Nicotianabenthamiana against TMV-U1 strain, resulting in mild symptoms instead of severe systemic necrosis. The mechanism of cross protection between HLSV and TMV is unknown. In the past, some researchers suggest that the protecting virus strain might occupy virus-specific replication sites within a cell leaving no room for the challenge virus. Quantitative real-time RT-PCR was performed to detect viral RNA levels during cross protection. HLSV accumulation increased in cross protected plants compared with that of single HLSV infected plants, while TMV decreased in cross protected plants. This suggests that there is a competition for host factors between HLSV and TMV for replication. To investigate the mechanism under the cross protection between HLSV and TMV, microarray analysis was conducted to examine the transcriptional levels of global host genes during cross protection, using Tobacco Gene Expression Microarray, 4x44 k slides. The transcriptional level of some host genes corresponded to accumulation level of TMV. Some host genes were up-regulated only by HLSV. Tobamovirus multiplication gene 1 (TOM1), essential for tobamovirus multiplication, was involved in competition for replication by HLSV and TMV during cross protection. Both HLSV and TMV accumulation decreased when NbTOM1 was silenced. A large quantity of HLSV resulted in decreased TMV accumulation in HLSV+TMV (100:1) co-infection. These results indicate that host genes involved in the plant defense response and virus multiplication are up-regulated by challenge virus TMV but not by protecting virus HLSV during cross protection.Cross protection is the phenomenon through which a mild strain virus suppresses symptoms induced by a closely related severe strain virus in infected plants. Hibiscus latent Singapore virus (HLSV) and Tobacco mosaic virus (TMV) are species within the genus tobamovirus. HLSV can protect  Earliion site .Arabidopsis thaliana (AtTOM1), a seven-pass membrane protein, interacts with replication protein encoded by TMV-Cg [AtTOM1 involved in tobamovirus replication [Nicotianatobacum (NtARL8), a small host GTP-binding protein, is also required for tobamovirus multiplication [In early cross protection studies, some researchers suggested that protective viruses might occupy virus-specific replication sites within a cell leaving no room for the challenge virus –21. Howey TMV-Cg . There alication –25. ADP-lication .Hibiscus and Nicotianabenthamiana plants. TMV can infect different tobacco species and induce different symptoms. Specifically, TMV induces systemic necrosis in Nbenthamiana. . Since HLSV causes mild mosaic symptoms, we tested whether HLSV can cross protect Nbenthamiana.  against TMV and to investigate the mechanism. We also examined if there is a competition between HLSV and TMV for NbTOM1which is essential for tobamovirus replication.Tobamovirus has one genomic RNA (gRNA) and three sub-genomic RNAs, sgRNA1 sgRNA2 and sg-coat protein RNA (LMC) . HoweverNbenthamiana. . To date, up to 44,000 genes and expressed sequence tag (EST) can be monitored in parallel. As Nbenthamiana.  gene expression microarray chips were not available, we had to compromise and used the closest tobacco gene expression microarray chips for N. tabacum genes, 4x44 k chip, to determine the transcriptional level of host gene changes in Nbenthamiana.  before and after TMV infection, while plants were pre-inoculated with HLSV.Microarray technology was used for global analysis of gene transcriptional levels among inoculation buffer (mock)-, HLSV-, TMV- and HLSV+TMV-inoculated Nbenthamiana. . TMV caused severe cell death on upper newly expanded leaves one week post inoculation, which was reduced and delayed by pre-inoculation with HLSV. At the same time, mock buffer or HLSV inoculation did not cause any cell death in Nbenthamiana.   compared with those infected with HLSV alone (H)  tract instead of an upstream pseudoknot domain (UPD) in the upstream of a t-RNA like structure (TLS) in the 3’-end of HLSV RNA . The PCRN. tabacum) chips . Hierarchical cluster analysis of transcriptional profiles for 24,237 genes or expressed sequence tags (ESTs) for Nbenthamiana.  inoculated with buffer (mock), HLSV, TMV and HLSV+TMV (cross protected plants pre-inoculated with HLSV 12 days earlier) was performed. Gene expression profiles for each of the 3 individual biological repeats , including those genes that respond to stress, defense, temperature stimulus, water deprivation, abiotic stimulus, detection of hormone, endogenous and ethylene stimuli, oxidation-reduction process or function in chloroplast, thylakoid, thylakoid membrane, plastid, and organelle sub-compartment  compared with TMV infection. These genes responded to stress, defense, osmotic stress, temperature stimulus, fungus, abiotic stimulus, high light intensity, salt stress, endogenous/hormonal and chemical stimuli. The microarray data has been submitted to database GEO under the NCBI database and an accession number GSE47180 is assigned.For an overview of global changes in transcriptional level of host genes before and after cross protection between HLSV and TMV, a microarray analysis was performed using tobacco , auxin repressed protein 1 (NbARP1), calmodulin 3 (NbCaM3), cysteine protease 2 (NbCP2), proteinase inhibitor (NbPI), 1-aminocyclopropane-1-carboxylate oxidase (NbACO), NbALY, CCR4-associated factor 1 (NbCAF1), catalase 1 (NbCAT1), heat shock protein 101 (NbHSP101), systemic acquired resistance 8.2m (NbSAR8.2m), wound induced protein kinase (NbWIPK), double WRKY type transfactor protein (NbWRKY7and NbWRKY8), NbTOM1, vacuolar processing enzyme 1 α (NbVPE1α) were validated using quantitative real-time RT-PCR. The magnitude of changes of selected genes obtained by quantitative real-time RT-PCR was in agreement with the values obtained from the microarray data  increased in single TMV infected plants rather than those of mock inoculated, HLSV infected or cross protected plants (HLSV+TMV). Additionally, the transcriptional level of the gene (NbAGO4-2) in Group 3 was unchanged in upper newly expanding leaves either from mock inoculation buffer, HLSV, TMV, or HLSV+TMV inoculated plants.A 20-day time course experiment was conducted to monitor the transcriptional level of selective genes, including NbAGO4-2 . The traNbTOM1 was essential for HLSV infection and if it was competed by HLSV and TMV, inoculation buffer (mock), HLSV, TMV, HLSV+TMV (100:1) and HLSV+TMV (1:1) were inoculated into Nbenthamiana.  either with no Agro-infiltration, overexpression of NbTOM1 or silencing of NbTOM1. At 40 h post inoculation (hpi), the transcriptional levels of NbTOM1 were found to be similar among the different treatments (NbTOM1 in pGreen-NbTOM1 infiltrated leaves (NbTOM1 decreased in NbTOM1-silenced leaves which were Agro-infiltrated with pGreen-NbTOM1(nt1-581) (NbTOM1 in buffer inoculated leaves (mock) without Agro-infiltration was set as a baseline  for the transcriptional level of NbTOM1. In Agro-infiltrated leaves with pGreen alone, the transcriptional level of NbTOM1 was similar to that of mock inoculated leaves. This indicated that the transcriptional level of NbTOM1 did not change with Agro-infiltration of the empty vector alone.To test if eatments . There wd leaves . Additiont1-581) . The traNbTOM1. In non-Agro-infiltrated plants inoculated with HLSV+TMV (100:1), the TMV RNA level decreased, as compared with that of single TMV infection. At the same time, in HLSV+TMV (1:1) co-infected leaves, the TMV accumulation increased  for comparison with HLSV alone, TMV alone, and HLSV+TMV co-infection with overexpression and silencing of ncreased . These rncreased , which iNbenthamiana.   co-infection but decreased in HLSV+TMV (1:1) co-infection  favored both virus replications , as compared with that of single TMV infected leaves at 5 dpi. HLSV CP level decreased in HLSV+TMV (1:1) infected leaves. This indicated that only large amount of HLSV inocula or higher level of its accumulation allowed it to compete effectively for Nbenthamiana. , while TMV causes severe systemic necrosis. In our study, we found that HLSV can cross protect Nbenthamiana.  against TMV, resulting in milder symptoms. Quantitative real-time RT-PCR and western blot were performed to detect the level of genomic RNA alone and total viral RNAs and CPs during cross protection. HLSV accumulation increased in cross protected plants, as compared with that of single HLSV infected plants, while TMV accumulation decreased in cross protected plants. These results suggested that in cross protected plants there might be changes in the transcriptional level of some host genes that can enhance HLSV accumulation. Moreover, the results also suggest that pre-infection of HLSV allowed it to compete with TMV more favorably by early sequestering of host factors for replication.HLSV and TMV-U1 are species of genus tobamovirus. HLSV causes mild puckering and slight mosaic symptoms in Nbenthamiana. , some genes changed in transcriptional levels which responded to stress, defense, environmental and hormone stimuli, oxidation-reduction process or function in organelles. Furthermore, the transcriptional levels of host genes responded to stress, defense, osmotic stress, environmental, hormone, biotic and abiotic stimuli at the beginning of cross protection. We further investigated the transcriptional patterns of selective host genes.To understand the transcriptional changes in cross protection, we conducted a microarray analysis using tobacco chips. With HLSV infection in NbARP1, NbCaM3, NbCP2 and NbPI were up-regulated in cross protected or HLSV-infected Nbenthamiana. . Auxin-response genes are controlled by auxin, resulting in regulating various growth and development [ARP1 related to plant defense. The CaM3 gene in N. tabacum activates NAD kinase which is also a cofactor of NADPH oxidase in producing reactive oxygen species (ROS) [NbCaM3 in cross protected Nbenthamiana. , as compared to TMV-infected plants, this suggests that ROS signaling is activated during cross protection. High level of ROS induced oxidation to carbohydrates, lipids, proteins, and DNA. ROS also influence a few plant hormone responses and affect many processes, such as systemic signaling, growth, development, abiotic stress responses, pathogen defense and programmed cell death (PCD) [CP2 belongs to the C1 family of papain-like cysteine proteases and in N. tabacum, it shares high amino acid similarity (68–72%) with KDEL-tailed plant cysteine proteases, which may be involved in PCD [CP2 in TMV infection has not been elucidated. Interestingly, the transcriptional level of NbCP2 was correlated with HLSV infection and was much higher in cross protected plants than single TMV infected Nbenthamiana. . Proteinase inhibitor (NbPI) was also up-regulated in cross protected Nbenthamiana. . Plant cysteine proteases play an instrumental role in PCD and PI may prevent unwanted cell death [Nbenthamiana. , the up-regulation of NbPI may function in preventing necrosis caused by TMV infection. Further studies can be conducted to ascertain the roles of NbCP2 and NbPI in cross protection.In Group 1, host genes elopment . To datees (ROS) . In viewth (PCD) . The CP2d in PCD . In addill death . In crosNbVPE1α, NbACO, NbSAR8.2m, NbWIPK, NbWRKY8, NbTOM1 and NbHSP101) in Group 2 were up-regulated in TMV infected Nbenthamiana. . The necrotic lesions at the sites of TMV infection is considered PCD in tobacco plants with N gene [VPE1α belongs to the caspase-like proteases. During TMV infection, VPE1α exhibits caspase-1 activity in TMV-infected tobacco leaves. Cell death was abolished upon treatment with caspase-1 and VPE inhibitors. Increased virus accumulation was also observed in RNAi VPE-silenced Nbenthamiana.  with temperature shift [Nbenthamiana. , the transcriptional level of NbVPE1α increased as compared with that of single HLSV infected Nbenthamiana. , but decreased as compared with that of plants infected with TMV alone. At present, it is unclear if the roles of VPE1a and CP2 overlap in PCD.Moreover, host genes , HLSV, HLSV+TMV (cross protected) and TMV infected plants. The transcriptional levels of these genes only dramatically up-regulated in plants infected solely with TMV and cross protected plants, but not in plants infected with HLSV alone. This indicates that the SA pathway is triggered whenever TMV is present.The hypersensitive response is accompanied by a marked increase in salicylic acid (SA) and rapid production of ROS . Plants TOM1 is a transmembrane protein in plants that serves as an attachment anchor for virus replication complexes in the host cell [TOM1 homologues gene results in reduced virus multiplication. HLSV may have a similar requirement for the TOM1 protein; consequently, in cross protected plants TMV would have to compete with HLSV for TOM1 and this could result in reduced accumulation of TMV. TOM1 was up-regulated with TMV infection but not with HLSV infection. This may be due to lower level of HLSV replication which failed to up-regulate TOM1. Meanwhile, the up-regulation of TOM1 in cross protected plants by TMV infection may facilitate HLSV replication, resulting in increased level of HLSV in cross protected plants. Heat shock protein 101 (HSP101) acts as a translational enhancer of TMV. It binds to the CAA-repeat motif of the 5’ Ω-region of the TMV RNA which recruits eIF4 [HSP101. Therefore, HLSV and TMV may also compete for HSP101 in cross protected plants.Accumulation of the protecting virus may exclude the challenge virus from cells by occupying important sites or by depleting host factors required for replication of the challenge virus . TOM1 isost cell . Subsequost cell  reaffirmits eIF4 . The CAAits eIF4 . It is bNtTOM1 and NtTOM3 in N. tabacum resulted in nearly complete inhibition of the multiplication of tobamoviruses [NbTOM1, a well studied host factor in tobamovirus replication, instead of NtTOM3, in Nbenthamiana.  for investigation during cross protection. In the competition between HLSV and TMV for NbTOM1, TMV accumulation decreased in HLSV+TMV (with a ratio of 100:1) co-infected plants with and without overexpression of NbTOM1 in comparison to TMV infection alone or HLSV+TMV (with a ratio of 1:1). This result confirms that there is competition for NbTOM1 between HLSV and TMV for replication. Moreover, a larger amount of HLSV enhanced its competiveness with TMV  or HLSV by mechanical inoculation. Two leaves on each plant were dusted with carborundum and inoculated with mock buffer (negative control) or purified HLSV [N. benthamianaat 20 dpi  samples were homogenized in liquid nitrogen, total RNA was extracted using the Trizol® Reagent . After the washing step, the total RNA pellet was air dried for 3 min and stored at -80°C. RNA was prepared using the same protocol for both microarray and quantitative real-time PCR experiments. Two µg of total RNA, oligodT20 and virus specific primers were used for first-strand cDNA synthesis using Superscript III® reverse transcriptase .Three youngest, HLSV systemically infected upper leaves  were harvested for total RNA extraction at 3, 7, 12, 15, 17 and 20 days post inoculation (dpi) with inoculation buffer (mock), HLSV, TMV and HLSV+TMV (pre-inoculated with HLSV 12 days prior to inoculation of TMV). For overexpression and silencing of Nbenthamiana. ) were harvested and homogenized with one volume of protein extraction buffer (0.15M Tris-HCl (pH 6.8), 10% of glycerol, 5 mM DTT, 2% of SDS) and 1/5 volume of 5X SDS loading dye and denatured in water bath at 100 °C for 5 min. Then the total proteins were incubated on ice for 5 min and centrifuged at 16 x 1,000 x g at 4 °C for 5 min. In the NbTOM1 competition experiment, total proteins were also extracted from Agro-infiltrated and virus infected leaves 5 dpi. The western blot was performed as previously described [Total proteins were extracted according to the same time points used for RNA extraction. Three leaves  samples and TMV samples at15 dpi with HLSV  were prepared. These 12 samples were sent to Genomax Technologies Pte Ltd (Singapore) for microarray hybridization using Agilent’s Gene Expression, 4x44K format. The data analysis was carried out using GeneSpring GX 12.1. Gene Ontology (GO) analysis was carried out using Genespring 12.1 with GO annotation curated from consortium by Agilent Technologies (USA).N. tabacum gene sequence returned was queried using BLAST, to identify if there were partial or full length sequences of Nbenthamiana.  homologues in the database of NCBI. If the desired sequences were available, software GenScript Real-time PCR Primer Design was used to design real-time primers. When identical genomic sequences in Nbenthamiana.  were not available; primers based on conserved domains of known homologous sequences from other species were designed to obtain partial gene sequences of Nbenthamiana. . Sequence alignment was carried out using software SeqMan from Lasergene (http://www.dnastar.com). Partial sequences of NbARP1 (KF051944), NbCaM3 (KF051945), NbCP2 (KF051946), NbPI (KF051947) and NbHSP101 (KF051948) were obtained by the method described above. After these partial sequences were obtained through reverse transcription (RT)-PCR and sequenced, real-time primers were designed using the GenScript Real-time PCR Primer Design. All primers for quantitative real-time PCR were selected by considering the predicted RNA secondary structure from The Mfold Web Server . Primers were synthesized by 1st Base Pte Ltd, Singapore. The desired gene fragments were amplified using first-strand cDNAs from healthy Nbenthamiana.  as templates. Single band corresponding to the predicted fragment size was sequenced using Applied Biosystems 3130 Genetic Analyzer (Applied Biosystems).Genes of interest with quantitatively significant changes in plant resistance and virus–host protein interactions were selected from the microarray results. First, the corresponding UniGene identifier for selected probes was entered into the database of NCBI, and Nbenthamiana.  cDNAs. A standard curve based on real-time PCR amplification of this 10-fold serial dilution of template was produced for each pair of real-time primers, by plotting the dilution factor against the CT value obtained for each dilution. All reactions were carried out in triplicate. The equation of the linear regression line, along with Pearson’s correlation coefficient (r), was used and amplification efficiencies (AEs) were calculated using the slope of the regression line: AE = (10(-1/slope) -1) x 100%. All the primer efficiencies are shown in t-test was used to calculate significant differences at the 0.05 (*) and 0.01 (**) levels of confidence, respectively. Amplification efficiencies of primer pairs among viral genes and NbACTIN (JQ256516) were similar. Similarly, amplification efficiencies of primer pairs among plant host genes and NbEF1α (AY206004) were similar. Therefore, NbACTIN or NbEF1α was used as an internal control for determining viral accumulation or transcriptional level of plant host genes.A 5-log dilution range was prepared using 10-fold serial dilutions of TM Real time PCR Detection system (Bio-Rad). The CT values obtained were automatically manipulated by the system. Housekeeping genes NbACTIN and NbEF1α were chosen as internal controls in the calculation of relative transcript levels. The quantitative real-time RT-PCR was performed as described previously [Quantitative real-time RT-PCR was performed to determine viral RNA levels and to investigate the expression of selected host genes of interest, using KAPA SYBR® FAST universal qPCR kit and CFX384eviously .NbTOM1 was obtained using GeneRacer® Kit with SuperScript® III RT and TOPO TA Cloning® Kit for Sequencing (Invitrogen). The partial sequence of NbTOM1 (AM261863.1) was used for gene specific primers design. Primers NbTOM1R583 and NbTOM1F347 were used for 5’- and 3’-RACE, following the protocol provided. The resultant PCR products were sequenced using Applied Biosystems 3130 Genetic Analyzer (Applied Biosystems). Amino acid alignment of different homologues of TOM1 was performed using online software MAFFT version 7 . The alignment result showed that NbTOM1 is highly conserved. Hydopathy plot of NbTOM1 was analyzed using online software kyte doolittle hydrophathy plot (http://gcat.davidson.edu/DGPB/kd/kyte-doolittle.htm). Similar to AtTOM1, NbTOM1also has 7 putative transmembrane regions  with restriction enzyme sites BamHI and XbaI was amplified by RT-PCR using primers NbTOM1F1 BamHI, NbTOMR581 XbaI and cDNA template from young healthy Nbenthamiana. . Construct pGreen-NbTOM1(nt1-581) was obtained by replacing of GFR fragment in pGreen with NbTOM1(nt1-581) between restriction enzyme sites BamHI and XbaI. Constructs pGreen-NbTOM1(nt1-581) and pGreen-NbTOM1 were transformed into Agrobacterium tumefaciens GV3101 for overexpression and silencing experiments.The ORF of Agrobacterium tumefaciens GV3101 harboring different constructs was subcultured individually in Luria-Bertani (LB) medium with antibiotics  at 28 °C with shaking until the OD600 reading reached 1.0. The bacterial culture was resuspended in Agroinfiltration solution  ethanesulfonic acid (MES) and incubated at RT for 3 h. For the overexpression experiment, 3 leaves per plant . Infiltrated leaves at 3 dpa were inoculated with buffer, HLSV or TMV purified virus, following the method and amount described above. Three plants were used for each inoculation. For the silencing experiment, the same types of Nbenthamiana.  plants were used but infiltrated with A. tumefaciens GV3101 containing pGreen-NbTOM1(nt1-581) or pGreen alone (negative control). Five days post Agro-infiltration, the same inoculation procedures as described in the overexpression experiment were used. For both overexpression and silencing experiments, total RNA was extracted from virus inoculated Nbenthamiana.  at 40 h post inoculation (hpi).Figure S1Amplification efficiencies of real-time primers.The amplification efficiencies of primers to be used in quantitative real-time PCR were assayed and found to fall within the 90% to 110% range. Red data points represent candidate primer pairs for the internal control. Blue data points represent primer pairs for selected genes of interest.(TIF)Click here for additional data file.Figure S2TOM1 homologues and Hydropathy plot analysis of NbTOM1.Amino acid alignment of  (A) Amino acid alignment of different homologues of TOM1. (B) Hydopathy plot analysis of NbTOM1.(TIF)Click here for additional data file.Table S1List of primers for reverse transcription, real time RT-PCR, determination of partial sequence, RACE or construction of clones.(XLSX)Click here for additional data file.


Postpartum depression (PPD)—the most common complication of childbirth—is a significant and prevalent public health problem that severely disrupts family interactions and can result in serious lasting consequences to the health of women and the healthy development of infants. These consequences increase in severity when left untreated; most women with PPD do not obtain help due to a range of logistical and attitudinal barriers.This pilot study was designed to test the feasibility, acceptability, and potential efficacy of an innovative and interactive guided Web-based intervention for postpartum depression, MomMoodBooster (MMB).A sample of 53 women who satisfied eligibility criteria  were invited to use the MMB program. Assessments occurred at screening/pretest, posttest (3 months following enrollment), and at 6 months follow-up.All six sessions of the program were completed by 87% (46/53) of participants. Participants were engaged with the program: visit days , number of visits , total duration of visits in hours , and number of sessions viewed out of six  all support high usage. Posttest data were collected from 89% of participants (47/53) and 6-month follow-up data were collected from 87% of participants (46/53). At pretest, 55% (29/53) of participants met PHQ-9 criteria for minor or major depression. At posttest, 90% (26/29) no longer met criteria.These findings support the expanded use and additional testing of the MMB program, including its implementation in a range of clinical and public health settings.Clinicaltrials.gov NCT00942721; http://clinicaltrials.gov/ct2/show/NCT00942721 (Archived by WebCite at http://www.webcitation.org/6KjYDvYkQ). Postpartum depression has been defined to include any major or subsyndromal depression present at any time during the first year after delivery , and it PPD is related to a range of biopsychosocial and cultural factors . PreviouThere are also significant economic and social costs  to the community. For example, Dagher et al  reportedGiven the limited empirical evidence supporting use of antidepressant medication with PPD ,22, therAlthough recent trials ,36 have Web-based PPD treatment may reduce both patient- and provider-level barriers to treatment uptake and thus extend the reach of helpful treatments to underserved mothers suffering from depression. For example, Web-based treatments can reduce feelings of stigma because participation is relatively anonymous and can be completed in women’s homes (thus avoiding travel) at times of their choosing without requiring childcare arrangements. Providers can recommend that women use an evidence-based Web-based PPD treatment program thus alleviating their concerns about training deficits and/or time required to provide treatment.An increasing number of Web-based depression interventions have emerged ,51-61. TBased on our review to date, there has been only one published report of the results of a Web-based depression intervention for postpartum women. In the randomized controlled trial (RCT) by O’Mahen et al based in England, 910 women with PPD symptoms  were ra), word choices, and selected videos. We described the formative research foundation for this MMB in a previous paper [The present study reports on the Web-based MomMoodBooster (MMB) program based on Milgrom’s adaptation of the Coping With Depression Course (CWDC)  for postus paper . This reParticipants (N=53) were recruited from two different research sites . Prospective participants were identified via birth records, nurse/health professional referrals, online advertisements, and news stories to local university and hospital settings.Upon receipt of a referral or direct contact from a prospective participant, each woman was contacted by a member of the research team to explain the study and obtain informed consent for participation. During the initial contact, a preliminary check of eligibility criteria was conducted. Preliminary screening criteria included <9 months postpartum, ≥18 years of age, home Internet access and use of personal email, and an EPDS score  from 12-Women meeting initial screening criteria then completed a phone-administered Structured Clinical Interview for DSM-IV Disorders (SCID) ,82 and tFollowing enrollment, participants worked through the MMB program and received weekly phone calls from a personal coach  who encouraged participants to use the program, to practice the recommended strategies, and to report their mood levels on a PHQ-9 assessment. Every effort was made to use the same personal coach for each participant on each call. The program automatically sent email reminders to encourage participants to log into the program.As described in Trained diagnostic interviewers conducted phone-based SCID interviews ,82. In oInterviewers also administered the HRSD ,83-86 byDuring screening, participants were asked to complete the EPDS, a brief, simple self-rated, 10-item measure developed to screen for symptoms of postpartum depression ,87. RespWe measured maternal age, delivery date and gestation, parity, education, history of previous treatment for depression, and household income.Participants were asked to complete six separate PHQ-9 assessments from pretest, posttest, and follow-up. Personal coaches administered the PHQ-9 during phone calls that corresponded to Sessions 3 and 5 of the MMB program. These serial PHQ-9 assessments were used for program evaluation, to provide participants with a useful assessment of their status, and as an important safety check of participant status ,88-90. PParticipants were asked to indicate how frequently over the previous week they had negative thoughts using the 30-item Automatic Thoughts Questionnaire (ATQ) ,93  to measure changes in activation, avoidance/rumination, work/school impairment, and social impairment  . Value oWe assessed women’s relationships with their partners using the Dyadic Adjustment Scale-7 (DAS-7) , an abbrWe included the Parenting Sense of Competence (PSOC) efficacy scale  that askBased on the work of Bandura  and MaciWe used industry-standard website analytic tools and planned database flags recommended by Peterson  to trackPersonal coaches also tracked the number and duration of calls with participants. After each call, personal coaches provided an impression of their working alliance with the participant  and the level of distraction during the call . We used open-ended items to ask participants to identify aspects of the program that were most helpful and least helpful. We also asked participants if they would recommend the program to other depressed postpartum women.We obtained a quantitative measure of usability by asking participants to complete our adapted version of the System Usability Scale (SUS) ,103, a 1We developed the MMB program using an iterative formative research process that included focus groups and usability testing . A detaiThe program consisted of the following six sequential sessions with each successive session becoming available weekly. Sessions were as follows: (1) Getting Started, (2) Managing Mood, (3) Increasing Pleasant Activities, (4) Managing Negative Thoughts, (5) Increasing Positive Thoughts, and (6) Planning for the Future. Each session opened with an autoplay host video that introduces the session goals. Webpages delivered content using text, programmed interactions, animations, and videos to present program content. Tunnel architecture  was usedThe program includes a number of features designed to encourage participant engagement and behavior change see -4. For eBecause social isolation and stigma are common in this population, MMB includes a private peer-based Web forum in which mothers can post messages as well as read and interact with the messages of other program participants. Finally, the program could be used by participants to send an email invitation to their partner encouraging them to visit a separate MMB informational website that described postpartum depression, the MMB program, and the important role of partners play ,106.As research shows, receiving email reminders can help to encourage greater adherence with Web-based interventions , MMB parThe entire program was facilitated by a series of phone calls with a personal coach. All coaches were graduate research assistants or research psychologists who had received training in the content of the MMB program, their roles as coaches versus therapists/counselors, and in their data collection responsibilities. Coach training started with a guided tour of the MMB program and its coach portal that summarized participant use of the features of each session. This was followed by a videoconference that included review of the coach manual that contained detailed scripts for each call, the coach data collection responsibilities, and a discussion of the role of the coach and the rationale for making calls . All coach calls were audiorecorded, and a subset was selected to monitor fidelity of implementation as well as reliability of phone-administered assessments.t tests.Changes in PHQ-9 scores across time were evaluated using an unconditional growth model nesting repeated measures within individuals. This multilevel model includes time as the only predictor, coded as the number of weeks since the pretest assessment, and allows the number and spacing of measurement occasions to vary across persons . A self-t tests were conducted for each measure across each of the 20 imputed datasets and reported pooled estimates in the results. To supplement tests of statistical significance, we computed partial point-biserial r as a measure of effect size in accordance with Rosenthal [r was defined as √(t2 / (t2 + df)); small effect size=0.14, medium effect size=0.36, and large effect size=0.51 [All analyses involved an intent-to-treat approach whereby missing data were addressed in one of two ways recommended by Schafer and Graham . We usedosenthal . Partialize=0.51 .Of the women who started the study, two were withdrawn because of concerns regarding self-harm and one woman withdrew of her own volition because she reported that she was feeling better and no longer wanted to be in the study. The resulting sample of 53 study participants had a mean age of 31.9 years (SD 5.1), a mean of 39.1 weeks (SD 2.4) gestation when their baby was born, and a mean number of 2.0 (SD 1.1) children. Mean baby age at the pretest was 5.5 months (SD 2.9). Participants were relatively well educated  and 59% (31/53) reported annual family income of at least $60,000. Based on the SCID at screening, 49% (26/53) met criteria for DSM-IV major depressive disorder. Pretest characteristics of participants are presented in t tests. Overall attrition was 13% (7/53) from pretest to 6-month follow-up. Attrition was not associated with demographic characteristics or pretest values on the outcome measures. Given the minimal rates of missing data and the low likelihood of bias due to attrition, maximum likelihood estimation and multiple imputation procedures were appropriate for modeling potential intervention effects. Note that imputation was used to handle both types of missing data .Of the remaining participants, 87% (46/53) completed all six sessions in the program. Posttest data were collected from 89% (47/53) on all key measures with the exception of the HRSD . Follow-up data at 6 months were collected from 87% of women (46/53). The extent to which attrition threatened the external validity of the study was evaluated using contingency table analyses and P<.001) with large effects at posttest  and 6-month follow-up . In terms of clinical significance, at pretest, 55% (29/53) participants met PHQ-9 criteria for minor or major depression. At posttest, 90% (26/29) no longer met these PHQ-9 criteria. Results also indicated that 77% (36/47) of the participants experienced a minimal clinically important difference  in their PHQ-9 depression scores from pretest to posttest.As shown in P<.001). The statistical model that included linear and quadratic growth  implied an average pretest PHQ-9 score of 11.49 (SE 0.48), which decreased over time indicating a significant improvement in participant depression. Specifically, the model revealed a significant initial linear decrease  that significantly decelerated over time . We also tested for differential trajectories in PHQ-9 scores between US and Australian participants by adding the main effect of region and the time by region interactions to the unconditional growth model described earlier. None of these parameters were statistically significant (P>.50), suggesting similar PHQ-9 trajectories between US and Australian participants.P<.001) with large effects at posttest  and 6-month follow-up .As noted in r=.66), BADS , PSOC , and self-efficacy . From pretest to 6-month follow-up, statistically significant and large effects were obtained on the ATQ , BADS , PSOC , and self-efficacy . Measures of the DAS from pretest to posttest and follow-up did not show significant change.Unobtrusive program use data indicated that mothers were engaged with the program: visit days ; number of visits ; total duration of visits in hours ; and number of sessions viewed out of six . A total of 96% (51/53) of participants kept track of their daily mood ratings at least once  and 92% (49/53) tracked the pleasant activities they wanted to accomplish each day . The website forum provided the opportunity to post and view content; 38% (19/53) of mothers  posted forum content, and 74% (39/53)  viewed content. In addition, the MMB partner support website was accessed by 34% (18/53) of the participants’ partners. Results on the System Usability Scale ,112 admiP=.021, partial r=.37). The linear slope parameter was also significantly related to the number of visit days to the program  and selected engagement activities  and the proportion of activities engaged in that involved entering personal data . Interestingly, the overall duration of program use was not significantly associated with the trajectories of the PHQ-9 scores.We explored associations between engagement and trajectories of PHQ-9 scores within a series of conditional growth models. These models included program engagement indicators as a composite measure as well as separately. Overall, the statistical models implied that program engagement was associated with additional decreases in PHQ-9 from pretest through follow-up. Specifically, the composite measure of program engagement was significantly related to the PHQ-9 linear slope parameter  of women agreed to receive personal coach calls. Coaches made a mean of 5.65 calls to each assigned participant . Mean total contact duration per participant summed over all calls was 96.99 minutes . Personal coaches reported, on average, that they had a good working alliance with participants  and reported low levels of distraction during the calls . At posttest, participants reported being quite satisfied with MMB features , and they rated personal coach calls as being helpful . Responses to open-ended questions about satisfaction are noted in At posttest we also asked participants “Since you enrolled in the MomMoodBooster program 3 months ago, which of the following products or programs have you used to manage your mood?”. A total of 30 out of 48 participants reported as follows: 12 (25.0%) read self-help books, 7 (14.6%) took medication for depression, 6 (12.5%) participated in an individual treatment program, 3 (6.3%) used hypnosis or acupuncture, 1 (2.1%) participated in a group treatment program, 1 (2.1%) participated in another Internet treatment program, and 30 (62.5%) participants indicated they had not participated in any other programs/products. Use of other programs for mood management was not significantly associated with the trajectories of the PHQ-9 scores.Pilot study results described in this report—when combined with results of our formative research —provide It is important to note that the relationship between participant engagement in the program and depression outcomes warrants further analysis as our measure of program use duration was not significantly associated with improvement in depression as measured by trajectories of the PHQ-9 scores. Elsewhere  we have Over the course of the program, participants showed significant improvements on clinician-rated HRSD and self-reported PHQ-9 assessments, and they sustained those improvements over the 6-month follow-up period. Fully 77% reported experiencing clinically important improvement in their PHQ-9 scores. Putative mechanisms of change showed corresponding improvements.Our 13% participant attrition is slightly higher than what has been reported for telephone-delivered therapies , and notWe believe that the highly encouraging results for participants using the MMB program were associated with three factors: (1) our adaptation and contextualization to PPD of Lewinsohn’s Coping with Depression Course, as embodied in Milgrom’s work, (2) MMB’s online engagement activities that encouraged participants to be actively involved, to spend time, and to follow treatment recommendations, and (3) personal coach calls that provided a key element of supportive accountability, which encouraged engagement and follow-through.There are several study limitations that should also be noted. For example, we used a quasi-experimental design without a randomized controlled condition, thus we were not able to control for potential threats to the internal validity such as biases due to selection or maturation effects. In addition, our relatively small sample size may limit the generalizability of the study findings. We also recruited a convenience sample, which may not be representative of depressed postpartum women, generally. In addition, participants were relatively well educated and had a relatively high socioeconomic status. Finally, we did not assess the maintenance of the treatment benefits beyond 6 months.We agree with the conclusion expressed by Lewis et al : “Given It would also be helpful to determine how program content might be adapted and delivered to reach low-income and minority postpartum depressed women by accommodating cultural differences , learninFinally, MMB could be expanded to include content on antenatal depression and/or content to enhance mother:infant interactions, two under-recognized and often untreated problems , 46 that


With the rapid development of P2P technology, P2P IPTV applications have received more and more attention. And program resource distribution is very important to P2P IPTV applications. In order to collect IPTV program resources, a distributed multi-protocol crawler is proposed. And the crawler has collected more than 13 million pieces of information of IPTV programs from 2009 to 2012. In addition, the distribution of IPTV programs is independent and incompact, resulting in chaos of program names, which obstructs searching and organizing programs. Thus, we focus on characteristic analysis of program resources, including the distributions of length of program names, the entropy of the character types, and hierarchy depth of programs. These analyses reveal the disorderly naming conventions of P2P IPTV programs. The analysis results can help to purify and extract useful information from chaotic names for better retrieval and accelerate automatic sorting of program and establishment of IPTV repository. In order to represent popularity of programs and to predict user behavior and popularity of hot programs over a period, we also put forward an analytical model of hot programs. Peer-to-Peer P2P) applications take advantage of resources such as storage, CPU cycles, content, or human presence available at the edge of the Internet to provide a service . With thP applicaP2P IPTV, also called P2P streaming, emerged recently as a novel framework to deliver TV programs or live events to a large number of viewers over the Internet. With the rapid large-scale popularization of broadband technology, P2P IPTV becomes the disruptive IP communication technology, which greatly revolutionizes people's lives and entertainment . SeveralThere are more and more P2P IPTV applications in the Internet now. And it is difficult to measure the applications because they use proprietary protocols. Source codes or official documents are scarcely published. However, the measurement of P2P IPTV applications is an important problem for the management and development of IPTV and several researchers have tried to address this issue. But none of them focused on program-list and its distribution of P2P IPTV. In this paper, we proposed a distributed multiprotocol crawler (DMP-Crawler) for collecting program resources in P2P IPTV networks. Moreover, we analyzed the characteristics of these IPTV programs and presented an analytical model of hot programs. The model can be used to infer the popular drama IPTV users at some time.The remainder of this paper is structured as follows. Internet Protocol Television (IPTV) denotes the transport of live streams and recorded movies or video clips by means of advanced packet-switched Internet technologies . ITU-T dOver the past decade, P2P technology has been a promising solution for the distribution of large-scale media and a large amount of P2P IPTV systems have been developed and widely deployed on the Internet. In this paper, we defined P2P IPTV as a technology that enabled users to transmit and receive multimedia services including television, video, audio, text, and graphic through P2P overlay networks with support for QoS/QoE, security, mobility, interactivity, and reliability. Through P2P IPTV, users can enjoy IPTV services anywhere. Now P2P IPTV applications are changing the way that we watch TV and movies.In 2000, Chu et al. proposed End System Multicast (ESM) , the firA typical P2P IPTV application is comprised of five components: media collection server (MCS), media distribution server (MDS), program-list server (PLS), tracker server , and end system . As illustrated in MCS gathers video data in two ways. Firstly, for live program, MCS gets video data from video grabber. Secondly, for video on demand (VoD), MCS reads video file directly, encodes video data according to some coding methods, and uploads the data to MDS.When coding data of a video, MCS will generate the related program name, program GUID , play link, category, and so forth and register the information in PLS. At the same time, MDS will register program GUID in TS.After receiving live data, MDS will distribute them to IPTV network. After receiving VoD data, MDS will store them firstly and distribute them when clients request them. We have introduced the video distribution protocol in detail in 2012 .The local peer requests the latest program-list file from PLS and updates it immediately after lunching the IPTV client. The list of program consists of program name, program GUID which is the most important identification of signal communication among peers, program descriptions, and so forth.After the local peer selects one program to watch videos, the peer registers itself to the tracker server and sends multiple query messages to the server to retrieve a small set of partner peers who are watching the same program. The information of partner peers includes IP address, TCP port, and UDP port. Upon receiving the initial list of partner peers, the local peer uses this seed peer list to harvest additional lists by periodically probing active peers which maintain a list of peers.After harvesting enough peers, the peer tries to connect the active ones or MDS to request video data for playback of the appointed program and launches a local media player  to play the video. To deal with the churn of peers, the local peer needs to actively seek new peers from its existing partners to update peer list. At the same time, it also rebroadcasts its current peer list to its partner peers.Our work is focused on P2P IPTV measurement has been extensively studied. The measuring methods can be classified into two types: passive tracing and active tracing approach.The passive approach is performed by deploying code at suitable points in the network infrastructure. The passive approach does not increase the network traffic. And it is often used to analyze and identify P2P IPTV traffic from general Internet traffic with the known behaviors . It is also used to capture IPTV traces and grasp the P2P IPTV application. Du et al.  and Tan In the active approach, the special crawler, like an ordinary client, is adopted to inject test packets into P2P IPTV network or send packets to servers and peers. Then the crawler follows packets and measures characters of IPTV network. Hei et al.  carried Most of existing research work surveyed the P2P IPTV network-centric metrics  or user-centric metrics . Our studies were primarily focused on program-list distribution of P2P IPTV applications because program resource distribution was very important to P2P IPTV applications. Our work surveyed the P2P IPTV content-centric metrics which were useful for prediction and monitoring of programs. In this paper, a distributed multiprotocol program crawler was proposed to collect various kinds of information of programs. Moreover, we also analyzed the characteristics of program resources and put forward an analytical model of hot program.In this section, we will present the basic principle of program-list distribution in P2P IPTV applications and illustrate a feasible and efficient architecture for crawling program-list.When the program-list is downloaded and extracted by an IPTV client, users can select a program to watch videos. So program-list distribution is very important in P2P IPTV applications. The program-list includes program name, categories, play-link, and descriptions. Play-link is the most important identification of signal communication among peers viewing the same program. A typical example of program metadata is shown in The client-server architecture, as shown in With the rapid increase in the number of programs, the size of program-list file becomes bigger and bigger. For example, PPTV had about 300 thousand programs in 2011, and the size of program-list file was more than 20 MB, which is a heavy burden to program-list servers and leads to bad experience to users. Some IPTV applications use compression method to decrease the file size, while others use multiple program-list files based on program categories. Furthermore, some IPTV applications encrypt program-list files to prevent hotlinking.In order to obtain program information of IPTV applications, it is necessary to summarize the principle of program-list distribution of the most of IPTV applications and decrypt the encrypt algorithm and XML metadata of program-list file.Then, an efficient distributed multiprotocol crawler (DMP-Crawler) was proposed to collect various kinds of information of programs in popular P2P IPTV applications. {Program name, IPTV application name} was used to uniquely identify a program. On the basis of crawler clients' and server's status, the crawler controller assigns tasks to multiple independent crawler clients through a task scheduling algorithm. Each crawler client periodically reports its crawling status as well as CPU and memory consumption to crawler controller.A crawler client mainly includes crawling engine, program-list crawling module, program-list extracting module, classification module, and data storage module. According to crawling task type, the crawler client invokes crawler engine, requests program-list file from program-list servers, and reports crawling status to crawler controller. When program-list file is downloaded, the crawler client extracts metadata of programs from the file, classifies these programs, and stores all information into database for further analyses.In order to understand naming rules of IPTV programs, characteristics of program naming were analyzed with statistical methods. Characteristics analysis of programs included distributions of the length of program names, the entropy of the character types, high-frequency symbols in the names, and distributions of the hierarchy depth of program names.c1  c2 ⋯ cn, Where n is the number of characters or length of PN and n = len(PN). ci   is a printable character in some coded character set, such as Chinese, English, Latin, and punctuation symbol. If len(PN) ≤ 10, the program has a short name. If 10 < len(PN) ≤ 20, the program has a medium name. If 20 < len(PN) ≤ 30, the program has a long name. If len(PN) > 30, the program has a super-long name.Program Name (PN) is composed of a serial of characters, PN = x denote the character type of program name. The set of value of x is denoted asLet a random variable se (UCD) .Uc denote the set of characters of program names, ci ∈ Uc.Let f : Uc → CharsType, every character of program name can be transformed to the corresponding character type as follows:xi ∈ CharsType, i = 1, 2, …, n.With a mapping function H(CharsType) denote the information entropy of xi, which is used to evaluate the chaos of program naming . If popularity level is between 0 and 4, median of corresponding interval is used as U. If popularity level is 5 and PPStream has not the same program, UPPTV = 3000 and UQQLive = 1800. If popularity level is 5 and PPStream has the same program, UPPTV and UQQLive are calculated byPPTV and QQLive offer 6-level popularity of programs. Every popularity level presents an interval of the number of viewers. Popularity levels of 0, 1, 2, 3, 4, and 5, respectively, represent , , , , , and [1000, + For a program, PPStream and PPfilm provide the number of its viewers, UUSee presents the ratio of its viewers, while PPTV and QQLive only offer 6-level popularity. Thus, we must normalize the number of viewers according to the number of online viewers of various IPTV applications. In June 2010, the maximum viewers of PPStream, UUSee, PPTV, and QQLive are about 20.0, 2.0, 11.0, and 6.6 million, respectively. The normalizing rules are as follows. Let's see the Meteor Shower together in that week. Moreover, the model can be used to predict popularity of hot programs in some time.In this paper, we have studied the program information collection in P2P IPTV applications. We proposed a distributed multiprotocol crawler to harvest program information of P2P IPTV applications. As far as we know, it is the first time that the detailed crawler for IPTV programs is presented. Characteristic analysis of programs was carried out. The results reveal the disorderly naming conventions of P2P IPTV program and can help to purify and extract useful information from chaos names for better retrieval. We also put forward an analytical model of hot programs to represent popularity of programs and predict user behaviors and popularity of hot programs within a period.Distribution of IPTV programs is independent and incompact, resulting in the chaos of program name, which obstructs searching and organizing programs. In the next work, we will focus on data mining of programs and establishment of IPTV repository.


Currently, β-blockers are used most frequently for the purpose of heart rate (HR) control in patients with atrial fibrillation (AF) in worldwide. Carvedilol is one of common β-blockers and known to be effective for hypertension and heart failure. However, little can be found the information about the HR-lowering effect of carvedilol in patients with AF without heart failure. Therefore, we conducted this study to investigate the effect of carvedilol on HR in 3-minute electrocardiogram (ECG) and total heart beats (THBs) in 24-hour Holter ECG monitoring in patients with persistent or permanent AF.A total of 13 hypertensive patients  with AF and HR 90 bpm or more were enrolled. All patients received carvedilol from 5 mg/day. The dose of drug was titrated every 4 weeks and raised to 10 or 20 mg/day if HR was 80 bpm or more.Mean HR was decreased from 101.9 ± 13.9 to 85.2 ± 15.2 bpm (P < 0.05) after treatment with carvedilol. THBs were also significantly decreased from 128 to 115 × 1,000/day (P < 0.001). Percent reduction in HR and THBs were 13.9% and 10.7%, respectively. The scores of Atrial Fibrillation Quality of Life Questionnaire (AFQLQ) did not change. Only one patient was required to discontinue carvedilol due to congestive heart failure.We observed that carvedilol certainly reduced HR in patients with chronic AF. We believe that the effect of carvedilol on the reduction in HR can contribute to the management of AF patients treated with rate-control strategy. Atrial fibrillation (AF) is a most common sustained arrhythmia in daily clinical practice. Since AF is a potent risk factor for disability and impairing quality of life (QOL) associated with cardiogenic ischemic stroke and congestive heart failure, AF is important disease to be managed. Current strategies for the management of AF include the medical treatment with antiarrhythmic drugs to maintain sinus rhythm or the use of rate-controlling drugs allowing AF to persist. In both approaches, the anticoagulation therapy should be recommended. According to the results from several large clinical trials after 2000 , the outA total of 13 patients with AF were enrolled in this study. All patients had been diagnosed hypertension and persistent or permanent AF prior to starting the carvedilol treatment. All patients exhibited heart rate of 90 beats/minute (bpm) or more evaluated by numbers of QRS complex during any one minute in 3-minute ECG; even though the patients had received any heart rate-lowering agents except β-blockers. Carvedilol was given to the patients who had no changes in their current medications for at least three months prior to starting carvedilol. Hypertension was diagnosed when office blood pressure was ≥ 140/90 mmHg , if the All patients were given carvedilol starting from a dose of 5 mg/day. After observation for 4 - 8 weeks, the dose of carvedilol was raised to 10 mg/day if patient’s resting heart rate was 80 bpm or more , 12 and 0.5) [The primary endpoints of this study were 1) heart rate evaluated by numbers of QRS complex during any one minute in 3-minute ECG, 2) total heart beats in 24-hour Holter ECG monitoring before and after treatment with carvedilol. Secondary endpoints were patient QOL scores  and adve0.5) , and widData are presented as the mean ± standard deviation (SD). Statistical differences of the parameters between at the baseline and at each observation period were analyzed by a one-way repeated-measures analysis of variance (ANOVA) followed by Student’s t-tests for paired data with the Bonferroni correction. Differences of the parameters between before and after treatment with carvedilol were analyzed by a paired Student’s t-test. Comparison among unrelated 2 or 3 groups were analyzed by Student’s t-test or one-way ANOVA. Differences with P-values of less than 0.05 were considered to be statistically significant. All statistical analyses were performed using the SigmaStat version 3.5 software program .The baseline characteristics of patients in the present study are shown in 2The changes in heart rate at each observation period are shown in The results of Holter ECG monitoring were shown in The scores of AFQLQ including either 3 subset  did not improve after treatment with carvedilol in patients with chronic AF .Adverse effects were observed in 3 cases. Of these, only one male patient was required to discontinue carvedilol 8 weeks after treatment with 5 mg/day due to the occurrence of congestive heart failure. Although his left ventricular function was preserved at 58% in ejection fraction, he was the sole patient suffered from old myocardial infarction and the oldest (86 years) in this study. One patient felt tinnitus during receiving carvedilol but he was able to complete the protocol with the dose of 20 mg/day. In another female patient, skin eruption appeared during observation period which was diagnosed asteatotic eczema, not an allergy for carvedilol. She could finish the protocol on her final dose of 10 mg/day. All adverse effects were not severe and the latter two incidents were probably not associated with carvedilol. One patient could not complete follow-up period except adverse effect because AF returned to sinus rhythm after finishing evaluation of parameters on the dose of 5 mg/day.Changes in the other parameters measured in the present study were summarized in The major finding of the present study was that carvedilol significantly reduced heart rate in 3-minute ECG and total heart beats in 24-hour Holter ECG monitoring. Although this study was conducted in a small number of subjects, promising results for primary endpoints were observed.1-adrenoreceptor blocking action [Carvedilol, a nonselective β-blocker, has not only β-adrenoreceptor blocking effect but also vasodilating effect resulting in the reduction in total peripheral vascular resistance. The latter is mainly thought to be caused by αg action . In addig action  and a pog action  but alsog action , 23.Even in stable outpatients with chronic AF, uncontrolled rapid heart rate can result in the development of congestive heart failure and/or impairment of QOL. Therefore, heart rate control is important and necessary to prevent heart failure and any impairment, though mortality in patients treated with rate-control strategy was comparable with those in rhythm-control strategy .Present study demonstrated that carvedilol could certainly reduce heart rate in patients with chronic AF. However, %change in heart rate was not consistent in all patients. In fact, %reduction in heart rate in the groups of lower doses of carvedilol was larger than that in the group of 20 mg, despite it did not reach significant difference. The reason for these results could be explained by that patients were not randomized to divide into 3 groups in this study and the final daily dose of carvedilol was chosen by titration according to heart rate before raising a dose and tolerance for this drug. Similarly, %reduction in heart rate in patients with other heart rate-lowering drugs was significant smaller than that without use of these drugs. These results indicated that the patients consequently needed higher doses of carvedilol and/or those with the use of other heart rate-lowering drugs were resistant to the heart rate-lowering therapy. The sympathetic nerve activity in these patients would have been higher.Since the casual heart rate can easily be modified by unstable situation, in particular the status of sympathetic nerve activity as well as white coat phenomenon on office blood pressure, total heart beats in 24-hour Holter ECG monitoring were evaluated to confirm the heart rate-lowering effect of carvedilol. Present study demonstrated that carvedilol could certainly reduce total heart beats in 24-hour Holter ECG monitoring in patients with chronic AF. An interesting finding was that carvedilol did not affect minimum heart rate despite maximum and mean heart rates significantly decreased; suggesting that carvedilol would not cause excessive response resulting in bradycardia. It would be beneficial for the management of AF patients to avoid any complication caused by bradycardia such as pacemaker implantation. Another important finding that total heart beats and mean heart rate in 24-hour Holter ECG were definitely decreased by the treatment with carvedilol in all subjects; even in some patients with increasing response to casual heart rate in the situation of outpatient clinic; indicating that the effect of heart rate-controlling drugs should be evaluated by not only casual heart rate but also total heart beats or mean heart rate using 24-hour Holter ECG monitoring.No improvement of AFQLQ scores could be found after treatment with carvedilol in the present study. In J-RHYTHM study , the AFQIt was required to discontinue carvedilol in only one case with old myocardial infarction. This fact taught us again that β-blockers should be prescribed with caution to elderly patients even though who have no history of heart failure and ejection fraction is within normal range.This study had several limitations. First, this study was performed in a single institution and had a small sample size. It was actually difficult to recruit patients for this study, because most AF patients had already received any β-blocker and their heart rates were well-controlled less than 90 bpm which was enroll criteria. However, even in a small number of subjects, the heart rate-lowering effect of carvedilol was obvious and statistically significant. Second, the dose of carvedilol was not randomized. Since the final daily doses of carvedilol were determined by titration, it could be explained the reason why %reduction in heart rate in patients receiving maximum dose of carvedilol was less than that in those receiving lower doses. However, the present method of titration to raise a dose of β-blocker would be more safety and recommended in real-world clinical situation.In conclusion, we observed that administration of carvedilol reduced heart rate in patients with chronic AF without congestive heart failure. We believe that the effect of carvedilol on the reduction in heart rate can contribute to the management of AF patients treated with rate-control strategy and the prevention from complications in future.


The project P.A.T.H.S. is an indigenously developed positive youth development program in Hong Kong. In the extension phase (2009/2010 school year), subjective outcome evaluation data were collected from 231 schools involving 89,068 participants after completion of the curricula-based Tier 1 Program. With schools as the units of analysis, results showed that participants generally had positive perceptions of the program content and implementers, with over four-fifth of the participants regarded the program as helpful to them. There were some significant grade differences in the subjective outcome evaluation findings, although the related effect size was not strong. Multiple regression analyses revealed that program content and program implementers predicted perceived effectiveness of the program. The present study suggests that irrespective of cohorts, students in the junior secondary years perceived the program to be beneficial to them. The increasing popularity of implementing effective adolescent prevention programs in recent decades has been a key initiative to tackle adolescent developmental problems –4. ReseaResearch findings showed that positive attitudes toward the program content and program implementers were associated with program outcomes –13. HowePrevention researchers noted the importance of providing culturally competent interventions for a given population –20. HoweThe Project “P.A.T.H.S. to Adulthood: A Jockey Club Youth Enhancement Scheme” is a large-scale positive youth development program designed for junior secondary school students  in Hong Kong . The worQualitative and quantitative data collected based on the original phase of the project generally suggested that participants (students and program implementers) perceived the program positively –35. HoweA total of 231 schools with 89,068 students joined the Project P.A.T.H.S. in the extension phase of the Full Implementation Phase in the school year 2009/2010.  A total of 577 aggregated data sets from the participating schools were collected across three grade levels . 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 participating schools incorporated the program into the formal curriculum , 52.69% used other modes  to implement the program. The mean number of social workers and teachers implementing the program per school was 1.71 (ranged from 0 to 7) and 5.11 (ranged from 0 to 27), respectively.After completion of the Tier 1 Program, the participants were invited to respond to a Subjective Outcome Evaluation Form (Form A) developed by the first author . The datThe Subjective Outcome Evaluation Form (Form A) was used. Broadly speaking, there are several parts in this evaluation form as follows:participants' perceptions of the program, such as program objectives, design, classroom atmosphere, interaction among the students, and the respondents' participation during class (10 items);participants' perceptions of the program implementers, such as the preparation of the instructor, professional attitude, involvement, and interaction with the students (10 items);participants' perceptions of the effectiveness of the program, such as promotion of different psychosocial competencies, resilience, and overall personal development (16 items);the extent to which the participants would recommend the program to other people with similar needs (1 item);the extent to which the participants would join similar programs in the future (1 item);overall satisfaction with the program (1 item);things that the participants learned from the program (open-ended question);things that the participants appreciated most (open-ended question);opinion about the instructor(s) (open-ended question);areas that require improvement (open-ended question).For the quantitative data, the implementers collecting the data in each school 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 reports, they were also requested to submit the soft copy of the consolidated data sheets. In the reports prepared by the schools, the workers were also required to estimate the degree of adherence to the program manuals . To facilitate the program evaluation, the research team developed an evaluation manual with standardized instructions for collecting the subjective outcome evaluation data . In addiPercentage findings were examined using descriptive statistics. A composite measure of each domain  was created based on the total scores of each factor divided by the number of items in that domain. Pearson correlation analysis was used to examine if the program content and program implementers were related to the program effectiveness. One-way analysis of variance (ANOVA) was used to assess the differences in the mean of each factor across grade levels. Multiple regression analysis was performed to compare which factor would predict the program effectiveness. All analyses were performed by using the Statistical Package for Social Sciences Version 19.0.Quantitative findings based on the closed-ended questions are presented in this paper. Several observations can be highlighted from the findings. In the first place, roughly four-fifth of the participants generally had positive perceptions of the program , includiAs shown in α = .98), 10 items related to the program implementers (α = .99), 16 items related to the benefits (α = 1.00), and the overall 36 items measuring program effectiveness (α = .99). Results of correlation analysis showed that both program content  and program implementers  were strongly associated with program effectiveness. These positive relationships were consistent across all grade levels  = 6.07, P < .01), program implementers  = 8.62, P < .01), program effectiveness  = 11.51, P < .01), and the total scale  = 9.85, P < .01)  across levels, a series of one-way ANOVAs were performed with different subjective outcome indicators as dependent variables and grade level  as an independent variable. Significant results were found for program content (P < .01) .P = .02) revealed that significant differences were found between Secondary 1 (M = 4.37) and Secondary 2 (M = 4.26) students toward their perceptions on program content (P < .01) and their perceptions on program implementers . Significant grade differences were also shown when comparing students' perceptions toward the program effectiveness . Similar results were revealed in the overall program effectiveness . It is noteworthy that the previous differences were not significant between Secondary 2 and 3 classes (P > .05). Overall speaking, junior students perceived the program more effective than their senior counterparts. However, it is noteworthy that the effect size of grade differences was not strong.Post hoc analysis using the Bonferroni adjustment (P < .01). On the other hand, program implementer was not associated with program effectiveness (P > .05). However, the result based on the Secondary 2 students showed that perception toward the program implementer was negatively associated with perceived program effectiveness . Further analyses showed that program content  had a significant predictive effect on program effectiveness while this relationship was not significant in program implementer . This model explained 71% of the variance toward the prediction of program effectiveness.The present findings revealed that the program participants generally rated their participation in the program positively. In line with the previous findings using various methods and collected from different sources –30, the The second aim of the study was to examine the relative influence of two program implementation factors  on program effectiveness. Results of the regression analyses indicated that program content but not program implementers had a significant predictive effect on program effectiveness outcome. In line with previous studies , 37–39, Another purpose of the study was to examine whether the relationships between program implementation factors and program evaluation outcomes would vary by the students' grade levels. Consistent with the previous study , SecondaIt is interesting to note the negative predictive effect of program implementers on perceived program effectiveness. Some might question whether this result was related to the program implementers' teaching background. It is noteworthy that all program implementers of the Tier 1 Program were all experienced teachers and frontline social workers who had at least 3 years of experience in working with youths and received relevant formalized training workshops for more than 20 hours. Second, previous study  showed tWhile the present study focused on the influence of two program implementation factors, it is possible that other facilitators  will also influence program effectiveness. For example, high levels of fidelity and increased cultural relevance of the program have been associated with program outcomes , 40, 41.Providing a positive developmental experience in early adolescence would promote individuals' different competencies and reduce negative outcomes . ConsistThere are several limitations of this study. First, the use of self-report measure from a single perspective is limited to give a full picture concerning subjective outcome evaluation. However, this approach is commonly used in program evaluation research , 9, 12. Despite the aforementioned limitations, the current study contributes to the positive youth development literature. It sheds light on what program components are associated with perceived program effectiveness. Shek et al.  argued t


Web-based computer-tailored approaches have the potential to be successful in supporting smoking cessation. However, the potential effects of such approaches for relapse prevention and the value of incorporating action planning strategies to effectively prevent smoking relapse have not been fully explored. The Stay Quit for You (SQ4U) study compared two Web-based computer-tailored smoking relapse prevention programs with different types of planning strategies versus a control group.To assess the efficacy of two Web-based computer-tailored programs in preventing smoking relapse compared with a control group. The action planning (AP) program provided tailored feedback at baseline and invited respondents to do 6 preparatory and coping planning assignments . The action planning plus (AP+) program was an extended version of the AP program that also provided tailored feedback at 11 time points after the quit attempt. Respondents in the control group only filled out questionnaires. The study also assessed possible dose–response relationships between abstinence and adherence to the programs.The study was a randomized controlled trial with three conditions: the control group, the AP program, and the AP+ program. Respondents were daily smokers (N = 2031), aged 18 to 65 years, who were motivated and willing to quit smoking within 1 month. The primary outcome was self-reported continued abstinence 12 months after baseline. Logistic regression analyses were conducted using three samples: (1) all respondents as randomly assigned, (2) a modified sample that excluded respondents who did not make a quit attempt in conformance with the program protocol, and (3) a minimum dose sample that also excluded respondents who did not adhere to at least one of the intervention elements. Observed case analyses and conservative analyses were conducted.P = .005) and the AP+ program  were significantly more effective than the control condition. Abstinence rates and effects differed per sample. Finally, the results suggest a dose–response relationship between abstinence and the number of program elements completed by the respondents.In the observed case analysis of the randomized sample, abstinence rates were 22% (45/202) in the control group versus 33% (63/190) in the AP program and 31% (53/174) in the AP+ program. The AP program  Smoking relapse rates can be extremely high (up to 90% in the first 3 months), and only 3%-5% of quitters maintain their quit attempt for 6 months or longer . The rolAdding action planning components to programs may be a promising strategy for improving smoking relapse prevention programs -12. PlanThe Internet has proven to be a promising delivery mode for health-promoting and lifestyle-changing interventions . In sum, the main goal of the Stay Quit for You (SQ4U) study was to assess the efficacy of two relapse prevention programs: (1) an action planning (AP) program that provided tailored feedback based on the baseline questionnaire and 6 preparatory and coping planning assignments, and (2) an action planning plus (AP+) program that extended the AP program by providing tailored feedback at 11 time points after the quit date. The efficacy of the programs was compared with that of a control group (with no intervention). Moreover, we aimed to assess possible dose–response relationships between abstinence and adherence to the number of program elements. First, we expected both programs to be more effective than the control condition in fostering continued abstinence 12 months after the start of the study (hypothesis 1). We expected the AP+ program to be the most effective. Moreover, we expected to find a dose–response relationship between continued abstinence and intervention dose (hypothesis 2). Finally, we will provide an overview of the respondents’ program evaluations.Ethics approval was obtained from the Medical Ethics Committee of Maastricht Academic Hospital and Maastricht University . The study is registered with the Dutch Trial Register (NTR1892).We recruited smokers by placing ads in local newspapers, distributing 10,000 flyers in the city of Maastricht, and placing online ads on the websites of national health funds, a national news page, and the Dutch Foundation for a Smoke-free Future. The ads referred the respondents to our research website for more information. All data were gathered via the Web and there was no face-to-face contact between respondents and the study team. A software program randomly assigned a total of 2681 respondents to one of the three conditions using a simple randomization type (see design below). The enrollment and inclusion of respondents is presented in The SQ4U study was a randomized controlled study with a control condition and two experimental conditions. Respondents registered via the research website and made their own login account (each time they were invited for participation they received this account in the invitation mail). After registration, respondents were randomly assigned to one of the three programs outlined in the Introduction. Respondents in the intervention groups were invited by email or text message  to perform intervention tasks . The same procedure was used to invite all respondents for the 12-month follow-up measurement. Reminder emails were sent when respondents did not respond to the follow-up measurement, which asked them to report on their smoking behavior using self-assessed questionnaires. Respondents who reported that they were abstinent were asked to take biochemical validation tests (see below). Respondents who completed all parts of their assigned SQ4U variant (including those in the control group) were eligible to win 1 of 20 prizes of €250. A more detailed description of the development, design, study course, biochemical validation, and intervention elements can be found elsewhere .We used cotinine assessments to validate reports of abstinence in a subsample (n = 70) of the respondents. This verified the nonsmoking status self-reported by respondents at the 12-month follow-up measurement. Only 1 (1%) respondent showed positive cotinine results and admitted to having smoked. Another respondent admitted to smoking when invited for biochemical validation. The smoking status for these 2 (3%) respondents was changed to relapse.Feedback focused on respondents’ perceptions of smoking and quitting and was based on previously tested effective computer tailoring programs that used the I-Change Model ,20. The Since planning assignments have proven to be promising strategies to foster cessation and prevent relapse, the SQ4U programs incorporated assignments designed to motivate respondents to use these strategies to make a quit attempt  and to prevent relapse . Two assignments focused on making and carrying out preparatory plans; 2 more assignments addressed coping planning. Finally, 1 assignment focused on a specific coping plan (making an emergency plan for coping in case of a lapse) and 1 assignment required making a specific preparatory plan (planning a reward for abstaining from smoking for some time).Studies that use ecological momentary assessments to gain in-depth, day-to-day information on the process of quitting have noted that low self-efficacy and negative affect preceded lapsing -40. TherThe following basic information was collected about each respondent:Demographic variables assessed age, gender, and educational level .Perceived stress was assessed by 5 items based on the Perceived Stress Scale [ss Scale  and was Level of depression was measured by 10 items  using the Center for Epidemiologic Studies Depression scale [on scale . The ansLevel of dependence was assessed by 5 items  based on an abbreviated Fagerström test [röm test ,44. The The following questions about intention and motivational factors were based on questions used in previous studies ,20,45-47Attitudes were measured on a 4-point scale  with four subscales measuring the following: (1) pros of not smoking, expressed by 9 statements representing positive expected outcomes  , (2) cons of not smoking, expressed by 9 statements representing negative expected outcomes  , (3) pros of relapse, expressed by 4 statements representing positive expected outcomes  , and (4) cons of relapse, expressed by 6 statements representing negative expected outcomes  .o Social support was measured by 5 items that asked about the support received from significant others  on a 4-point scale . A “not applicable” response was coded as missing. We created an index and used these scores in the analyses.o Modeling was assessed by 5 items that measured the smoking status of the partner  and residential children, parents, colleagues, and friends . The items were coded into three category scales . The items were summed and formed an index that we used in the analyses; smoking status of the partner was included separately in the analyses.o Self-efficacy was assessed by 13 items that asked whether respondents thought they would be able to refrain from smoking in various smoking-related high-risk situations such as parties . Recovery self-efficacy was assessed by 7 items that asked whether respondents thought they would be able to resume a smoking cessation program after a lapse  . Answers were given on a 5-point scale  and the mean score was used in the analyses.o Preparatory planning was assessed by 12 items Continued abstinence at 12 months after baseline was the primary outcome. In line with the definitions provided by Hughes et al , we defiThe most common approach to analyzing the effects of interventions is to include all respondents randomly assigned to the programs. The advantage to this approach is that it reflects the situation as it is likely to occur in practice . This strategy also maintains the balance between randomly assigned groups and preserves sample sizes ,50. On tsample as randomized, including all respondents. Since this study focused on relapse prevention and therefore on continued abstinence, we also report on smaller samples:Sample 1 is the the modified sample, excluded respondents who indicated after their quit date as well as at follow-up that they did not make a quit attempt, and those who reported that they had quit less than 320 days before the follow-up measurement (this is after about 2 weeks after the first month in which they were supposed to make an attempt). We excluded the latter group because one of the inclusion criteria was that respondents needed to set a quit date within 1 month after inclusion. Including respondents who explicitly stated that they made their quit attempt much later or even too close to the follow-up measurement would result in differences between respondents in the time frame from the quit attempt to the follow-up measurement.Sample 2, referred to as minimum dose sample, excluded respondents who did not adhere to at least one element of the program they were assigned to  in addition to meeting the exclusion criteria in the modified sample.Sample 3, referred to as the For all three samples, we conducted an observed case analysis (only including respondents with follow-up data) and a conservative analysis in which we assumed that participants missing at follow-up had relapsed to smoking. We used a logistic regression analysis to compare the efficacy of the control condition and the SQ4U programs to foster continued smoking abstinence after 12 months. Differences in baseline factors  were assessed using chi-square tests for categorical variables and analysis of variance for continuous variables. Attrition was analyzed by logistic regression and included baseline factors. To preserve power, we included only baseline factors on which the three conditions significantly differed at baseline as well as the factors that significantly predicted dropout at follow-up as covariates in the effect analyses. Listwise deletion with regard to missing values was used. Finally, chi-square tests were used to assess the existence of dose-response relationships within the SQ4U programs using the observed cases in sample 2 (the modified sample) to conform to the methods used by Borland et al .P > .05) differences between the three conditions on the baseline measurements of perceived stress, depression, intention strength, social influence, attitude, self-efficacy and recovery self-efficacy, and preparatory planning. (P = .06) and AP+  programs and respondents who were younger , were male , had a lower education level , perceived fewer advantages to relapse , and had low levels of self-efficacy . In the control condition, 434 of 636 (68.2%) were lost to follow-up versus 508 of 698 (72.8%) in the AP program and 523 of 697 (75.0%) in the AP+ program . AttritiP = .005), sample 2 , and sample 3  when including observed cases only. The AP+ program was, however, only significant in sample 1 . In the conservative analyses, both programs were significantly more effective than the control condition only in sample 3 . Finally, having high levels of self-efficacy was the only consistent predictor of continued abstinence in all these analyses.21 = 7.4, P < .007; AP+: χ21 = 14.7, P < .001) and feedback moments  and confirmed higher abstinence rates when more planning assignments or questionnaires after the quit attempt were completed. On average, respondents in the program groups adhered to 4 out of 6 planning assignments and 6 out of 11 feedback questionnaires.The main goal of this study was to evaluate the efficacy of two Web-based smoking relapse prevention programs (AP and AP+) in the SQ4U study with regard to 12-month continued smoking abstinence. Furthermore, we aimed to assess dose-response associations. Despite the potential of the Internet, a recurrent problem in Internet trials is low adherence to the programs . These lThe results of all three observed case analyses  revealed significant effects in favor of the AP program. We can conclude that most of the analyses support our first hypothesis that planning strategies can be effective in preventing relapse among smokers who are motivated to quit smoking. The AP+ program, on the other hand, only proved to be significantly more effective than the control condition in the randomized sample (sample 1). The approach for sample 2 seems to have created a bias against the AP+ program by excluding respondents who did not make a quit attempt during the study, which resulted in more exclusions of relapsers (since nonquitters cannot be considered to be continued abstinent at follow-up) in the control condition than in the AP+ program (which consisted of elements designed to foster making a quit attempt). This approach may therefore have been too conservative. Furthermore, additional power analyses showed that 2623 respondents would have been needed to find significant differences in abstinence rate between the control group  and the AP+ program group . Therefore, the lack of significance in sample 2 may be due to power issues. Another possible explanation for lack of significant effect for the AP+ program in sample 2 and sample 3 may be that the program was too intensive and therefore resulted in an overload for the respondents that negatively influenced its efficacy. A comparable result was found in an earlier study conducted among vocational students, which tested the efficacy of a standard in-school program, a computer-tailored program, and a combined program . This stWhen conducting conservative analyses, we found the AP and AP+ programs to be significantly more effective than the control condition in the minimum dose sample (sample 3). However, given the large dropout rate, this conservative approach (coding missing participants as relapsers) may be too conservative. Additional descriptive analyses indicated that about 60% of the respondents who dropped out at follow-up were nonsmokers at their last visit, indicating that interpreting all missing cases as treatment failures may be too conservative, a finding also supported by others [The abstinence rate of 22% in the control group is another notable finding, since self-quitters generally reach abstinence rates of only 3%-5% . A possiFinally, the dose-response relationship between abstinence and the number of program elements suggests that a dose-response association may exist. This is because abstinence rates increased by up to 53% 33/62) in the AP program and 51% (36/70) in the AP+ program when doing 5 to 6 planning assignments, and up to 61% (20/33) in the AP+ program when filling out 10-11 feedback questionnaires (on which feedback was provided). These findings suggest, in line with hypothesis 2, that the efficacy of the programs depends on adherence to the program, also found in previous studies ,61. Our  in the AThe SQ4U study was subject to limitations. The first limitation is that the planning assignments and feedback moments were provided at fixed times, while the varying levels of adherence found in our study suggest that programs should perhaps provide support when the respondent needs it most . Research is needed to explore the potential additional efficacy of such an approach. Second, the cut-off point for the minimum dose sample (sample 3) is not based on empirical findings and needs to be explored in additional studies. Third, because of medical ethics guidelines, we could not prevent respondents from using additional help to quit smoking. The use of additional help, however, may interfere with the effects of the programs and may be beneficial or counterproductive. Further research is needed to explore which additional aids may have positive or negative effects. Fourth, our study had a high rate of loss to follow-up , an issue that is very common in comparable studies ,21,63,64Aside from these limitations, our SQ4U study is the first to test the efficacy of incorporating planning assignments in a Web-based computer-tailored relapse prevention program and of combining planning assignments with multiple tailored feedback moments after the quit date. The study reflected on the findings from different samples, and the results pointed out the importance of using planning strategies and tailored feedback moments after the quit date for smokers who are motivated to quit. Previous studies indicated that a lack of preparatory planning is associated with smoking relapse ,9. Our c