This study had a threefold aim: to test the value of stakeholder involvement in HTA to reduce evidence gaps and interpret findings; and to assess a medical device by applying the EUnetHTA Core Model (CM) in South Africa and thus ultimately provide a first overview of evidence for potential widespread adoption of the technology in a primary health care (PHC) setting. Used in primary healthcare setting for obstetric use, the technology under assessment is a low-cost continuous wave Doppler ultrasound (DUS).The scoping of the assessment was defined by involving policy makers in selecting the domains and corresponding questions relevant to the ultrasound and its use. Additionally, hospital managers were invited to respond to dichotomous questions on the criteria for procurement. To substantiate evidence obtained from an initial literature review, different stakeholders were identified and consulted. The evidence generated fromall steps was used to populate the high-ranked assessment elements of the CM.The HTA on continuous-wave DUS incorporated the evidence on organizational, ethical, and social value of its use together with effectiveness, safety, and cost-effectiveness of the technology. The domains on “health problem” and “safety” had a higher rank than the rest of the nine domains. Unexplained fetal mortality is the largest single contributor to perinatal deaths in South Africa. Pregnant women in PHC setting were examined using a continuous-wave DUS, after their routine antenatal visit. The healthcare professionals interviewed, indicated the benefit in the use of continuous-wave DUS in the PHC setting and the need for training.Collection and generation of evidence based on the HTA CM and the chosen decision criteria provided a generalized but structured guidance on the methodology. Several questions were not applicable for the technology and the context of its use and elimination of those that are inappropriate for the African context, resulted in a pragmatic solution. Engaging and consulting local stakeholders was imperative to understand the context, reduce evidence gaps, and address the uncertainties in the evidence, ultimately paving the way for technology adoption. Given the ongoing studies and the evolving evidence base, the potential of this technology should be reassessed. Every Newborn Action Plan to end preventable deaths, endorsed by the United Nations member states at the World Health Assembly in 2014, set a stillbirth target of 12 per 1000 births or less by 2030. SSA countries are still far from achieving this goal [Globally, maternal and child mortality remain unacceptably high, despite significant progress in recent years ; reducinIn many resource-poor settings, the availability and quality of care in health facilities are not sufficient to hinder adverse maternal or fetal outcomes , 5. WhilA system-based approach focusing on improving the quality of care in health facilities and ensuring the delivery of essential healthcare services is necessary to reduce maternal and perinatal mortality in LMICs . In SoutWith this in mind, the South African Medical Research Council (SAMRC), Tygerberg Research Unit in Cape Town, and Centre for Scientific and Industrial Research (CSIR) developed a novel portable continuous-wave DUS, the Umbiflow™, to be used in remote areas and PHC settings. Currently, the technology is undergoing CE tests for market access, and in collaboration with World Health Organization (WHO), is tested in various cohort studies in South Africa and abroad.Health Technology Assessment (HTA) is used to evaluate the potential for adoption of the Umbiflow™ technology. HTA enables evidence-based decision-making on the introduction and use of safe, effective, and efficient technologies at various levels of the healthcare system. Its methodology has been developed substantially over the past twenty years; for instance, the European Network for Health Technology Assessment, (EUnetHTA) Core Model™ provides a comprehensive framework for conducting HTA. The Core Model (CM) was developed in the context of co-operation between European countries. It provides a validated and preference-oriented structured methodology for the assessment of health technologies . South AIn emerging settings, and especially when the technology under investigation is not yet fully established, it is necessary to consider a broad range of evidence to obtain a full picture of the consequences of the technology’s implementation. To increase the acceptance of the HTA findings, involving the relevant stakeholders throughout the HTA process is beneficial, beginning with the scoping of the assessment , 20.Evaluate a technology, the Umbiflow, which is at an earlier stage of adoption, by application of the EUnetHTA Core Model in a non-European setting;Demonstrate the value of stakeholder engagement and consultation to mitigate evidence gaps, address uncertainties, and interpret findings when evaluating technologies in an emerging setting with limited resources;Provide a first overview of evidence for the potential widespread adoption of Umbiflow™ in PHC in South Africa.This study aims to:The CM, which enables integration of various dimensions of a technology Fig.  and the Considering that, the application of HTA for medical devices (MDs) at the PHC level in South Africa is nascent, applying a validated standardized HTA methodology for MDs can provide a framework for collecting and synthesizing information and sharing of results . The CM District health managers were invited for a workshop on June 6, 2019, at the University of Pretoria to define the scope of HTA for this case study. The Centre for Maternal, Fetal, Newborn and Child Health Care Strategies, University of Pretoria helped to contact and distribute the email invitations to senior managers in Tshwane Health District. Out of the 26 managers invited, 24 participated in the ranking exercise resulting in a response rate of 92.3%. Information on HTA, the CM, and the objective of the assessment was prepared and presented to the managers in advance (2 May 2019). The objective of the workshop was to select and rank the AEs according to the relevance of the evidence needed for informed decisions. One author (DM) and trained researchers from the Centre facilitated the meeting and the ranking exercise. For each domain and AE, a 5-point Likert scale was applied, where “1” was least relevant and “5” was most relevant. Median scores were calculated per choice to characterize the category above and below which 50 percent of the scores fall. Interquartile ranges (IQR) were calculated to evaluate the degree of consensus per choice. Ratings with a median of <  = 2 and a narrow IQR (between 1 and 2) were considered to have reached consensus on the least relevant. A median of >  = 4 and an IQR between 4 and 5 were considered to be most relevant  framework for healthcare decision-making  were choThe principal investigator of the cohort studies (RP) facilitated the distribution of the email invitation. The email included a cover letter inviting the CEOs to participate and described the study objectives and the list of criteria. The invitation stated that the information obtained will be used to prepare guidance towards developing an assessment tool and will be published. Invitations were sent by mail to all nine-study sites; the email communication and collection of responses took place between June and September 2019. Three out of the nine CEOs invited agreed to participate and returned filled-out questionnaires to the authors.Population: Target population in these regions – low-risk singleton pregnant patients of > 28 weeks gestation or with symphysis fundal height (SFH) measurement of 26–30 cm if gestational age was unknown.Intervention: Use of continuous-wave DUS.Comparator: No screening using ultrasoundOutcome: patient-relevant outcomes Time: open to September 2019Study types: No restrictions to the type of studyWhile steps 1 and 2 served to define the scope and main principles of the assessment process, steps 3 and 4 aimed to collect evidence targeting Umbiflow™. In Step 3, the following databases were searched using search strategies based on the PICOTS framework delineated below: PubMed (MEDLINE), EMBASE, HTA CRD, and the INAHTA database.First, published literature on continuous-wave DUS and its assessment was searched using the key words linked with Boolean operators. The search results were screened by one author (DM) and information was extracted from included studies based on a semi-structured information collection guide. After expert consultation (Step 4), this step 3 was revisited as additional criteria such as “low-risk” AND “third trimester” were included. Further targeted searches were conducted to identify potentially missed literature specifically on the technology’s technical properties, safety aspects, and application. The reference lists of all identified sources were searched for further relevant evidence.Two authors who are also clinical investigators on Umbiflow (RP and TMH), provided unpublished data, additional literature, and direct expertise to complement the evidence generated by the literature search. The intent was to collate information on technical features, the health problem, and clinical practice using a structured tool  and “safety” (SAF) had a median of 5 and the rest of the 9 domains had a median of 4. However, there was a variance observed in the IQR. 5 of the 9 domains including CUR and SAF reached a consensus with a strong agreement (IQR between 4 and 5) on their relevance. In the case of the other domains, the IQR varied between 3 and 5. For instance, managers were uncertain about the necessity of evidence on organizational implications (ORG) and questioned the appropriateness of detailed technical evaluation (TEC).Variation was also observed across AEs within the individual domains  on the importance of improvement in-patient reported outcomes and contextual criteria, such as priority of the population and equity of access as relevant decision criteria. The responses are shown in Table  to 1 on The evidence map Table  illustraIn Step 3, a total of 65 relevant sources of evidence were collected following the search in bibliographic databases, expert consultation and hand searching the reference lists of already identified sources. The flow of information is documented in a PRISMA flowchart  was mainly obtained from global and local literature on maternal and child health Step 3), supplemented by information provided during expert consultation (Step 4). Information on the technical characteristics (TEC) of the continuous-wave DUS in general and Umbiflow™ in particular was retrieved from technical literature and in consultation with the experts; users (Step 4) provided information on training needs and characteristics. For safety (SAF), the expert consultation yielded additional details on usability and type of errors. Evidence on economics (ECO) was obtained from the completed Master’s thesis on cost analysis and a conference abstract (paper unpublished) on cost-effectiveness analysis, shared by the PI. The site visit described in the methodology (Step 4) gave further insight into communication requirement and patient acceptance of the technology. Information on legal matters (LEG) was difficult to obtain; the two acts mentioned in Table , supplemThe detailed responses provided by the nurse practitioners, midwives and clinicians through the survey questionnaire provided insight on the use of the Umbiflow™ for obstetric services in its intended setting in the South African health system. Eight nurses and six clinicians responded to the survey.The nurses informed that utilization of these additional Doppler ultrasound services led to complications in work processes, misunderstandings and difficulties arising from having to share the examination rooms limiting privacy for patients. They recommended that trainees start using the device right after the training period to minimize reading errors. Computer literacy is mandatory, as sometimes assistance in dealing with computer malfunctioning can take time. They also pointed out the communication flow among doctors and nurses on duty at the centres should be maintained, as currently the technology is not included in the standard of care.Clinicians welcomed an innovative solution, effective and low cost, addressing the need to prevent stillbirths. However, not all clinicians used it themselves. One of the clinicians perceived the use of Umbiflow™ as beneficial for patient care and early management. The technology had the potential to improve the current patient pathway by earlier recognition of fetus at risk for growth restriction at the local clinic level. Another clinician indicated that this could help in reduction of serious adverse events and resulting litigations. They were uncertain about the real cost of the technology when adopted into standard care and disagreed on the need for extra staff. A few suggested that the midwives currently employed could be trained on using the technology. A clinician stated that computer literacy is mandatory and another indicated that funding could be an influencing factor. Overall, they found that it would be beneficial at the PHC setting.A mapping of the evidence according to the CM assessment elements is shown in Table .The following sections summarize the best available evidence on Umbiflow™ for the primary care setting in South Africa. Diagnosis using continuous wave DUS was evaluated and compared with usual care i.e. non-use of DUS or other forms of USIn South Africa, unexplained fetal mortality is the largest single contributor to perinatal deaths . A quartCurrently, Umbiflow™ is used in the context of the ongoing cohort trials. After receiving their routine ANC visit, the women would be taken by the nurse or midwife to an examination room for the scan to be performed. The procedure of the examination is explained to the patient by either the nurse or the clinician present and the patient is asked to sign a consent form. Due to the high burden and abundant research, evidence on the health problem was readily available from the literature on maternal and child health care, as also highlighted in other studies . HoweverUmbiflow™, is a continuous-wave DUS device for use at PHC facilities and antenatal clinics. The software processes the US signals to generate a high quality waveform depiction of the umbilical blood flow. The waveforms are displayed on the computer screen. The “resistance index” (RI) which can be directly linked to the functioning of the placenta  is calcuDUS can produce biological effects such as tissue heating representing a potential health risk. However, the continuous-wave DUS have low output intensity in comparison to pulse wave Doppler . NonetheThe potential disadvantages include false-positive and false-negative results, although these rates are typically low , 31. If Evidence on effectiveness of continuous-wave DUS was mainly obtained from literature, supplemented by information specifically on Umbiflow™ obtained from consultation with experts and users. All studies on Umbiflow™ were cohort studies, conducted in South Africa; randomized trials have not been conducted.The studies on Umbfilow™ reported diagnosis related adverse events. Nkosi et al.  determinIn 2005, Theron et al.  examinedTimely detection of abnormalities in the blood flow in the uterine artery followed by management of undiagnosed placental insufficiency could lead to prevention of perinatal deaths , 28, 34.The evidence for economic impact of use of DUS in a clinical setting was taken  from grey literature. Rossouw et al.  showed tThe literature on Umbiflow™ and consultation with the users and experts provided evidence on organizational aspects. Healthcare professionals including nurses or, midwives can use the device after receiving short training to detect correct soundwave and visually interpret a correct wave pattern on the computer screen . The leaInformation provided from current users of the technology in South Africa suggests that they sometimes lack resources to provide services in informative and proper manner . Additional infrastructure, such as extra examination room, is not required due to the portability feature of the machine, and screening can be integrated within the organizational infrastructure associated with standard care see Fig. . HoweverSection 14 of the National Health Act  of SouthThe evidence on ethical aspect of using Umbiflow™ was extracted from literature on DUS. The use of Umbiflow™ is expected to lead to detection of anomalies in the third trimester. As with other ultrasounds, the relative uncertainties in realization of the promise of the benefits have to balance the psychological benefit of patients wanting to be informed about the well-being (in some cases the first time) of the fetus. This subjective benefit must be weighed against inconvenience of situations leading to unneeded referral to a district hospital or can lead to adverse outcome from unnecessary interventions, in case of false positives. The Umbiflow™ screening is done only with patient consent. Not all pregnant women visiting the clinics are willing to be screened, which could be due to religious, cultural, or spiritual beliefs –41.Patients are required to provide their consent before Umbiflow™ examination. Nurses at the CHCs confirmed that patients favoured the technology. They stated that, most patients were not knowledgeable on how to care for their unborn babies (e.g. intake of nutrients) and connect with them. The patients were impressed about the possibility of diagnosis and intervention before birth and some wished for an examination.This study reports on the value of stakeholder engagement and consultation during scoping evidence. It tests the feasibility of using the EUnetHTA Core Model in a non-European country to assess continuous-wave DUS technologyfor adoption in low resourced PHC setting and highlight the potential organizational impact and clinical benefit of a simple low-cost technology in such a setting.First, consensus was sought on the relevancy of the HTA CM domains and the guided questions. Briefly, the domains, CUR and SAF and three others, EFF, ETH and SOC had received a median of 5 and 4 respectively and a narrow IQR . The result of the ranking led to four other domains having a wider IQR . Since some of the issues within these domains had a narrower IQR, these issues were considered. Since the model has 134 assessment elements, the final number selected was smaller, and the scope was more targeted. As with other adaptations, few of the issues were rearranged as they were viewed suitable in a different domain .The scoring could have been influenced by the fact that the health services are free of charge for maternal, child healthcare and procurement and financial administration of PHC falls under district health office. Consensus was reached with a wider IQR (e.g. 3 to 5) for the evidence needed for organizational or legal aspects, as well as technical characteristics. This may be because the expression “technical characteristics,” is misleading for decision-makers. Due to the newness of the HTA concept and the CM among these stakeholders, misunderstanding and misjudgment of the selection could have resulted in error in the ranking of the domains and the respective AEs.Second, this work sought to understand the decision process for procurement of the technology . Generalization of the decision criteria is not possible at this stage as only three hospital managers responded to the questionnaire; however, their informational needs seem to be largely covered by the domains prioritized in this study. The AdHopHTA  project, which is a European Project on hospital-based HTA aims to promote collaboration of hospital-based HTA initiatives. Unlike the recommendation given in the AdHopHTA guideline  consensuThird, the inclusion of experts and users of the technology in a standardized manner in the evidence scoping process reduced the gaps in identified evidence, adding to the understanding of the appropriateness, acceptability, accessibility, and perceived affordability of the technology in its intended setting of application.Fourth, the synthesis of collected evidence shows that screening using continuous-wave DUS may be better suited than only SFH measurements in detecting pregnancies at risk of stillbirth. Heazell et al.  in theirThe assessment carried out in this study demonstrates the promise of Umbiflow™ in context by drawing on additional, qualitative judgments on the functioning of the device, its proposed benefits, and the plausibility that its adoption will provide the claimed improvements. To mitigate uncertainty in the absence of robust randomized control trials, experts were consulted, and stakeholders involved, which aided the assessment process. However, it is important to reiterate the limitations of expert opinion as evidence for HTA, given its substantial potential for bias.Involving the decision-makers on the ranking of the domains and the criteria for assessment sensitized them on the usefulness of CM and their acceptance on the relevancy of the evidence. The necessity of broader upstream consideration, besides, cost-effectiveness early on in the technology lifecycle  can contOne of the advantage of Umbiflow™ is that an experienced sonographer is not needed. However, skill levels and scanning method may differ between the operators and may need the intervention of the clinician on duty. However, use is simple for the nurses and they could master the techniques within short time.The selection of assessment domains and elements based on deliberation is challenging due to the diversity of user demands and preferences. Furthermore, none of the district managers and hospital decision makers involved in this study requested further clarifications or information. It is therefore uncertain how these stakeholders interpreted the description of the individual AEs. Due to the complexity and newness of the CM, some respondents may have misunderstood and not selected certain relevant AEs.Since 2005, further development and improvement of the technology incorporating latest mobile and information technologies, software development has taken place. However, no studies have compared previous models to the current models and therefore it is unclear whether results obtained from previous models are generalizable to the model currently under study.This study did not consult gynecologists who are unfamiliar with continuous-wave DUS or do not work in the PHC setting. They could have provided their perspective on the benefit of a continuous-wave DUS to be used at the PHC level.Involvement of the research institute funding the project may have the potential for introducing bias in the reporting of outcomes.This study tested the applicability of the HTA CM to evaluate the value of a continuous-wave DUS, the Umbiflow before adoption in a low-resource setting. Mapping a set of decision criteria before the assessment process addressed the perceived gaps in evidence. Collection and generation of evidence based on the HTA CM and the chosen decision criteria provided a generalized but structured guidance on the methodology. Several issues did not apply for the technology and the context of its use. To streamline the issues and thus the assessment elements, careful appraisal and application to other classes of MDs to eliminate those that do not fit into the African context will be required.Engaging and consulting stakeholders locally was imperative to understand the context, reduce evidence gaps and address the uncertainties in the evidence, ultimately paving the way for technology adoption. Transparency in the assessment process and method is vital, as the assessment involved experience and elements of judgement. The consideration of risks associated with continuous-wave DUS use and its low cost need to be balanced with the acceptance and the promise of the technology in the context. Post-introduction, further robust evidence and its analysis will be essential to determine the realised value and thus the future use of this technology, which is competing with similar innovative technology.Additional file1: Table S1a. Step 1: Identification of criteria necessary to decide on adoption of a technology in the hospitals. Table S1b. STEP 2: Identification of elements necessary to assess Umbiflow. Table S1c. STEP 4: Consultation of clinical and technical expert on Umbiflow. Table S1d: STEP 5: User Questionnaire. Fig. S1f: Prisma Flowchart (DOCX 84 KB)


The forecasts of local severe storms (LSS) are highly dependent on how well the pre-convection environment is characterized in the numerical weather prediction (NWP) model analysis. The usefulness of the forecasts is highly dependent on how frequently the forecast is updated. Therefore, the data latency is critical for assimilation into regional NWP models for it to be able to assimilate more data within the data cut-off window. These low latency data can be obtained through direct broadcast sites and direct receiving systems. Observing system experiments (OSE) were performed to study the impact of data latency on the LSS forecasts. The experiments assimilated all existing observations including conventional data  and satellite sounder radiance data (AMSU-A (The Advanced Microwave Sounding Unit-A), ATMS (Advanced Technology Microwave Sounder), CrIS (Cross-track Infrared Sounder), and IASI (Infrared Atmospheric Sounding Interferometer)). They were carried out in a nested domain with a horizontal resolution of 9 km and 3 km in the weather research and forecasting (WRF) model. The forecast quality scores of the LSS precipitation forecasts were calculated and compared with different data cut-off widows to evaluate the impact of data latency. The results showed that low latency can lead to an improved and positive impact on precipitation and other forecasts, which indicates the potential application of LEO direct broadcast (DB) data in a high-resolution regional NWP for LSS forecasts. The advanced infrared (IR) and microwave (MW) sounders  onboard The new generation of geostationary satellites such as the FengYun-4 (FY4) series , GeostatAssimilating the low latency data from low earth orbit (LEO) and geostationary (GEO) into high resolution regional NWP models demonstrates a process for improving rapidly changing weather forecasts. Impact studies have been conducted through observing system experiments (OSEs) on the assimilation of radiances in regional NWP models. The focus has been on the impact of latency from polar orbiting satellite sounder data due to the current limited sounding capability from GEO orbit, as above-mentioned. In general, there is a trade-off between the number of observations and latency. Low latency ensures that observations are closer to the model analysis time, which is beneficial to NWP, but may result in fewer observations available for the model. In this study, all available observations including conventional data and satellite data were tested within different data latency schemes in the regional NWP model for LSS case simulation. The equitable threat score (ETS)/false alarm rate (FAR)/probability of detection (POD) scores of the LSS precipitation forecasts were calculated and compared with different data cut-off widows to evaluate the impact of data latency.The rest of this article is organized as follows. The current polar orbiting satellites such as from Suomi-NPP, JPSS, and Metop-A/B have atmospheric sounding capability in the pre-convection environment and low latency can be obtained through DB sites over the CONUS and adjacent regions. DB is the most rapid way to obtain the satellite observations from the sensor to the ground processing system. According to the NOAA Space Platform Requirements Working Group (SPRWG), which represents user needs, data latency is defined as the time it takes for the sensor to make the observation until the time the observation or product is available to the primary NOAA users  forecasters or NCEP), so making the observation or product available to NOAA users must therefore include the data processing time. The processing time is dependent on the observation or product and can be a substantial fraction of the total latency . For exaIn this study, the satellite data latency impacts were tested in an LSS study in regional NWP. To increase the latency impacts on the forecast results, the latency time was set as follows: 3-h, 2-h, 1-h, and no latency. A three-dimensional variational data assimilation (3Dvar) method was used for all of the experiments, with a 6-h assimilation window at the analysis time. Therefore, the 3-h latency represents the data starting at 3-h ahead of the analysis time to the analysis time; the 2-h latency represents the data starting at 3-h ahead of the analysis time to 1-h after the analysis time; the 1-h latency represents the data starting at 3-h ahead of the analysis time to 2-h after the analysis time; and no latency represents the data starting at 3-h ahead of the analysis time to 3-h after the analysis time. The 3-h latency was the largest latency with the smallest amount of satellite data, and the no latency condition provided the largest amount of satellite data during the 6-h assimilation window. The no latency condition is the ideal condition since it provides the most information at the time of analysis.Based on the required latency conditions of 3-h, 2-h, 1-h, and no latency, the original 6-hourly observations for both the conventional data and satellite observations were divided into every 3-h, 4-h, and 5-h. The 3-h data translate to a 3-h latency, 4-h data translate to a 2-h latency, and the 5-h data translate to a 1-h latency . If all Observations from selected channels of AMSU-A, Advanced Technology Microwave Sounder (ATMS), CrIS, and Infrared Atmospheric Sounding Interferometer (IASI)  are listTwo typical storm cases were selected in order to evaluate the data latency impact on the LSS. Stage IV precipitation dataset from NCEP as well as GOES-16 water vapor channel brightness temperatures (BTs) were used to detect the LSS case. Based on Stage IV and GOES-16 brightness temperatures, one LSS case ran from 000 UTC on 24 June to 1800 UTC on 24 June, 2018 (Case I), and another LSS case was from 0000 UTC on 25 June to 1200 UTC on 25 June 2018 (Case II). The 18-h accumulated precipitation for Case I is plotted in The Stage IV dataset was used as the “truth” for verifying the precipitation forecast. The Stage IV analysis was based on the multi-sensor hourly/6-h “Stage III” analyses  produced by the 12 River Forecast Centers (RFCs) in CONUS . NCEP moThe Developmental Testbed Center (DTC), supported the Community Gridpoint Statistical Interpolation (GSI) system, was used as the data assimilation system, which has the capability of assimilating nearly all of the existing observations including those from radiosondes, aircraft, microwave and infrared sounders, and radar. It is primarily a 3-Dvar system, and also has the option to be used as a hybrid data assimilation system . The hybSince the LSS Case I ran from 0000 UTC on 24 June to 1800 UTC on 24 June, 2018, the experiments started 6-h earlier, which was 1800 UTC on 23 June to 1800 UTC on 24 June, 2018. The assimilation time was 1800 UTC 23 June, and was followed by the forecasts from 0000 UTC on 24 June to 1800 UTC on 24 June, 2018. The 3-h latency represents the data only available from 1500 UTC 23 June to 1800 UTC 23 June; the 2-h latency represents the data available from 1500 UTC 23 June to 1900 UTC 23 June; and the 1-h latency represents the data available from 1500 UTC 23 June to 2000 UTC 23 June . The expLSS Case II was from 0000 UTC on 25 June to 1200 UTC on 25 June, 2018, where the experiments started from 0000 UTC 24 June, followed by a 36-h forecast. The 3-h latency represents the data from 2100 UTC 23 June to 0000 UTC 24 June; 2-h latency contains the data from 2100 UTC 23 June to 0100 UTC 24 June; 1-h latency contains the data from 2100 UTC 23 June to 0200 UTC 24 June; and no latency contains the data from 2100 UTC 23 June to 0300 UTC 24 June. All the experimental designs and the data assimilation schemes were the same as Case I.The Advanced Research WRF (WRF-ARW) v 3.6.1 was used as the regional NWP model. WRF-ARW was developed by NCAR and is broadly used in both research studies and regional operational centers. The horizontal resolution of the regional model was 9 km and 3 km nested domains. The vertical layers were 50 layers from the surface to 10 hPa. The calculation time step was every 20 s. This model setting is an emulation of RAP/HRRR. The NCEP GDAS/FNL 0.25-degree data were used as the initial and boundary conditions for the regional model simulation. The cumulus schemes were not required for the WRF-ARW model since the horizontal resolutions of the models were less than 10 km. The Thompson aerosol-aware microphysics scheme was used to simulate the LSS precipitation. The RRTMG radiation scheme was used to calculate the longwave and shortwave radiation. The Yonesei University Scheme (YUS) was used as the planetary boundary layer (PBL) scheme. The pattern of the simulated rainfall was similar to the observations when using these physical schemes, however, the simulated precipitation was stronger than the observations, which was due to the 3 km high resolution of the inner, nested domain.For the LSS Case I, precipitation is one of the most important features for weather forecasting. To further evaluate the impact of latency impacts on the precipitation forecast, the equitable threat score (ETS), probability of detection (POD), and false alarm ratio (FAR) ,24 scoreIn addition to evaluating the precipitation amounts, the forecast fields (T/Q/U/V) were also compared with the radiosonde profiles. The radiosonde stations at 1800 UTC on 23 June and 0000 UTC on 24 June, 2018 are shown in The root mean square errors (RMSEs) of the variables (T/Q/U/V) were calculated for all four experiments . The smaInstead of showing the results from individual atmospheric fields, an overall evaluation strategy was carried out. The purpose of this strategy was to use one single parameter to characterize the overall impact for the LSS simulations. The RMSEs of temperature (T), moisture (Q), and winds (U/V) compared with radiosondes  were useTemperature (T), 10%Moisture (Q), 10%U-wind (U), 10%V-wind (V), 10%1-ETS, 20%1-POD, 20%FAR, 20%The precipitation scores were given relatively large weights because of their importance in the LSS simulation. Atmospheric fields were calculated at the last analysis time  and for every 6-h forecast  for Case I. The atmospheric fields were calculated at the last analysis time (0000 UTC 24 June 2018) and for every 6-h forecast  for Case II. The precipitation scores were calculated for every 6-h accumulated rainfall measurement at 0000 UTC, 0600 UTC, 1200 UTC, and 1800 UTC on 24 June for Case I, and at 0000 UTC, 0600 UT, and 1200 UTC on 25 June for Case II.Using the method described above, the final normalized RMSEs of the four groups of experiments were calculated with a confidence interval of 95%. For Case I, comparing the four groups of experiments, the improvement from the 3-h latency to the 2-h latency was about 2.3%, from the 3-h latency to the 1-h latency was about 2.9%, and from the 3-h latency to no-latency was about 3.9% . For CasThe forecast of LSS and other rapidly changing weather events depends on how frequently and quickly the forecasts are updated. The low latency sounder data from satellites are very important in improving the pre-convection atmospheric conditions in NWP based, short-range forecasts. Such low latency data from polar orbiting satellites are available from direct broadcast (DB) sites, while the low latency data from geostationary satellites are available from GRB. In this study, the impact of low latency from sounders onboard polar orbiting satellites were demonstrated. Our findings indicate that (1) data latency directly affects the amount of data that can be assimilated into an NWP system and for data coverage, almost all types of satellite observations are increased from 3-h latency to no latency; (2) low latency from polar orbiting satellites results in better forecasts for precipitation and forecast fields (T/Q/U/V) of 1-h latency and no latency are much closer to the observations, and these low latency LEO data can be obtained via DB sites; and (3) the final normalized RMSEs of T/Q/U/V/1-ETS/1-POD/FAR indicate the following order in terms of better impact: no latency > 1-h latency > 2-h latency > 3-h latency. As the no latency condition provides the most observations to the assimilation system, it produced the best results for the LSS forecast.Two typical LSS cases were demonstrated in this study and the impact of different latencies on regional NWP-based forecasts were clearly distinguished, indicating that the forecasts are sensitive to the amount of sounder data assimilated. The impact, however, is dependent on many other factors including, but not limited to, the parent model used for the initial and boundary conditions for the regional NWP model, the sounder observational characteristics , data assimilation system, and weather situations. It is worth noting that the data assimilation technique is extremely important for low latency data assimilation: more data can be assimilated with a 4DVAR system and a large assimilation window. Additionally, a combination of an advanced satellite data assimilation system and the low latency data could improve high impact weather forecasts. Furthermore, geostationary-based high temporal and spatial resolution observations or derived products such as moisture and dynamic information are very useful for improving tropical cyclone forecasts, especially the rapid scan based mesoscale atmospheric motion vectors (AMVs) in the inner core region. Such information can be obtained via the GRB system. It should be noted that GEO data from GRB have almost no latency; however, the processing time for deriving the products  becomes important for timely assimilation for rapid update of the regional NWP model. In all circumstances, efficient data processing is critical to ensure low latency from both LEO and GEO for these applications.The results showed that low latency can lead to an improved and positive impact on precipitation and other forecasts, which further indicates the potential of applying LEO DB data in high regional NWP for LSS forecasts.


The possibility of expanding the proposed technique for the synthesis of magnetic composite with embedded biologically active substance (BAS) of the 2-arylaminopyrimidine group was shown. The composition, morphology, structural features, and magnetic characteristics of the nanocomposites synthesized with and without BAS were studied. The introduction of BAS into the composite synthesis resulted in minor changes in the structural and physical properties. The specificity of the chemical bonds between BAS and the hydroxyapatite-magnetite core was revealed. The kinetics of the BAS release in a solution simulating the stomach environment was studied. The cytotoxicity of (HAP)FexOy and (HAP)FexOy + BAS composites was studied in vitro using the primary culture of human liver carcinoma cells HepG2. The synthesized magnetic composites with BAS have a high potential for use in the biomedical field, for example, as carriers for magnetically controlled drug delivery and materials for bone tissue engineering.Magnetic nanocomposites based on hydroxyapatite were prepared by a one-step process using the hydrothermal coprecipitation method to sinter iron oxides (Fe Then, over the next 3 h, the remainder of the substance was slowly released. Thus, there was an almost complete release of the biologically active compound from (HAP)FexOy + BAS.The kinetic curves are nonlinear. Almost 80% of the active substance xO and (HAP)FexOy + BAS on biological objects. We conducted methyltetrazolium tests (MTT) using human liver carcinoma cells HepG2. The results are shown in For applications in biotechnology or medicine, it is important to understand the effect of initial (HAP)FexOy composite. This effect is enhanced with an increase in the concentration of NPs in the solution. Interestingly, at low concentrations of NPs (HAP)FexOy (up to 0.1 mg/mL), the cell death parameter has negative values, which indicates that the presence of the (HAP)FexOy composite in the cellular environment in small amounts is a favorable factor for cell development.The analysis of the data in 2 groups in the structure at various positions of the molecule. As a result, the formed composite will be promising as a therapeutic agent for the treatment of bone tumors.To summarize, it should be noted that the size of the studied nanocomposites with drugs allows them to move freely through the vessels, and the presence of the magnetic part in the composition makes it possible to move against the bloodstream. Thanks to these two peculiarities, the drugs can be easily delivered to the affected areas. In addition, a composite based on a magnetic carrier with hydroxyapatite can be used to attach an antitumor drug containing NHαradiation. The spectral analysis was completed with the use of the Bruker AXSDIFFRAC.EV Av.4.2 and the international database ICDD PDF-2. For surface characterization, the Fourier-transform infrared (FTIR) transmission spectra were recorded by the Bruker Tenzor 27 Fourier spectrometer. The measurements were taken in the wavelength range from 400 to 4000 nm. All spectra (32 scans at 4.0 cm−1 resolution and rationed to the appropriate background spectra) were recorded at room temperature.The characterization of morphological features was conducted by using a number of techniques including scanning transmission electron microscopy  at simultaneous bright-field and annular dark-field imaging regimes, energy dispersive X-ray analysis , and X-ray diffraction analysis  using Cu KThe magnetic characteristics of the composites were studied by a vibrating sample magnetometer  in magnetic fields up to 30 kOe at room temperature.xOy + BAS were studied in a solution simulating the environment in the stomach . The precipitate (HAP)FexOy + BAS (250 mg) was placed in the dialysis tube  and incubated at 37 °C in 200 mL of model solution. Aliquots of the solution were taken at certain time intervals, while the volume was replenished with an equal amount of the same solution at a temperature of 37 °C. The amount of BAS released from the biocomposite was determined spectrophotometrically  by comparing it to the previously obtained reference plots depicting the absorption of the BAS solution (at λ = 260 nm) vs. its concentration.The kinetics of the benzamide release from biocomposites (HAP)FexOy and (HAP)FexOy + BAS composites was studied in vitro by the methyltetrazolium test (MTT) assay with different NP concentrations from 0.02 to 1.0 mg/mL using the primary culture of human liver carcinoma cells HepG2.The cytotoxicity of (HAP)Fe2 incubator (Herra Cell) at 37 °C, 5% CO2, and 80% relative humidity on 96-well plates (seed concentration 50–70 thousand cells/mL). Samples of NPs dissolved in Fetal Bovine Serum  were added to the wells with adherent cells (second day of cultivation). After a 24-h exposure of the samples, the total cell mitochondrial dehydrogenase activity in each well was measured photometrically in the MTT. This test is based on the ability of living metabolically active cells to convert tetrazoline salt (MTS) into formazan, which is soluble in the culture medium. Thus, the absorption of formazan is directly proportional to the number of viable cells in the culture. The CellTiter 96® AQueous One Solution Cell Proliferation Assay (MTS), Promega kit was used for MTT. To measure the absorption of formazan, the cells were incubated with MTS for 4 h in a thermostat, and the measurement of the absorption of formazan at λ = 490 nm was performed on automatic microplate photometer EIX808, BioTek Instruments Inc, Winooski, VT, USA. The toxicity of nanoparticles was assessed by IC50.The MTT is an assay to identify metabolic disorders, namely, the dysfunction of the mitochondria reflecting the effect on cell viability. The cells were grown in a CO3O4 and maghemite γ-Fe2O3). The composites had weak ferromagnetic properties with a saturation field of about 30 kOe. The combination of ferromagnetic and biocompatible materials makes the synthesized composite promising for use as a carrier for targeted drug delivery. Composites (HAP)FexOy + BAS with adsorbed biologically active substances represent a bioactive nanosystem ready for in vivo applications, for example, for the treatment of bone diseases. An efficacy test based on the benzamide kinetics demonstrated that 80% of the active substance was released within the first 2 h. The effect of BAS bound to the surface of the composite (HAP)FexOy on cells of human liver carcinoma HepG2 was demonstrated.Using a simple one-stage method, nanosized iron oxides NPs embedded in hydroxyapatite and in a biologically active compound (BAS) of the 2-arylaminopyrimidine series containing a pharmacophore fragment for antitumor therapy were obtained. The characterization of the composition, morphology, and structural features of the synthesized nanocomposites confirmed the presence of iron oxides with a spinel-type structure (magnetite Fe


In the introductory chapter, Muresan and Orna-Montesinos provide an overview of the multiple dimensions of academic literacy development, with a focus on its relevance for plurilingual scholars engaged in academic research writing and publishing processes. They situate the ethnographic and pedagogical studies presented in the subsequent chapters within a cognitive/socio-cultural theoretical framework, providing insights into higher education and academic literacy in glocal contexts. Literacy, as an overarching concept, encompasses multiple dimensions of reading and writing abilities. As a term it has been used to promote a view of writing as social, personal, cognitive and attitudinal practice . As we expect to illustrate throughout the volume, there is sufficient evidence across geographical contexts worldwide regarding the challenges scholars face in the process of acquiring academic literacy in an L1 and in other languages. Pedagogical interventions can, therefore, play a beneficial role, particularly for enhancing awareness of discourse and genre conventions, and for raising rhetorical consciousness through appropriate tasks and materials  that underlie academic enculturation, the latter conceptualised by Prior and Bilbro  as the pInspired by previous research perspectives on the complex uses of academic languages in changing times  contexts, the volume starts with a selection of chapters that provide empirically based reflections on and enquiry into linguistic policies, norms or guidelines regarding the use of both academic English and other academic languages. These contributions also explore the impact of co-existing, controversial academic norms and guidelines on research writing in different linguistic eco-systems.In Chap. 10.1007/978-3-030-62877-2_2, Hynninen analyses the textual trajectory of a successful research paper, co-authored by six multilingual scholars. Text history data allow her to explore how different actors are allocated literacy broker roles and how they negotiate the writing norms and conventions for their interventions in the process of academic text production. In Chap. 10.1007/978-3-030-62877-2_3, Giannoni offers a critical overview of the language requirements and opportunities for thesis submission in languages other than English at UK universities. The implications of vague linguistic policies for academic literacy development are discussed in the light of recent research on multilingualism in higher education. Chapter 10.1007/978-3-030-62877-2_4 starts with the provocative question, “What constitutes ‘good’ academic writing” for multilingual students in EMI programs? McCambridge critically discusses the interplay of different academic writing norms and underlines the importance of supporting the students’ academic literacy development in ways that would help them to understand and negotiate the meaning of the different kinds of literacy practices and norms they will encounter.This section includes studies on academic writing development that draw on ethnographic or ethno-methodological enquiry, with data collected from observation, interviews and questionnaire-based surveys, conducted with graduate, Master and doctoral students, in a variety of disciplines and a diversity of international academic contexts .Chapter 10.1007/978-3-030-62877-2_5 focuses on the development of literacy in professional and academic contexts using a protocol-assisted modelling (PAM) approach, implemented to help student writers enrolled in a technical communication program to develop audience awareness by constructing a more accurate mental model of how readers think and react to information. Dressen-Hammouda discusses how the PAM method, applied in a French academic setting, contributes to the students’ literacy development by helping them better adapt their attitudes, behaviours and abilities to often unstated and shifting professional expectations. The emergence of situated work-based literacy development is thus linked by the author to mastering professional genres as well as to building disciplinary or professional identity and epistemology.Chapter 10.1007/978-3-030-62877-2_6 explores the development of academic writing literacy in a group of Spanish doctoral students participating in a writing course. Through a thematic analysis of the difficulties and challenges faced by students in their writing processes in English as an additional language, Guillén-Galve and Vela-Tafalla critically discuss how the acquisition of operational skills appears to be based on the identification of sources and strategies of independent learning and of self-efficacy, complemented by literacy brokering practices.Chapter 10.1007/978-3-030-62877-2_7 reports on the implementation of an EMI program which seeks to develop students’ academic writing, at the University of Iceland. In order to explore the students’ perceptions, Prinz and Arnbjörnsdóttir have conducted pre- and post-course surveys, with a focus on the students’ ability to regulate academic writing and their writing self-efficiency beliefs. Strategy instruction in writing appeared to help students to transfer conceptual knowledge about academic writing to functional writing skills and, thus, to develop the operational strategies and skills needed to become autonomous writers.Chapter 10.1007/978-3-030-62877-2_8 builds on an ethnographic study of a group of novice Chemistry researchers (in the US academic context) participating in a series of writing workshops with a focus on science communication genres. McCarty debates the perception of a clear divide between disciplinary writing addressed to specialists and science communication (Sci comm), targeted at non-specialist audiences. These novice writers question the creation of the narrative of science as newsworthy and the incorporation of more nuanced information about the research process. The author concludes that learning to write these new genres to address non-specialist audiences in new contexts imposes a more flexible approach to writing, one in which textual innovation results in the expression of learners’ shifting identity as scientists.The chapters in this section take further the exploration of academic literacy development journeys by placing a special focus on authorial voice, manifestations of identity, or the researcher’s and participants’ self-reflection and self-representation in the process of knowledge co-construction. The truly international dimension of the studies reported on here is reflected not only by the range of academic contexts where the chapter authors are based , but also by the diversity of linguistic and cultural backgrounds of the participants in their research, whose original country contexts included, for instance, Bosnia-and-Herzegovina, Brazil, China, Korea, R. N. Macedonia, Malta, Norway, Portugal, Romania, the UK, Ukraine.Chapter 10.1007/978-3-030-62877-2_9 focuses on the development of authorial voice in multilingual international students writing their theses in an additional language. Seeking to provide both students and supervisors with clear and pertinent advice on how to develop and express authorial voice, Morton and Storch critically evaluate the treatment of voice in thesis writing guidebooks and online material produced by universities as well as by popular blogs. Their research revealed that the resources targeting students were simplistic, providing only limited advice on authorial voice, and therefore, they stress the role of supervisors in guiding doctoral students to acquire strategies that can contribute to the development of writers’ authorial voice across disciplines.self, revealed through personal opinions, authoritativeness and presence in the interviews conducted. The study focuses on the manifestation of identity as a linguistic phenomenon, that is, on the discoursal resources which convey the writers’ personal opinions, beliefs, and attitudes, and which are used to justify their actions during the thesis writing process. This scrutiny of linguistic choices sheds light into how the students’ identities and own versions of reality are constructed. It also foregrounds a complex, multiaspectual nature of their self-presentation as anxious, supported, independent or triumphant writers.In Chap. 10.1007/978-3-030-62877-2_10, Bekar and Yakhontova report on a qualitative study of the various aspects of student writers’ Chapter 10.1007/978-3-030-62877-2_11 provides an account of the author’s own experience as a facilitator in writing conference groups for graduate students writing their thesis. In her ethnographic study, Mochizuki examines knowledge and meaning co-creation between the participants and herself, as a researcher, aiming to understand the significance of the role of researcher reflexivity in academic literacy development. The findings presented show how her interaction with the participants has contributed to transforming their views and to the negotiation of their identities and goals. The chapter illustrates how direct observation and reflexivity allow the researcher to be actively involved not only in knowledge gathering but also in knowledge construction.The studies included here delve into multilingual scholars’ literacy development stages, exploring the challenges they face in constructing academic texts, the strategies they have developed and the resources they are resorting to.In Chap. 10.1007/978-3-030-62877-2_12, Habibie presents the findings of a case study that explored the strategies, pedagogies and mentorship practices of a multilingual early-career academic in writing for scholarly publication. The author framed his ethnographically oriented study resorting to Tardy’s  notion oIn Chap. 10.1007/978-3-030-62877-2_13, Villares explores the perceptions of Spanish multilingual scholars regarding academic literacy development. The main challenges referred to in interviews consisted in both internal factors  and external factors . In addition, the study reveals the scholars’ perceptions of linguistic disadvantage during the writing and manuscript submission process. The use of both individual learning-by-doing strategies and collaborative strategies highlights the crucial role of the social aspect of academic literacy development. The implementation of policy decisions which foster the enculturation process of novice researchers and the mastery of academic literacy are discussed as a response to insufficient training and institutional support services.Chapter 10.1007/978-3-030-62877-2_14 explores academics’ perspectives on the development of feedback and scholarly writing literacies. Using concept map-mediated interviews, Gravett provides insights into academics’ experiences on moving from the highly emotive nature of learning from critical feedback and rejection, to taking critical feedback forward in order to offer a considered response. Despite the benefits of the collaborative nature of the peer review process, the study exposes the perception of power inequalities illustrated by the pressures experienced by multilingual scholars writing in English and the concerns about the debilitating and frustrating nature of the review process which might lead to the lack of faith in reviewers’ credibility, motivation or expertise.Chapter 10.1007/978-3-030-62877-2_15 presents longitudinal interview data from two plurilingual early career researchers participating in a writing for publication tutoring programme. Janssen and Crites explain how the evolution of the participants’ writing practices is connected to the interaction with academic literacy brokers and to the development of their research networks. Their findings show how engagement in networks with different literacy brokers  or collaboration and face-to-face discussion with other members of their community of practice, including friends, colleagues, co-authors, play a crucial role in mediating the publication process.In Chap. 10.1007/978-3-030-62877-2_16, Tercero brings to the fore the challenges and changes experienced by academia in the spring of 2020, which caught both students and instructors in Higher Education fairly unprepared. On the basis of the findings of a small-scale exploratory study of instructor and student perceptions of their online writing courses, the author proposes a framework for designing and teaching an online academic writing course for L2 writers. As Tercero concludes, the COVID-19 pandemic might have fostered the expansion of online teaching and learning in the near future in unprecedented ways, which makes the design of quality online teaching and learning a crucial endeavour.coda chapter, Englander and Corcoran review recent research on multilingual scholars’ trajectories and experiences in writing academic texts to bring to the fore the need for addressing advanced stages of literacy development from multiple perspectives. After highlighting the conceptual complexity of literacy, with its multilayered and intersecting dimensions, the authors engage with several salient themes addressed in the contributions to this volume. They underline the “variety of ethnographic research methodologies” employed in the studies included in this collection, as well as the value of bringing together such a range of “glocalized perspectives from broad geolinguisitic locales”. Englander and Corcoran conclude by problematising possible implications of the current tendencies towards achieving homogeneity in academic publishing and invite for further reflections on the multiple facets of academic knowledge exchange.In this


Contextualised evidence to generate local solutions on the progressive path to universal health coverage is essential. However, this evidence must be translated into action. Knowledge translation (KT) experts have highlighted the plausible mechanisms to foster the uptake of evidence. The objective of this study was to assess the extent to which structures are in place to boost uptake of evidence, in countries of the WHO African Region.Employing a cross-sectional survey, we collected data on the availability of structures to foster the uptake of evidence into policy in 35 out of the 47 member states of the WHO African Region. Data were analysed using a simple counting of the presence or absence of such structures.Less than half of the countries had evidence collation and synthesis mechanisms. The lack of such mechanisms presents a missed opportunity to identify comprehensive solutions that can respond to health sector challenges. Close to 50% of the countries had KT platforms in place. However, the availability of these was in several forms, as an institution-based platform, as an annual event to disseminate evidence and as a series of conferences at the national level. In some countries, KT was mainstreamed into routine health sector performance review processes. Several challenges impacted the functionality of the KT platforms including inadequate funding and lack of dedicated personnel. Regarding dissemination of evidence, sharing reports, scientific publications and one-off presentations in meetings were the main approaches employed.The availability of KT platforms in the WHO African countries can be described as at best and non-existent at the worst. The current structures, where these exist, cannot adequately foster KT. Knowledge translation platforms need to be viewed as sector-wide platforms and mainstreamed in routine health sector performance reviews and policymaking processes. Funds for their functionality must be planned for as part of the health sector budget. Dissemination of evidence needs to be viewed differently to embrace the concept of “disseminate for impact”. Further, funding for dissemination activities needs to be planned for as part of the evidence generation plan. The case has been made for contextualised evidence in the search for local solutions and innovation on the progressive path to universal health coverage (UHC). More pertinent to this aspiration is evidence being translated into action. Knowledge translation (KT) experts have been preoccupied with this topic for the last two decades and have highlighted plausible mechanisms to foster the use of evidence in decision-making. Amongst the favourable factors are the availability of high-quality, timely and contextualised evidence providing economically feasible recommendation; the Ministry of Health’s (MoH) capacity to lead the KT process; the availability of institutionalised platforms for engagement between researchers and policymakers including civil society; the mechanisms to coordinate evidence generation and synthesis mainstreamed within the MoH; and the partnerships for KT (involvement of stakeholders throughout the process to improve trust and build interest including communities) –3.The type and quality of evidence have been a subject of debate with a preference for systematic reviews and peer-reviewed research . In as mIn some African countries, partnerships for KT were institutionalised (in 2005) through Evidence-Informed Policy Networks (EVIPNet) which were established as knowledge translation platforms (KTP) to promote the systematic use of health research evidence in policymaking. These bring together policymakers, researchers and civil society to foster the uptake of the best scientific evidence in both policy development and policy implementation . An evalThe definition of KT indeed embodies these favourable parameters as “the dynamic, iterative process including the synthesis (… emphasising the need for synthesis platforms..), dissemination, exchange (… the need for effective dissemination as a two-way mechanism..) and ethically sound application of knowledge to improve health, strengthen the health care system and provide more effective health services and products (…. the need for broad evidence beyond the efficacy of interventions…)” . In thisThe objective of this study was to assess the extent to which structures are in place to foster the uptake of evidence which is an essential element in the progressive realisation of UHC, in countries of the WHO African Region. Much of the work in the area of KT has focussed on defining what KT is and what it takes to translate evidence into policy with reference to a specific policy process which may not necessarily require all the KT structures to be in place. Attempts to detail required structures for KT have derived mainly from published literature which focused largely on high-income countries. Our analysis contributes to available literature from two fronts, namely, assessing the extent to which there is the presence of a broad range of structures which are beneficial to a wide range of policy process and, secondly, employing primary data from a large set of African countries.As part of a broader assessment in which data collection was conducted between December 2017 and August 2018, we employed a cross-sectional survey design using a semi-structured mailed questionnaire. All the 47 member states of the WHO Africa Region were included in the survey, and 35 responded (response rate of 74%). Prior to undertaking the study, country teams  were trained on filling in the questionnaire. The Ministry of Health focal point for research or the head of the national health research coordination institute primarily completed the questionnaire as the arrangements differed from one country to another. The completed questionnaire was validated by an in-country team comprising representatives of institutions conducting health research, the head of the national research coordination institution, the focal point for research in the WHO Country Office and the focal point for research in the Ministry of Health. Data were collected on the structures that foster knowledge translation specifically the availability of (1) an evidence collation mechanism; (2) platform for translating and communicating research to inform health policy and practice, as well as the performance of the platform and challenges faced; and (3) ways in which evidence is disseminated.Data were processed in a Microsoft Excel® spreadsheet and basic descriptive and comparative analysis conducted.This study was a standing request by the Ministers of Health of the WHO African Region, and the ethical approval to undertake the survey was granted by the WHO African Regional Office’s Ethics Review Committee.A lot of evidence is generated in countries through research, routine information systems and evaluation studies. Further, the evidence is generated on different aspects ranging from health systems, biomedical science and service delivery. No single study can provide all required answers to inform policy decisions, thus the need for collation and synthesis of all available evidence.As shown in Table Sixteen out of 35 countries (46%) had KT platforms in place. However, the availability of these was in several forms, as an institution-based platform organised and managed by the national research institute , as an annual event to disseminate evidence  and as a series of conferences at the national level . In some countries such as Rwanda, knowledge translation was mainstreamed into routine health sector performance review processes. In Kenya and Guinea-Bissau, although reported as “in place”, the platform was still under development to be embedded in the National Health Observatory (Kenya) and as part of the committee to implement the national research agenda (Guinea-Bissau).Noteworthy is the innovative approach employed by Senegal that instituted a capacity building programme on knowledge translation for policymakers and researchers. Niger, on the other hand, has an institutionalised mechanism for multi-sectoral consultation and exchange in health research.Several challenges impacting the functionality of the KT platforms were reported. Inadequate funding was a major issue, and several annual dissemination forums had not been held in several countries, for example, The Gambia that had not held such forums for 4 years due to lack of funding. The poor synthesis and presentation of research results to guide policy dialogue were also noted as a hindrance (Tanzania).Suboptimal functionality was reported due to the lack of dedicated personnel. These challenges are exacerbated by not clearly defining the role of institutions , weak capacity of researchers and policymakers and the environment-related issues such as Information and Communication Technologies (ICT) to ensure the functionality of KT platforms. There seem to be no agreed set of indicators for measuring the functionality of KT platforms, and using proxy indicators to assess progress made on the challenges described above will be a good starting point worth a future study.As shown in Table Nearly half of the countries had evidence collation and synthesis mechanisms and knowledge translation platforms to foster the uptake of evidence in policy development and implementation. No single source of evidence can provide comprehensive options to a policy question, and as such evidence from routine systems, several research studies and evaluation reports must be synthesised to provide timely and comprehensive answers. Knowledge translation platforms have been instrumental in improving the uptake of evidence . El-JardThe absence of such presents a missed opportunity to realising evidence-based dialogue and decision-making on one hand and waste of resources on the other. Generation of evidence is not an end in itself, and as such, its use in improving service delivery needs to be viewed as a return on investment. El-Jardali et al.  highlighWhere KT platforms existed, there was an inherent weakness that may impact negatively on their functionality—for example, being institution-based limits the extent to which stakeholders can be involved because of the limited convening power of national research institutes. Being annual events does not offer much benefit, given the fact that decision-making is an ongoing process. Worst still, several of these annual events had been missed due to the lack of funding. The poor synthesis and presentation of research results, as was reported in Tanzania, negatively impacts the uptake of evidence. This situation reinforces the need to strengthen individual and institutional capacities in not just research but also policy-oriented evidence synthesis and science communication.Amongst the barriers to uptake of evidence is the lack of appreciation of each other’s world of operation between policymakers and researchers . To thisRegarding dissemination of evidence, the approaches employed predominantly were sharing reports, scientific publications and presentation in meetings. Such approaches do not offer much reach for several reasons; access to scientific publications is a challenge because of limited access to the Internet and journal that are not open access. This is compounded by the poor reading culture, which is a documented barrier . The limAlthough KT structures are still suboptimal, there is documented evidence of the improved quality of health policies underpinned by concrete context-appropriate evidence in Zambia, Uganda, Cameroon, and Ethiopia where KT platforms played an integral role . In thesOur assessment focused on the extent to which structures are in place to foster the uptake of evidence in countries of the WHO African Region. We did not undertake an in-depth assessment of the functionality of these structures and possible solutions to address identified challenges. We, however, believe our findings provide valuable information that can spur action in improving the uptake of evidence. In as much as the functionality of such structures is important, these must be in place in the first place.The availability of KT platforms in the WHO African countries can be described as suboptimal at best and non-existent at the worst. The current structures, where these exist can not adequately foster KT. The starting point would be to have structures established where these are lacking. Further, knowledge translation platforms need to be viewed as sector-wide platforms and mainstreamed in routing health sector performance review and policymaking processes. Funds for their functionality must be planned for as part of the health sector budget. Regarding the dissemination of evidence, sharing reports, scientific publications and one-off presentations in meeting approaches employed currently in the majority of countries have already been shown to have minimal impact. Dissemination of evidence needs to be viewed differently to embrace the concept of “disseminate for impact”. Further, funding for dissemination activities needs to be planned for as part of the evidence generation plan.


Actinic keratoses (AK) are common lesions of the skin that can be effectively treated with several lesion- and field-directed treatments. Clinical practice guidelines assist physicians in choosing the appropriate treatment options for their patients. Here, we aimed to systematically identify and evaluate the methodological quality of currently available guidelines for AK. Guidelines published within the last 5 years were identified in a systematic search of guideline databases, Medline and Embase. Then, six independent reviewers evaluated the methodological quality using the tools “Appraisal of Guidelines for Research and Evaluation” (AGREE II) and “Recommendation EXcellence” (AGREE-REX). The Kruskal–Wallis (H) test was used to explore differences among subgroups and Spearman’s correlation to examine the relationship between individual domains. Three guidelines developed by consortia from Canada, Germany and the United Kingdom were eligible for the evaluation. The German guideline achieved the highest scores, fulfilling 65 to 92% of the criteria in AGREE II and 67 to 84% in AGREE-REX, whereas the Canadian guideline scored 31 to 71% of the criteria in AGREE II and 33 to 46% in AGREE-REX. The domains “stakeholder involvement“ and “values and preferences“ were identified as methodological weaknesses requiring particular attention and improvement in future guideline efforts. Actinic keratoses (AK) are common lesions of chronically sun-damaged keratinocytes in the epidermis, the upper layer of the skin . They arOver the last decades, a broad variety of options have been licensed for AK treatment. They include lesion-directed options as cryotherapy and fractional laser therapy, which are suitable to treat single AK lesions. Another approach comprises field-directed treatments, which are usually deployed to treat larger areas of sun-damaged skin, for instance photodynamic therapy (PDT), which may be also effective in other skin diseases such as acne vulgaris, as recently shown by Del Duca et al. , microneIn this study, we aimed to assess the methodological strengths and weaknesses of all currently available international guidelines on AK treatment using the two assessment instruments “Appraisal of Guidelines for Research and Evaluation (AGREE) II” and “AGREE-REX: Recommendation EXcellence” ,15. The In our appraisal, we only included guidelines developed by national or international consortia focusing on more than one option for the management of AK. They had to be published within the last 5 years, i.e., 2015–2019, as we only wanted to evaluate the most up-to-date guidelines. Furthermore, only English or German publications were included. Guidelines that had already expired or were not developed based on a systematic literature search followed by a structured consensus process, e.g., expert consent-based guidelines, were excluded.In order to identify potential guidelines for the evaluation, we systematically searched several guideline databases as well as Medline and Embase (both via Ovid) until 23 October 2019. The search included the terms “actinic keratosis/keratoses”, “solar keratoses”, “field cancerization”, “senile keratoses” and “precancerous lesions”. Besides, cross-references of included guidelines were screened as well. The detailed search strategies are shown in https://www.agreetrust.org/ (last access: 31 May 2020) was used for evaluating the guidelines with the AGREE II instrument, whereas internally piloted data extraction spreadsheets (Microsoft Excel 2010) were used for the evaluation with AGREE-REX.Background information including title, consortia and/or authors, country of origin, publication date, methodological approach and scope of all eligible guidelines were collected. Then, six independent reviewers  evaluated their methodological quality using AGREE II and AGREE-REX as described previously . Using Ap-values < 0.05 were considered statistically significant. Ratings were grouped in the three categories “strongly agree” (6 and 7 points), “partly agree” (3 to 5 points) and “strongly disagree” (1 and 2 points) and Fleiss’ Kappa was calculated in order to assess the interrater agreement of the six reviewers [Scores were calculated for each domain according to the instructions provided in the AGREE II and AGREE-REX instrument user manuals ,17. Totaeviewers . SPSS Stn = 126) and title and abstract screening, nine records remained for full-text review. Six records were excluded, as they had already expired (n = 2) [n = 1) [n = 1) [n = 1) [We initially identified 2612 records when searching the databases . After t (n = 2) ,20, only [n = 1) , were no [n = 1)  or did n [n = 1) . Another [n = 1) . Finally [n = 1) , the gui [n = 1) ,10,25. TThe interrater agreement of the six reviewers regarding AGREE II and AGREE-REX was rated as fair with a Fleiss’ Kappa of 0.299 (95% CI 0.263–0.336).p = 0.01).This domain evaluates whether the main objectives of the guideline and the population for whom it was developed are clearly described. The average score was 5.17 ±1.49, . The Gerp = 0.012) and the UK guideline (p = 0.009).This domain covers the topics involvement of appropriate stakeholders and whether the views of the users that should deploy the guideline are represented. The average score was 4.39 (±1.86). The German guideline achieved a very high value of 92%, while the UK and Canadian guidelines achieved only 37 and 41%, respectively. The German guideline significantly differed from both the Canadian (p = 0.006).The methodological approaches including a systematic and transparent identification of evidence are covered by the items of this domain. The mean score was 4.99 (±1.44). Again, the German guideline was rated as the one with the best methodological quality achieving 89% whereas the UK and the Canadian guidelines were rated worse with 63 and 48%, respectively. The German guideline also significantly differed from the Canadian guideline in this domain . Both the German and the UK guideline fulfilled almost all criteria  and also the Canadian guideline fulfilled more than 2/3 of the criteria (71%).p = 0.004).Processes concerning guideline implementation are evaluated in this domain. The mean score was 4.08 (±1.20). The German and UK guidelines achieved similar results (65 and 58%), while the Canadian guideline achieved the lowest rates fulfilling only 31% of the criteria. The German and Canadian guidelines also significantly differed in this domain (p = 0.035).The role of funding and competing interest of the experts that were involved in the development process is evaluated in this domain. The mean score was 5.64 (± 1.23). Again, the German guideline was rated as the best (92%) followed by the UK (78%) and Canadian guideline (63%). Similar to the other domains, the Canadian and the German guidelines were rated to be significantly different of each other , and the German guideline was rated as the one with the best overall quality (83%). The UK and Canadian guidelines were rated lower with 63 and 47%, respectively. All reviewers recommended to use the German guideline without any modifications. The use of the UK guideline was also recommended, but half of the reviewers rated to use it with modifications. In contrast, the ratings regarding the recommendation to use the Canadian guideline were ambiguous: two reviewers rated to use it, two to use it with modifications while another two reviewers recommended not to use this guideline.p = 0.002).This domain assesses whether the recommendations were developed based on a thorough review of the existing literature and whether they are applicable for the intended users . The mean score was 4.89 (±1.20). The fulfilled criteria in this domain ranged from 45% (Canada) and 65% (UK) to 84% (Germany). In this domain, the German and the Canadian guidelines significantly differed from each other (p = 0.004). This domain evaluates whether the preferences of the intended users, patients, policy/decision-makers and guideline developers have been taken into consideration during the guideline development process. The mean score was 3.92 (±1.16). The German guideline achieved 67%, whereas the UK and the Canadian guidelines were rated similar . Here, the German and Canadian guidelines significantly differed again (p = 0.004).This domain asks how suitable the recommendations are for the patients and/or the health care system in which they should be implemented. The mean score of this domain was 4.83 (±1.11). The German guideline achieved the highest rates with 78%. The UK guideline was rated lower with 68%, and the Canadian guideline was rated with the lowest scores (46%). The German and Canadian guidelines also significantly differed in this domain  and published in 2015 was not included in this evaluation, as it had already expired in July 2018 .Developing guidelines and keeping them up-do-date is labor- and cost-intensive. In the field of AK, developers are confronted with a vast number of treatment options including several monotherapies as well as combinations of them. Scanning all the evidence available is time-consuming and difficult. Besides, the quality of the body of evidence varies across interventions, making it difficult to compare the efficacy of different approaches and derive recommendations. However, regular updating is crucial for maintaining the quality of the provided guidance as seen in the case of ingenol mebutate (IMB), which was approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) as a topical intervention for AK in 2012 . RecentlThe German guideline achieved the highest scores in all domains of AGREE II and AGREE-REX ranging from 65% (applicability) to 92% . On the other hand, the Canadian guideline was rated as the guideline with the poorest methodological quality in our appraisal with scores ranging from 31% (applicability) to 71% (clarity of presentation). Overall, the domain “clarity of presentation” was rated best among all evaluated domains ranging from 71% (Canadian guideline) to 91% (German guideline), indicating that the recommendations provided by the guidelines are unambiguous and clear and can be easily found in the guideline texts. In contrast, the domains “applicability” and “values and preferences” achieved the lowest scores ranging from 31 to 65% and 33 to 67%, respectively. Interestingly, these two domains also achieved only low scores in a recent appraisal of currently available evidence- and consensus-based melanoma guidelines , indicatMajor differences between the guidelines were observed in the evaluation of the domain “stakeholder involvement”. Here, the German guideline achieved a good result of 92%, whereas both the UK and the Canadian guideline were rated worse, achieving only 37 and 41%, respectively. The lack of participation of important target groups may severely hamper the implementation of the recommendations into the real world setting. Thus, when updating these guidelines, developers should particularly focus on this part to improve the overall quality in the future. Especially patient representatives should ultimately be involved in the development of guidelines and might be actively approached through patient support groups.Overall, the German guideline achieved the highest scores in all domains in both instruments. This might be due to the fact that the AWMF and DKG, which guide the process of oncological guideline development in Germany, provide not only support but also build a solid methodological framework of rules for the guideline authors they have to adhere to. Besides, the German guideline provided by far the most detailed This study has several limitations. We only evaluated the methodological quality of the guidelines, but not the content or the medical content of the recommendations themselves. This might be problematic as seen in the abovementioned case of IMB. Furthermore, we cannot fully exclude that the six reviewers may have been biased as all of them are from Germany. Additionally, three members of this research team  were at least partly involved in the development process of the evaluated German guideline. However, these three were not part of the appraisal team and did not evaluate the quality of any guideline. Furthermore, the language restrictions to English and German may have led to the exclusion of relevant guidelines and may have introduced risk for selection bias.Taken together, we identified three currently available guidelines on AK treatment that were published within the last five years. Two of them showed substantial methodological weaknesses. Only the German guideline, which was rated as the best in this evaluation, fulfilled most of the evaluated criteria and, therefore, may be used as a role model for developing or updating future guidelines. Paying special attention to the domains “applicability” and “values and preferences” that achieved low scores in all three guidelines is required.