Although the number of alcohol-related treatments in app stores is proliferating, none of them are based on a psychological framework and supported by empirical evidence. Cue exposure treatment (CET) with urge-specific coping skills (USCS) is often used in Danish treatment settings. It is an evidence-based psychological approach that focuses on promoting “confrontation with alcohol cues” as a means of reducing urges and the likelihood of relapse.The objective of this study was to describe the design and development of a CET-based smartphone app; an innovative delivery pathway for treating alcohol use disorder (AUD).The treatment is based on Monty and coworkers’ manual for CET with USCS (2002). It was created by a multidisciplinary team of psychiatrists, psychologists, programmers, and graphic designers as well as patients with AUD. A database was developed for the purpose of registering and monitoring training activities. A final version of the CET app and database was developed after several user tests.The final version of the CET app includes an introduction, 4 sessions featuring USCS, 8 alcohol exposure videos promoting the use of one of the USCS, and a results component providing an overview of training activities and potential progress. Real-time urges are measured before, during, and after exposure to alcohol cues and are registered in the app together with other training activity variables. Data packages are continuously sent in encrypted form to an external database and will be merged with other data  in the future.The CET smartphone app is currently being tested at a large-scale, randomized controlled trial with the aim of clarifying whether it can be classified as an evidence-based treatment solution. The app has the potential to augment the reach of psychological treatment for AUD. Alcohol use disorder (AUD) contributes to a substantial number of contacts with the treatment system ,2, givenWithin the Danish treatment system, individuals with AUD are most commonly treated with motivational interviewing, cognitive behavior therapy and family therapy, classified as evidence-based treatments ,11. In sWhen addressing the need for AUD treatment (such as CET), it is evident that the duration of the treatment is decreasing and that it is increasingly being used in group—rather than individual sessions were found appropriate and reasonable . HoweverMobile eHealth interventions have the potential to play a crucial role in the future provision of continuing care and relapse prevention helping to lower the socioeconomic burden on the health care system by decreasing the number of contacts it gets, as well as augmenting the reach of relevant treatment. However, there is a need for more transparency regarding the underlying psychological framework of mobile eHealth interventions, their design, and development, as well as the provision of evidence to gain more knowledge about their effectiveness.In order to add to the evidence base for mobile eHealth interventions, a CET smartphone app that mimics CET with USCS was designed and developed and is currently being tested in a large-scale, randomized controlled trial  ,32.The objective of this paper was to describe the design and development of a manual-based smartphone app that mimics CET with USCS, which is currently being delivered in Danish inpatient and outpatient clinics. The CET app has the potential to contribute to the reach of evidence-based psychological treatment for AUD.CET features in treatment programs being used in Danish alcohol clinics in both inpatient and outpatient treatment settings. CET is most commonly used in combination with various urge-specific coping-strategies (USCS), due to the promising outcomes shown -17. WhenThe initial plan for the structure and content of the app was developed by a group of psychiatrists and a psychologist relying on the aforementioned manual. When converting the manual, designing the app as simply, intuitively, and feasibly as possible was of utmost importance, given that the target population may have very different cognitive profiles -36. AlthAlong with the smartphone app, an online database was designed and developed in the system which can monitor patients’ data in real-time.The open-source Linux-based operating system Android was selected as the platform for developing the smartphone app. A customized version of Java in Eclipse (Oracle Corporation) was used as the main programming language. An online server is registered for the database and monitoring of the treatment process remotely.The information in the app is presented in text format and read out loud simultaneously.The software requires patients to train on a regular basis and sends a text reminder for this. As little is known about the effectiveness of intensive CET -17,37-42A CET therapist provides patients with both oral and written information about the app prior to the commencement of treatment. Patients can download the app directly onto their smartphones if they already have one. Otherwise, they can borrow a smartphone from the alcohol treatment clinic.Log-in page (part A), patients are provided with a user ID that is easy to remember and that assures anonymity, permitting them to login to the CET treatment program  Alone or alone at home after work, watching TV, bored, and (2) Social events: after work, with friends, or celebration. Patients are encouraged to choose healthy alternatives that will form the basis for new habits.Summary of every session, it is recommended that patients use the associated coping strategy when confronted with alcohol and risk situations in real life; however, in line with the safety functions featured in the Introduction to CET component, they are also advised against actively seeking out risk situations.In the Session icons change their colors from red to yellow and then from yellow to green, to indicate not trained, moderately trained, and trained.To ensure that each strategy is trained at least once, it is not possible for patients to proceed to the next session until they have completed the previous session. While the strategies are being trained, the Exposure icon remains locked until all strategies have been trained.The As illustrated in The app contains 8 different alcohol videos comprising the following categories: ordinary beer, strong beer, alchopops, red wine, white wine, brown spirits , white spirits , and hard liquor. One of these should be selected. Patients can select for their preferred beverage to feature in the exposure material or vary the beverage used from one session to the next. The alcohol video is selected from the list presented in Exposure icon, they must register which USCS they want to train. They can then proceed to the exposure session.It is possible for patients to go directly to the exposure videos after they have been trained for all the USCS, as there is no need to repeat the abovementioned information to them every time they watch a video. When patients click on the Real-time cue-induced urges are measured at 3 time points: (1) at the baseline (before exposure), (2) when the urge is expected to peak (during exposure/4 min), and (3) at the endpoint (after exposure). Urges are measured on an 11-point Likert scale, ranging from 0 (no urges) to 10 (severe urges). As can be seen in My progress.Based on these measures, 3-point graphic illustrations of urge development during exposure can be produced. Proxy measures of the intensity of the urge induced by the selected exposure video and the effectiveness of the selected USCS in reducing the urge can also be calculated. The first measure is calculated by subtracting the baseline measure from the peak measure. The effectiveness of the USCS is calculated by subtracting the endpoint measure from the peak measure. These algorithms together with other training activity variables are used to calculate the results in My progress. My progress displays several measures and graphs allowing patients to keep track of their training activities and potential advances in controlling cue reactivity.As illustrated in A s shown in Data from these measures are recorded in the database in order to register and monitor training activities. The data would be used to measure the extent to which each USCS is applied by patients, as well as the effectiveness of each USCS and the CET intervention in general.user ID, time of using the app, applied strategy, and the real-time urge data. As already mentioned, the user IDs that we use to identify patients do not contain any personal information and are encrypted when being transferred through the Web domain to the database. The external webhosting provider, DanDomain A/S, DK, is responsible for the server and the database, and has signed an agreement with the hosts of the project to ensure that rules regarding safety and ethics are met. The database cannot be accessed by any members of the research group before all data have been collected; only contracted data managers have access to the database at this time. Any access and changes made to the database is recorded and documented.Along with the smartphone app, an online database was designed and developed in the system which can monitor patients’ data in real-time. After the patients have used a USCS, the app saves the data package locally on their phones and directs them automatically to the online database (as long as there is Internet connection). The data package includes The user IDs will be used to merge data from the database with data from other sources  suitable for personal identifiers.This paper describes the design and development of a smartphone app that mimics the CET treatment delivered to AUD patients in Danish inpatient and outpatient clinics.Although CET along with USCS is widely used in Denmark, studies providing evidence for the effectiveness of this treatment are yet to be conducted. If we draw on the evidence from international studies, CET has, in its conventional delivery form, demonstrated superior performance to meditation and relaxation techniques -17,38, aThe critical question, then, is whether this evidence-based AUD intervention demonstrates an effect when converted into a smartphone app. To answer this question, we based the present app on a behavioristic psychological framework and embedded the examination of it in a large-scale, randomized controlled trial. About 300 AUD individuals were randomized into 1 of the following 3 aftercare treatment groups: (1) CET as a mobile phone app (n=100); (2) CET as a group therapy (n=100); and (3) treatment as usual (n=100). The 2 experimental CET conditions were based on the same manual, and the treatment as usual consisted of a single follow-up session to observe how patients were doing and whether further treatment was needed. The real-time urge measures were applied in both experimental CET conditions, and a number of effect measures were conducted for all enrolled participants ,35.The experimental design allows for comparison between the experimental groups and the nonactive controls, which adds to the general knowledge base pertaining to the effectiveness of CET targeting AUD. Of more importance is the fact that the study design allows for a comparison between the 2 experimental conditions on USCS, real-time urges and effect measures, which clarifies whether it is beneficial for patients to progress from CET group sessions to using a CET smartphone app.It is hypothesized that the experimental groups will achieve better outcomes compared with controls on primary and secondary effect measures, including alcohol consumption, urges or cravings and coping skills. It is a more of an explorative research question that answers whether similar or improved results for one of the CET conditions will be found. Thus, the study context will either validate or falsify the app as an evidenced-based treatment form.Obviously, the app might have a number of disadvantages compared with CET group sessions, which may hinder its effectiveness as a pathway for treatment delivery. First, the alcohol exposure videos aim to target possibly all the individuals in the study population, hereby including several alcohol brands at the expense of the individually tailored exposure. Second, patients cannot smell the alcohol shown in the videos, and we know that smell is the only sense that is linked directly to the frontolimbic reward system -49. ThirAlthough there exists a gap in knowledge about the effectiveness of evidence-based psychological treatment delivered through mobile devices , alcoholDespite the lack of availability of theory-driven and empirically supported apps, many new intervention initiatives targeting both subclinical and clinical AUD populations are seen in research ,55-58. TIt is our hope that the present CET app will contribute to the availability of evidence-based mental health apps targeting AUD. Future work will customize the CET app according to the findings generated by the longitudinal randomized controlled trial in which the examination of this app is embedded in.


DDT was among the initial persistent organic pollutants listed under the Stockholm Convention and continues to be used for control of malaria and other vector-borne diseases in accordance with its provisions on acceptable purposes. Trends in the production and use of DDT were evaluated over the period 2001–2014.Available data on global production of DDT showed a 32% decline over the reporting period, from 5144 to 3491 metric tons of active ingredient p.a. Similarly, global use of DDT, for control of malaria and leishmaniasis, showed a 30% decline over the period 2001–2014, from 5388 metric tons p.a. to 3772 metric tons p.a. India has been by far the largest producer and user of DDT. In some countries, DDT is used in response to the development of resistance in malaria vectors against pyrethroid and carbamate insecticides. Some other countries have stopped using DDT, in compliance to the Convention, or in response to DDT resistance in malaria vectors. Progress has been made in establishing or amending national legal measures on DDT, with the majority of countries reportedly having measures in place that prohibit, or restrict, the production, import, export and use of DDT. Limitations in achieving the objectives of the Stockholm Convention with regard to DDT include major shortcomings in periodic reporting by Parties to the Stockholm Convention, and deficiencies in reporting to the DDT Register.Global production and global use of DDT have shown a modest decline since the adoption of the Stockholm Convention. The organochlorine dichlorodiphenyltrichloroethane (DDT) has been listed under the Stockholm Convention, with the main objective to protect human health and the environment from persistent organic pollutants (POPs) . The ConParties to the Convention (i.e. countries and other entities) can produce and use DDT for disease vector control in accordance with WHO recommendations and when locally safe, effective and affordable alternatives are not available. A DDT Register has been established under the Stockholm Convention in which countries are obliged to report their intention to produce or use DDT . The conTo accelerate progress in achieving the Convention’s objective regarding DDT, a roadmap has been prepared to assist Parties with steps needed to make alternatives available for a sustainable transition away from DDT . MoreoveA previous contribution reviewed the global status of DDT in 2007/08 . As an uThis paper was prepared in the context of an effectiveness evaluation undertaken pursuant to Article 16 of the Stockholm Convention . The purThe scope of this paper is to present changes in quantities in production and use of DDT, including progress in legal measures taken by countries to prohibit or restrict the production, use, import and export. Changes in DDT levels in humans and the environment have been reported elsewhere , 9. As tData on legal measures taken by countries in relation to DDT were obtained from official national reports for the Stockholm Convention, which Parties to the Stockholm Convention are obliged to complete and submit to the Secretariat of the Convention every 4 years. Three reporting cycles have been completed Table ; these nThe primary source of data on production, use, import and export of DDT was the official country responses to the DDT questionnaire, which Parties to the Stockholm Convention and that produce or use DDT for control of malaria and other vector-borne diseases, are required to complete and submit once every 3 years , 11. TheProduction data were available from the DDT questionnaire from 2007 onwards (for China: from 2006 onwards). Production data prior to this year were obtained from project proposals submitted to the global environment facility, and workshop presentations by party delegates in the context of the Stockholm Convention . No prodData on DDT use that were obtained from the DDT questionnaire showed various data gaps. Therefore, we supplemented the questionnaire data with data available from WHO for the period 2001–2009 . Data onData on import and export of DDT were solely obtained from the DDT questionnaire.The majority of Parties to the Stockholm Convention reported having legal measures in place that prohibit, or restrict, the production, import, export and use of DDT Table . The datWhen comparing the situation before and after 2001, it is evident that major progress has been made in terms of countries adopting or amending their legal measures on DDT following adoption of the Stockholm Convention. Roughly half of the countries with legal measures in place have established or amended these measures after the year 2001. The Convention entered into force in May, 2004; from this year, Parties to the Convention were obliged to conform to it. Interestingly, the progress was most significant during the initial years after adoption of the Convention, 2001–2004. Of this progress, 35–67% was in 2001–2003. These observations confirm our assumption that compliance to the Convention began before Parties were obliged to conform to the Convention.Since 2003, there have been three countries reporting production of DDT: India, China and the Democratic People’s Republic of Korea (DPR Korea). During the period 2003–2007, average production was 5144 metric tons per annum, but during the period 2008–2014, average production was 3491 metric tons p.a.—a decline of 32% during the 12-year period , only India, Mozambique and South Africa reported their use of DDT. In addition, independent publications indicate that five other countries, namely Botswana, Gambia, Namibia, Swaziland and Zimbabwe, have ongoing use of DDT for control or elimination of malaria –19; thesDPR Korea used DDT mainly in agriculture and forestry (91–97% of DDT used), which are not acceptable purposes under the Stockholm Convention; the remainder was used in public health . No receDDT has been reported for control of anopheline mosquito vectors of malaria and phlebotomine sandfly vectors of leishmaniasis. India has been using DDT both for control of malaria and leishmaniasis. Data from WHO indicate that over the period 2000–2009, 19% of the global use of DDT was for leishmaniasis control; the remaining 81% being for malaria control .Over the period 2003–2014, global annual use was 9% higher than global annual production of DDT, which suggests that some DDT was used from previous stocks.During the period 2001–14, twelve African countries have reported on their import of DDT for use in their malaria control programmes. Up until 2009, imports originated predominantly from China, but after China discontinued its DDT production in 2008, it stopped its export in 2010. From then onwards, imports originated solely from India. South Africa has a formulation facility at which imported technical-grade DDT has been formulated and re-packaged for national use and for distribution to other African countries. Ethiopia also had a formulation facility for DDT, which was discontinued in 2009.Inadequate data were available for a global assessment of obsolete stocks and waste of DDT or amounts that were sent for environmentally sound disposal.The years following the adoption, and entry into force, of the Stockholm Convention have seen a modest decline in the global production and use of DDT. Evidently, the Stockholm Convention ‘tool’ has not been the only factor influencing this trend. Other contemporaneous factors which influenced DDT use included the up- or downscaling of operations of indoor residual spraying, and the detected levels of insecticide resistance.In this respect, it is important to reiterate the developments that contributed to the acceptable purpose of continued use of DDT for disease vector control under the Convention. In 1996, South Africa had withdrawn DDT from its malaria control programme in Northern Kwazulu-Natal, switching to a pyrethroid insecticide instead, but this policy change had a negative outcome. Soon, malaria incidence rates increased sharply, and entomological investigations revealed that the culprit, a very efficient vector species, had re-invaded the country after DDT spraying had stopped and was highly resistant to the pyrethroid insecticides being used . RevertiInsecticide resistance in malaria vectors against DDT and other recommended insecticides, particularly pyrethroids, is sweeping across Africa , 23. ThiContrasting the irregular use of DDT across sub-Saharan Africa, the pattern in India has been relatively constant. India has used large quantities of DDT, to protect sizable human populations at risk of malaria and leishmaniasis with indoor residual spraying. It is significant that India has partly shifted its DDT use from malaria control towards leishmaniasis control—possibly in response to low DDT susceptibility in malaria vectors . Further changes in DDT use could be foreseen in view of recent reports on high levels of DDT resistance detected in the sandfly vectors of leishmaniasis , 26. ConThe experiences with insecticide resistance demonstrate the critical importance for countries to establish the technical capacity for monitoring of insecticide susceptibility, and for quality assurance of interventions, in order to facilitate timely and evidence-based decision-making on vector control . More deReadily available vector control methods that do not rely on chemical insecticides, such as house improvement and larval source management, deserve increased attention in future integrated vector management strategies –32, as dThe reported progress in countries across the globe in establishing or amending legal measures to prohibit or restrict DDT is encouraging, because it consolidates the path towards elimination of DDT use. Nevertheless, implementation of these legal measures will remain a challenge in many countries. WHO has highlighted critical shortcomings in how countries endemic with malaria and other major vector-borne diseases are regulating, managing and monitoring public health pesticides, which include DDT, particularly in WHO’s African Region , 35. ForSeveral limitations in implementation of the Stockholm Convention can be identified with regard to DDT, some of which may also apply to other POPs. The periodic national reporting to the Conference of the Parties has generally been deficient, with a low response rate and inaccurate or incomplete information contained in many submitted reports. In particular, the assessment and reporting on obsolete stocks, waste and disposal of DDT should be improved. Similarly, the response rate to the DDT Questionnaire has been inadequate, with several countries for which independent information sources indicate ongoing use of DDT failing to fulfill this specific requirement under the Convention –19. TherMoreover, there are deficiencies in the DDT Register. As of December 2016, seventeen Parties to the Convention were listed in the DDT Register, some of which current users of DDT. However, some Parties, which are known users of DDT, have not listed themselves in the DDT Register despite the obligation under the Convention. These shortcomings highlight the importance of establishing a quality assurance mechanism for reporting and a compliance mechanism, including non-compliance determination and possible measures in case of non-compliance.DDT continues to be used for control of malaria and leishmaniasis in accordance with the acceptable purpose under the Stockholm Convention. Following the adoption, and entry into force, of the Convention, there has been a modest decline in both global production and global use.In some countries, DDT is used in response to the development of resistance of malaria vectors against pyrethroid and carbamate insecticides. Several other countries have switched to alternatives to DDT, in compliance to the Convention, or, after resistance monitoring demonstrated high levels of DDT resistance. This has contributed to the modest decline in the global use of DDT. The declining trend is expected to continue in the years ahead in view of recent data on DDT resistance in vectors of malaria and leishmaniasis.Major progress has been made by countries establishing or amending their legal measures on DDT since the Stockholm Convention was adopted in 2001. These developments, together with instruments such as the roadmap on development of alternatives of DDT , consoliImplementation of the Stockholm Convention with regard to DDT, is constrained by major shortcomings in the national reporting, DDT questionnaire responses, and DDT Register. This calls for quality assurance of reporting and a compliance mechanism. Data on obsolete stocks, waste and disposal of DDT require particular attention.


The possibility to replicate and reproduce published research results is one of the biggest challenges in all areas of science. In computational neuroscience, there are thousands of models available. However, it is rarely possible to reimplement the models based on the information in the original publication, let alone rerun the models just because the model implementations have not been made publicly available. We evaluate and discuss the comparability of a versatile choice of simulation tools: tools for biochemical reactions and spiking neuronal networks, and relatively new tools for growth in cell cultures. The replicability and reproducibility issues are considered for computational models that are equally diverse, including the models for intracellular signal transduction of neurons and glial cells, in addition to single glial cells, neuron-glia interactions, and selected examples of spiking neuronal networks. We also address the comparability of the simulation results with one another to comprehend if the studied models can be used to answer similar research questions. In addition to presenting the challenges in reproducibility and replicability of published results in computational neuroscience, we highlight the need for developing recommendations and good practices for publishing simulation tools and computational models. Model validation and flexible model description must be an integral part of the tool used to simulate and develop computational models. Constant improvement on experimental techniques and recording protocols leads to increasing knowledge about the biophysical mechanisms in neural systems. This poses new challenges for computational neuroscience: extended or completely new computational methods and models may be required. Careful evaluation and categorization of the existing models and tools provide a foundation for these future needs, for constructing multiscale models or extending the models to incorporate additional or more detailed biophysical mechanisms. Improving the quality of publications in computational neuroscience, enabling progressive building of advanced computational models and tools, can be achieved only through adopting publishing standards which underline replicability and reproducibility of research results. All areas of science are facing problems with reproducibility and replicability Baker, , and comThere is an evident need to evaluate, compare, and systematize tools and models. With the increasing number of published models, it is becoming difficult to evaluate the unique contribution in each of them or assess the scientific rigor. The published articles might provide incomplete information, due to accidental mistakes or limited space and publication format. The original model implementations are not always available. The overhead of model reimplementation and reproduction of the results could be significant. More systematic model description  presenting the biochemical network, and these equations are then solved numerically when simulating the model. However, for example, in XPPAUT, the model is directly implemented using the ODEs and not the chemical reactions. Several of the tools also provide stochastic approaches to model and simulate the reactions  based on extensive statistical characterization of dendritic morphology in developing circuits conducted by the authors of the simulation tool . To specify a model in Cortex3D, a user should write Java module containing the description of model components, interactions between the components, and model parameters. The output of the simulation tool is an Extensible Markup Language (XML) schema compatible with NeuroML containing the details of the obtained model. The simulation tool also integrates Java packages that allow visualization of the simulation evolution. We tested and compared NETMORPH and Cortex3D by implementing and running the same model compatible with both tools and evaluating the simulated data. In addition to tool evaluation, we were interested in promoting the usefulness of these new and underutilized simulation tools.Cortex3D is a simulation platform that supports modeling biophysical and mechanistic details of neural development. As such it does not specify any particular model but rather a set of underlying mechanisms that can be used to implement and simulate user-defined models. The mechanisms embedded into the simulation tool include discretization of space occupied by a model, production, diffusion, degradation, and reactions between chemical species, the effect of mechanical and chemical forces between components of the model, and movement of objects inside the model. The model is solved at a fixed time grid. Parts of the model represented by dynamical equations are solved using Euler method, but numerical integration is replaced by analytical solution whenever possible to avoid overshoot for large time steps. The simulation tool is organized into layers of abstraction, with the discretization of space mapped into the lowest layer, the physical properties of the objects being specified one layer above, and the biological properties mapped into the top two layers. Most of the user-defined model properties can be specified in the top “cell” layer  in addition to different intracellular chemical species taken into account either in neurons or astrocytes.Data analysis: Description of the methods used to analyze in silico data from spiking neuronal network models.In this section, we give an overview of computational models used in our reproducibility, replicability, and comparability studies. These include the models of intracellular signal transduction for neurons and glial cells, in addition to single glial cells, neuron-glia interactions, and neuronal networks. We tabulated the following properties for the models whenever suitable:Some of the models we used in this study were found available in model repositories. These repositories are listed in Table More than a hundred intracellular biochemical species are important in synaptic plasticity. Hundreds of neuronal signal transduction models have been developed to test the criticality of different chemical species. Several reviews of the models exist, some focus on just a few different models whereas others give an overview of more than hundred models . In this study, we do not consider recent attempts to model the effects of non-neuronal cells, and we also leave out the mean field approaches to modeling the same type of experiments and data. The 10 selected studies are summarized in Table Spiking neuronal network models are numerous in the literature and used to model various phenomena and brain structures. In order to constrain this evaluation to a reasonable set of models, we selected only those models which are developed for the spontaneously synchronized population activity from dissociated neuronal cultures We here evaluate first the simulation tools we used for biochemical reactions, growth in cell cultures, and spiking neuronal networks, and last the computational models for signal transduction in neurons, astrocytes, and spiking neuronal networks.Ⓡ was required for Systems Biology Toolbox and SimTool. Second, the lack of standards and interfaces between tools also made the comparability problematic. For example related to SBML import, graphical user interfaces designed to help the SBML import were not intuitive, the error messages were not informative enough, and not all the SBML levels were supported. Furthermore, for stochastic simulations with the Gillespie stochastic simulation algorithm, all the chemical reactions in the model had to be implemented as irreversible. Although the test case was implemented and exported with only irreversible reactions, we found simulation tools that mistook some of the irreversible reactions for reversible reactions during the SBML import and thus, we were not able to run stochastic simulations with these tools  with PyNN (version 0.8.0) used as an interface and Brian (version 2.0). All of the tested packages are well documented and additional support is offered through user groups. The general tendency to develop Python based simulation tools or Python interface to simulation tools saves time when analyzing the obtained simulation results, since the same Python modules for analysis and visualization of data can be combined with each simulation tool. Parallelization is supported by NEST and PyNN, however it is still under development in Brian. An earlier version of Brian offers a model fitting method for tuning the statistics of the interspike intervals in spiking neuron models. In Brian version 2.0, this option is under development. NEST and PyNN do not provide direct tools for model fitting. However, both Brian and NEST can easily be combined with external Python modules for model fitting. For fast exploration of models, for example in the early phase of model development, or for incorporating nonstandard biophysical mechanisms in the model, Brian offered more flexibility. In NEST and PyNN, the components of the model have to be either selected from the list of existing models or implemented by extending the simulation tool to include new models. Brian provides more flexible framework for implementation of user-defined models. Model components are specified directly as strings of ODEs. Various models can easily be implemented, however they still rely on the existing functionalities of the simulation tool.Based on our large review of postsynaptic signal transduction models for long-term potentiation and depression  connectivity in order to avoid implementation errors. For example, in one of the publications the authors described network connectivity as “scale-free random” but then assigned a number of outputs to each neuron using a uniform random instead of a power-law distribution. The two studies by Mäki-Marttunen et al.  and LonaThe comparison between simulated and experimental data requires extensive data analysis. The lack of standardization of methodology and the ambiguity in presentation of the applied algorithms pose additional obstacles to reproducibility and replicability. All of the models under consideration generated the same type of data, the spontaneous activity exhibiting network-wide bursts, thus the intervals of intensive spiking activity reflecting global synchronization. The analysis of this data often consists of two steps: bursts detection, segmenting the population spike-data into intervals containing bursts, and computing the statistics of different quantitative measures based on the burst detection or on original non-segmented data. Burst detection itself might not be very reliable. A recent review article conducted evaluation of a broad range of burst detection methods and tested them against a carefully crafted benchmark data . Three out of 10 listed studies provide the full model implementation, namely Masquelier and Deco  used in the article. Attempt to run the biggest matrix failed most likely due to memory issues. However, we managed to replicate the rasterplots in Figure 2A by Lonardoni et al.  and after modifying one parameter. In a smaller network, the burst propagation in Figure 2B by Lonardoni et al. (Ⓡ format (version R2010a/R2011b) using own code and it was possible to replicate it. The second, LIF model, is available in PyNEST format (Python version 2.4.3 and NEST version 2.0.0). The software versions are indicated in the code. We managed to replicate the result using Python version 2.7 and NEST version 2.2.1. Running the same code in a newer version of the simulation tool, NEST version 2.8.0, failed to produce any bursting dynamics. All of the studies provided well-documented models and full set of parameters. However, the replicability of the results was hindered by common problems related to versions of the utilized software. These examples illustrate the need to provide detailed information about simulation environment, in addition to model description and implementation.The simulation tools range from the custom-made software in MATLABand Deco , Mäki-Maand Deco , and Lonand Deco . From thand Deco  is availi et al.  is availi et al.  using a i et al.  was somei et al. . The stui et al.  containsFigure We separated all tested reproducibility and replicability models , by providing interface for adding new components (NEURON), or by providing unit checks (Brian), offer easier manipulation and modification of the model. For the same reason, the simulation tools of this type allow easier extension and reuse of the published models. Several existing tools support development of multiscale models [MOOSE (Ray et al., Has the model been checked carefully in the review process and can it produce the results in the publication?Is the quality of the code sufficient?Is the model properly validated against experimental wet-lab data and correctly representing the biological findings?What new biological, modeling, and computational aspects the model provides on top of the previously published models?Are all the details of the model equations and biological components given in the publication in a clear way, preferably in a tabular format?Which programming language or simulation tool was used to implement the model, which data analysis methods were used, and are the implementation of the model and data analysis methods available online?Our findings on a specific set of published models for different biological systems stress the importance of a variety of aspects of model development. The following challenges and questions are relevant:It is important to emphasize that a good-quality model implementation supplied with the original publication improves not only replicability of the study but also understanding of the model itself. This is already important during the review process. Reviewers should have the possibility to rerun the model code, check the simulated results, and compare the simulated and experimental data during the review process (see also Eglen et al., Best practices for description of neuronal network models (Nordlie et al., Throughout this study, we evaluated, reimplemented and reproduced, and replicated a range of models incorporating different levels of biological details and modeling scales. The models and biological mechanisms included some relatively conventional examples but also some that only recently attracted larger attention within the computational community. As the experimental methodology and protocols advance and various neurobiological mechanisms become better understood, the new challenges for computational modeling emerge. Few examples are molecular diffusion in synaptic clefts, dendritic spines, and in other neural compartments (Chay et al., All the above suggestions would greatly improve the replicability and reproducibility of the published results, reduce the time needed to compare the model details and results, and support model reuse in complementary studies or in the studies extending the range of biophysical mechanisms and experimental data.TM: Designed the study, acquired and reimplemented the neuronal signal transduction and astrocyte models, simulated the models, evaluated and tabulated the results, and coordinated the production of the final version; JA: Designed the study, evaluated the simulation tools for growth and spiking neuronal networks, acquired and reran the spiking neuronal network models, and evaluated and tabulated the results; RH: Contributed to the design of the study, reimplemented, simulated, and evaluated an astrocyte model, contributed to the testing of the simulation tools for growth, and interpreted biological terminology and knowledge; HT: Contributed to the design of the study, contributed to the interpretation of network growth and activity studies, and interpreted biological terminology; M-LL: Conceived, funded, and designed the study, took part in the selection and evaluation of all models and tools, and interpreted the results in terms of replicability and reproducibility. All contributed to the drafting of the manuscript and approved the final version of the manuscript. All other work reported in the present publication, as motivation for the topic, is cited and is based on the work done previously in Computational Neuroscience Research Group in Tampere, Finland.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.


The French healthcare system is a universal healthcare system with no financial barrier to access to health services and cancer drugs. The objective of the study is to investigate associations between, on the one hand, incidence and survival of patients diagnosed with lung cancer in France and, on the other, the socioeconomic deprivation and population density of their municipality of residence. A national, longitudinal analysis using data from the French National Hospital database crossed with the population density of the municipality and a social deprivation index based on census data aggregated at the municipality level. For lung cancer diagnosed at the metastatic stage, one-year and two-year survival was not associated with the population density of the municipality of residence. In contrast, mortality was higher for people living in very deprived, deprived and privileged areas compared to very privileged areas . Similar associations are also observed in patients diagnosed with non-metastatic disease . Despite a universal healthcare coverage, survival inequalities in patients with lung cancer can be observed in France with respect to certain socioeconomic indicators. With an incidence rate of 41.9 cases per 100,000 individuals in 2012, lung cancer is the fourth most frequent cancer in terms of incident cases in Europe and the leading cause of cancer-related death , 4.Socioeconomic disparities in access to healthcare for patients with lung cancer have been identified in many countries –7. TheseThe French health care system ensures universal coverage for healthcare through public health insurance funds. In theory, there are no financial barriers to access to health services , and sociological and geographical differences should play only a marginal role in outcomes of lung cancer. Nonetheless, data addressing such influences are very limited. The objective of the TERRITOIRE study was to investigate potential associations between socioeconomic markers and lung cancer incidence and survival in France.Programme de Médicalisation des Systèmes d’Information) relating to all hospitalised patients, crossed with geographically aggregated socioeconomic variables at the lowest local authority level (the commune), documented in the databases of the national census of the French national statistics office (INSEE) through individual patient postcodes.This was a retrospective, longitudinal analysis using data extracted from the French National Hospital database . These patients were identified through an ICD-10 code for lung cancer (C34) as PD, RD or SAD for any hospital stay in 2011. Patients were divided into one group diagnosed at the metastatic stage and a second group diagnosed at the non-metastatic stage, since these two groups have a very different prognosis. Metastatic disease was identified from three different sources, namely an ICD-10 code for metastatic disease, hospitalisation in palliative care as a first hospitalisation for lung cancer or administration of chemotherapy for metastatic disease.Each patient was followed for two years from the initial hospital stay. Patients who died over the two-year follow-up period were censored at the date of death or at the time of the last observation. For each patient, information was documented at the time of initial hospitalisation on gender, age at diagnosis, type of hospital where the patient was first admitted for lung cancer management and the presence of significant chronic comorbidities  identified as PD, RD or SAD in the patient discharge record. Survival status at one and two years of follow-up was determined. These are the time horizons conventionally used in clinical trials and cancer registries, and thus allow comparison of our data with others. Since the cause of death is not documented, mortality corresponds to all-cause mortality. Death elsewhere than in the hospital is not documented.commune) for each patient at the time of the initial hospitalisation was determined from their postcode. Patients whose postcode was not documented in the PMSI database were excluded from the analysis. The commune is the lowest tier of local authority in France and generally consists of a single population centre together with any surrounding hamlets or countryside, with a typical area of 10–50 km2. There are around 36,000 such municipalities in France. Data were retrieved from the French national statistics office (INSEE) on the sociodemographic make-up of each municipality and used to classify them in terms of population density and social deprivation. Based on the national census data of 2011 and the surface area of the commune, the population density of the municipality was categorised by quartile into four classes: very low, low, high and very high population density. Municipalities were ranked on the basis of a social deprivation index (SDI) determined on the basis of unemployment rate, median household income, the percentage of high school graduates in the adult population and the percentage of blue-collar workers in the active population  for metastatic disease and 18.9 months [18.4–19.1] for non-metastatic disease.p >0.05; Schoenfeld’s partial residual).In multivariate analyses, one and two-year survival in patients with non-metastatic disease at diagnosis was higher in younger patients and in women. The presence of renal insufficiency and respiratory insufficiency was associated with poor survival, whereas COPD, and to a lesser extent, hypertension, were associated with improved survival . No diffFor patients with metastatic disease at diagnosis, one and two-year survival was also higher in younger patients and in women . Renal acommune where the patient lived. In particular, one- and two- year survival was significantly lower in patients living in socially deprived areas compared to very privileged ones. These differences were observed both for cancers that were diagnosed at the metastatic stage and for those diagnosed at the non-metastatic stage. With respect to the population density of the municipality, no such association with survival was observed.In this nationwide cohort study, we observed significant socio-geographic inequalities in the incidence and survival of patients with lung cancer in France. Other than demographic and clinical variables that have been reported previously to be associated with survival, such as sex, age, disease stage and comorbidities, our study also demonstrated differences in survival related to the level of social deprivation of the As previously demonstrated elsewhere , stage aLess data are available on the relationship between comorbidities and survival in lung cancer. Our study shows that, regardless of the stage of the disease at diagnosis, comorbid kidney failure and chronic respiratory impairment were negatively associated with survival whereas the presence of COPD appeared to be protective in non-metastatic disease. It could be postulated that such a protective effect could be due to the fact that patients with COPD are likely to be already followed by a pulmonologist before their cancer develops, thus increasing the probability of early diagnosis and management by a specialist. A Danish study of 13,045 patients with lung cancer  recentlyeg migration), social deprivation (eg education and employment status) and land use. Poorer survival was observed in more rural areas [Survival inequalities in patients with lung cancer have been the subject of numerous recent studies and our findings are in line with those of several other population based studies of the impact of social inequalities on survival of patients with lung cancer, both in universal ,4,6 and al areas . Studiesal areas  and the al areas , 24 haveal areas . In an aal areas . Nonethep ≤0.01).One of the difficulties in interpreting such studies lies in the non-uniform definition of social deprivation used, notably since individual components of deprivation, such as low education level, may also be associated with risk factors for lung cancer, such as smoking. Of interest in this respect is a recent French nationwide observational study which analysed potential links between vulnerable social status, identified using a validated questionnaire (EPICES), exposure to lung cancer risk factors and access to healthcare, through telephone interviews of a representative sample of 1603 subjects . The socper capita lung cancer mortality in rural areas of the United States was driven by higher rural smoking rates [This type of study does not allow the causes of the inequity in survival according to socio-geographic disparity to be addressed directly. However, a number of hypotheses may be put forward which may be useful to orientate future research. For example, a study in Scotland has demonstrated that cancer patients living in rural areas have lower care expectations than their urban counterparts , which mng rates . In addiThis study was performed using data from the PMSI database. This choice was based on the fact that this is an exhaustive data on patients with lung cancer at a national level. Although regional or local cancer patient registries exist in France, there is no specific national registry for lung cancer with longitudinal data. Since the PMSI database has been used to attribute hospital funding on a pay by activity basis since 2005, the quality and exhaustiveness of data coding has improved considerably, and a recent comparison of standardised incidence ratios for cancer determined from the PMSI and from local cancer registries has shown that the two sources provide very similar estimates . AlthougThe strengths of our study include the population-based approach, with a cohort of all lung cancer patients managed in France in one year. Nonetheless, the use of this data source presents certain drawbacks. Firstly, it is not possible to characterise the tumour with respect to histological type or detailed stage of cancer  in the PMSI database, since this information is not captured in the DRG code used to define the hospital stay. This lack of access to disease and treatment variables is a major limitation of the study, since such variables may influence the association between geographic variables and survival. However, the proportion of patients with metastatic disease at diagnosis in our study (53%) is close to that observed in a recent nationwide survey of lung cancer in France based on patient records which used TMN codes (58% in 2010) . AlthougSecondly, our individual-level demographic variables were limited to gender and age and we lack information on important variables such as smoking status. Thirdly, it is also possible that a competing risk of death from causes other than lung cancer played a part in the observed overall mortality rates. Certain competing causes of death such as injury may also be associated with social deprivation, and some contamination from such causes cannot be excluded. Nonetheless, we have assumed that the major contribution to death in our sample will be lung cancer itself. Some imprecision also arises since certain patients with lung cancer do not die in hospital and thus will not be captured in the PMSI database. However, an exhaustive survey of the relationship between place and cause of death in France has demonstrated that around 80% of patients who die from lung cancer die in hospital . In addiThe originality of our study lies in the use of a nationwide comprehensive health insurance database to identify cases. Firstly, this has the advantage of ensuring quasi-exhaustiveness of case identification, and thus eliminating the problem of sampling bias which is common to registry studies. Secondly, comparisons are possible with other diseases identifiable in the same database to detect potential disease-specific barriers to health equality. Finally, similar approaches can be taken in other countries where nationwide comprehensive health insurance databases exist, such as Scandinavia, in order to identify country-specific differences in health equality.Although France is a highly egalitarian country with a free, universal healthcare system, this study found survival inequalities in patients with lung cancer related to residential socioeconomic indicators. It will be important to understand these associations in order to propose and implement strategies to ensure territorial equity in opportunity for patients diagnosed with lung cancer.


Background: In early 1990s, Tanzania like other African countries, adopted health sector reform (HSR). The most strongly held centralisation system that informed the nature of services provision including health was, thus, disintegrated giving rise to decentralisation system. It was within the realm of HSR process, user fees were introduced in the health sector. Along with user fees, various types of health insurances, including the Community Health Fund (CHF), were introduced. While the country’s level of enrolment in the CHF is low, there are marked variations among districts. This paper highlights the role of decentralised health management and leadership practices in the uptake of the CHF in Tanzania.Methods: A comparative exploratory case study of high and low performing districts was carried out. In-depth interviews were conducted with the members of the Council Health Service Board (CHSB), Council Health Management Team (CHMT), Health Facility Committees (HFCs), in-charges of health facilities, healthcare providers, and Community Development Officers (CDOs). Minutes of the meetings of the committees and district annual health plans and district annual implementation reports were also used to verify and triangulate the data. Thematic analysis was adopted to analyse the collected data. We employed both inductive and deductive (mixed coding) to arrive to the themes.Results: There were no differences in the level of education and experience of the district health managers in the two study districts. Almost all district health managers responsible for the management of the CHF had attended some training on management and leadership. However, there were variations in the personal initiatives of the top-district health leaders, particularly the district health managers, the council health services board and local government officials. Similarly, there were differences in the supervision mechanisms, and incentives available for the health providers, HFCs and board members in the two study districts.Conclusion: This paper adds to the stock of knowledge on CHFs functioning in Tanzania. By comparing the best practices with the worst practices, the paper contributes valuable insights on how CHF can be scaled up and maintained. The study clearly indicates that the performance of the community-based health financing largely depends on the personal initiatives of the top-district health leaders, particularly the district health managers and local government officials. This implies that the regional health management team (RHMT) and the Ministry of Health and Social Welfare (MoHSW) should strengthen supportive supervision mechanisms to the district health managers and health facilities. More important, there is need for the MoHSW to provide opportunities for the well performing districts to share good practices to other districts in order to increase uptake of the community-based health insurance. User fees are charges levied at the point of service use and are supposed to reduce frivolous consumption of health services, increase quality of services available and, in turn, increase utilisation of services.2 The introduction of user fees in the health sector reduced people’s access to health services, especially the poor and the most vulnerable groups of the society.5 To offset the negative effects of user fees, many low- and middle-income countries (LMICs) have introduced various types of health insurance schemes, including community-based health insurance (CBHI). CBHI schemes are noted for the principal role of a community’s involvement in raising, pooling, allocating, purchasing, and supervision of the health financing arrangement. Their beneficiaries are individuals with no form of financial protection or ability to cover the cost of healthcare services and the schemes are voluntary in nature.6 While CBHI schemes are criticised for the limited extent of resource generation and pooling, they have been shown to facilitate and improve access to healthcare services, especially among children and pregnant women8 as well as the rural poor and informal workers.9In early 1990s, Tanzania like other African countries, adopted health sector reform (HSR). The most strongly held centralisation system that informed the nature of services provision including health was, thus, disintegrated giving rise to decentralisation system.10 According to the CHF Act, the objectives of the fund are to: mobilise financial resources from the community for provision of healthcare services to its members; provide quality and affordable healthcare services; and improve healthcare services management in the communities.10 The scheme started operating in 1996 as a pilot study in Igunga district. The CHF membership is given on voluntary basis in which a household contributes an annual payment. The annual payment for the household is defined by the respective districts. The amount paid by the household entitles a particular household to a basic package of health services at a primary healthcare facility and hospital level in some districts.11 The funds collected by the district are doubled by a “matching grant” from the central government.13 Poor households which are unable to pay are supposed to be issued CHF membership card or an exemption letter.10 The powers to issue exemptions is vested into the Ward Health Committee after receiving recommendations from the village council.10 At the district level, the CHF is managed by the Council Health Service Board (CHSB) with representatives from the district authorities, public healthcare providers, private healthcare providers, and the community. At the ward and village level, the Ward and Village Development Committees, respectively, and the Health Facility Committees (HFCs) are responsible for mobilising people to join the CHF, overseeing premium collections, evaluating CHF operations and granting exemptions to poor households which are unable to pay.11 The ministry responsible for health and the ministry responsible for local government are required to provide advice and technical support to the fund and monitor and evaluate the activities of the fund.10Based on the potential benefits of the CBHI scheme, the government of Tanzania officially introduced Community Health Fund (CHF) through Act No 1 of 2001.17 In some case, these schemes have provided some form of reductions in out-of-pocket payments14 while in other cases there is no significant impact on out-of-pocket payments, the use of health services or health status.17Over the past decade, several systematic reviews that assessed the impact of the CBHI schemes on health status, the use of health services and financial protection have reported mixed results.18 Despite these achievements, the country level enrolment rate has remained as low as 9.2%.19Likewise, in Tanzania studies that have assessed the performance of the CHF schemes have reported mixed results. In some districts in Tanzania, CHF has managed to provide financial protection against health shocks to their members by reducing the level of out-pocket payment for healthcare.22; poor quality of health services in the health facilities, particularly shortage of drugs, lack of essential medical supplies, lack of diagnostic equipment, and long waiting hours among others.24The widely cited factors for the low enrolment in CHF include low economic status of the households25 Some districts have recorded higher performance in terms of enrolment relatively above the national average, and other districts are still far below the national average. High performing districts are but not limited to Iramba (54%), Bariadi (40.9%), and Singida rural (27.2%). Districts with poor uptake of CHF in Tanzania include Liwale (8.0%), Rungwe (6.5%), and Iringa (10%). Other districts include Ulanga, Kyela, Lindi, and Mbinga.26Although studies indicate that CHF in Tanzania is ineffective in its implementation, there are wide variations between districts.27 This study, therefore, explored the role of management and leadership practices in the performance of CHF in the context of the decentralised health systems. Health managers, like other managers, perform four broad functions: planning, organising, leading, and controlling.28 While the debate about achieving universal health coverage in LMICs focuses more on financial constraints, there is increasing evidence that weak management and leadership capacity is a major obstacle to service delivery in many countries.30 This paper has the potential to advance knowledge on the role of leadership and management in the implementation of community-based health insurance schemes at this time when many LMICs are working towards progress to universal health coverage.While studies that have assessed factors associated with uptake of CHBI exist, we are not aware of previous studies that have explored the role of leadership and management practices in the uptake of the CBHI schemes in LMICs. The recent systematic review reported that lack of funds, poor quality of healthcare, and lack of trust were the major reasons for low CBHI coverage in LMICs.Tanzania operates a decentralised health system, organized around three functional levels: district (primary level), regional (secondary level), and referral hospitals (tertiary level). Within the framework of the ongoing local government reforms, regional and district councils have full responsibilities for delivering health services within their areas of jurisdiction, and report administratively to the Prime Minister’s Office Regional Administration and Local Government (PMO-RALG).The district councils have mandate for planning, implementation, monitoring and evaluation of health services. Each council has a District Medical Officer (DMO) who heads the Council Health Management Team (CHMT) and is answerable to the District Executive Director (DED), the head of the council. CHMTs are responsible for provision of services in dispensaries, health centres and district or district-designated hospitals. The Regional Health Management Teams (RHMTs) are responsible for interpreting health policies at the regional level. The Ministry of Health and Social Welfare (MoHSW) is responsible for policy formulation, supervision, and regulation for all health services throughout the country, as well as playing a direct role in the management of tertiary health services.The Ministry of Finance and Economic Affairs (MoFEA) manages the overall revenue, expenditure, and financing. Its duties include preparing the Central Government budget and determining expenditure allocations to different Government institutions. The President’s Office, Public Service Management (PO-PSM) assists in matters of personnel and administration pertaining to public service in the entire government system. This includes responsibilities for personnel policies, administration and coordination of training and recruitment.The study was conducted in Iramba and Iringa rural districts in Singida and Iringa regions, respectively. The study adopted an exploratory case study design focusing on two districts one being a high performing district and the other being a low performing district. The CHF performance in this study refers to increased enrolments, retention of members, provision of benefit package to members, and management of the CHF funds. The exploratory case study is appropriate in investigating phenomena characterized by a lack of detailed preliminary research, especially formulated hypotheses that can be tested. This study design provided researchers with a high degree of flexibility and independence with regard to the data collection. The “high” and “poor” performing district was based on the increased enrolments, retention of members, provision of benefit package to members, and management of the CHF funds. Iramba, the high performing district had CHF enrolment growing faster from 12% in 2009 to 54% in 2013. While Iringa district with poor performance had 1.7% of CHF enrolment in 2009 to 10% in 2013. In terms of provision of benefit packages to members, in Iringa district services were limited to one health facility where members had registered while in Iramba district, CHF members could access services at any primary healthcare facility within the district.A sample of 78 respondents was used, 39 from each district. The sample was drawn from health providers, district health managers, and other health stakeholders in the two districts. The sampled respondents included members of the CHMT, CHSB, Health Facility Governing Committees (HFGCs), in-charge of the health facilities, the Community Development Officer (CDO), and district CHF coordinators. Purposive sampling technique was used to select respondents. The main criterion for the selection of the participants was their involvement in the management of the CHF. In each district, 3 health centres and 4 dispensaries were purposively selected in consultation of the district health managers. The health facilities were selected mainly based on the geographical accessibility and operation of the CHF for at least 1 year. In Iringa district, health centres that were selected included Isimani, Kiponzelo, and Nzihi and dispensaries were Tanangozi, Kalenga, and Weru. In Iramba district, health centres that were involved in the research included Mgongo, Ndago, and Kyengege while dispensaries were Bomani, Mbelekese, and Misigiri.Data were primarily collected by the first author using in-depth interviews involving key respondents. The purpose of in-depth interviews was to collect information from a wide range of people who had first-hand knowledge about the CHF operations. A semi-structured interview guide was developed to assist the interviews with key respondents. The use of semi-structured interview guide enabled participants to express their views and to elaborate on issues that they felt were most relevant and important. Interviews were carried out until saturation point was reached, meaning that no new concepts were emerging from the interviews.In-depth interviews as well as minutes of the committee meetings were analysed using thematic approach. The unit of analysis was individual respondents as well as teams. The data analysis involved a number of steps. The data analysis firstly involved a process of familiarisation with the data by listening to the audio-recordings and reading the transcripts and notes from the minutes several times and noting ideas. Secondly, the first author developed a code manual based on the research objectives of the study. A list of initial themes was drawn up, based on the objectives of the study. The process of theme generation was reviewed and refined by going back and forth between the themes and the codes, as well as between the themes and the transcripts until the final themes were defined. We, therefore, employed both inductive and deductive approaches (mixed coding) to arrive to the themes. Thirdly, the transcripts of each interview were read through and responses were identified and were then coded manually in accordance with the identified themes. Fourthly, data were sorted and grouped together under patterns that were considered accurate, complete, and generalisable. As patterns of meaning surfaced, similarities and differences were identified. Finally, data were summarised and synthesised, retaining as much as possible the key expressions of respondents. After this analysis, data were triangulated to allow comparison across different categories of respondents.This section presents key findings of the study organised in five themes namely: characteristics of the district health managers; uptake of CHF in the study districts; personal initiatives of the district health managers to increase uptake of CHF; supportive mechanism exerted by district health managers; and motivation and incentive mechanisms.The age of the respondents ranged from 18 to 51. As indicated in In terms of experience of stakeholders in the health sector, the findings did not reveal any huge difference among the two districts. As indicated in However, interview with CHF coordinators in both districts revealed difference in experience. In Iringa district, the CHF coordinator had only 1 year of experience. In addition, apart from being the CHF coordinator, he had to attend other duties concerning community development which greatly affected his performance as a CHF coordinator.“Due to my little experience, I should have been left to concentrate on CHF matters only. You know, coming in the office without knowing what you will exactly deal with, dwarf my experience and above all jeopardize CHF performance in the district” (IDI with CHF coordinator).It was evident from the interviews that the duties of CHF Coordinator were too demanding and required enough time to handle them. These duties included preparing monthly, quarterly and annual reports and budget; coordinating all CHF-related activities in the district, ensuring proper filing and managing membership data, and provide technical support to the CHF stakeholders in the district. In Iramba district, the CHF coordinator had stayed in the position for 4 years and was seen to have greater command of the above stipulated job descriptions.In terms of training and managerial skills, the findings indicate that the vast majority of the district health managers in Iramba district had attended some training on managerial skills. Likewise, in Iringa district, majority of the district health managers had attended training on managerial skills. The most cited managerial training courses included management and supportive supervision, health system management, human resources management, and health information management.25 On the other hand, in Iringa district, CHF was launched in 1999 and in that year enrolment stood at 5%. Since then, there has been fluctuation in the CHF enrolment such that by 2009 enrolment drastically dropped to 1.7%.31CHF was introduced in Iramba district in 1998. In that year, 5.5% of total households were CHF members. The registration declined from 5.5% to 0.1% between June 1998 and March 1999. Ten years later, that is in 2009, the CHF enrolment grew to reach 12.0%. Since then, the district has experienced drastic increase in the enrolment such that by 2013 the enrolment recorded 54% of CHF members.The analysis of interviews revealed that in Iramba district there were a number of initiatives taken by the district health managers aimed at increasing the uptake of CHF compared to Iringa district. Such initiatives included monthly evaluation of CHF performance, formation of hypothetical households who join CHF, introduction of mobile CHF and referral system, overhauling CHF and user fee payment system as well as community sensitisation aimed at making people join CHF.To start with, Iramba district conducted monthly review of CHF performance. This was done through monthly meetings involving HFCs. The MoHSW’s guideline requires that HFCs meet quarterly. In those meetings, the HFCs discussed achievements, challenges and prospects of CHF in their respective health facility and reports were submitted to the CHMT on a monthly basis. As a custom, CHMT met from first to fifth each month to discuss reports from each health facility. This was a pre-condition for the in-charge of a health facility to get a token, mostly transport allowance as well as per diem for one day. Health facilities whose reports were rejected were sternly warned and the in-charges of the health facilities were not given transport allowance and per diem. The vast majority of respondents reported that this initiative significantly increased enrolment of CHF in Iramba district. On the contrary, In Iringa district, respondents across all levels rarely reported initiatives taken to increase the uptake of CHF. It is not surprising that CHF enrolment in Iringa district was disappointingly low.Secondly, in Iramba, the district health managers formed hypothetical households who were obliged to join CHF. Respondents reported that elders who were unable to pay CHF premiums were grouped in 10s which formed one household and the village government paid on their behalf. Also primary and secondary school students were grouped into 10s and 5s, respectively. Each primary school student paid TShs 1000 per year , and those of secondary school paid TShs 2000 per year  making total of TShs 10 000 of a single household. Those who were working in informal sector like petty traders (Machinga) and motorcycle drivers (Bodaboda) also formed hypothetical household of 10s and then joined CHF quite smoothly. The findings from all respondents revealed that this initiative helped significantly in increasing the uptake of CHF in Iramba district.Thirdly, Iramba district’s attempt to introduce portable CHF and referral system were commended by respondents as an initiative that motivated members to join CHF. According to our respondents, in Iramba district, when CHF members got sick, they could access health services at any primary healthcare facility within the district. In terms of the referral system, CHF members were referred to the health centres and to the district hospital. It was found out that CHF members who were referred to the district hospital could utilize up to a maximum of TSh 20 000  from the CHF fund to cover expenses. The CHF members were required to pay additional costs, if any. In contrast, in Iringa district, the CHF benefits were limited to one primary healthcare facility  closest to the residence of the member and were not transferable to other healthcare providers in the district.Fourthly, Iramba district increased the rate of user fee payments in order to encourage households to enrol with CHF. The district council increased the amount of user fees from TShs 1000 to TShs 3000 at the dispensary level, and from TShs 1500 to TShs 4000 at the health centre. At the same time, the annual premium for the CHF was changed from TShs 5000 to TShs 10 000 per household. This initiative was taken by CHMT and approved by the Full Council in 2012. The vast majority of respondents reported that increase of the amounts of out-pocket payments significantly increased the enrolment to CHF. Commenting on the benefits accrued from overhauling payment scheme, one respondent remarked.“From the day the payment scheme was overhauled, it is very rare to find patients who pay at the point of service delivery. Almost all of them are CHF members. We are now used to the truth that those who pay at the point of service delivery are mostly new comers to our district” .In contrast, in Iringa district, the payment scheme for CHF and user fees were found out to have remained the same for over 15 years since the introduction of CHF in 1999. The annual premium for CHF was TSh 5000 while the use fee was TSh 2000 per facility visit. The analysis of interviews with the in-charges of the health facilities in Iringa district revealed that patients preferred to pay TShs 2000 to get treatment instead of paying TShs 5000 as CHF premium annually. According to the members of the HFCs, the vast majority of patients were not happy with the quality of health services provided in the primary healthcare facilities.Kuku mmoja CHF mwaka mzima kwa kaya” meaning “selling one chicken enables a family to buy CHF premium for the whole year.” This slogan encouraged household members to keep chicken that would enable them to join CHF easily. Commenting on how sensitisation had re-energised CHF uptake one respondent put it this way:Furthermore, Iramba district had introduced an innovative and participatory sensitisation process. In Iramba, sensitisation was not only done by the members of CHMT, CHSB, or HFCs but also it encompassed all district council management team led by the District Commissioner (DC) and the DED. The analysis of interview with CHMT members revealed that CHF had been made a permanent agenda and so was widely discussed in formal and informal meetings. For example, every Friday heads of departments met with the DED to discuss various issues. The CHMT members reported that CHF was made a permanent agenda in those Friday meeting. The DC on his part had designed a slogan known in Kiswahili as ““Our success in CHF enrolment for three years now has not come by accident. Our sensitisation has penetrated the whole community. In Iramba, CHF is everywhere. Our hamlet chair persons, Village Executive Officers (VEOs), Ward Executive Officers (WEOs), Ward Councillors above all DCs and DEDs have done a commendable job” (IDI with a CHSB member).In contrast, in Iringa, the vast majority of respondents reported that sensitisation was rarely carried out. Although CHMT mentioned it as a way of recruiting new members and retaining the old ones, it was reported as a dormant exercise. This was made clear by the CHSB members who argued that they had not been involved in any sensitisation exercises for two years since they were chosen. Similarly, the majority of the in-charges of the health facilities who were interviewed eloquently reported that they had confined their sensitisation exercise to what may be termed as “indoor sensitisation.” That is, they largely relied on the sensitisations done by the health providers at the health facility.The study explored the extent to which health facility in-charges are provided with support for effective implementation of CHF. It was evident from the analysis of interviews that in Iramba respondents felt satisfied with the support provided by the district health managers. Supporting mechanism that were said to be exerted to the health facilities included but not limited to constant encouragement of HSF who work in remote areas, continued coaching of HSF, regular visits of the district health managers to the health facilities, frequent and friendly communication between district health managers and HSF. On the contrary, in Iringa district the vast majority of the CHMT members felt that the support provided by the district health managers to the health facilities was inadequate. One respondent exemplified it this way:“I don’t think we are delivering the needed support to our Health Facility Staff (HFSs). For instance, for a week now I have been seeing several in-charges coming to these premises asking for procedures of purchasing drugs since the drugs that had been sent by MSD was over, but no one attends them. You know, before being a CHMT member I was the in-charge of a health facility and I experienced the same. There are times you really lose hope” (IDI with a CHMT member).The findings revealed that both Iramba and Iringa districts had a system of motivating their HSF and health committees. The marked difference was evidenced in the type of motivation, consistency and modality that were used in implementing motivation and incentive schemes.The analysis of findings revealed that in Iramba, there was a clear schedule of providing motivation and incentive scheme to the HFSs contrary to Iringa. In Iramba district, it was evident that extra duty allowance was timely paid to HFS on a monthly basis based on their rank. Clinical officers received TShs 50 000, senior nurses received TShs 40 000 and auxiliary nurses were paid TShs 30 000. Additionally, on-call allowance was timely given on a monthly basis. Clinical officers were paid TShs 60 000 and nurses were paid TShs 30 000. When asked the extent to which they were satisfied with the incentives one respondent remarked this way:“I have worked in 5 different district councils to date. Sincerely, I have not seen the district council that pays extra duty allowance and on-call allowance timely like Iramba. I cannot keep this secret my brother; Iramba is exceptional when it comes to the question of motivating health providers .It was revealed that the CHF was the main source of fund which was used to pay incentives to health providers and district health managers as well as health committees. Iramba district was able to generate enough funds from CHF. According to the 2013/2014, Comprehensive Council Health Plan (CCHP), Iramba district had collected TShs 227 690 495 from CHF in 2012/2013 and the district was expected to collect TShs 394 508 403 from CHF during 2013/2014 financial year. In Iringa district, on the contrary, findings revealed that even though extra duty and on-call allowances were stipulated in the guideline, the exercise was constrained by irregularity in paying the suggested amount. This problem was compounded by the councils’ heavy reliance on the basket fund (donor funds). It was evident that there was frequent delay in the disbursement of the basket fund to the district councils. This largely affected the payment of incentives to the health providers, district health managers as well as HFCs. For instance, in the financial year 2012/2013, Iringa district collected only TShs 34 269 100 from the CHF. One CHMT member in Iringa district recounted:“We have good plans that are, however, interfered by the government’s delay to disburse fund timely. Sometimes three months can elapse without receiving any coin from the government. How can we pay say on-call allowances under such circumstances? We are making all our efforts but we mostly prove failure” (IDI with CHMT member).The findings revealed that both Iramba and Iringa districts had a system of motivating their health committees. Like health providers and district health managers, the marked difference was evidenced in the type of motivation, consistency and modality that were used in implementing motivation and incentive schemes. The analysis of interviews revealed that in Iringa, HFC members were paid allowance of TShs 5000 after each meeting which were convened quarterly. Thus, annually the HFGCs received a total of TShs 20 000. However, the findings further revealed that HFGCs did not get the allowance immediately after the meeting. Sometimes, the payment was delayed until the next meeting which largely affected morale of the committee members.In contrast, in Iramba district, payments for the HFGCs worked well. Committee members were paid after each meeting which was convened monthly. The chairperson and secretary of the committee were paid TShs 3000 and other committee members were paid TShs 2000. The committee members reported that they were paid immediately after the meeting. While the amount of allowance paid was reportedly small, the vast majority of the committee members felt satisfied and motivated. In addition, the fact that in Iramba the committees met monthly to discuss issues pertaining to the performance of their health facility and CHF in general, it largely increased the uptake of CHF. It needs to be noted that the MoHSW guideline stipulated HFGCs to meet quarterly. Additional meetings are held at the discretion of the respective district councils.In Iringa district, the CHSB members were paid a flat rate of TShs 80 000 after every meeting which were normally convened quarterly. The analysis of interviews revealed that in Iringa district, the CHSB members rarely got an opportunity to visit health facilities. They largely waited for reports from CHMT who normally did supportive supervision to the health facilities. One CHSB member complained:“I assure you, we have never visited any health facility. Believe me, this is my second tenure as a CHSB member. When I visit my nearest health facility for medical reasons, I am merely treated just like any other citizen because very few health providers know me as an CHSB member. 3-4 months can elapse without us engaging in any health-related matters until the meeting is convened. Under such a situation do you expect the CHF to perform better?” (IDI with CHDB member).In contrast, the CHSB in Iramba district displayed outwardly enjoyment of their position in the district. In Iramba district, the chairperson and the secretary of the CHSB were paid TShs 200 000 while other members of the board were paid TShs 150 000 after each meeting which were normally convened quarterly. Additionally, when the CHSB members visited health facilities they were paid allowances. One CHSB member noted:We are so grateful to our district council for what they do to us, especially when we hear the cries that other CHSB face in other districts. The district has given us a wide room for us to perform our tasks without any interference. We are even privileged that when we attend medical care at Kiomboi hospital, we do not stand in queues.”“This paper has described the experiences of the district and local level actors in implementing community health insurance in Tanzania. In this section, we expand on the key issues raised by the respondents with reference to other studies on the implementation of health policies in developing countries.The findings of the study did not reveal major differences among district health managers in the two study districts in terms of demographic characteristics of managers, management education and training, and management practices, although in the overall Iramba (the high performing district) scored slightly higher than Iringa rural (the low performing district) on some indicators. There were substantial differences in favour of Iramba district on one key indicator of leadership namely: personal initiatives of the top-district level leaders and district health managers to get things done.32 For example, a study done in Indonesia found out no major differences between the study districts in terms of demographic characteristics of managers, management education and training, and management practices. However, there were important differences in two key leadership indicators namely: personal initiatives to get things done and fairness in handling staff disciplinary matters.32 Nevertheless, the authors felt that there was insufficient evidence to support the assumption that the differences in performance of district health system were related to the differences in the performance of district health managers.It is evident that the variation in the uptake of the CHF reported in this study was largely attributed to personal initiatives of the top-district level leaders and the district health managers. This finding corresponds with earlier studies on decentralised district health management in developing countries.33 It was evident that in Iramba district the high rate of enrolment in CHF was largely attributed to the personal initiatives of the top-district leaders such as DED and the DC as well as the DMO. Such an initiative was seen in a number of ways like introduction of monthly evaluation of the performance for CHF, formation of hypothetical households, introduction of portable CHF health service package and referral system as well as overhauling of payment system. The CHF design in Iramba district which provided opportunity for the CHF members to access health services at any primary health facility in the district was more attractive. A recent study in Tanzania reported that people are usually mobile, which includes their occasional travelling from one place to another for various socio-economic or business commitments.34 This implies that the CHF design that requires members to access services in a fixed health facility which is closest to one’s place of domicile seems to be inappropriate.However, qualitative studies done in Tanzania found out that managerial and leadership practices of the district health managers, including effective supervision and personal initiatives of the top-district health officials coupled with incentives, were the major factors for the good performance of the district health system.35 calls job-related stress which is associated with low level of job satisfaction, high rate of burnout, absenteeism and notoriously high hesitancy to serve the community. Studies have indicated that subordinates who lack support from their managers rarely put extra effort, are distracted from job performance and less motivated to perform beyond maximum requirement.36 In Iramba district, on the other hand, as CHF uptake kept improving, HSF and managers continued to be creative, reflective, enthusiastic and ambitious in ensuring that CHF enrolment continued to increase. Bradley et al37 report that in districts where HSF receive the needed support from their superiors, the HSF experienced sense of self efficacy, felt motivated and satisfied and consequently performed impressively in discharging their duties.The high performance of CHF in Iramba district was also due to effective support mechanism that was rendered to the health facilities by the district health managers. In Iringa, CHF was affected by absence of laudable attempt to support the HSF. In districts like Iringa where the HSF were modestly supported by the district health managers, they suffered from what Marberry38 a body of evidence suggests that where motivation has been consistently applied, particularly to the HSF and health committees, has resulted into higher achievement of set standards even beyond.39 This has been true with regard to CHF performance in Iramba district than in Iringa district. Findings in Iramba revealed that HSF as well as health committees enjoyed reasonable motivation. This presumably had an impact in improving the uptake of CHF.Although human motivation has been considered by psychologists to be a very difficult undertaking,This study relied primarily on the review of minutes and in-depth interviews with key actors involved in the management of the CHF in the study districts. The study focused on supply side factors that determine CHF performance (management and leadership from the supply side). We recognise that the demand factors such as household’s ability to pay may also influence the performance of the CHF. In addition, this study did not explore contextual factors in the two study districts which might also explain the observed differences in the performance of the CHF. Future studies could focus on both supply and demand side factors in order to understand better the actual practices of CHF scheme in Tanzania. Notwithstanding these limitations, the study provides good insights into factors for the diverse performance of the community-based health insurance scheme in Tanzania.This paper was meant to explore the role of decentralised district health management and leadership practices on the uptake of community health insurance in Tanzania. The paper adds to the stock of knowledge on CHFs functioning in Tanzania where the practice is still relatively new compared to other countries in Africa and elsewhere. By comparing the best practices with the worst practices, the paper contributes valuable insights on how CHF can be scaled up and maintained.The findings of this study provide insufficient evidence to support the assumption that the differences in the performance of the study districts in terms of uptake of CHF is related to the differences in the leadership and management practices and behaviours of the district health managers. No major differences were found among district health managers in the two study districts in terms of management and leadership skills and behaviour, although in the overall Iramba district scored slightly higher than Iringa rural district on some indicators.The variation in the implementation of the community health insurance scheme reported in this study suggests that district health managers and local leaders were able to exercise considerable discretion in the implementation of the CHF scheme. It is mainly due to the personal initiatives of the top-district health leaders, particularly the district health managers and local government officials which led to the variations in the performance of the two study districts in terms on the uptake of the CHF. Additionally, availability of health services, effective supervision mechanisms, and incentives for the HFCs and board members had significant impact on the performance of the districts. The policy-makers, particularly the MoHSW and RHMTs, should strengthen supportive supervision mechanisms to the district health managers and health facilities. More important, there is need for the MoHSW to provide opportunities for the well performing districts to share good practices to other districts in order to increase uptake of the community-based health insurance. Furthermore, there is need for active collaboration between the district health managers and local level leaders such as councillors, ward and village leaders, as well as HFCs. These categories of actors are very important in the implementation of the policies.This work was part of the dissertation of the first author for Master of Arts in Development Management submitted at the University of Dar es Salaam, Dar es Salaam, Tanzania. The study was supported by SIDA SAREC. We are also grateful to the local government officials, district health authorities, and other stakeholders in the study districts for participating in the study. The views expressed in this study are interpretation of the authors of data received in the study areas. No blame should be laid on the supporting individuals and/or institutions.The research on whose data this paper is based was approved by the University of Dar es Salaam, Dar es Salaam, Tanzania on behalf of the Government of Tanzania and the Tanzania Commission for Science and Technology. The research clearance was also approved by the regional and district authorities in their respective administrative areas. Verbal informed consent was sought from prospective respondents before starting the interview. All respondents were granted rights to withdraw from the interview any time they wished. Confidentiality of information given by informants was rightly observed. All interviews were tape recorded with participants’ consent and transcripts were stored in a manner that protected confidentiality.Authors declare that they have no competing interests.CJ conceived the study, participated in data collection and analysis and drafted the manuscript. SOM supervised data collection and analysis and provided major contributions to the manuscript. Both authors read and approved the final manuscript.1Mkwawa University College of Education, Iringa, Tanzania. 2Institute of Development Studies, University of Dar es Salaam, Dar es Salaam, Tanzania.The regional health management team (RHMT) and the Ministry of Health and Social Welfare (MoHSW) should strengthen supportive supervision mechanisms to the district health managers.The MoHSW should provide opportunities for the well performing districts to share good practices to other districts in order to increase uptake of the community-based health insurance.The MoHSW and the Ministry responsible for regional administration and local government need to make sure that incentives to the health providers, Health Facility Committees (HFCs) and board members are available and paid in time.In order to effectively implement community-based health insurance, there is need to actively engage all stakeholders, including the public in the implementation of policies at the local level. The public, through health facility (user) committees should actively participate in monitoring the availability of quality health services in the health facilities.