Knowledge translation (KT) and related terms have variously been defined as process and as products. In this paper we contribute to debates on effective KT, specifically knowledge brokering, by describing an adaptation of Program Science that aligns with the real-world of public health activities.We describe an adaptation of the Program Science framework to our knowledge translation and brokering planning and projects at the National Collaborating Centre for Infectious Diseases. The systematic approach allows for layering of knowledge year to year and translating knowledge from one infectious disease content area to another. Using a recent forum on syphilis outbreaks as an example, we also demonstrate the value of using Program Science to shape the design and delivery of the knowledge brokering event.The use of scientific knowledge to improve public health program design, implementation and evaluation forms the basis for the program science framework. Providing the right public health information to the right audience at the right time can foster long-term outcomes of networks and new partnerships which can potentially improve delivery of public health services. Knowledis , nor on broker, creating opportunities for exchange of evidence that lead to integrating evidence in practice and policy [The breadth of the audiences and the thematic areas encompassing infectious diseases are vast, with priorities shifting as the epidemiology of infectious diseases changes globally and locally. To overcome these challenges a variety of methods are needed to facilitate mobilization of evidence and knowledge across the “know-do gap”  in diffed policy , 7, 8.Developing and sustaining inter-connected knowledge products is key for achieving longer term knowledge translation objectives and supporting the advancement of public health. Given often competing priorities, advancing knowledge translation for public health requires forward-looking and coordinated choices. To ensure that NCCID addresses priority areas, meets the needs of stakeholders and audiences, and remains nimble and responsive to emerging infectious diseases, we have adapted and applied a Program Science framework to shape our five-year plan and our annual activities, ensuring continued engagement of stakeholders, enduring relationship with our key audiences in public health and re-affirming our credibility within our thematic areas.Program science is the systematic application of theoretical and empirical knowledge to optimize the scale, quality and impact of public health programs , 10. It There are three domains to program science which mirror a program cycle: i) strategic planning; ii) program implementation; and iii) program management and evaluation Table . The strWork led by the National Agency for the Control of AIDS (NACA) in Nigeria provides an example of a Program Science framework applied at the country level. NACA conducted epidemic appraisals – including geographic mapping and enumeration of key populations most at risk for HIV and assessing relevant behavioural patterns -- to understand local heterogeneity in the HIV epidemic. The results of these appraisals were used to develop state-specific plans, with detailed program monitoring, for HIV prevention , 13.To address complex public health questions such as HIV, public health program managers and policy makers require timely evidence to inform their decision-making. NCCID adapted and applied the Program Science framework as an internal operational approach with the goal of using a systematic approach to the development and implementation of our knowledge brokering work plans.Each year we develop activities and knowledge products for brokering with public health audiences within the Program Science framework domains: strategic planning related to the drivers of infectious diseases and identification of where burden of disease is a priority; public health responses and interventions; and monitoring and evaluation programs and policies Table . This alwithin a topic area using an example from work on syphilis.In the course of adapting Program Science to our work planning, it became evident that knowledge brokering activities do not or should not always be located in one domain over another, but the framework nevertheless serves as a guide. In the following section, we illustrate this application of program science Syphilis has re-emerged from a state of very low incidence in North America to 23,872 syphilis cases reported in 2015  in the United States . Men whostrategic planning (domain one). Participants then presented cases of their program implementation responses (domain two) – promising practices as well as efforts that were not deemed successful. Program monitoring and evaluation (domain three) were not emphasized in the course of the day-and-a-half meeting, although new results from mathematical modelling of syphilis in Manitoba suggests the value of targeting urban-dwelling individuals at risk for syphilis reinfections and can inform near-future strategic planning and subsequent program interventions, demonstrating the iterative nature of program science.Responding to requests from networks of practitioners and programmers across Canada, NCCID planned an event in the fall of 2016 to provide a broader perspective of the changing epidemiology, bringing together both urban and northern and rural public health personnel . In consNCCID’s report and analysis of the meeting (unpublished) is a summary of interventions that have been tried including those with limited effect and those that show some promise, with an analysis of contextual barriers and enablers related to these interventions. Commonalities for the northern and urban syphilis epidemics were identified, including the need to strengthen sexual health promotion and inclusive access to health services and de-emphasize “risky” sexual activity. Different interventions were also discussed, as in the priority of addressing sexual and gender-based violence in arctic and rural communities, in comparison to discussions of successful use of social media apps for urban male communities.NCCID staff did not use the syphilis event to explicitly engage participants in an exploration of Program Science. However, we found that organizing our thinking within the framework as we prepared for the event, and in communicating the results after the event, clarified where there are knowledge gaps and opportunities for further knowledge brokering in this topic area . NCCID’s role in creating a space for conversation between urban and northern public health players also sparked a new network of medical officers of health in rural, remote and northern Canada which will generate new occasions for translating lessons to other priority areas in communicable diseases. In our assessment, these outcomes signify real-world and pragmatic examples of closing the “know-do” gap, while at the same time fitting knowledge brokering with public health information and program cycles; outcomes which have been seen by Urquart et al.  but whicThe use of scientific knowledge to improve public health program design, implementation and evaluation forms the basis for the program science framework. Providing the right public health information to the right audience at the right time has the potential to improve delivery of public health services.Knowledge translation and brokering of evidence to support decision-making in public health requires assessment of the knowledge itself, understanding of the audiences and continued engagement. Program Science provides a useful framework to guide knowledge translation work for infectious diseases and public health and allows for the iterative process that is critical for success and responsiveness of public health programs. In this paper, we describe the adaptation and application of the Program Science framework to NCCID’s work in knowledge brokering. This systematic approach allows for layering of knowledge year to year and translating knowledge from one infectious disease content area to another. The progress of projects within the thematic areas, covering the domains of program science allows for incorporation of guidance from the audience, adaptation to changing needs, and the inclusion of evolving best practices in the choice of tools and knowledge products that are provided by the knowledge broker. These allow for continued relevance and ongoing partnerships to feed into a dynamic work plan. We will monitor whether the Program Science framework facilitates approaches to the three domains that transcend different topics.


Recent advances in mobile technologies have created new opportunities to reach broadly into populations that are vulnerable to health disparities. However, mobile health  strategies could paradoxically increase health disparities, if low socioeconomic status individuals lack the technical or literacy skills needed to navigate mHealth programs.The aim of this study was to determine whether patients from vulnerable populations could successfully navigate and complete an mHealth patient decision aid.We analyzed usability data from a randomized controlled trial of an iPad program designed to promote colorectal cancer (CRC) screening. The trial was conducted in six primary care practices and enrolled 450 patients, aged 50-74 years, who were due for CRC screening. The iPad program included a self-survey and randomly displayed either a screening decision aid or a video about diet and exercise. We measured participant ability to complete the program without assistance and participant-rated program usability.P=.006). Only 6.9% (31/450) of the participants needed some assistance to complete the program. In multivariable logistic regression, being a member of a vulnerable population was not associated with needing assistance. Only older age, less use of text messaging , and lack of Internet use predicted needing assistance.Two-thirds of the participants (305/450) were members of a vulnerable population . Over 92% (417/450) of the participants rated the program highly on all three usability items (90.8% for vulnerable participants vs 96.6% for nonvulnerable participants, Individuals who are vulnerable to health disparities can successfully use well-designed mHealth programs. Future research should investigate whether mHealth interventions can reduce health disparities. Income, education, and race are powerful social determinants of health. Low socioeconomic status (SES) individuals and underrepresented minorities are at heightened risk for a variety of poor health outcomes, including shorter life expectancy and increased incidence of cancer and chronic diseases -4. One pRecent advances in mobile technologies have created new opportunities to reach broadly into vulnerable populations, potentially decreasing informational barriers. Over the last 10 years, the growing ownership of cell phones, smartphones, and tablet devices has shrunk the digital divide. Over 90% of Americans own a cell phone with no significant differences seen by income, education, or race . AdditioMany health care professionals are now using tablets or other mobile devices to assist patient care delivery ,9, and tColorectal cancer (CRC) is a source of health disparities. Individuals who are less educated, poorer, and members of minority populations are less likely to be screened for CRC and consequently, more likely to develop and die from CRC ,13-15. TIf members of vulnerable populations experience greater difficulty using our mHealth program, our intervention could increase, rather than decrease, CRC-related health disparities. Indeed, prior studies found that members of vulnerable populations frequently encounter difficulties using Web-based or mHealth apps ,17. HoweWe designed a user-friendly mHealth iPad program for use by older individuals, many of whom we assumed would have little prior technology experience. Because over one-third of Americans have limited literacy skills, we also assumed many users would have reading difficulties . We chosOur program, called mPATH , begins with a self-administered survey to collect basic health information. Each screen displays a single question with large intuitive response buttons, as recommended by others  19,24].,24.19,24A team of experts in mobile app development, health literacy, and CRC screening developed the prototype, which was then refined based on pilot testing with a convenience sample of 40 primary care patients.We enrolled English-speaking patients scheduled for a routine medical visit at one of six community-based primary care practices affiliated with a large academic medical center in North Carolina. All six practices shared a common electronic health record. We queried the electronic health record weekly to identify patients who were between the ages of 50 and 74 years and had no evidence of current CRC screening .We excluded patients who were already scheduled for a colonoscopy, were flagged as needing an interpreter, had a personal history of CRC, or had a potentially short life expectancy . A research assistant called potentially eligible patients to inform them of the study and confirm their eligibility using a brief telephone survey. Additional study exclusion criteria assessed in the telephone eligibility survey included having a prior history of colon polyps, having a family history of CRC, and presence of rectal bleeding in the last month.Eligible patients were asked to arrive at the clinic 45-60 minutes before their scheduled medical visit to enroll in the study and complete the mPATH iPad program. All participants provided a written informed consent, and the study was approved by the Wake Forest Health Sciences Institutional Review Board (IRB# 00023575).The participants completed the mPATH program in a private location in the clinic immediately before their scheduled medical visit. They were given minimal instructions about how to use the program. The research assistant simply handed the participants the iPad, told them to touch the “start” button on the screen when they were ready to begin, and stated the narrator would walk them through the program. The research assistant then waited outside the room while the participants completed the program and instructed them to come to the door when they needed help using the program.As described previously, the mPATH program begins with a 29-item self-administered survey. Then it randomly displays either a previously validated 8.7-minute CRC screening decision aid  or a 4.3The participants self-reported their race or ethnicity, cell phone ownership, use of the Internet, and use of SMS text messaging. We assessed health literacy using the validated item, “How confident are you filling out medical forms by yourself?” with responses varying on a 5-point Likert scale from “Extremely” to “Not at all” . ConsistOur primary outcome of interest was program usability, measured objectively and subjectively. Objectively, the research assistant counted the number of times a participant came to the door to ask for assistance to complete the program. The research assistant also recorded if a caregiver was present and helped the participant use the program. We measured the participants’ subjective rating of the program using three items from the System Usability Scale  and an additional adjective rating of the overall user-friendliness  .This study was designed to assess the impact of mPATH on 6-month CRC screening rates. The participants were randomly assigned with equal probability to receive within the mPATH program either the CRC screening decision aid or the diet and exercise video. A total sample size of 450 participants was required to detect a 12% absolute difference in screening rates between the two groups, with 80% power at the 5% two-sided level of significance assuming a 20% screening rate in the control group. The participants are still being followed for the primary objective; in this paper we review the baseline data associated with the usability of the mPATH program.The participants were classified as being a member of a vulnerable population if they met the criteria described above. Time spent completing the mPATH program was calculated in minutes based on timestamps recorded by the iPad when the program began and when it ended. Chi-square tests (or Fisher exact tests) were used to assess the differences in user-friendliness and the usability scale items between those participants who were and were not classified as vulnerable. Needing assistance was dichotomized as none versus some, and chi-square tests were used to assess the association of this measure with demographic variables, health literacy, and technology use.P values < .05 were considered significant.Logistic regression was used to determine whether being a member of a vulnerable population was associated with needing assistance after adjusting for other factors. Covariates included age, gender, owning a cell phone, Internet use, and frequency of texting. Separate logistic models included the components used to define vulnerability. To create more parsimonious models, we used a backward stepping algorithm removing any covariate that was not significant at a level < .20. All analyses were done using SAS, version 9.3 ; Between June 2014 and May 2016, we enrolled 450 participants, all of whom completed the mPATH iPad program. Participant demographics are displayed in P=.15).The participants rated the overall user-friendliness of mPATH highly. Over 97% of both vulnerable and nonvulnerable participants rated the user-friendliness as “excellent” or “good” . SimilarP<.001).The mean (standard deviation) time to complete the mPATH program was 22.8 (5.2) minutes for the CRC screening version (which included a few more survey items and a longer video), and 17.6 (4.6) minutes for the control version. Overall, adjusting for arm, the vulnerable group averaged 3.9 (0.46) minutes longer in completing the mPATH program (Only 6.9% (31/450) of the participants needed some assistance to complete the program . The main reason that participants needed assistance was forgetting to touch the “Next” button to advance the program. A few participants became confused when they kept their finger too long on a phrase, which triggered the iPad to highlight the text. We prevented future occurrences of this user error by disabling the “copy and paste” native functionality of the iPad.P<.01). Factors associated with needing assistance to complete the program in bivariate analyses included limited health literacy, low household income, older age, and less technology use  of vulnerable participants needed some assistance compared with 1.4% (2/145) of nonvulnerable participants (logy use . Race waP=.11). As vulnerable population was not significant, we looked at models that included the individual components that defined it . None of these components were statistically significant; only older age, less use of SMS text messaging, and lack of Internet use remained associated with needing assistance in both the full and reduced models ; usability in specific subpopulations could differ from what we observed. Finally, to decrease participant response burden, we included only a subset of items from the System Usability Scale.Future studies should investigate which program features are most important for usability, and whether mHealth interventions can reduce health disparities. Results from our study examining the impact of mPATH on receipt of CRC screening will be forthcoming.In summary, we found that members of vulnerable populations could successfully use an mHealth program designed for individuals with limited literacy and technology skills. After controlling for other factors, literacy level and income did not predict usability. Race did not predict usability even in unadjusted analyses. These results indicate that properly designed mHealth interventions can reach broadly across populations.


Mw 8.8 megathrust earthquake that occurred on 27 February 2010 offshore the Maule region of central Chile triggered a destructive tsunami. Whether the earthquake rupture extended to the shallow part of the plate boundary near the trench remains controversial. The up-dip limit of rupture during large subduction zone earthquakes has important implications for tsunami generation and for the rheological behavior of the sedimentary prism in accretionary margins. However, in general, the slip models derived from tsunami wave modeling and seismological data are poorly constrained by direct seafloor geodetic observations. We difference swath bathymetric data acquired across the trench in 2008, 2011 and 2012 and find ~3–5 m of uplift of the seafloor landward of the deformation front, at the eastern edge of the trench. Modeling suggests this is compatible with slip extending seaward, at least, to within ~6 km of the deformation front. After the Mw 9.0 Tohoku-oki earthquake, this result for the Maule earthquake represents only the second time that repeated bathymetric data has been used to detect the deformation following megathrust earthquakes, providing methodological guidelines for this relatively inexpensive way of obtaining seafloor geodetic data across subduction zone.The  Large slip near the Japanese trench has been reported for the 2011 Mw9.0 Tohoku earthquake by inversion of seismological data and tsunami waveforms12The Maule earthquake occurred in a region of the Nazca-South America subduction zone where the trench is filled by ~1.5 s (~2 km) of sediment and the accretionary prism is 40–50 km wide11Multi-beam bathymetric data were collected in 2008 as part of a geophysical survey along a track crossing the subsequent region of maximum uplift ILOCA, . This trThe elevation differences were then divided into a sequence of segments along the ILOCA profile. Within each segment, a histogram was formed and a scaled T-student probability density function was used to calculate the mean elevation and its variance  and vertical (uz) displacements of the post-earthquake data along profile A-A’6ertainty , probablertainty , which certainty .et al.Our results is consistent with the inference of Yue In order to define the properties of the interplate boundary near the trench, it is important to investigate if the observed uplift was co-seismic or whether it can represent post-seismic stress relaxation. The observed seafloor deformation is potentially the combination of coseismic motion, afterslip, visco-elastic relaxation and fault relocking. After-slip occurs when the rupture zone slips in the same direction as the main event and decays rapidly over time252327et al.et al.et al.2631Due to the scarcity of offshore observations, no observations of the post-seismic deformation in the up-dip zone of the megathrust earthquakes are available for most events. For the Maule earthquake, Bedford The evidence discussed above suggests that most of the deformation that we observe was generated during the Maule earthquake. However, it is difficult to ensure that the deformation reached the zone near the trench during the co-seismic rupture, because the post-seismic bathymetry was acquired several months after the earthquake. Then, the observed deformation for Maule earthquake could be generated during the co-seismic rupture but also in a short period after the earthquake (clearly before 1 year after the main event).Why the rupture propagated updip of the normal seismogenic zone is not fully understood. In general, one would expect the accretionary prism adjacent to the deformation front, which is thought to be comprised of poorly consolidated material, to have a velocity strengthening behavior. However, if the base of the accretionary prism is in a conditionally stable frictional regime, velocity weakening behavior can be induced by high rupture velocity due to an earthquake nucleated in a deeper unstable zoneThe outermost portion of the wedge  is comprised of poorly consolidated material that should have a velocity strengthening behavior. In that case, the friction on the plate boundary increases during the earthquake, which stopped the rupture propagation and generated co-seismic compressional elastic (or brittle) deformation inside the wedgeet al.The result indicates that slip can occur near the trench in accretionary margins as well as in an erosive margin, like the northern Japanese subduction zone. Our conclusion that slips extended, at least, to ~6 km landward of the deformation front along profile A-A’ is consistent with the inference of Yue Due to the high costs of operation, only few stations for seafloor GPS-Acoustic observations can be installed to study large portions of subduction zones. Therefore, the repeating bathymetry method represents a complementary technique to cover large portions of the margin with enough resolution to study the seafloor deformation during the seismic events, at least for large earthquakes. For this reason, our result highlights the importance of systematic acquisition of high-quality bathymetric data along seismic gaps in convergent margins to compare with post-earthquake measurements, in order to have a better understanding of the co-seismic and post-seismic seafloor deformation.Two years before the Maule earthquake , the ILOCA track was acquired by the R/V RSS James Cook under the project SBF 574 of IFM-GEOMAR. After the earthquake, the same bathymetric track was acquired in March 2011 and in May 2012 by the R/V Melville during the expeditions of the NSF projects Chilean Earthquake Rupture Survey and ChilePEPPER. Before and after the main event, there are pairs of tracks that were navigated in opposite directions (NW-SE and SE-NW), which after joint processing of the data, allows to decrease the pitch and roll effects on the resulting processed bathymetry. In 2008, the ILOCA track was surveyed three times using a Kongsberg EM120 12 kHz multibeam echo; twice in the direction from southeast to northwest (seaward) and once from northwest to southeast (landward). The vessel speed was nominally 4–6 kts for all three surveys. In 2011, using the EM122 multibeam echo sounder, two swaths were collected over this same track; one going seaward and one landward at a nominal speed of 12 kts. In 2012, the EM122 aboard R/V Melville was again used to collect one swath in the seaward direction at nominally 12 kts. The processing of the multibeam bathymetric data was performed using the MB-System software package. Manipulations of the bathymetric grids were implemented with MATLAB routines. Data visualizations were made by using OasisMontaj and GMT software.°. The individual pings were then manually edited in order to flag any beams that were erroneous, but not detected using the automatic method. All data were then tide corrected using the MB-System variant of the OTPS2 tide correction software, which combines a low-resolution global model with a high-resolution local model. Next, to ensure consistent calculation of seafloor depths a composite sound speed structure was compiled along the ILOCA track. Four expendable bathythermographs (XBT) profiles collected along the track in 2012 were combined with a surface to seafloor conductivity, temperature and depth (CTD) profile collected midway along the track in 2011  of the median depth while across track beams were flagged if they were a distance less than 1% or more than 20% of the median depth from adjacent beams (50 m/1000 m in 5000 m depth). Additionally, beams were automatically flagged if the across track beam to beam angle exceeded 45 in 2011 . FinallyAs was mentioned in the main text, the direct difference between the bathymetry, before and after the earthquake, shows that only a central band of the data has physical meaning. An increase of errors from the center of the track to the borders is inherent to the multibeam technique. In particular, an error in the beam angle  generates a minimum error in the calculated depth at the center of the track, but its effects increase rapidly in function to the beam anglez) observed in that segment . The result of this L1 norm minimization shows a clear uplift of 3 m during the earthquake, landward from the deformation front and an almost null vertical deformation seaward from the deformation front. Considering that this technique is highly dependent on uz variations  and a vertical displacement of the same seafloor shape, i.e, a translation without internal deformation. Therefore, if we know these horizontal and vertical displacements, we can restore the bathymetry acquired after the earthquake to its original position (before the earthquake), and then, to compare this “corrected” bathymetry with the bathymetry acquired before the earthquake. We can use, for instance, a L1 norm to compare the bathymetries obtaining a value near zero if the horizontal and vertical displacement applied are corrects. Based on this simple criterion, we calculated both displacement values .Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


In this study, we developed a time-resolved fluoroimmunoassay (TRFIA) system for simultaneous quantification of aCL IgG and IgM. A 96-well microtiter plate precoated with the complex of cardiolipin from bovine heart and bovine β2GPI was incubated with the anticardiolipin IgG and IgM standard substance or serum, and the conjugate of Eu3+-labeled anti-human IgG and Sm3+-labeled anti-human IgM was pipetted to the wells to form a tipical double-antibody-sandwich immunoreactions; finally the fluorescent intensity of Eu3+ and Sm3+ was detected to reflect the quantity of anticardiolipin IgG and IgM. This assay showed a good relationship between fluorescence intensities and the concentration of anticardiolipin antibody(aCL) IgG and IgM, with a low-end sensitivity of 0.1 U/ml for IgG and 0.1 U/ml for IgM, respectively. The intra- and inter-assay coefficients of variation (CV) of the calibrators was 3.0% and 4.51% for IgG, and 2.76% and 4.45% for IgM. The average recovery was 100.38% for aCL IgG and 100.45% for aCL IgM. For serum samples, the results of our method showed a good correlation with those obtained with ELISA kit. Simultaneous detection of aCL-IgG and aCL-IgM in the same reaction well can optimize assay performance by avoiding potential influence of different reaction conditions-timing, and well-to-well difference in concentration and characteristics of cardiolipin antigen. The results of a combo aCL-IgG and aCL-IgM assay for the same sample are more consistent and more reliable. This dual-label time-resolved fluoroimmunoassay is sensitive for detecting aCL IgG and IgM across a wide concentration range with stable reagents and may assist in the clinical diagnosis of antiphospholipid syndrome.The autoimmune disease antiphospholipid syndrome (APS) is characterized by the presence of anticardiolipin antibodies (aCL), along with anti-β In 1983, Harris et al. developed the first aCL test [Anticardiolipin antibodies (aCL) are autoimmune antibodies that target the negatively charged cardiolipin on the platelet and the cytomembrane of the endotheliocyte. They are the main antiphospholipid antibodies (aPL), along with anti-βaCL test  includesaCL test . Thus, iaCL test –8. Howev3+, Sm3+, Dy3+ and Tb3+) as tracers, TRFIA distinguishes itself by its wide detection range, high sensitivity (10−18 mol/ L), and less susceptibility to matrix interference, and has been well accepted as an ideal quantitative detection method for many analyses of clinical and biological importance. Moreover, the features that the detection windows and testing wavelengths of the four lanthanides were clearly distinguishable from each other makes it possible to be exploited in TRFIA to analyze even four analyses at a time. Of all the 15 lanthanides, Eu3+ is the most commonly used label in time-resolved fluorometry-based analysis because of its higher fluorescence yield and lower background than other lanthanide complexes. Sm3+ has been suggested as counterpart to Eu3+ in a dual-label system because it has equal excitation wavelengths (340nm) to Eu3+ as well as that it can be measured in the enhancement solution (β-NTA contained) optimized for Eu3+ detection [3+ and Tb3+ are another suggested pair in dual-label systems, but the enhancement solution optimized for Eu3+ detection cannot be used for Tb3+ since the later requires fluorinated aliphatic β-diketone for simultaneous detection [3+ and Sm3+ as tracers in this study. Assay characteristics were determined and correlation and comparison to ELISA were performed. Clinical specificity was investigated with 510 samples from patients with other autoimmune manifistations. First, aCL antigen-the complex of cardiolipin from bovin heart and bovine β2GPI was precoated on the microtiter plate; second, the standard substance or serum was added into the wells of plate to incubate with aCL antigen; then, we pipetted conjugate of Eu3+-labeled anti-human IgG and Sm3+-labeled anti-human IgM to the wells to form a tipical double-antibody-sandwich immunoreactions; last, we added enhancement solution to each well and detected the fluorescent intensity using auto DELFIA 1235 TRFIA analyzer. Simultaneously detection for aCL-IgG and aCL-IgM in the same reaction well can avoid the influence brought out by different reaction conditions, different reaction duration and different concentration and characteristics of cardiolipin antigen in ELISA kit. So, the detection results of aCL-IgG and aCL-IgM for the same sample are more consistent and more reliable.TRFIA is a novel non-isotopic labeling technology developed in 1980s –12. Havietection . Eu3+ anetection , albeit etection . With reetection  and the Solid-phase antigen (the complex of cardiolipin from bovine heart plus bovine β2GPI), diethylenetriamine tetraacetic acid (DTTA), monoclonal rabbit anti-human IgM and IgG were purchased from Sigma . Cardiolipin solution used in this study was purchased from Sigma , which originated from bovin heart. 96-well polystyrene microtiter plates were obtained from Nunc International . Bovine serum albumin (BSA) were supplied by the Institute of Biological Products Department of Health . Eu3+- and Sm3+- labeling kits were purchased from PE company . PD-10 column and Sepharose CL-6B column (1×40cm) were from the Pharmacia Company . Enzyme-linked immunosorbent assay (ELISA) kits for aCL-IgG and aCL-IgM detection were purchased from Orgentec Diagnostika Gmbh . Auto DELFIA1235 TRFIA analyzer was supplied by Perkin-Elmer Life and Analytical Science/Wallac Oy . All additional chemicals and reagents used were of analytical grade.2CO3-NaHCO3 (pH 8.5) and 0.155 mol/L NaCl. Elution buffer included 50 mmol/L Tris-HC1 (pH 7.8), 0.9% NaC1, and 0.05% NaN3. Assay buffer consisted of 50 mmol/L Tris-HCl (pH 7.8), 0.9% NaC1, 0.2% BSA, 0.05% NaN3, 20 μmol/L DTPA, and 0.1% Tween-20. Washing solution was a Tris-HCl buffered saline solution (pH 7.8) which contained 0.9% NaCl, 0.2% Tween-20, and 0.05% NaN3. Enhancement solution was a 0.1 mol/L acetate-phthalate buffer (pH 3.2) that comprised of 0.1% triton X-100, 15 μmol /L β-naphthoyltriflu oroacetone (β-NTA), and 50 μmol/L tri-n-octylphosphine oxide.Labeling buffer contained 50 mmol/L Na2GPI was diluted to be coating buffer with 50 mmol/L Na2CO3-NaHCO3 buffer (pH 9.6), and 200μl coating buffer was added to each well of 96-well polystyrene microtiter plate and incubated overnight at 4°C. The coating buffer was discarded and each well was blocked with 200μl of 3g/L BSA for 2 hours on a miniorbital shaker. The blocking buffer was discarded and plates were dried under vacuum, stored at -20°C in a sealed plastic bag with desiccant until use.The complex of cardiolipin from bovine heart and bovine β3+-labeling of monoclonal rabbit anti-human IgM was performed using a Sm3+-labeling kit strictly according to the manufacture’s instructions. Referring to the manual and previous report [2CO3-NaHCO3) containing 0.155mol/L NaCl. Then the protein peak fractions were collected and concentrated to 2g/L. 500μl of the obtained purified second antibody was mixed with 0.2mg lyophilized Sm3+-DTTA, and stirred vigorously for 20 h at 25°C. The resulting mixture was then fractionated on a Sepharose CL-6B column (1×40cm)  and eluted with 80 mmol/L Tris-HCl buffer (pH 7.8). The absorbance values of the eluate were measured at 280 nm to obtain protein peak concentrations. After purification, added equal amount of AR glycerin before aliquoted and stored at -20°C until use.Sms report –19, the 3+chelates using a Eu3+-labeling kit and the procedure was the same as the above-mentioned IgM labeling procedure.Monoclonal rabbit anti-human IgG was labeled with Eu52 serum specimens from patients with APS were collected for the correlation study. 50 serum samples from healthy volunteers referred to our hospital and 510 serum samples from patients with other auto-immune disease  were collected to test for clinical specificity. All serum specimens were separated at 2360g for 20min at room temperature after collection and stored at -70°C for further analysis. This specimen collection was approved by the Affiliated Wuxi People’s Hospital of Nanjing Medical University. All participants provided written informed consent to participate in this study.3+-labeled anti-human IgG and Sm3+-labeled anti-human IgM conjugates are added into each well of the plate, incubated with shaking for 30min at 25°C. After incubation, a second washing step removes unbound conjugate. Next an enhancement solution is pipetted to each well and shaken for 5 min before reading the fluorescent intensity. Calibration curves were plotted and concentrations of aCL IgG and IgM in samples were determined using Multicalc software program. All procedures were automatically performed by auto DELFIA 1235 TRFIA analyzer with the process designed by our laboratory  in the patient sample bind to the antigen coated on the surface of the reaction wells. After incubation with shaking for 30 min at 25°C, a washing step removes unbound and non-specifically bound serum or plasma components. Euboratory .These ELISAs are indirect enzyme linked immune assay. Specific antibodies (aCL IgM or IgG) in the patient sample bind to the antigen (purified cardiolipin and beta-2-glycoprotien I) coated on the surface of the reaction wells. After incubation, a washing step removes unbound and non-specifically bound serum or plasma components. Next, the enzyme conjugate (HRP-labeled anti-human IgG or HRP-labeled anti-human IgM) is added and binds to the immobilized antibody-antigen-complexes. After incubation, a second washing step removes unbound enzyme conjugate. Then the substrate solution is added and the bound enzyme conjugate hydrolyses the substrate forming a blue coloured product. Addition of an acid stops the reaction generating a yellow end-product. The intensity of the yellow color correlates with the concentration of the antibody-antigen-complex and can be measured photometrically at 450 nm.Controls were made from three pools of mixed serum specimens with high, intermediate and low concentrations of aCL IgG and IgM were aliquoted and stored at -20°C. Intra- assay precision was determined with 25 reps in one assay testing all three controls; inter-assay precision was determined by running each conrol in duplicate for ten runs. The linear range of the assay was determined by testing serial dilutions of samples from patients with the highest aCL IgG and IgM concentration.n = 20) of the zero standard plus 2SD in the calibration curve.The sensitivity of the assay was calculated from the mean fluorescent counts  respectively and then compared with values obtained with the one stored in routine conditions.Data were analyzed using the SPSS 13.0 software. Regression analysis and analysis of variance were used to calculate correlation and to test linearity, respectively. Inter-assay and intra-assay variation was calculated using the coefficient of variation.3+-anti-human IgG antibody was purified by Sepharose CL-6B column and the first eluent peak was collected. According to the Eu3+ standard in the labeling kit as a reference, the first peak contained 77.4 μmol/L of Eu3+ and 9.5 μmol/L of protein, so each anti-human IgG may couple 8.1 Eu3+ ions on average. The labeling rate of Sm3+-anti-human IgM antibody was calculated in the same way. On average there may 7.9 Sm3+ ions per each anti-human IgM antibody according to its first peak obtained 77.4μmol/L of Sm3+ and 10.3 μmol/L of antibody.Eu2 for that of aCL IgG and Y = 2.2889+0.71707X+0.0323X2 for the calibration curve of aCL IgM, where X is the concentration of aCL IgG (U/ml) or aCL IgM (U/ml), and Y is fluorescence intensity.As showed in The precision of the assay was also analyzed by measuring three pools of mixed serum specimens with high, intermediate and low concentration of aCL IgM and IgG 25 times in one series (intra-assay) and in duplicate in ten different series. As shown in Recovery with the dual-label TRFIA was determined using dilutions of three specimens with known concentrations of aCL IgG and IgM. The observed values were divided by the expected values to calculate the coefficient of recovery. As shown in Concentration results of 52 serum samples determined by dual-label assay were compared with those obtained with ELISA kit. The scatterplots illustrated that the dual-label assay correlated well with ELISA , and theDiluted a specimen with strong-positive aCL IgG from 4792.32 U/ml to 0.585 U/ml, and detected the serial dilutions with the established dual-label TRFIA as well as ELISA. The curve of detectable range of the two methods was showed in The established aCL IgG/IgM dual-label TRFIA immunoassay was then applied to analyze the aCL IgG and IgM levels of serum specimens from 50 healthy volunteers and only one case of false-positive was produced, that is, the specificity of the assay was 98%. 510 serum specimens from patients with scleroderma, nephrotic syndrome, ankylosing spondylitis, cerebral infarction, lupus nephritis, Sjogren syndrome, systemic lupus erythematosus, rheumatoid arthritis were also collected and tested. The stability of the dual-label TRFIA kit and the commercial ELISA kits was investigated. After 7 days at 37°C, the stressed kit performance was compared to kits stored under normal conditions. There was a 15.8% decrease in the signal for aCL IgG and 14.7% decrease for aCL IgM. The ELISA kits demonstrated a greater decrease, 33.9% for aCL IgG and 37.6% for aCL IgM. In addition, we observed that the counts of fluorescent intensity obtained by the dual-label TRFIA kit was very stable even after overnight storage. The ODs obtained with the commercial ELISA one decreased quickly over time.Additionally, because of its independence of the disintegration of the labeling compound, the stability of the aCL IgG/IgM dual-label TRFIA kits were substantially better than the ELISA ones.As shown in A new dual assay for anti-cardiolipin IgG and IgM has been developed utilizing a time resolved fluoroimmunoassay. The dual assay has good precision, a low analytical sensitivity, a good dilution recovery, a wide detection range and good correlation to an established method. Clinical specificity is 98% when evaluated against normal and greater than 90% when evaluated with samples from other disease states. The reagents are stable to heat stress and the fluorescence is stable over time. Compared to the commercial ELISA kits, the new assay had a larger assay range enabling better detection of low concentration samples as well as quantitation of high samples without further dilution and assay. Simultaneous detection of both aCL IgG and aCL IgM, as compared to two separate ELISAs, eliminates the possibility of differing reaction times and conditions, and possible sample instability. Time and labor are saved with running only one assay and not two. This new, dual TRFIA for anti-cardiolipin IgG and IgM has demonstrated good analytical and clinical performance and will enable the laboratory to provide analysis of these analytes in a routine manner.


Stand Up Australia intervention was designed to reduce prolonged sitting in the workplace by addressing influences at multiple-levels, including the organisation, the environment, and the individual. Intervention success has been achieved within the context of randomised controlled trials, where research staff deliver several of the key intervention components. This study describes the initial step in the multi-phase process of scaling up the Stand Up Australia intervention for workplace translation.Too much sitting is now recognised as a common risk factor for several health outcomes, with the workplace identified as a key setting in which to address prolonged sitting time. The Stand Up Australia were adapted in collaboration with funding partner Workplace Health and Safety Queensland to ensure consistency and compatibility with existing government frameworks and resources. In recognition of the key role of workplace champions in facilitating workplace health promotion programs, the BeUpstanding program™ is designed to be delivered through a stand-alone, free, website-based toolkit using a ‘train the champion’ approach.A research-government partnership was critical in funding and informing the prototype for the scaled up BeUpstanding program™. Evidence, protocols and materials from The BeUpstanding program™ was influenced by the increasing recognition of prolonged sitting as an emerging health issue as well as industry demand. The research-government partnership was critical in informing and resourcing the development of the scaled-up program. Recent estimates suggest that, on average, 75% of the workday is spent in this posture, with much of this time accrued in prolonged unbroken bouts of 30 minutes or more One of the interventions that has effectively reduced workplace sitting is the Stand Up Australia intervention 2.The Stand Up Australia program of research aims to understand the benefits of reducing prolonged sitting in the workplace. This program, initiated in 2009, spans across epidemiological Stand Up VictoriaIn 2011, funding was awarded from the Australian National Health and Medical Research Council (APP#1002706) and VicHealth to evaluate the Stand Up Australia intervention. Following a successful pilot A key theme arising from the multi-method assessment of the various Stand Up Australia evaluations 3.In December 2014, the findings from the Stand Up Australia body of work were presented at the annual Australian Workplace Health Promotion conference . Following this presentation, the research team were approached by a representative from Workplace Health and Safety Queensland (WHSQ) Healthy Workers Initiative (HWI). Through the auspices of the Healthier. Happier. Workplaces Initiative, WHSQ were interested in sourcing an evidence based workplace program to address excessive occupational sitting that could be made widely available to workplaces to improve occupational health. The objective of WHSQ is to build the capacity of workplaces to plan, implement and evaluate workplace health and wellbeing programs, manage chronic disease risk factors, as well as address Hazardous Manual Tasks risk factors. As such, the proposed adoption of a program based on the Stand Up Australia intervention directly aligned with WHSQ's objective.Funding from the Healthier, Happier Workplace Grant Program was successfully obtained through WHSQ in February 2015. Such rapid funding availability, outside the normal grant cycle , was a critical element in rapidly progressing the translation process. In addition to the dedicated funding, additional in-kind support  was provided by WHSQ staff, through the Healthy Worker Inititiave Unit and Ergonomics Unit. Both of these areas had identified excessive occupational sitting as a priority area.4.As part of the process for widescale uptake by workplaces, and to differentiate the program from the research intervention, the Stand Up Australia intervention was rebadged and redeveloped as the BeUpstanding program™. While the core elements of the original intervention remained, several adaptions (described below) were necessary to ensure feasibility and consistency with the best practice Work Health and Well-being framework. These were discussed and agreed upon in a series of meetings with the government team, which included a specialist ergonomist, project manager specialising in workplace health and well-being, and senior leaders.4.1.One of the primary requirements was for the program to be able to be delivered with no/low cost for workplaces. Therefore, one of the key adaptions was the transferral of the administration of the program delivery and evaluation from the research team to a workplace champion (identified by the workplace). To facilitate this, a comprehensive, stand-alone, free toolkit was developed to provide workplace champions with a guide and resources to facilitate organisational buy in, and support delivery and evaluation of the program in their workplace. An online web-based format for the toolkit was chosen as it allowed for: increased reach of the program; rapid communication and evidence updates; integration of multi-media platforms; and, was a cost-effective mode of delivery. The toolkit follows a step-by-step process and uses a ‘train the champion’ approach.4.2.The materials and protocols from Stand Up Australia, alongside other evidence based research and health promotion materials and models, were used to inform the toolkit materials. Materials were adapted to follow five steps, consistent with existing guides Tools to support each of these steps  were developed. Other key adaptions from the original materials included the modification of wording to be less researcher oriented, more consumer friendly and understandable at the general population level, and the increased use of graphics to convey the intervention messages and goals of the program. Videos  were created as a tool for promoting buy in, raising awareness of the program and the key messages of stand up, sit less, move more, and to promote staff discussion (facilitated by the workplace champion). The evaluation framework used in the precursor trial was shortened in length and scope to be feasible for implementation without researcher input, resulting in the creation of an online, self-completion questionnaire. In addition, a component addressing the business case for reducing sitting in the workplace (not required previously in the research context), was developed. This component, which was based on the business case fact sheet developed by Comcare in 2012 [31], provides background evidence about the impacts of too much sitting, the return on investment for workplaces for supporting a healthy workplace, and suggests cost effective solutions to reduce the risks associated with too much sitting.5.This paper described the first phase of the translation of an evidence-based intervention – Stand Up Australia – into practice. Key elements for translation included: development of a research-government partnership leading to funding for, and collaborative adaption of, the original program for widescale uptake; and, the integration of program buy in, delivery and evaluation systems within the online toolkit. In subsequent phases, pilot testing in a range of workplaces will provide key insights into the success of initial adaptations with regard to feasibility of implementation, as well the effectiveness of the program on awareness, culture, and behaviour change in different work environments and job roles. This feedback and evaluation will inform Phase 3 (toolkit optimisation). This staged process of translation allows for appropriate time and testing, with further adaptations informed by the practice based evidence generated. The online format is particularly well-suited for this ongoing and evidence-driven optimisation. In conclusion, strong research-government partnerships and a supportive funding climate were critical elements for achieving the first stage of translation of the evidence-based Stand Up Australia program. Maintaining and expanding these partnerships will be vital to ensure success through the next stages of translation.


An interim evaluation was conducted to understand the implementation quality of the Tier 1 Program (Secondary 2 Curriculum) of the Project P.A.T.H.S.  in the Experimental Implementation Phase. Twenty-five schools were randomly selected to participate in personal and/or telephone interviews to provide information on the implementation details of the program and perceived attributes of the worker-support scheme . Results showed that a majority of the workers perceived that the students had positive responses to the program and the program was helpful to the students. They also identified several good aspects in the program and the Co-Walker Scheme, albeit expressing some negative comments on the program design and difficulties in the implementation process. In conjunction with other findings reported previously, the present findings suggest that the Tier 1 Program is well received by different stakeholders and it promotes the positive development of secondary school students in Hong Kong.


This paper reports a qualitative evaluation study conducted to explore the perceptions of students who joined the Tier 1 Program of the Project P.A.T.H.S. A total of 92 students were randomly selected to participate in 10 focus groups, which provided qualitative data for the study. With specific focus on how the informants described the program, the descriptors used were primarily positive; the metaphors named by the informants that could stand for the program were basically positive. Program participants also perceived the program to be beneficial in different psychosocial domains. The present study lends further support to the effectiveness of the Tier 1 Program of the Project P.A.T.H.S. in promoting holistic development in Chinese adolescents.


Agentes Polivalentes Elementares (APEs). We assessed the contribution of the program to improved care–seeking and appropriate treatment of childhood febrile illness in Nampula Province.Large scale evaluations in several settings have demonstrated that lay community health workers can be trained to provide quality case management of childhood illnesses. In 2010, Mozambique introduced the integrated community case management (iCCM) strategy to reach children in remote areas with care provided through We used a post–test quasi–experimental design with three intervention and one comparison districts to compare access and appropriateness of care for sick children in Nampula province. We carried out a household survey in the study districts to measure levels of care–seeking and treatment of childhood fever after approximately two years of full implementation of the iCCM program in the intervention districts. We also assessed consistency of care with standard case management protocols comparing children receiving care from (APEs) to those receiving care from first–level health facilities.A total of 773 children 6–59 months with fever in the last two weeks were included in the study. In iCCM served areas, APEs were the predominant source of care and treatment; 87.1%  of children 6–59 months with fever who sought care were taken first to an APE and APEs accounted for 86.2% (95% CI 79.7–92.7) of all first–line antimalarial treatments. Public health facilities were the leading source of care in comparison areas, providing care to 86.1% (95% CI 79.0–93.3) of children with fever taken for care outside the home. Timeliness of treatment was significantly better in intervention areas, where 63.9% (95% CI 54.4–73.3) of children received treatment within 24 hours of symptom onset compared to 37.5% (95% CI 31.1–43.9) in comparison areas. Children taken first to an APE were more likely to receive a rapid diagnostic test (RDT)  and to have their respiratory rate assessed  compared to children taken to health facilities . Overall, 61.3% (95% CI 51.5–71.0) of children with fever receiving care from APEs received the correct drug within 24 hours and for the correct duration compared to 26.0% (95% CI 18.2–33.9) of those receiving care from health facilities.iCCM contributed to improved timely and appropriate treatment for fever for children living far from facilities. Trained, supplied and supervised APEs provided care consistent with iCCM protocols and performed significantly better than first level facilities on most measures of adherence to case management protocols. These findings reinforce the need for comprehensive efforts to strengthen the health system in Mozambique to enable reliable support for quality of case management of childhood illness at both health facility and community levels. An estimated 5.9 million children die each year before reaching their fifth birthday; about half of these deaths are caused by infectious diseases . Among cAgentes Polivalentes Elementares (APEs) who provide iCCM services to communities located 8–25km from the nearest health facility [Mozambique is one of just 12 low–income countries to achieve its Millennium Development Goal (MDG) of reducing child mortality by two–thirds or more between 1990 and 2015 [facility ,7.Although there is global evidence that CHWs are capable of providing quality iCCM services –10, therSave the Children (SC), with funding from the Canadian International Development Agency  provided support to the Mozambican MOH for implementing iCCM from 2009 to 2013, with a focus on malaria (fever) management, the leading cause of child deaths. We present the findings of a quasi–experimental evaluation of the APE iCCM program that compares levels of care–seeking and timely and appropriate treatment coverage for fever in an intervention area with a well–supported iCCM program to levels in a comparison area where the APE iCCM program had yet to be implemented. We also compare consistency of care provided by APEs and first level health facilities with established cases management protocols.In Mozambique, community–based health services are provided through the APEs. The APE cadre was established in 1978, but services were disrupted due to the protracted civil war, which ended in 1992 . In 2010Under the revitalized program, APEs receive 18 weeks of training organized into four blocks; iCCM is covered for one week during the third block . APEs arUnidade Sanitária. Children presenting with fever or a history of fever are tested for malaria with a rapid diagnostic test. Children between 6–59 months with a positive RDT for malaria receive artemether–lumefantrine (AL) and paracetamol from the APE. A child with a negative test is given paracetamol, and referred to the first level health facility. Children 2–59 months with cough/difficult breathing are assessed for fast breathing by counting breathes for one minute using a digital timer. A child with respiratory rate above the WHO age–specific cut–off point is classified as fast–breathing pneumonia and treated with amoxicillin dispersible tablets. Children aged 2–59 months presenting with diarrhea are treated with recommended doses of ORS and zinc.Under the iCCM protocol, APEs assess children 2–59 months for general danger signs as a first step . If geneAt first level health facilities, providers follow a similar algorithm based on WHO’s Integrated Management of Childhood Illness (IMCI) protocol. According to the protocol, all children presenting with fever should be tested for malaria with an RDT and if positive, given the first–line antimalarial (AL). Fever is treated with either paracetamol in suspension or tablets. Those presenting with cough/difficult breathing should be assessed by counting breaths for one minute using a timer (or if not available a watch or mobile phone). Under MOH protocols, those with fast–breathing pneumonia receive amoxicillin or cotrimoxazole in suspension (MOH protocol was amended in early 2011 to include amoxicillin as first line treatment). Children with diarrhea should receive ORS and zinc. First level health facilities typically provide IMCI services 5 days per week (Monday to Friday) from 7:00am to 3:00pm. However, health staff live on the facility grounds so in theory, they can attend to severely ill children or those with danger signs at any time. The first level facilities are usually staffed with a medical technician (Técnico de Medicina), or/and a general nurse or MCH nurse. Both nurses and medical technicians receive 30 months training. Medicines and supplies for treatment of child illness  are meant to be provided to facilities monthly through provincial and district medical stores.Save the Children provided support for iCCM implementation, with a focus on fever management, in 10 districts in Nampula province and five districts in Gaza province from 2009 to 2013. APEs satisfied national eligibility criteria including the ability to read and write in Portuguese and complete basic arithmetic. In 2010, SC trained and equipped 319 APEs across the 15 districts to deliver iCCM services. These APEs were trained before the MOH had finalized the curriculum and manuals for the revitalized APE program, a task which was completed in October 2011. Thus, the first group of APEs trained by SC received six days of iCCM training based on training modules developed by SC together with the MOH. The training included a mix of classroom exercises and clinical practical sessions to provide the necessary knowledge and skills related to iCCM. Later, this iCCM module was adapted and incorporated into the larger, national APE curriculum and training package. The APEs received a week long refresher training in March 2012.Training activities were implemented using a cascade model, in which SC and MOH master trainers trained health facility staff and SC–employed district coordinators, who in turn trained the APEs At the end of the training, APEs were administered a clinical competency assessment and APEs who passed were awarded certificates upon completion of the training and provided a kit of essential drugs and supplies. The APEs kept the kit at the health post, which served as iCCM delivery site as well. The kit included: medicines specified by the national iCCM protocol including AL, amoxicillin, ORS, and zinc; respiratory timers; job aids; and a treatment register. The APEs received stipend support from Save the Children and MOH .During the project implementation period, SC provided technical support including development and adaptation of tools, training, monitoring, and supervision. Save the Children trained MOH staff at district and health facility levels in supervision and supply chain support. APEs were supervised monthly within their communities by district and facility based MOH staff trained on iCCM protocols, monitoring and supervision. SC placed staff at district level to support and mentor the MOH staff to supervise and monitor APEs. AL, amoxicillin, and malaria RDTs were procured by SC through local suppliers approved by the MoH. The medicines procured by SC were supplemented with medicines  from the MOH system. Additionally, SC transported these medicines and supplies from the provincial capital to the districts and, in some cases, to the APEs’ reference health facility. Medicines were procured and distributed to the APEs based on number of cases treated reported by APEs.Nampula province is located in the north of Mozambique and, as of 2013, had an estimated population of more than 4.7 million. Nampula province was chosen for the endline study given that more than 90% of under–five children targeted through SC support were located within the province. We conducted a household survey in areas with iCCM services in three intervention districts  that had received SC support and one comparison district, Mossuril, where the APE revitalization and iCCM program had yet to be rolled out  and 61 158 children under five. Mossuril, the comparison district, was selected for the evaluation as it was geographically proximate to the intervention areas (located adjacent to Monapo district) and had a similar health service profile, with a total population of 119 223 with 10 government health facilities.A cross–sectional household survey was conducted in Nampula province in November 2012 after approximately two years of program implementation. The sample size of 600 households from the three intervention districts and 600 households from the comparison district was powered to detect a 20% difference in fever  treatment between intervention and comparison areas, assuming a fever prevalence of 27% and baseline treatment of 42%. Households with children aged 2–59 months were selected using a two–stage sampling procedure. In intervention districts, 30 APE catchment areas were selected with equal probability (ten per district) and in the comparison areas 30 census enumeration areas that were at least 8 km from nearest health facility (and therefore eligible for implementation of iCCM program) were sampled proportional–to–size from a listing of all eligible enumeration areas. A mapping team sketched basic maps of each selected survey cluster prior to the start of fieldwork. The maps identified boundaries of each cluster, landmarks, and buildings to allow data collection teams to locate selected households. The catchment area population of the APEs ranged from a population of 500 to 2000, located 8–25km from the nearest health facility . Any APE catchment area exceeding 300 households was broken down into smaller units of 150–200 households and the unit containing the APE health post was selected for the household listing. Within each selected cluster, all households were listed and households with children 2–59 months were identified by asking the household head whether any children in that age range were resident; from those listings, 20 households with at least one child aged 2–59 months were selected using systematic random sampling. Within each selected household, one mother or caregiver was randomly selected to be interviewed regarding recent child illness and care–seeking behaviors.The questionnaire was modeled after the UNICEF Multiple Indicator Cluster Survey (MICS) questionnaire (version 4) and included three modules: household, caregiver, and children under–five . The queData collection was led by the National Institute of Statistics  in Portuguese) with technical support from SC. Data collectors with prior experience of conducting national household surveys were recruited and trained for six days, including one day of field practice. Data collection was completed in October and November 2012 by four teams of five members each, including a team leader trained to supervise the data collectors, review completed questionnaires, and perform the household sampling. Two field coordinators from INE and two from SC monitored data collection to ensure quality control of data. Data were entered into CSPro by a team of four data entry clerks and double data entry was used to ensure quality; any data discrepancies were reconciled prior to analysis.The data were analyzed in Stata IC 11.1 . Data analysis involved calculating frequencies and cross tabulations of care seeking, coverage and consistency of care indicators .Treatment coverage: Proportion of children 6–59 months with fever in the last two weeks who received AL.Timely and appropriate treatment coverage: Proportion of children 6–59 months with fever in the last two weeks who received AL within 24 hours of onset of symptoms.Consistency of reported care with standard case management protocols: APEs vs first–line health facilities as first place of careAppropriate assessment:Respiratory rate assessment for cough or difficult breathing: proportion of children aged 2–59 months with cough and fast/difficult breathing whose respiratory rate was assessed.RDT for fever: Proportion of children aged 6–59 months presenting with fever who were administered an RDTCommunication of results:RDT result communication: Proportion of children 6–59 months presenting with fever who were administered an RDT and whose caregiver were told the results of the test.Appropriate treatment of fever:Correct medication: proportion of children 6–59 months with fever who received AL.Rationale use of antibiotics: proportion of children 6–59 months with fever only who did not receive antibiotics.Timely treatment: proportion of children 6–59 months with fever receiving AL who initiated treatment within 24 hours of onset of symptoms.Correct duration: proportion of children 6–59 months with fever receiving AL who took AL for the recommended for 3 days.Overall appropriate treatment: proportion of children 6–59 months with fever who initiated AL treatment within 24 hours and took medication for three days.Provision of first dose and follow-up of children with fever treated by an APE:First dose: proportion of children 6–59 months who received AL from APE who took first dose in presence of APE.Follow–up: proportion of children 6–59 months who received AL from APE who returned for follow–up.We applied a standard set of metrics captured in household surveys to compare levels of care–seeking and treatment coverage in intervention and comparison areas  taken first to private clinics, pharmacies, drug shops, informal care providers, or public sector hospitals were excluded from the analysis to allow direct comparison of first level facilities with APEs and sick children who were taken for subsequent care after visiting an APE of first–line government facility (n = 25) were excluded as it would not be possible to differentiate clearly what care was provided by what provider.Ethical clearance was obtained for the survey from the Ministry of Health Bioethics Committee in Mozambique. Informed oral consent was obtained from every respondent and documented by interviewers on the survey tools.Among the 1200 households surveyed with at least one child aged 2–59 months, information was collected for 1531 (753 intervention and 778 comparison) among 1534 eligible children. Characteristics of households are presented in P = 0.003) (P = 0.007). Among those seeking care for fever from a formal public or private source, 87.9% (95% CI 82.6–93.2) received AL in intervention areas compared to 74.1% (95%CI 66.0–82.2) in the comparison areas. The largest differences between intervention and comparison areas were seen in the timeliness of treatment initiation. In iCCM areas where APEs were providing care in the community, 63.9% (95% CI 54.4–73.3) of children with fever initiated AL treatment within 24 hours of symptom onset whereas in comparison areas 37.5% (95% CI 31.1–43.9) of children with fever initiated AL treatment within 24 hours (P = 0.000). APEs were the predominant source of care and treatment in the intervention areas; 87.1% (95% CI 80.8–93.4) of children 6–59 months with fever who sought care were taken first to an APE, who accounted for 86.2% (95% CI 79.7–92.7) of all first–line antimalarial treatments. Public health facilities were the leading source of care in comparison areas, providing care to 86.1% (95% CI 79.0–93.3) of children 6–59 months with fever who were taken for care outside the home.A total of 773 children 6–59 months (346 intervention and 427 comparison) were reported to have fever in the two weeks before the survey. Levels of appropriate care–seeking from formal public or private providers for fever were significantly higher in areas with iCCM compared to those without iCCM  and to take AL for the recommended 3 days . Overall, 74.1% (95% CI 64.6–83.6) of RDT+ cases managed by APEs received the correct drug within 24 hours and took for 3 days compared with 36.0% (95% CI 21.0–51.0) of RDT+ cases managed by health facilities. The number of RDT– cases was too small  to analyze.We also looked at the results for the subset of children 6–59 months with RDT+ results. Of caregivers who received the RDT results, reported malaria positivity levels were high . Due to the higher rates of RDT testing and disclosure of results among children managed by APEs, 65.3% of children with fever cared for by APEs in the sample (162/248) were reported RDT+ compared to 29.5% of children with fever cared for by first level health facilities (86/292). Nearly all RDT+ cases received AL , but RDT+ children who received AL from APEs were significantly more likely to receive AL within 24 hours  took the first dose in the presence of the APE and 70.1% (95% CI 62.9–77.4%) returned to the APE for follow–up. Data were not available for first dose or follow–up for children with fever managed by health facilities.Our results demonstrate that trained and well–supported APEs implementing iCCM can contribute substantially to timely care and treatment of childhood illnesses in rural Mozambique. A cross–sectional household survey conducted after approximately two years of iCCM implementation showed higher levels of appropriate care–seeking in areas with iCCM services compared to similar areas without iCCM services. Critically, the provision of iCCM by community–based APEs contributed to timely treatment for fever, likely due in large part to bringing curative care closer to the home and reducing delays in seeking appropriate care. Timely treatment is especially important for children with symptoms of malaria and pneumonia, where treatment within 24 hours of symptom onset is linked to improved outcomes ,19. ChilOur findings provide evidence that well–supported APEs can deliver care consistent with country iCCM protocols. In study areas, the APEs provided care aligned with national guidelines and performed as well as or better than facility–based providers for measures of appropriate assessment, counselling and treatment. Children with fever taken first to APEs were significantly more likely to receive an RDT, to be counselled on the RDT results, and to receive treatment with AL than children taken to first–level facilities. Children receiving care from APEs were also more likely to have their respiratory rate assessed and inappropriate treatment with antibiotics for fever only was low, helping to allay concerns regarding the ability of CHWs to manage suspected pneumonia . HoweverThese results were achieved within a well–supported APE program, which is critical for interpreting the findings in the context of the future of iCCM programs implemented by MOH with minimal external support. The iCCM program in Nampula was implemented with support from Save the Children, which provided technical staff and transport to conduct monthly onsite supervision of APEs. In addition to supervision, the APEs in the SC program areas were well supported with a reliable supply of materials and medications (and not reliant on MOH supply chain). Program data collected through interviews, observations and record review for the 30 APEs in the selected intervention clusters alongside the household survey indicated that the majority of APEs had the necessary supplies and medicines for iCCM provision: 90% had a functional timer; 87% had RDTs in stock; 80% had AL in stock; and 80% had first–line antibiotics available . SuperviOur findings highlight the need for greater attention to the management of childhood illness at first level facilities and increased investment in broader health systems strengthening beyond short–term, mostly vertical supports . Poor adThis study is one of the first to our knowledge to use household surveys to assess aspects of consistency with iCCM/IMCI protocols. Specifically, the indicators on counting of respiratory rate, communication of RDT results, provision of first dose, and follow–up visits have not previously been measured in standard household surveys. Although these indicators have not been validated, they ask caregivers to recall noteworthy events during the examination and/or treatment course for a relatively short recall period of two weeks. A register review of activity documentation by APEs from the 30 intervention clusters found similar levels of recorded respiratory rate counting and RDT administration to that reported by caregivers during the household survey; 87% of APEs had RDT test results recorded for the five most recent cases of fever and 63% had respiratory rates documented for the five most recent cough cases . We propSeveral limitations should be recognized when considering our findings. The study design was constrained by limited funding and time for evaluation and we did not have a baseline against which to measure change over time. To obtain a sufficient sample size, we only sampled households in which a child aged 2–59 months was identified during household listing. Although care was taken to identify all such households during the household listing stage, errors in age measurement or absence of any respondent in these households may have excluded some eligible households from the sample. Additionally, our sample relied on the comparison of the intervention districts to one comparison district. This sampling strategy was necessary given the rapid national roll–out of iCCM in Mozambique, but can make the results challenging to interpret as one cannot quantify or account for the potential influence of local contextual differences . AlthougThis study demonstrates that well–trained and supported APEs providing iCCM significantly contributed to improved timely and appropriate treatment of fever in rural Mozambique. Demand for iCCM was strong as evidenced by high levels of utilization of APEs as first source of care in program areas. In addition, APEs provided care that was consistent with iCCM protocols and performed significantly better than first level facilities on most measures of adherence to case management protocols. These findings reinforce the need for comprehensive efforts to strengthen the health system in Mozambique to enable reliable support for quality of case management of childhood illness at both health facility and community levels.


After a natural disaster like an earthquake about 15% of the population experience a post-traumatic stress disorder (PTSD). However, even those without a diagnosis of PTSD can suffer from disorders of the affective sphere, including anxiety, depression and alteration of emotion recognition. The objective of this study was to investigate the neuropsychological and emotional profile of students living in the earthquake-affected areas of L’Aquila, Italy. A group of students living in L’Aquila at the time of the 2009 earthquake was recruited, and compared to a control group of students not living in any earthquake-affected areas. Participants were assessed by means of the Beck Depression Inventory (BDI) scale, the State-Trait Anxiety Inventory (STAI), the Insomnia Severity Index (ISI), the Intolerance of Uncertainty Scale Short Form, the Uncertainty Response Scale (URS), the Anxiety Sensitivity Index 3 (ASI-3), and the Eysenck Personality Questionnaire-Revised Short Form (EPQ-RS). Participants also took part in two behavioral experiments aimed at evaluating their ability to recognize facial expressions  and to evaluate emotionally evocative scenes ). Results showed that students living in the earthquake-affected areas had a general increase of anxiety and anticipation of threats. Moreover, students living in the earthquake-affected areas showed a significantly higher overall accuracy in recognizing facial expressions as compared to controls. No significant differences between the two groups were detected in the evaluation of emotionally evocative scenes. The novel result lies in the greater accuracy of earthquake victims in recognizing facial expressions, despite the lack of differences from controls in evaluating affective evocative scenes. The trauma exposure may have increased vigilance for threats in earthquake victims, leading them to systematically pay attention to potential signs of approaching threats, such as emotional facial expressions, thus progressively developing particular “emotional expertise.” After a natural disaster, like an earthquake, population has an increased vulnerability to developing psychological and psychiatric disorders. The most frequently reported is Post-Traumatic Stress Disorder (PTSD), which is a mental health problem triggered by life-threatening events  a few weeks after a disaster or other shocking events to reduce psychopathological symptoms, in particular those related to PTSD  earthquake-exposed and not exposed students may show a similar emotional profile without significant differences in processing emotional stimuli, whether these be facial expression or emotional evocative scenes; (ii) earthquake-exposed students may have developed an increased and generalized sensitivity to emotional information, resulting in increased accuracy in processing all kinds of emotional information, both emotional facial expressions and emotionally evocative scenes; and (iii) earthquake-exposed students may show a selective increased accuracy in recognizing emotional facial expression, despite an unchanged perception of their own internal emotional responses to evocative scenes not involving faces. The results of the present study might provide empirical evidence about the engagement of specific coping and resilience strategies in young adults after an environmental traumatic event.The earthquake epicenter of L’Aquila  was used as the experimental setting. On April 6th 2009, L’Aquila was hit by an earthquake lasting 20 s and with a magnitude of 6.3 on the moment magnitude scale. The earthquake caused 309 deaths and the destruction of the city, with 65,000 inhabitants being forced to leave their homes. The main earthquake was followed by thousands of aftershocks in the subsequent months with a severe psychological burden on the whole population. About 7 years after this devastating earthquake, with the city only partially rebuilt, the population experienced additional earthquakes (August and October 2016 and January 2017). Although not causing further destruction, these resulted in great psychological distress for the people of L’Aquila, who had not yet recovered from the psychological, social and economic consequences of the 2009 earthquake.A sample of students living in L’Aquila at the time of the 2009 earthquake was recruited for the participation in the study. To be included, participants had to fulfill the following criteria: age >18 years at the time of the inclusion; stable residence in L’Aquila at the time of the 2009 earthquake; no history of previous or coexistent neurological or psychiatric diseases, including PTSD, or assumption of drugs or substances acting on the central nervous system; and signed informed consent to participate in the study. A control group of students, matched by age and sex, not living in any earthquake-affected areas, was recruited and used for comparison: these participants were all psychologically healthy individuals without a personal or family history of mental illness. The whole sample included 107 students. Forty-eight subjects belonged to the experimental earthquake-exposed group  and 59 to the control group .The research protocol was approved by the Internal Review Board of the University of L’Aquila (01/2017). The study was conducted in accordance with the ethical standards of the Helsinki Declaration and signed informed consent was obtained from all the participants.All participants were assessed by means of the following formalized measures: the Beck Depression Inventory  were taken from the Ekman and Friesen set of Pictures of Facial Affect  the one corresponding to the subjectively evoked emotion; the response was scored 1 if the subject selected the emotional category consistently evocated by the image, otherwise the response was scored 0. Then, the subjects had to rate how strong their own emotional response was on a scale of 1–9 .p < 0.0033 according to Bonferroni’s correction for multiple comparisons. For the behavioral measures  a three-way mixed analysis of variance (ANOVA) was performed, with emotion as a within-subject factor and with group and sex as between-subject factors.For the self-reported measures, a multivariate analysis of variance was performed with group and sex as independent variables and with scores on the self-reported measures as dependent variables. Level for statistical significance was set at F = 1.885; p = 0.035, partial eta squared = 0.241) and for sex  = 2.698; p = 0.45, partial eta squared = 0.230). The interaction between group and sex was not significant (p > 0.05).The multivariate results showed significant effects for group  = 9.079, p = 0.003, partial eta squared = 0.081), URS Emotional Uncertainty  = 15.399, p = 0.0001, partial eta squared = 0.130), STAI-2  = 10.036, p = 0.002, partial eta squared = 0.089), ASI Total Score  = 12.740, p = 0.001, partial eta squared = 0.110), ASI Cognitive Concerns  = 10.944, p = 0.001, partial eta squared = 0.096), ASI Social Concerns  = 11.777, p = 0.0001, partial eta squared = 0.118), and EPQ Neuroticism Scale  = 10.260, p = 0.002, partial eta squared = 0.091). No other difference was significant at the Bonferroni corrected p value.For group  = 15.322, p = 0.0001, partial eta squared = 0.129), with females scoring higher  than males . No other univariate effect was significant at the Bonferroni corrected p value.For sex, there was only a significant univariate effect for IUS-12  = 36.897, p = 0.0001, partial eta squared = 0.264), with recognition of fear (0.60) being worse than all other emotions . Results also showed significant main effects of group  = 16.832, p = 0.0001, partial eta squared = 0.140), with overall accuracy being higher in earthquake victims  than in controls , and of sex  = 4.208, p = 0.043, partial eta squared = 0.039), with females  being more accurate than males . No interaction was significant . Post hoc Bonferroni’s pairwise comparisons on the main effect of emotion demonstrated that recognition of happiness was significantly easier than all other emotions , followed by surprise (p = 0.01 vs. remaining emotions). No significant differences were detected between recognition of anger, sadness, or disgust , whereas recognition of fear was significantly worse than all other emotions (p = 0.005).Percentages of correct responses are shown in Table F = 37.942, p = 0.0001, partial eta squared = 0.271), with happy faces (6.72) being rated more intense than all other emotion expressions . Results also showed a marginally significant main effect of sex  = 3.939, p = 0.050, partial eta squared = 0.037), with females’ rating  being higher than males’ , whereas the main effect of group was not significant (p > 0.05). No interaction was significant . Post hoc Bonferroni’s pairwise comparisons on the main effect of emotion showed that rating of emotional intensity was significantly higher for happiness with respect to all the other emotions (p = 0.030), followed by surprise, fear and disgust which were rated significantly more intense than anger and sadness (p = 0.0001). Ratings of surprise, fear and disgust did not significantly differ from each other (p > 0.05).For intensity rating on correctly recognized emotions, we performed the same ANOVA as above, and results showed a significant main effect of emotion (p > 0.05) but showed a significant main effect of emotion  = 39.545, p = 0.0001, partial eta squared = 0.277), with the rating of scenes evocating anger (0.59) being more difficult as compared to the other emotions . Post hoc Bonferroni’s pairwise comparisons demonstrated that the rating of scenes evocating anger was significantly more difficult than that of the other emotions . No significant differences were detected between the rating of scenes evocating anger and disgust and between scenes eliciting sadness and happiness ; the rating of scenes eliciting sadness and happiness was significantly easier that that concerning the other emotions .Emotional category ratings are shown in Table F = 10.362, p = 0.002, partial eta squared = 0.091), with females’ rating  being more higher than males’ , whereas the main effect of group was not significant (p > 0.05). Moreover, results showed a significant effect of emotion  = 37.678, p = 0.0001, partial eta squared = 0.229), with scenes evocating anger (7.56) being rated as more intense than all other scenes . Post hoc Bonferroni’s pairwise comparisons on the main effect of emotion showed that the rating of emotional intensity was significantly higher for scenes evocating anger with respect to all the other scenes (p = 0.0001), whereas the ratings of scenes evocating happiness, fear, sadness and disgust did not significantly differ between each other (p > 0.05).Intensity ratings on correct responses were analyzed by the same three-way mixed ANOVA as above, and results showed a significant main effect of sex . This result is again consistent with the findings of Bell et al.  who suggThe novel result of the present study was that the higher accuracy in emotional faces recognition was a specific emotional response to the traumatic event rather than the expression of a general, heightened sensitivity to affective information. This was demonstrated by the findings that earthquake victims did not show any difference from non-exposed participants in evaluating the nature of their own reaction to the presentation of affective scenes not involving faces. A dissociation between explicit recognition of emotional facial expressions and evaluation of affective scenes has been previously reported by our group in studies on clinical populations with specific neurological disorders involving damage of motor and of sensory pathways, respectively (Pistoia et al., Bianchini et al.  investigOne possible limitation of the study lies in the fact that we tested the processing of emotional faces by employing highly prototypical stimuli displaying emotional faces with a straight gaze, as previously made in most of the studies addressing the same issue. However, one should take into account that such a laboratory setting cannot completely simulate the action of processing emotional facial expressions in real-life situations (Hess and Blairy, From a translational point of view, the present findings could pave the way for the implementation of specific preventive and treatment options for earthquake-exposed people by exploiting available techniques of cognitive biases modification, such as attentional bias modification (MacLeod and Clarke, In conclusion, the present study indicates a greater accuracy of earthquake victims in recognizing facial expressions, despite the lack of difference from controls in evaluating emotionally evocative scenes. A possible explanation for this effect is that trauma exposure increases threat detection in earthquake victims, leading them to systematically pay much more attention to every kind of potential sign of threat. This may lead people exposed to trauma to progressively develop specific, “emotional expertise.” Further studies are necessary to confirm our findings and to implement preventive and treatment approaches to boost resilience and encourage coping strategies in exposed populations.FP, MC, AC, MGD, AS, GC and SS provided their substantial contributions to the conception of the work, the acquisition, analysis and interpretation of data and to the writing of the draft manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.