches, such as objective outcome evaluation based on developmental indicators, program participants' subjective evaluation, and process evaluation must be conducted for the purpose of triangulation. The second limitation of the present study is that only two general indicators of program quality and program implementers' performance were used to predict overall effectiveness of the project, which makes it impossible to identify specific aspects that are particularly important for program success. Besides, different factors may increase/decrease the program effects in different areas. For example, good performance of the teacher may have particular effects in strengthening students' bonding with teachers. Future studies may include different indicators of program content and implementers as well as program effectiveness in the prediction model. Thirdly, previous studies have revealed that school and organization characteristics influence program effectiveness and implementation quality –36. Thes


To compare and contrast three models of community mental health services in low-income settings.Primary and secondary data collected before, during, and after site visits to mental health programs in Nigeria, the Philippines, and India.Qualitative case study methodology.Data were collected through interviews and observations during site visits to the programs, as well as from reviews of documentary evidence.A set of narrative topics and program indicators were used to compare and contrast three community mental health programs in low-income countries. This allowed us to identify a diversity of service delivery models, common challenges, and the strengths and weaknesses of each program. More definitive evaluations will require the establishment of data collection methods and information systems that provide data about the clinical and social outcomes of clients, as well as their use of services.Community mental health programs in low-income countries face a number of challenges. Using a case study methodology developed for this purpose, it is possible to compare programs and begin to assess the effectiveness of diverse service delivery models. The Lancet [PLoS Medicine [Global Mental Health has emerged as a significant field in public health , as evide Lancet -7 and PLMedicine -14, as wMedicine  and the Medicine . HoweverMedicine . The CasThe three programs that are the foci of this paper are:• Services for People with Disabilities, Abuja, Federal Capital Territory, Nigeria;• Holy Face Rehabilitation Center for Mental Health, Tabaco City, Albay Province, the Philippines;• Asia Psychosocial Rehabilitation Program, Karakonam, Kerala, India.The programs that were to be the subjects of the case studies were selected by the CBM Mental Health Advisory Working Group. All of the programs described here are funded, in part, by CBM, an international non-governmental organization that funds programs for persons with disabilities in many of the world's poorest countries.A qualitative case study methodology was employed to document the services of the three programs. The major component of the study was site visits (by AC) of five to ten days to each program: November 2008 and January 2009 (Nigeria), June 2009 (the Philippines), and November 2009 (India). Site visit activities included accompanying staff in the field and on home visits, observing community clinics, visiting with Self-Help Groups, and interviewing staff. Whenever possible, documentary evidence was utilized to confirm and/or augment the information collected during site visits.Information about the programs was collected according to a set of narrative topics and program-level indicators Table  that werObservations, information about the programs and interviews with key personnel were documented by AC in narrative accounts of site visits. When possible, interviews were audio-recorded and then transcribed. Program records were reviewed to collect statistical data. Information was also derived from documents, e.g. brochures, materials on the internet, annual reports, and periodic site visit reports by CBM staff. After the site visits, AC often asked (via email) program and CBM staff to fill in gaps in the information already collected.Following the site visits, AC converted the narrative accounts, transcripts of interviews, and, whenever possible, the documentary evidence, into text files that were analyzed  according to the narrative topics and program-level indicators. Site visit reports were then prepared by AC and, to be certain that the reports were accurate and did not contain significant gaps, circulated among the heads of the programs, the CBM Mental Health Advisory Working Group, and the co-authors at LSHTM. To present the results here, we have arranged information about the programs into the following domains: History and context; Pathways to care and characteristics of clients; Treatment coverage; Accessibility of services; Clinical interventions; Psychosocial Interventions; Referral pathways; Outcomes.The three programs discussed here all began operations in the period 2004-2006 when CBM piloted a number of community mental health programs in order to assess their feasibility and effectiveness when carried out as components of Community-Based Rehabilitation projects in LIC. The program in Abuja, Services for People with Disabilities, was established because several CBM staff recognized the need for mental health care - mainly for psychosis and epilepsy - in Nigeria. The Holy Face Rehabilitation Center for Mental Health, in Tabaco City, the Philippines, was established, first, as a result of discussions between CBM and the Brothers of Charity - a non-governmental organization with a focus on care for persons with mental disorders - and, second, because a Bishop in the Bicol Region of the Philippines appealed to the Brothers to provide care for mentally ill indigents. The Asia Psychosocial Rehabilitation Program evolved out of the crisis brought about by the December 2004 Indian Ocean tsunami that devastated communities on the southwestern coast of India in the states of Kerala and Tamil Nadu.The Abuja program operates in the Federal Capital Territory of Nigeria, which encompasses the central city of Abuja, a number of satellite towns, and large rural areas with dispersed populations. The Catholic Archdiocese of Abuja operates and partially funds the program. CBM provides about half the funding. The long-term goal is to have the Archdiocese support the program entirely, with CBM providing expertise and occasional financial assistance. Mental health services are just one component of Services for People With Disabilities, a Community-Based Rehabilitation program that provides services for a range of physical disabilities, as well as psychosocial interventions to promote economic integration and social inclusion. The program employs 17 field workers who are each based in a different zone of the Federal Capital Territory. The field workers are responsible for case-finding and follow-up of all clients, not just those receiving mental health services. One community psychiatric nurse is responsible for the clinical care of all mental health clients Table .The Tabaco City program was established as a residential facility for people with chronic psychoses and an outpatient clinic for individuals suffering from a range of mental disorders. The program receives funding from the Brothers of Charity and, through the end of 2010 received support from CBM Australia, which is presently reviewing a Tabaco City program proposal for multi-year support. Two local municipalities - Tiwi and Tabaco City - provide limited funding for clients in the residential program and for the purchase of medications for outpatients. The inpatient and outpatient facilities are located about 12 km from the center of Tabaco City, on 10 acres of a former coconut plantation at the foot of Mt. Mayon, an active volcano. The staff consists of two social workers, three nurses, one psychiatrist (who works one day a week), and one field worker who have a degree in sociology. The program also employs administrative and house keeping staff. In addition, several of the resident Brothers of Charity conduct classes for the residential clients , one part-time psychologist, three social workers, and 10 community volunteers Table .Salaries for staff in all of the programs are comparatively low, particularly for the lay mental health workers in the Abuja and Karakonam programs.The programs all function in regions with high levels of poverty. According to the Human Development Index, a composite measure of life expectancy, education levels, and standard of living, the areas in which the Karakonam program functions appear to be better off than Albay Province and Nigeria as a whole Table .Health services, in general, are lacking in Abuja, and virtually nonexistent for neuropsychiatric disorders. The Karakonam program operates within a complex health system of private, non-profit, government, and Ayurvedic services - although the available practitioners are not sufficiently trained to treat mental disorders effectively. The Tabaco City program operates in a setting somewhere in-between, although Albay Province, with its hospitals  more closely resembles the southwest coastal region of India than Abuja. Seeking the help of traditional or alternative healers is common in Nigeria and India; anecdotal evidence suggests that this is not true in Albay Province. In regard to mental health services, specifically, precise data are not available for the program settings. However, data from the WHO Project Atlas  indicateBecause of the size of the catchment areas, or in the case of the Karakonam program the need to travel one to two hours from the hospital to reach the communities being served, provision of transportation for staff is critical. The Abuja program provides field workers with motorbikes. The program also owns a pick-up truck that is used to transport the community psychiatric nurse and the psychiatrist when conducting field visits. The Tabaco City program mostly relies on public transportation for staff to travel to meetings in the community. Staff are reimbursed for these costs. Hospital-based staff in the Karakonam program are driven to the catchment areas by a car service that is associated with the hospital. A motorbike was given to one of the social workers so that he could travel among the catchment areas. The community volunteers walk or take public transportation in the course of their fieldwork or to attend meetings at the hospital. The program reimburses them for their transportation costs.The Abuja program field workers and the Karakonam program community volunteers conduct active case-finding. This entails going house-to-house in search of potential clients and consulting key informants, e.g., village chiefs or parish priests. However, there are major differences in the approaches to case-finding. First, the Abuja program field workers are responsible for locating persons with mental disorders and persons with physical disabilities, while the Karakonam program community volunteers are only trying to locate persons with mental disorders. Second, since the Karakonam program was established in response to the tsunami, it was originally oriented to identifying persons suffering from common mental disorders. In contrast, the mental health component of the Abuja program was established because of the burden of epilepsy and psychosis in Nigeria, and the recognition that treatments for these disorders would be feasible and effective in the context of a community-based rehabilitation program Table .The Tabaco City program does not conduct case-finding and depends on referrals from local government health workers and two non-governmental organizations that provide community rehabilitation services in Albay Province Table .All three programs conduct out-reach activities, e.g., consultations with government officials, other non-governmental organizations, and community leaders, as well as holding public meetings to inform people about the services offered. The Abuja program trains members of the community to recognize and refer individuals to the local field worker. The Tabaco City program trains municipal and non-governmental health workers to refer individuals and to follow-up current clients. Soon after it started, the Karakonam program trained school teachers to recognize and refer children who were displaying behavioral problems Table .One can also assume that former or current clients act as informal sources of referral by suggesting to friends or family members that they seek help for a mental disorder by visiting an Abuja program field worker in his office, going to the weekly outpatient clinic at the Tabaco City program, or attending one of the monthly community clinics provided by the Karakonam program.Even though the programs all provide multiple pathways to care, the clinical characteristics of clients in the three programs are markedly different Table . This isAs can be seen in Table Together, these data suggest that, according to the available epidemiological evidence, the three programs are reaching only a tiny fraction of potential clients. Furthermore, one might speculate that large geographic or political boundaries are not necessarily accurate reflections of actual service areas. For example, the Bicol Region is the stated catchment area of the Tabaco City program, but a review of records indicates that the vast majority of clients come from Albay Province. In the case of the Abuja and the Karakonam programs, determining the effective composition of the mental health service areas will require further research, i.e., mapping where clients reside.Accessing services does not appear to be an issue for clients of the Abuja and Karakonam programs. The former provides most treatment in the homes of clients, whereas the latter provides services in the community and at the hospital, which is readily accessible via public transportation. However, the small number of clients in the Abuja program leads one to speculate that barriers to care do exist. Further research is required to identify those barriers.Even though the Tabaco City program provides services to the largest number of clients, its distance from city center and the expense of transportation are barriers to care. We were told that some families could not afford the expense of transportation to the facility. As a result, clients stopped attending the program's day hospital services when a free daily van service was discontinued because of budget cuts. Budget cuts also forced the program to discontinue its van service to the weekly outpatient clinic. Fortunately, Tabaco City now operates the van service and the outpatient clinic continues in operation.The Abuja program operates a drug revolving fund that sells medications at a small fraction above cost, which is generally affordable to clients and families. CBM also maintains a fund to help those who cannot afford the medications. Anecdotal reports suggest that the cost of medication to clients in the Tabaco City program, even though it is sold on a sliding scale, leads to a degree of non-adherence. No doubt, the cost of outpatient sessions (between $2.25 and $4.50) also makes services inaccessible for some clients.The Karakonam program, using its own funds, provides medication free of charge to clients. This is possible, at least in part, because medications are comparatively inexpensive in India.The Abuja program community psychiatric nurse is responsible for the diagnosis and medication management of all mental health clients. Clinical care takes place during home visits or at a clinic in a remote rural community. Psychiatrists in the Tabaco City and Karakonam programs provide clinical care during outpatient or community clinics Table .Medication is the mainstay of treatment in all three programs. Limited funding means that the Abuja and Tabaco City programs must rely on older, less expensive medications. An additional challenge for the Abuja program is ensuring the quality of medications since much of what is available in Nigeria is of poor quality . TherefoUnlike the other programs, the Karakonam program has specialists who have the time and expertise to provide formal psychotherapy.The Tabaco City and Karakonam programs offer inpatient services. However, the former limits admissions to chronic patients who do not require acute care, while the latter provides care in a hospital with extensive resources and is capable of caring for persons who are acutely ill.None of the three programs are well-equipped to handle emergencies in the community, although the Karakonam program is in the best position to mobilize resources if necessary.The Abuja and Karakonam programs follow-up clients regularly. The Abuja program community psychiatric nurse tries to see clients once a month. During these visits, the nurse will, if necessary dispense medications. Field workers attend these visits and will visit clients at other times, too. The Karakonam community volunteers visit clients twice a month. Clients mostly receive their medications in the community clinics or at the hospital, although community volunteers do make home deliveries of medications to about 10% of the clients. The Tabaco City program relies, for the most part, on municipal and non-governmental organization community health workers to follow-up clients.All of the programs have organized Self-Help Groups, referred to as Family-Support Groups in the Tabaco City program.The Tabaco City program has organized Family Support Groups in several communities of Albay Province Table . One advThe Karakonam program offers the broadest range of psychosocial interventions. Follow-up sessions with community volunteers may include interventions aimed at improving self-care, activities of daily living, and social functioning. Community volunteers also provide informal counseling, e.g., listening, relaxation techniques, and support for caregivers. Additionally, community volunteers organize and run on-going promotion and prevention activities for groups of children (6-15 years), adolescents (16-19 years), and adults. Topics discussed in the groups include nutrition, hygiene, study skills, stress management, substance abuse, mental illness, and (for with the adults) communicable and chronic illnesses. The program also has organized Self-Help Groups for women, which, in addition to providing social support, undertake income-generating activities, e.g., soap making, tailoring, selling cloth with printed designs, and operating small shops. Unlike the groups organized by the other programs, the groups organized by the Karakonam program are open to all women, and, thus, may provide clients and care-givers greater opportunities for social integration.The Abuja program recently started one Self-Help Group in each of three zones. Plans are in place to eventually organize groups in all of the zones. The intention of the groups is to foster advocacy, provide peer support, and participate in livelihood activities.The absence of psychiatric services in the Federal Capital Territory makes it difficult for the Abuja program to refer cases for specialist services - this is only possible if a family can bring the client to a better-resourced city. Clients can be referred to other components of the community-based rehabilitation program, e.g., the economic integration program, but such referrals are not made frequently. The Tabaco City program has not established official referral pathways with a nearby medical center and a psychiatric hospital. In contrast, because the Karakonam program is based at a hospital that also maintains community primary care centers, referring clients for treatment of physical disorders or inpatient psychiatric care is done routinely.Although all of the programs collect data, none organize it so that statistics are readily available on the number of clients receiving services or clients' basic clinical and sociodemographic characteristics. Nor can the programs provide data about the treatments that clients are receiving, the length of time clients have been in treatment, or the consistency with which clients have accessed services. Last, data on the outcomes of intervention are not available. However, this is changing. The Karakonam program has (as of September 2009) initiated monitoring of clinical, functional, and caregiver outcomes, as well as client satisfaction. Additionally, the Abuja program is currently piloting a data collection system that will enable the generation of routine process and outcome data.This paper describes the results of case studies of three community mental health programs in LIC. Information was collected according to a set of narrative topics and program-level indicators, then analyzed and organized to describe, compare, and contrast the programs. In this way, we found a diversity of service delivery models, common challenges, and unique strengths and weaknesses of each program. Furthermore, the case study methodology that we developed was found to be a useful tool to examine the strategies used by community mental health programs to deliver services within the constraints of low-resource settings.Two common challenges were found. Above all, without CBM funding it is unlikely that any of the programs would continue to exist, at least in their present form. Without CBM funding and technical expertise the Catholic Archdiocese of Abuja would likely reduce the scope of the Abuja program, and there is no guarantee that the mental health services would be retained. Without funding from CBM the Brothers of Charity would, no doubt, continue to support the Tabaco City program but would probably be forced to curtail or discontinue the community programs and the weekly outpatient clinic. The Karakonam program might survive without CBM funding, but only if the Dr Somerville Memorial CSI Medical College & Hospital managed to secure other sources of support.The second challenge is the comparative lack of human resources. In Abuja, there are no psychiatrists to which the program community psychiatric nurse can refer challenging cases. For the Tabaco City program the situation is different: there are psychiatrists in Albay Province but, at least when the program was established, it was difficult to find one who would accept the position. In contrast, the Karakonam program has been successful in recruiting qualified psychiatrists and social workers - probably because it is based at a teaching hospital - but there is always the danger that they will be lured away by higher salaries in the United Kingdom, North America, or Australia. It is also difficult to retain female community volunteers because after getting married they often stop working. Hiring men as community volunteers is not easy since men can make much more money working as fishermen.Despite the challenges, the programs all have strengths. Most importantly, all manage to function and deliver services to persons who, without those services, would likely be neglected. In addition, program staff must be given credit for their support and respect for clients, and the ability to remain positive and dedicated even though their work is physically and emotionally difficult, pays poorly, and offers little chance for advancement within any of the programs.Nevertheless, one must not ignore obvious weaknesses. For example, despite the size of its target population, the Abuja program has provided services to relatively few clients. The program could also be criticized for its lack of specialist support for the community psychiatric nurse. Two weaknesses can be readily identified in the Tabaco City program. First, its clinical staff is not large enough to handle the number of residential or outpatient clients. Second, its relatively isolated location means that it is difficult to consider it a community-based program. The Karakonam program is well-resourced with specialists who are willing to work in community settings, knowledgeable and skilled community volunteers, a wide range of medications, and access to a large hospital. At the same time, this means it is not a likely candidate as a model for most low-income settings.The programs described here represent a range of service models : from anThe evidence presented here also suggests that when planning or establishing programs it is critical to consider whether program resources are reasonably sufficient for providing services in the intended catchment area. For example, the Abuja program community psychiatric nurse must travel many hours and long distances to visit clients in each of the 18 zones of the Federal Capital Territory, and the Tabaco City program psychiatrist must see 70-120 clients during each outpatient clinic. Both situations demand tremendous efforts. Whether these efforts are sustainable and/or undermine the quality of services is a question that must be examined.A major strength of the case study methodology that we have developed is its ability to provide detailed descriptions of models of care and how they function within specific sociocultural and socioeconomic contexts. Using a defined set of narrative topics and program-level indicators also allows one to compare and contrast the programs, whether they utilize the same or different models. A knowledge base of case studies would be an invaluable resource in attempts to scale up mental health service in LIC.The methodology that was the basis for our case studies has several limitations. First, most of the evidence was collected during relatively short site visits. Longer visits would have allowed the collection of more information and the opportunity for more verification of the information that was collected. Second, to reduce the possibility of bias the case studies were carried out by an independent observer. However, this is an expensive process and it is unlikely that programs in LIC will have the resources necessary to commission independent case studies.Third, more focused research is necessary to assess certain aspects of the programs. For example, client and family satisfaction is an important issue but one that is not easily assessed. Client reports of satisfaction of services may not accurately reflect objective measures of clinical services , and, evLack of data was the greatest limitation on our ability to evaluate the effectiveness of interventions. None of the programs had information systems that could easily generate routine process data, and even if process data were available, we believe that clinical and social outcome data are essential for evaluation of program effectiveness . UnfortuWe believe that one of the major challenges to scaling-up mental health services is the lack of evidence about the community-based strategies that are effective in delivering efficacious interventions to populations in LIC. The qualitative case study methodology that was used to describe programs in Nigeria, the Philippines, and India begins to address that need by describing service models as they function in practice. The methodology also makes it possible to compare and contrast different models. Finally, case studies such as these generate questions for further investigation and set the stage for more rigorous evaluations of effectiveness ,28.CBR: Community-Based Rehabilitation; CMD: Common Mental Disorder; CV: Community Volunteer; CPN: Community Psychiatric Nurse; FSG: Family Support Group; FW: Field Worker; NGO: Non-Governmental Organization; SHG: Self-Help GroupCBM International funded the Case Studies Project, which is lead by Prof Vikram Patel and employs Drs Alex Cohen and Mary De Silva. Drs Julian Eaton and Birgit Radtke are members of the CBM Mental Health Advisory Working Group. Dr Christina George and Bro Victor Manuel lead programs that are supported by CBM International.AC, VP, MDS, JE, and BR all contributed to the concept and design of the research. AC conducted the site visits, collected data, drafted the manuscript. CG and VM hosted the site visits and reviewed the manuscript for accuracy. All authors reviewed the manuscript and assisted in revising it for important intellectual content. All authors have participated sufficiently in the work to take public responsibility for appropriate portions of the content. All authors have read and approved the final manuscript.AC is a Senior Lecturer, MDS is a Lecturer, and VP is a Professor of International Mental Health in the Faculty of Epidemiology and Population Health at the London School of Hygiene & Tropical Medicine. VP is also a Wellcome Trust Senior Research Fellow in Clinical Science. JE is the CBM Mental Health Advisor for West Africa. BR is the CBM Programme Director for Community Mental Health. CG is an Associate Professor, Department of Psychiatry, Dr Somervell Memorial Medical College. VM is the Director of Holy Face Rehabilitation Center for Mental Health.