The objective of this article is to summarize the state of the literature surrounding the use of ketamine as a neuroprotective agent following cardiac arrest.Five electronic databases were used to search for studies related to the use of ketamine for neuroprotection following cardiac arrest. This search was performed once in May 2020, and an updated search was conducted in May 2021 and March 2022.All searches combined retrieved 181 results; no clinical trials were identified. As such, the authors were limited to writing a scoping review of the literature rather than a systematic review.The current state of the literature describes the mechanism of action of ketamine as a neuroprotective agent through its action as an NMDA antagonist. There is evidence of its efficacy as a neuroprotective agent in preclinical models of cardiac arrest. Current published clinical work supports the use of ketamine ameliorating neurologic outcomes in other conditions such as epilepsy, traumatic brain injury, and depression. The current state of the literature is reflective of the notion that the use of ketamine following cardiac arrest may result in improved neurologic outcomes. Future research directions should focus on the use of ketamine as a possible clinical intervention following cardiac arrest. Ketamine holds promise as a neuroprotective agent through attenuating damage caused by the excitotoxic cascade. Though extensively studied in a stroke model, application to post‐cardiac arrest brain injury has been overlooked. This scoping review summarizes the mechanism of ketamine neuroprotection as applicable to post‐cardiac arrest brain injury, and existing evidence for the benefits of its use. The first search was completed by a health sciences research librarian on May 28, 2020. The search was then updated, and repeated on May 28, 2021, and March 4, 2022, each time with dates limited to the time between searches. Results of each search are available as Appendices 3The results of the first search revealed 37 papers. A total of 73 articles were retrieved based on the results of the second search and 71 during the last search. All three sets of results revealed no clinical trials that have directly investigated the application of ketamine as sedation to improve neurological outcomes. As such, it was not possible for the authors to conduct a systematic review. Instead, detailed literature and scoping review based on the results of our search were undertaken to summarize the evidence supporting the use of ketamine as a neuroprotective agent in the context of CA. Results of all searches are available in Appendices 4As the cerebrum requires 15%–20% of cardiac output to maintain function,Upon resuscitation of the patient and subsequent ROSC, oxygen is returned to injured tissues that have already adapted to consumption at diminished rates. This imbalance of oxygen delivery and utilization gives rise to a secondary form of damage known as the “second hit” or “reperfusion injury” of PCABI.Other pathophysiological conditions resulting from secondary injury include anemia, impaired autoregulation, hypo‐ or hypercapnia‐associated vascular response, hyperoxia leading to increased free radicals, and hyperthermia.PCABI results in apoptosis of neurons, particularly in the highly metabolically active hippocampal and neocortical areas. Clinical manifestations of this damage include impairments in memory, executive functioning, and visual‐motor skills.One opportunity for clinical intervention to attenuate damage caused by excitotoxicity is the administration of ketamine. The role of ketamine in inhibiting the excitotoxic process is two‐fold; in interfering with the ability of glutamate‐containing vesicles to bind to the presynaptic membrane (via reduction of presynaptic protein attachment receptors) and in non‐competitive antagonism of NMDA receptors, specifically those with the GluN2B subunit.Indeed, there is evidence in preclinical models of the protective effects of ketamine on neuronal apoptosis. A summary of these studies can be found in Table p = 0.069). Markers of neuronal injury (neurofilament‐H and neuron‐specific enolase) were also significantly lower in subjects who received ketamine treatment.A more recent preclinical study published by Giuliano et al.2 saturation and reduced neuronal cell loss in rats treated with S(+) ketamine; this effect was more pronounced in animals randomized to the higher dose group (90 mg). Finally, a study conducted by Engelhard et al. showed that administration of 1 mg/kg/min of S(+)‐ketamine and O2 prior to incomplete cerebral ischemia in rats resulted in reduced expression of pro‐apoptotic proteins (Bax) and increased in anti‐apoptotic proteins (Bcl2), as evidenced by the results of Western Blot analysis.Investigations into relative neuroprotective effects of different isomeric forms of ketamine have also been completed. Proescholdt et al. investigated the effect of S(+) versus R(−) stereoisomers of ketamine on functional and structural outcomes following induction of global forebrain ischemia in a rat model.In addition to preclinical research, there is a growing body of evidence from clinical literature about the use of ketamine for neuroprotection following a variety of neurologic insults. For example, the use of ketamine in the setting of severe epilepsy resistant to anticonvulsants and benzodiazepines has been met with success.Additionally, Hudetz et al. conducted a study investigating the effect of ketamine on postoperative cognitive dysfunction following cardiac surgery.Finally, the administration of ketamine has also been found to reduce spreading depolarizations accompanying acute brain injury in patients suffering from traumatic brain injury, subarachnoid hemorrhage, and malignant hemispheric stroke. These depolarizations are believed to lead to the breakdown of functional neurons and are associated with poor patient outcomes.The results of this scoping review demonstrate a clear link between the mechanism of PCABI and the ability of ketamine to inhibit its progression. Early work suggests potential for benefit of using ketamine as a sedative in the emergency post‐CA setting to improve the neurological outcome of CA patients. However, the application of ketamine for neuroprotection following CA has not been widely investigated in the clinical setting. The authors feel the lack of trials directly investigating this relationship may be caused by the tendency of researchers to use a stroke model to represent ischemic damage in both the preclinical and clinical settings. The lack of CA‐based neuroprotection trials results in a missed opportunity for the patient population that may benefit from such interventions the most. Similarly, the use of ketamine to improve neurological outcomes has been investigated in many different types of neurological conditions but has yet to be applied to CA patients. Together, the use of CA as an appropriate experimental model as well the application of neuroprotective effects of ketamine to this population have been overlooked in work done to date, setting the stage for an excellent future research opportunity.Differences in the receptor‐antagonist mechanism of ketamine versus memantine have been the focus of many recent studies. It is hypothesized that memantine is more effective at inhibiting NMDA receptor subtypes containing the GluN2A subunit, in contrast to those with the 2B subunit targeted by ketamine.Newer work by Glasgow et al.Although a promising future research direction, the results of this scoping review should be interpreted primarily as hypothesis‐generating. Results of rigorous clinical studies are needed to provide a higher level of evidence for the use ketamine for neuroprotection. Other NMDA receptor antagonists, such as memantine, may also be considered.4.1In the past, clinicians have been trained to consider neurological injury as a contraindication for the use of ketamine as a sedative.5Limitations of this article include the lack of systematic review procedures to appraise available evidence and meta‐analyze research results. This limitation could not be addressed due to the lack of clinical trials evaluating the topic of this literature review, in addition to the large heterogeneity of types of studies and reports retrieved by the results of the literature search. As such, the body of knowledge summarized in this article is intended to serve as a scoping review only and not a formal analysis of available evidence.6Ketamine has shown promise in attenuating neurologic injury caused by CA. The authors propose that the administration of ketamine following ROSC in CA patients may result in improved neurologic outcomes. However, evidence from the literature is indirect, based on in vitro or other neurological models, and thus should be interpreted cautiously. CA provides an excellent model to study the neuroprotective effects of ketamine in future research efforts.The manuscript complies with all instructions to the authors. All authors have met authorship requirements, and the final manuscript was approved by all authors. This manuscript has not been published elsewhere and is not under consideration by another journal. MO, AW, GA, TL, IK, and GM contributed to developing the concepts and layout of the article. GM was responsible for coming up with search terms and concept for the literature review. MO was responsible for conducting the literature search alongside research librarians, reviewing relevant sources, writing the manuscript, and referencing the works cited. AW, GA, TL, IK, and GM contributed to editing the article and adding relevant information about supporting studies or physiological concepts mentioned.No authors hold any conflicts of interest.Appendix S1Click here for additional data file.Appendix S2Click here for additional data file.Appendix S3Click here for additional data file.


The COVID-19 pandemic has highlighted the importance of evidence-based clinical decision-making. Clinical management guidelines (CMGs) may help reduce morbidity and mortality by improving the quality of clinical decisions. This systematic review aims to evaluate the availability, inclusivity, and quality of pandemic influenza CMGs, to identify gaps that can be addressed to strengthen pandemic preparedness in this area.Ovid Medline, Ovid Embase, TRIP (Turning Research Into Practice), and Guideline Central were searched systematically from January 2008 to 23rd June 2022, complemented by a grey literature search till 16th June 2022. Pandemic influenza CMGs including supportive care or empirical treatment recommendations were included. Two reviewers independently extracted data from the included studies and assessed their quality using AGREE II . The findings are presented narratively.Forty-eight CMGs were included. They were produced in high- , upper-middle- , and lower-middle  income countries, or by international organisations . Most CMGs  were over 5 years old. Guidelines included treatment recommendations for children , pregnant women , people with immunosuppression , and older adults . Many CMGs were of low quality . All recommended oseltamivir; recommendations for other neuraminidase inhibitors and supportive care were limited and at times contradictory. Only 56% (27/48) and 27% (13/48) addressed oxygen and fluid therapy, respectively.Our data highlights the limited availability of up-to-date pandemic influenza CMGs globally. Of those identified, many were limited in scope and quality and several lacked recommendations for specific at-risk populations. Recommendations on supportive care, the mainstay of treatment, were limited and heterogeneous. The most recent guideline highlighted that the evidence-base to support antiviral treatment recommendations is still limited. There is an urgent need for trials into treatment and supportive care strategies including for different risk populations. New evidence should be incorporated into globally accessible guidelines, to benefit patient outcomes. A ‘living guideline’ framework is recommended and further research into guideline implementation in different resourced settings, particularly low- and middle-income countries.The online version contains supplementary material available at 10.1186/s12916-022-02616-6. Clinical management guidelines (CMGs) are evidence-based tools to facilitate clinical decision-making and access to the best available evidence-based care.The CMGs provided early in the COVID-19 pandemic were of limited quality and scope.Supportive care is the main treatment for many (re-) emerging infections, and early access to evidence-based supportive care can improve patient outcomes.There is limited availability of pandemic influenza CMGs globally, most were developed for upper-middle and higher-income settings.Many CMGs were of limited quality and were produced more than 5 years ago, many during the H1N1 pandemic and only one had been updated since then.There were limited, heterogeneous and at times contradictory recommendations on supportive care, and limited recommendations for different at-risk populations.All CMGs recommended oseltamivir, but with variations in recommendations for pregnant women. Recommendations on additional neuraminidase inhibitors were conflicting, reflecting the limited evidence-base to support recommendations.The data highlight a need to ensure mechanisms for regular updates of pandemic influenza CMGs are considered at the development stage, to ensure publicly available CMGs are up to date, providing the best available evidence-based treatment and supportive care recommendations, for different at-risk populations.The limited scope highlights a need for investments into trials to identify effective treatments and supportive care strategies to benefit patient care and outcomes.A living guideline framework with mechanisms for integrating new evidence and dissemination, with close links between researchers and guideline developers from different settings, is needed to improve the quality, inclusivity, and availability of evidence-based care recommendations.Further research is needed into the implementation of CMGs from development to the front line in different settings and contexts.Influenza pandemics are one of the greatest global health threats, potentially causing millions of deaths and huge socioeconomic disruption. The ever-present threat of pandemic influenza and experiences with the COVID-19 pandemic emphasise the critical importance of pandemic preparedness.The 1918 influenza pandemic, previously labelled “the deadliest pandemic of modern age” . Most rePublic health and government preparedness activities have largely focused on surveillance, reporting, epidemiological modelling, and prevention and control , 10. HowThe COVID-19 pandemic has also highlighted issues of inequity in access to care globally . VariatiAccess to evidence-based clinical management guidelines (CMGs) can be a vital tool in the clinical response to a pandemic –22. ClinThe aim of this review is to identify gaps in access to evidence-based pandemic influenza CMGs for different at-risk populations globally and assess variations in supportive care and treatment recommendations that may have an impact on outcomes and implementation of clinical trial response to pandemics.We conducted a systematic review of the literature focused on pandemic influenza CMGs. This review followed the Cochrane systematic review guidance  and was We searched three databases ) and a guideline repository  from 1 January 2008 to 23rd June 2022. The date was restricted from 2008 onwards to include recent CMGs incorporating recommendations based on the latest developments, whilst also ensuring we included those produced in response to the influenza A pandemic  , 38.We validated the search strategy by testing the terms before finalising the search strategy. We identified keywords and phrases from an initial set of pandemic influenza guidelines, identified from clinical experts and hand-searches in the planning stages. From these, we identified associated MeSH/Emtree terms, subject headings, and indexes from specific databases. The search strings were then tested against the initial standard set to ensure the quality of the final search strings used for the review.We complemented the search with a grey literature search which was completed on the 16th of June 2022. We searched Google Scholar to retrieve relevant records from 1 January 2008 with the first 500 hits screened. Additionally, to identify a globally representative sample of international and national CMGs, we conducted a google search using pre-defined keywords in Spanish, French, German, Mandarin, Arabic, and Russian. Finally, we contacted clinical network members of the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC)  in regioWe defined CMGs as documents (developed using systematic or non-systematic methodologies) that provided recommendations on supportive care or empirical treatments to guide practice, in line with the WHO’s  definition. These included guidelines aimed at children (0 to <18 years old), adults, pregnant women, older people (> 65 years old), and/or people living with HIV . SupportAfter deduplication, search results were screened independently by two reviewers using Rayyan, a systematic review software . The artWe extracted data as per the methodological requirements described in the design and conduct of systematic reviews of clinical guidelines produced by Johnston et al.  Data extThe extracted data was analysed to assess availability, inclusivity scope and quality using descriptive analysis. Availability was assessed by whether up-to-date CMGs could be identified. The CMGs were stratified by origin: (1) international organisations (e.g. WHO) and (2) national organisations  or National Public health institutes). Inclusivity was assessed on the inclusion of recommendations targeting the whole population, including infants, children, adults, pregnant women, older people, as well as people living with HIV/immunosuppression. Statistical analysis was performed in the R language for statistical computing version 4.0.2 , 45 withThe quality was assessed by two reviewers independently using the Appraisal of Guidelines for Research & Evaluation (AGREE) II tool . The tooOverall domain scores were calculated as per the AGREE II tool user manual, converting the sum of individual scores from each reviewer into a standardised percentage of the maximum score possible for each domain . GuideliThere was no patient public involvement in this project due to the ongoing pandemic constraints.Of a total of 1817 records identified, 48 met the eligibility criteria  CMGs focused on clinical management of A(H1N1) %, 30/48 , 79, 92,Most CMGs were aimed for high- 42%, 20/48) , 91, 96 2%, 20/48Most CMGs  included supportive care recommendations tailored for children , 92–95, The median overall quality score of all the CMGs was 3 out of 7 (range: 1–7). Most  were assessed as of low quality  , 95, 96,There were wide variations in the individual domain scores which assess different aspects of CMG development. Most CMGs scored well in the “scope and purpose” domain (median (IQR): 67% (48–79%)) and “clarity of presentation” domain (median (IQR): 74% (63–81%)), showing recommendations were usually clearly structured and presented. Generally, CMGs scored lower for “rigour of development” (median (IQR) 25% (14–44%)) domain. This domain is considered a strong quality indicator of a CMG, providing up-to-date, evidence-based information . Similarp=0.048)  compared to those produced by a national organisation   of CMGs recommended the use or conditional use of zanamivir , 95, 96,There was little variability in the recommended dosage of neuraminidase inhibitors (oseltamivir and zanamivir) for adults and children (including infants). In adults, the recommended dose of oseltamivir, when available, was consistent at 75 mg twice per day for 5 days (once per day for 10 days for chemoprophylactic use) –93, 95, There was generally a consensus in recommendations for pregnant women, 50% (24/48) of CMGs providing advice recommended oseltamivir or zanamivir , 90, 96,Sixty-three per cent (30/48) , 90, 96 Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae [Around half of the CMGs 54%, 26/48) recommended antibiotics if a patient shows clinical signs of bacterial pneumonia or secondary bacterial infection %, 26/48 –93, 96. fluenzae , 73, 74., oxygen therapy was addressed in 56% (27/48) of CMGs [There were limited and varied recommendations on supportive care , others specified that these should only be used as part of clinical trials , 108. ClDeveloping evidence-based CMGs is resource intensive, requiring wide stakeholder engagement, and evidence appraisals, and resources for regular reviews and updates. The low quality of many of the guidelines indicates that this may be beyond the resources available in many nations. The guidelines produced by international organisations that can be adapted and adopted globally may provide a more feasible, robust, and sustainable model. To achieve this, guidelines must be tailored for different regions’ endemicity, risk factors, and drug resistance. Global coordination will reduce the risk of proliferation of heterogenous CMGs with limited scope and value and save valuable resources.Our study is not without limitations. Although substantial efforts were made to identify CMGs, including targeted searches in different languages, there is still a possibility that some local CMGs were not retrieved. This may partly explain the limited CMGs from low-income countries and the WHO African region especially. Some of the included guidelines were of limited scope, however, after much discussion involving clinicians and global collaborators, these guidelines were included, as they reflect the limited guidance available to clinicians. Despite identifying diverse CMGs in multiple languages, due to translations some nuances of the CMGs may have been lost. Nonetheless, using a diverse team and a combination of search methods, a wide range of CMGs were identified which highlighted concerning gaps in the availability, inclusivity, scope, and quality of available CMGs. Additionally, although the AGREE II tool assesses the methodological quality of CMGs, it does not assess the validity of the treatment recommendations. Despite these limitations, our review identified concerning gaps in the availability and standardisation of pandemic influenza CMGs and limited treatment and supportive care recommendations. The recently updated CMG by WHO addresses some of these limitations, but also highlights that the evidence base is still lacking . ClinicaOur data highlights the limited availability of high-quality, up-to-date pandemic influenza CMGs globally, especially in LMICs. Most of those identified were of limited quality, scope, and inclusivity. The most recent guideline updated this year shows that the evidence-base to support antiviral treatment recommendations is still limited. Our data highlights a need for updating of existing pandemic influenza guidelines, to ensure they provide the latest evidence-based recommendations, inclusive of different at-risk populations. There is a clear role for an improved framework for CMG development, including mechanisms for regular review updates, and dissemination to improve access to evidence-based care recommendations for different at-risk populations. A ‘living guideline’ framework is recommended.Our data shows an urgent need for trials into effective supportive care, host-directed and antiviral treatment strategies and for new evidence to be incorporated into globally accessible guidelines, to benefit patient outcomes. Moreover, research into the implementation of CMGs in lower-resourced settings.Additional file 1: Details of the search strategy. S1.1. Database search strategy. S1.1.2. Updated database search strategy. S1.2. Google scholar search strategy. S1.2.2. Updated google scholar search strategy. S1.3. Google engine search strategy.Additional file 2: Data extraction form. S2.1. Data extraction form.Additional file 3: Additional figure Figure S3.1. PRISMA diagramAdditional file 4: Additional tables Table S4.1. Characteristics of identified CMGs. Table S4.2. CMG recommendations for treatment and supportive care. Table S4.3. Oseltamivir treatment and chemoprophylactic doses for children and infants.


Number of children ever born to women of reproductive age forms a core component of fertility and is vital to the population dynamics in any country. Using Bangladesh Multiple Indicator Cluster Survey 2019 data, we fitted a novel weighted Bayesian Poisson regression model to identify multi-level individual, household, regional and societal factors of the number of children ever born among married women of reproductive age in Bangladesh. We explored the robustness of our results using multiple prior distributions, and presented the Metropolis algorithm for posterior realizations. The method is compared with regular Bayesian Poisson regression model using a Weighted Bayesian Information Criterion. Factors identified emphasize the need to revisit and strengthen the existing fertility-reduction programs and policies in Bangladesh.The online version contains supplementary material available at 10.1007/s44199-022-00044-2. During the last century, the world has experienced an exponential growth of its human population increasing from 1.65 billion in 1900 to 6 billion in 1999 , 71. EvePopulation dynamics in a country is an important tool for the government and non-government organizations for planning and policy making. Among many forces that have been driving population dynamics, the most important determinant is the fertility . FertiliBangladesh, a country in South Asia, has experienced a steady decline in its fertility rate over years: specifically, a reduction from 4.5 in 1990 to 2.3 in 2019 . Even thThe focus of this paper is to use novel survey-weighted Bayesian Poisson regression model to understand the roles of individual, household, community, and regional factors that explain CEB which is important for devising policies to further reduce fertility in Bangladesh. Previous studies linked CEB to woman’s age, age at marriage, education, husband’s education and religion , 61. InfPoisson distribution is a popular choice to model a count variable where its mean and variance are represented by the rate of occurrence of an event . The eveIn contrast, Bayesian Poisson regression combines information from the data and knowledge extracted from experts’ beliefs via likelihood function, prior, and posterior distribution of the model parameters . El-SayyIn this paper, we propose a likelihood-based Bayesian Poisson regression model when the likelihood contribution from an observation is adjusted by its weight to model the number of CEB to married women of reproductive age in Bangladesh. We illustrated our proposed model with several prior distributions  and showThus, the major objectives of this study are to 1) use a novel weighted Bayesian Poisson regression model that incorporates survey weights to explain CEB in order to assess the effects of individual, household, regional factors on CEB, 2) describe the related inference and implementation process, and assess the robustness of the results across various priors, and 3) establish and assess the societal determinants of CEB using a recent, nationally representative, and large survey data from Bangladesh.Section Individual, household, regional data are obtained from the Bangladesh Multiple Indicator Cluster Survey of 2019 (MICS 2019) conducted by the joint efforts of the Bangladesh Bureau of Statistics and United Nations Children’s Fund . In addi9 report .This MICS 2019 data contain information for a total of 68,709 women of reproductive age of In this study, the response variable is the number of children ever born (CEB) among currently married women of reproductive age in Bangladesh. Figure ariables . Adult lariables .Fig. 1BaY be the number of children ever born (CEB) to a married woman of reproductive age in Bangladesh. As in \documentmentclass2pt{minimWe denote the prior distribution, which reflects our prior belief, for terature . The vagterature  which isterature , 91, oftta point . In addita point  is usefuAssuming independence among the regression coefficients 0,1,…,p) , the joiL2 norm that performs regularization like a Ridge regression [First, we have considered a Normal prior  with dengression , all \doL1 norm constraint when The second prior distribution we have used is a Laplace prior  with denhe LASSO .The third prior we considered is a Cauchy distribution  with dene priors .Figure L(.) and The joint posterior distribution of entclass1pt{minimation Eq.  as folloo method  nor a Gio method  to genero method .Sample a proposal state rCalculate the acceptance ratio Accept or reject the proposal with The proposal distribution We approximate the posterior distribution of lgorithm . For a gn, and Akaike Information Criterion  and Bayentclass1pt{minimaFirst, we provide the computational details for the weighted Poisson regression model with the normal prior. The same procedure is followed by all other models and priors.Inspired by the specification process of the null hypothesis in statistical literature , we consR [qnorm, qlaplace and qchauchy for the Normal, Laplace and Cauchy priors by providing the appropriate prior probability coverage. The values of R [qnorm, qlaplace and qchauchy for the Normal, Laplace and Cauchy priors by providing the appropriate prior probability coverage. The values of Following the recommendation in , we used using R  statemen using R  statemenentclass1pt{minimaj \in -0., +0.25$$k using trial and error method. After few attempts, we optimized k to be 1/6 and ran the algorithm for a total of 105,000 times, which provided an acceptance rate [We determined the value of nce rate  of \docuthinning . The “thWe examined the auto-correlation function (ACF) against lag for the selected variables . We determined that the successive iterations of the parameters from their respective posterior distribution were highly correlated which motivated us to save every 100th iterations (after burn-in) of the MCMC samples. The ACFs for these variables were rechecked after burn-in and thinning (figure is not shown), which showed negligible correlation between successive thinned iterations , 84. TheThe summary of the analytic sample is presented in Table Table ion test . The lasentclass1pt{minimaResults in Table Based on exploratory analysis , the quadratic effect of woman’s age on the number of CEB has been considered Table . Figure Based on similar exploratory analysis , the quadratic effect of husband’s age on the number of CEB has been considered Table . Figure The number of CEB was significantly associated with woman’s education. Women with education preschool or none and elementary have entclass1pt{minimaIn this study, the media exposure of women was inversely associated with CEB , Khulna, Mymensing, Rajshahi, Rangpur and Sylhet. Islam et al.  studied entclass1pt{minimaIn this study, effects of societal variables  such as adult literacy and contraceptive prevalence rates on the number of CEB among married women reproductive age in Bangladesh have been studied for which the result follows. The district level adult literacy rate and CEB were significantly associated: For ten percent increase in the district level adult literacy rate, the number of CEB decreases by entclass1pt{minimaSimilar to the effect of the district level adult literacy rate, the association between district level CPR on CEB is appeared to be significant: For ten percent increase of district level CPR, the number of CEB decreases by entclass1pt{minimaTables Some of the estimates and/or the confidence intervals of IRR were strikingly different across the weighted and unweighted models. For instance, the estimated coefficients for the rural area relative to urban area were 1.02 and 1.01 for the unweighted and weighted models, respectively. According to weighted model, the number of CEB in the rural area is insignificantly higher than the urban area since CIs are overlapping. On the other hand, the unweighted model shows that the CEB is significantly higher in the rural area than in the urban area. This is because, the unweighted model does not take into consideration the sampling weight for the women for which the average weight is higher in the urban area (1.15 versus 0.96).As another example, the estimates of the IRRs for ethnicity using the unweighted and weighted models were 1.17 and 1.12, respectively, even though both estimates were statistically significant. The large differences in the estimates from the two models were due to larger mean sampling weights for the women with Bengali ethnicity of 1.01 than for the women of non-Bengali ethnicity of 0.48.Following the idea presented in , the objSince there were barely any change for the factors age at marriage, woman’s age, husband’s age, woman’s education, media exposure, wealth index, area, adult literacy rate and CPR, we claim that the estimates of parameters in the proposed model are robust. However, we point out some negligible evidence of shrinkage for the weighted Poisson regression model reported across Tables This large-scale and nationally representative study suggests that woman’s fertility behavior is significantly associated with individual, household, and area-level factors in Bangladesh. After adjustment of sampling weight, the performance of the model, measured in terms of Weighted Bayesian Information Criterion, has been improved. The findings of this study suggest that existing family planning and reproductive health programs should be strengthened further in order to achieve the fertility target, with a focus not only on individual and household level factors, but also on area-level societal factors.The observed association between decreased likelihood of CEB for increased age at marriage has been consistent with earlier studies , 70, 80.Education plays an important role in explaining CEB in Bangladesh. Educated women are more likely to have less expected number of CEB, which is supported by an earlier study on fertility in 38 developing countries including Bangladesh . Similared women , 98, 100It is well known that the links between education and fertility vary across countries and over time . For exaMoreover, women with exposure to the media have  studies , 79. ExpThe differential of fertility among different ethnic groups had been studied in the United Kingdom by Coleman and Dubuc . Their rCongruent with previous research , 61, 80,ulations , our stuThe urban and rural differential of fertility has been a widely studied factor in Bangladesh , 57, 58,Individual and household level variables only tell part of the narrative of fertility decline, and studies that focus solely on them are more likely to ignore the impact of group-level factors (i.e. community or neighbourhood). Our study suggested that district-level social environmental features  are inversely related to the number of CEB. Women who live in communities with a higher literacy rate may have better access to health care, greater information and awareness about family planning, and higher autonomy in decision-making , all of This research provides a foundation for the need of incorporating district-level social environmental features in planning fertility control strategies . Implementing educational initiatives at the local level has the potential to educate residents and change community norms regarding family planning, which could have a positive impact on fertility reduction. By increasing awareness and access to services, increased education can enhance contraceptive use, thereby contributing to fertility reduction . PolicymThe results of this study show that the expected number of birth per woman in Bangladesh has been declined from 6.95 in 1970 and 2.06 in 2017 to 1.97 in 2019. The two administrative divisions (Chittagong with mean CEB 2.29 and Sylhet with 2.41) are performing very poorly relative to the national average. In contrast, the Khulna and Rajshahi divisions outperform the other divisions as well as the national average. These findings are supported by earlier study . To furtFrom methodological perspective, Hastie and Tibshirani, Fortheringham et al. , 29 and The 2019 MICS survey  had emphOverall, this study quantified the exposition of different factors operating at individual, household, and area-levels with fertility behaviour of women in Bangladesh. The key factors are age at marriage, ages of woman and spouse, education, media exposure, household wealth, place of residence, district level adult literacy rate, contraceptive use rate, and administrative divisions. Since Bangladesh may need to further reduce its fertility rate, it is important that policymakers continue to support expenditure in educational programs, increase awareness to family planning, and enhance access to family planning services. In addition, stronger mass media campaign promoting the benefits of family planning may result in a shift in attitudes against large families. Identifying geographical regions to prioritize intervention is also important for the government and non-government organizations.This study had a few limitations. A cause-and-effect link between outcome and exposure or covariates could not be established owing to the cross-sectional nature of the data. There may be recall or social desirability bias during the data collection process; however, this is a common problem in survey data, and survey administrators always strive to reduce these biases, making them less likely to influence overall findings. We did not have access to several other variables  which may be important for policy formation and warrant further investigation. Despite these limitations, the MICS data from Bangladesh represents a large survey sample that can be utilised to evaluate fertility patterns and associated factors.Supplementary file1 (PDF 5487 KB)Below is the link to the electronic supplementary material.


Sir,Multivitamin use and the risk of preeclampsia: a systematic review and meta‐analysis.This is a reply to the comment by Lo and LoDue to the limited evidence base, Lo and Lo suggest that our review should have included studies investigating fortified food. In our systematic review protocol that was prospectively registered in PROSPERO (registration no. CRD42021214153) prior to the literature search, we clearly indicated that we would only include studies with multivitamins taken as tablets and capsules. We hypothesized that including fortified food could potentially lead to a significant risk of bias due to the difficulties in measuring the actual daily intake of a given food. Hence, fortified foods were not included. In the light of a surprisingly limited evidence base, we agree that it could be interesting to synthesize the evidence regarding fortified food intake and the risk of preeclampsia in future reviews.Lo and Lo question the exclusion of a randomized study by Chen et al.In the meta‐analysis of adjusted observational data, we excluded the data from Catov et al. due to their use of a hazard ratio instead of an odds ratio.In conclusion, the discussions above show that the GRADE approach is a valuable tool when doing systematic reviews. Despite some disagreements, the conclusion remains the same. The evidence that multivitamin reduces the risk of preeclampsia is low or very low.


Poverty and health illiteracy, combined with inappropriate systems to track disease and infection rates, contribute to children-and-mothers’ poor adherence to nutrient-rich foods intake in Bangladesh. Although risk factors for child and pregnant women malnutrition have been explored, the relationship between Bangladeshi adults’ nutrition literacy and their demographics and personal beliefs remains unknown. The purpose of this study was to examine the association between adults’ nutrition literacy, demographics and personal beliefs in a large sample of Bangladeshi adults.Four hundred adults from two districts (Dhaka and Chattogram) of Bangladesh participated in a cross-sectional survey. Data were collected by interviews using a structured questionnaire containing the Nutrition Literacy Scale. Multiple linear regression models were employed to analyze associations between nutrition literacy and related factors.SD: 3.7; range: 11–32) on a scale of 32. Multiple linear regression revealed that being a businessman  or private employee , having a higher family income , and a higher educational level were positively associated with higher nutrition literacy scores compared to their counterparts. Participants who had ever completed a nutrition-related course , and who perceived themselves as having a need for accessing nutrition-related information were positively associated with the higher nutrition literacy compared to their counterparts.The mean nutrition literacy score was 21.6 (Findings from this study suggest the need for an integrated response plan involving educational interventions and accessible dietary plans targeting adult populations to enhance their nutritional literacy. Globallculture” , 4.Bangladesh is a low-income South Asian Country, with large diet-related disparities. Diet-related disparities in this region are mainly defined by differences in eating behaviors and nutrition intake patterns between socioeconomic groups . A GlobaFollowing the WHO guidelines in nutrition, the Bangladesh Government enacted the National Dietary Guideline for Bangladesh in 2015 to extend the advanced knowledge and skills related to food choices, preferences and appropriate food preparation. A key agenda of the country’s National Nutrition Policy  and the Currently, the leading biomedical policy in South Asia gives little attention to health literacy programs . For exaA range of factors such as mothers’ educational level, perception of health, unhealthy food consumption status, and having a positive body perception has been linked with nutrition literacy . A previA handful of studies have been conducted on nutrition literacy among different subgroups of the population  in Turkey , 26, TaiTwo major districts in Bangladesh were chosen as the primary data collection sites for this cross-sectional study; Dhaka and Chattogram. Dhaka is the capital city of Bangladesh and is densely populated with over 20 million residents . Chattogn = z2pq/d2, where n is the required sample size, z is 1.96 at 95% confidence interval, d is the margin of error at 5% (standard deviation of 0.05), and q = 1–p. Since there was no previous study on nutrition literacy in Bangladesh, p = 50% was used. Similarly, the probability of expected prevalence was used 50% in several previous studies  from the two selected districts to explore their nutrition literacy and associated factors. Participants were recruited and surveyed by home visits upon assessing the following eligibility criteria: (i) individuals aged ≥ 18 years, and (ii) Bangladeshi nationality by birth. Individuals who were ill and absent in the home during data collection were excluded from this study. The sample size was calculated using the formula of single sample proportion test , n = z2p studies –39. Thus studies –42 we anvia in-person interviews from May to September 2021 by trained data collectors with a hard copy of the structured questionnaire. The interviewers were well-trained nutrition and food science students who had a potential knowledge on the basics of human nutrition and dietary habits. Six interviewers, who were trained by the lead investigator of the study, visited the study area and were responsible for data collection. The lead investigator of the study arranged an online training session to train data collectors on the different sections of the questionnaire, data collection techniques, and inclusion/exclusion criteria of the study. The questionnaire was back-translated from English into Bengali (native language) for appropriate communication during data collection. The draft version of the questionnaire was piloted among a randomly selected group of adults (n = 20) to identify any ambiguous or unclear items and to gain a better insight on the amount of time needed for the interview. Based on the findings of the piloted questionnaire, modifications were made to several variables as test respondents noted that aspects of these questions or statements were unclear. For example, we removed several questions from the independent variables such as self-rated health status and disease name. Moreover, data collectors carried a printed copy of “Bangladeshi Food Pyramid” at the time of final data collection and showed it to the participants were necessary to easily make able to understand items 4 and 5 of the nutrition literacy scale. The results of the pilot survey were not included in this study. It took approximately 10–15 min for each interview. The obtained data were initially entered on a Google sheet.Data were collected The study survey comprised of 28 items which were split up into two sections: (i) socio-demographic, behavioral and nutrition-related information (20 items) and (ii) assessment nutrition literacy (8 items). The first section of the questionnaire was developed for this study by the research team. The questionnaire for the assessment of nutrition literacy was retrieved from the previous literature of Liao et al. .Nutrition literacy was the dependent variable in this study and was assessed by a modified nutrition literacy scale containing 8-items that was previously developed and validated by Liao et al. . The scaVarious socio-demographic, behavioral, and nutritional-related perceptual information was captured in this study. Respondents’ personal and behavioral characteristics such as age, gender, religion, occupation, education, marital status, family size, residence, household income, individual, and family history of diseases, physical activity level, smoking status, self-perceived body mass index (BMI), were included in this study. All variables except age and income were reported as categorical measures. These two variables (age and income) were initially outlined as continuous variables, but later it was categorized according to Petry  and Bannp-values < 0.05) in the unadjusted model were included in the adjusted linear regression model. All assumptions were checked regarding linear regression after fitting the model. Regression coefficients (B) and standard errors (SE) were used to quantify associations. All statistical analyses were done using STATA (BE version 17.0) and SPSS (IBM version 23.0) and statistical significance was set at p < 0.05.Descriptive statistics  were computed to summarize variables of interest. A one-way analysis of variance (ANOVA) (if the independent variables had more than two categories) and independent-sample t-tests (if the independent variables had two categories) were used to compare nutrition literacy scores across the different background variables. Multiple linear regression models were applied to assess the factors associated with nutrition literacy. Statistically significant variables  of the Department of Food Microbiology, Patuakhali Science and Technology University, Bangladesh. Written consent was obtained from the participants after discussing the purpose of the study, the confidentiality of their data, and after assuring the participant that this research would not be harmful to them. Moreover, participants were notified that they could withdraw from the study at any time without being affected and none of their identifying information would be used in study data analysis or dissemination.Of the 400 adults that participated in the study, 61.5% were male, 58.3% were aged between 18 and 29 years [mean age 30.3 years (± 8.7)], and 33% were college students. Less than half of the respondents (41.3%) had a graduate-level education or above. The majority of respondents (74.8%) were permanent residents of the metropolitan areas. Nearly two-thirds (63.0%) respondents’ family monthly income was ≤ 40,000 Bangladeshi taka (USD 465). About 81.8% of respondents had no smoking habits and 25% self-identified as having a nutrition-related disease. Many respondents (88%) reported they prioritized a healthy diet and three-quarters of the respondents (71%) reported that they ate meals outside of the home on a daily or weekly basis. Most of the respondents (93.2%) reported a self-perceived need for accessing nutrition information. Only six percent of participants had completed an actual nutrition-related course .SD = 3.7, range: 11–32) on a scale of 32.0. The overall positive response rate for nutrition literacy was 67.5% (21.6/32.0 × 100), indicating a moderate level of nutrition literacy among the participants. Nutrition literacy scores significantly varied by study location (p = 0.029), respondents’ gender (p = 0.009), age (p = 0.015), occupation (p = 0.027), education level (p < 0.001), marital status (p = 0.026), monthly family income (p < 0.001), priority of eating a healthy diet (p < 0.001), nutrition-related course participation, and self-perceived need to access nutrition information (p < 0.001) (The mean nutrition literacy score was 21.6 (< 0.001) . Respondp < 0.001). Respondents who were businessman  or a private employee , had a higher nutrition literacy scores compared to their counterparts. Respondents who had an education level above primary (elementary education) had higher nutrition literacy scores compared to their counterparts . Respondents whose family income > 40,000 BDT/month were positively associated with higher nutrition literacy scores compared to their counterparts . Respondents who had taken a nutrition-related course were positively associated with higher nutrition literacy scores compared to those who had never taken a nutrition-related course . Finally, respondents who perceived themselves as having a need for access to nutrition-related information had higher nutrition literacy scores than those who didn’t feel any need at all .The adjusted estimated effects of the factors associated with nutrition literacy among Bangladeshi adults are shown in Our cross-sectional survey explored nutrition literacy and associated factors in Bangladeshi adults. Collectively, our study demonstrated that nutrition literacy was moderate and associated with socioeconomic characteristics, such as residence, occupation, education level, family income, and personal beliefs or actions such as taking a nutrition-related course and the self-perceived need for access to nutrition-related information. Findings of the current study suggest that nutrition literacy should be prioritized at the policy level as an outcome of sociodemographic factors and diet quality in the path to a healthy diet, and to improve nutrition literacy rates in the Bangladeshi adult population.Overall, the findings reported moderate nutrition literacy among respondents, which is consistent with the finding of other studies conducted among adolescents and young adults in Turkey , 26. A pFrom the perspective of “social determinants of health,” social factors may potentially impact acquiring nutrition literacy, cooking skills, and food and nutrition-related decisions due to potential health benefits . The preAligning with previous findings , 57, theIn addition, income is one of the crucial indicators that could show the impact of socio-economic status on nutrition literacy . CorroboOne intuitive finding from this study showed that respondents who had ever taken a nutrition-related course were more likely to have a higher nutrition literacy score compared to those who had never taken nutrition-related courses. This has been found in other studies , 59, 60 The urgency of understanding the nutrition-related facts  is crucial in developing countries like Bangladesh where nutrition transition is evident , 61–63. Undoubtedly, improvements in the social determinants of health  are imperative to improve nutrition literacy, dietary diversity, and healthy diets for the at-risk populations. However, these are long-term measures that take time to materialize in health gains, therefore, policy changes incorporating a multi-sector approach involving non-governmental organizations, dieticians, nutritionists and agriculturists may be more effective at improving nutrition literacy in developing countries like Bangladesh. Such actionable steps might be changing the design of nutrition labeling, creating more employment opportunities for nutrition professionals such as dieticians or nutritionists at the district- and community-level health facilities so that individuals can easily access food and nutrition-related information.There are several strengths to this research. This was one of the first studies to explore nutrition literacy and its risk factors based on a large sample of the Bangladeshi adult population. These preliminary findings provide a baseline for policymakers and public health practitioners to aid with the development and implementation of evidence-based interventions and initiatives to improve nutrition literacy rates in Bangladesh. The present study employed methodological and analytical rigor with detailed and reproducible approaches for future research in this area. The use of a validated study tool for measuring the outcome of interest represents an additional strength of this study.However, this study was not without limitations. First, the cross-sectional nature of this study does not allow for causal interpretations. Secondly, the study was conducted in only two regions of Bangladesh (Dhaka and Chattogram), so the findings cannot be generalized across the country. Further studies particularly incorporating other vulnerable areas  of Bangladesh such as rural areas, hill tracts and coastal regions are highly recommended. Finally, there is the possibility of social desirability and reporting biases from the respondents due to the self-report nature of the measurements used in this study.The current study found a moderate level of nutrition literacy among adults in Bangladesh and revealed several socio-demographic factors  and personal beliefs  associated with nutrition literacy scores. The findings of this study suggest a need for: (i) developing and implementing evidence-based health promotion interventions to improve nutrition education and behaviors of adults, (ii) basic nutrition education programs  in primary and secondary schools that involve local healthcare facilities such as hospitals or community clinics especially targeting low socioeconomic groups, (iii) free nutrition-related courses or programs (in-person and online) where individuals can get a fundamental understanding of food and nutrition, and (iv) public awareness programs on diet plans and desirable dietary patterns to intake affordable traditional and seasonal foods through various platforms such as television broadcasting, newspaper, radio, and social media outlets. These steps, in combination with a focus on agricultural production levels, could contribute to the healthier choices of food by people that will result in the achievement of the Bangladesh Government’s nutrition-related Sustainable Development Goals by 2030.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Research Ethical Committee (REC) of the Department of Food Microbiology, Patuakhali Science and Technology University, Bangladesh. The patients/participants provided their written informed consent to participate in this study.MB: conceptualization, study design, and writing—original draft . MH: visualization, validation, and writing—critically reviewing and editing. SK: data curation and analysis. TA and MA: methodology, data collection and input, and literature review. KB: critically revised the manuscript for intellectual content. A-AS: writing—original draft preparation (discussion section). TD and NM: visualization and writing—reviewing and editing. JF: writing—original draft preparation (introduction section). MK: conceptualization, writing—reviewing, editing, and supervision. All authors read and approved the submitted version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


In this work, quantitative research is carried out on the importance that educators give to literacy work in early childhood education classrooms and the impact that the COVID-19 pandemic and the use of facemasks have had on it. To this end, a survey designed for this purpose has been used, which has been passed on to a set of 112 Spanish early childhood educators. The teachers surveyed occupy different positions in the classroom , and, in addition, they themselves learned to read from different methods of literacy learning . The results found in this study indicate that educators express intermediate evaluations of the importance of literacy work in the classroom, higher if it is done through digital resources, and higher for the synthetic method than for the analytical method. In addition, the impact of the use of masks on literacy learning was rated as very negative. On the other hand, gaps have been identified in the above perceptions by the position occupied in the classroom and by the method used to learn to read. Finally, some actions are suggested to homogenize the perceptions of the different professionals, and some lines of research are proposed. The COVID-19 pandemic situation has been a turning point in daily life, resulting in major changes in daily, social, and work habits ,3. AmongLanguage acquisition is a natural process that occurs in early childhood, which is directly related to the child’s socioemotional development . It shouAfter a period based on online teaching, especially in the early stages of the pandemic, the return to schools has meant the adoption of safety and hygiene measures to prevent the spread of the virus , highligThis visual–gestural component is part of the basis for optimal communication between transmitter and receiver. In this sense, the sound affection caused using the facemask fluctuates according to its typology, oscillating for surgical facemasks around 4 dB, while for FFP2 around 12 dB .This attenuation of sound in the transmission of the message causes various effects in the sender, e.g., vocal and respiratory efforts that cause a state of fatigue in the subject ,14. ThisIn this regard, the use of transparent facemasks in the teaching-learning process seems to be a resource that solves part of the limitations in communication generated by opaque facemasks, since the visual signals of the communication process are exposed . This faDespite this, in noisy situations, as may be the case in a kindergarten classroom, the use of transparent facemasks is strongly recommended, since the sound attenuation is compensated by a better view of the facial field of the transmitter. This type of facemask in turn leads to access to components that allow the message to be deciphered, e.g., lip reading or the visualization of facial expressions that directly expose the emotional state of the subject . This meEven so, to counteract the sound affectation caused by facemasks, the educational world has often resorted to the use of microphones to improve communication , which hIn addition to this circumstance, the use of the facemask by early childhood education students, who, despite not being obliged to use it—unlike teachers—have shown great frustration due to communication and socialization problems between student–student and student–teacher . In thisSince the beginning of the COVID-19 pandemic, there have been publications warning of the difficulties that the introduction of facemasks in schools posed for education, at the level of communication, interpretation of language and expression of emotions . Some ofIn particular, it has been shown that facemasks have made it difficult for children to express feelings of disgust and have made them more prone to anxiety and fear , an effeThis way, this research is focused on the impact of the COVID-19 pandemic, particularly the use of facemasks, on literacy learning in early childhood education (3 to 6 years of age). Specifically, a statistical analysis is made of the opinion of early childhood education teachers in Spain regarding the use of facemasks in the classroom and the problems this generates in relation to the teaching–learning process of literacy at this educational stage. The study distinguishes the opinions of the different generalist and specialist teachers involved in the teaching of literacy and also differentiates by the method  with which the participating teachers learned to read and write.Specifically, the general objective of this research is to describe the opinion of early childhood education professionals on (i) literacy work in the classroom, (ii) the different methods for teaching it, and (iii) the influence of the COVID-19 pandemic and the use of facemasks on the development of literacy in students. In particular, the following specific objectives are pursued in this work: (i) to analyze the assessments of Spanish early childhood education teachers about the importance of working on literacy in the classroom and of doing so through digital resources; (ii) to study the assessments made by these professionals of the effectiveness of each of the possible methods of working on literacy ; (iii) to examine the influence of the use of facemasks on the achievement of literacy objectives in early childhood education during the COVID-19 pandemic; (iv) to identify differences in the above assessments by the teacher’s position in the classroom and, within each possible position, by the method with which the teacher learned to read; and (v) to analyze whether the COVID-19 pandemic has altered participants’ perception of the need for classroom reinforcement with a speech-language pathologist.Two independent variables are considered in the research : (i) posImportance given by the participants to the teaching of literacy in early childhood education;Importance of the use of digital resources and information and communication technologies (ICT) in the process of teaching literacy in early childhood education;Assessment of the effectiveness of the analytical method in learning literacy;Assessment of the effectiveness of the synthetic method in learning literacy;Assessment of the impact of the COVID-19 pandemic on the development of literacy in early childhood education students;Degree of negative impact of the use of facemasks on the development of literacy in early childhood education students;Perception of the need for speech-language intervention in the classroom before and after the pandemic.The following dependent variables are defined as quantitative variables measured on a scale of 1 to 5:This study involves 112 active Spanish early childhood education professionals, including generalist teachers and technicians and also specialists in different educational fields related to literacy. Specifically, among the participants there are group tutors and support technicians, teachers specializing in bilingualism, and teachers specializing in SH  or TP. Participants were chosen through a non-probability convenience sampling process.The distribution of the proportions of each of the above positions in the sample is shown in In this research, a survey designed for this purpose has been used to delimit the sociological and professional profile of the participants and to obtain their opinions on the variables studied. In the survey, the following aspects of the sociological and educative profile of the participants are assessed: (i) gender; (ii) age; (iii) position held in the early childhood education classroom; (iv) teaching experience; and (v) method by which the participant learned to read . Participants are then asked a set of 15 Likert-type questions valued from 1 to 5 to measure the teachers’ perception of the dependent variables analyzed . In the p-value = 0.78) and explain 64.3% of the variance  and the absolute fit indices are also good . The validation of the psychometric dimensions of the survey has been tested based on Pearson’s correlation coefficients . These cTM. The teachers answered to the survey voluntarily, freely, and anonymously. The protocol was approved by the Ethics Committee of the research project to which the authors belong. All the answers were validated . The validation of the instrument was conducted after the response collection process before statistical analysis of results.In this work, quantitative research is performed based on the answers to the survey that has been passed to the participating teachers. They were contacted by email and were given access to the survey instrument through GoogleFormsThe validation of the survey was carried out by means of an exploratory factor analysis (EFA) of the answers, which served to identify the latent factors that explain the survey. Questions 14 and 15 of the survey have not been introduced in the EFA because the intention is assessing the last dependent variable of the study (perception of the need for speech-language intervention) by comparing the mean results of question 14 (perception before the pandemic) and question 15 (perception after the pandemic). The theoretical model derived from the EFA was confirmed by means of confirmatory factor analysis (CFA) statistics. The validation of the psychometric dimensions was achieved through the computation of Pearson correlation coefficients of the different factors defined by the EFA among themselves and with respect to the global survey. The descriptive statistics of the answers of the first 13 questions of the survey (means and standard deviations) have then been analyzed, both globally and differentiating the participants according to their position in the classroom. The ANOVA test was applied to identify significant differences in the answers by position held. In the variables where such differences exist, the multifactor ANOVA test (MANOVA) has been applied to analyze whether, within each position, there are differences in the corresponding assessments due to the method by which the participants learned to read. Finally, the mean values of questions 14 and 15 were compared using the t-test and the ANOVA test (when the sample is differentiated by the position occupied in the classroom). In all tests, 0.05 has been taken as the level of statistical significance.In Differentiating the participants by the position they occupy in the classroom, significant differences are observed in the mean values of the importance of literacy in early childhood education and of the influence of the use of facemasks on the students’ literacy development . SH and p-value = 0.0039). Among group tutors, there is no difference in the evaluation of the importance of literacy when the sample is differentiated by the method used to learn to read. However, the participants who learned to read with the synthetic method are those who perceive a more negative influence of the use of the facemasks on the development of literacy in all positions and with significant differences , except for the bilingualism specialists, among whom no differences by learning method are appreciated . Specifically, reciated .p-value = 0.0009) found the difference between the means to be significant. Therefore, the pandemic has led to a significant increase in teachers’ assessment of the need for speech-language intervention in the early childhood classroom. In this regard, the ANOVA test does not identify statistically significant differences by position in the classroom , a specific study would be necessary. On the other hand, the size of the sample used, and the distribution of the participants (mostly women) preclude a sufficiently significant quantitative study of the differences by age, experience or gender of the variables studied. Therefore, in order to study the existence of gaps in the perceptions of educators and to ensure greater representativeness of the sample, it is proposed to increase the sample size by ensuring a reasonably homogeneous distribution with respect to the sociological aspects mentioned. Finally, if the sample of professionals studied could be expanded to include teachers from different locations, it would be possible to analyze whether there is any type of geographic variable that influences the evaluations expressed.On the other hand, it would be interesting to conduct a correlational study of teachers’ perceptions of the impact of the use of facemasks on children’s literacy learning and emotional life, in order to check whether teachers establish some kind of dependence between both areas, as the literature points out ,25,30,31Based on the results of the study, it is suggested that teachers, specialists and generalists, work in a more coordinated manner in their respective didactic actions in the classroom. This would probably make it possible to homogenize the perceptions that the different professionals have of literacy and, therefore, the criteria for didactic action with respect to it. In addition, it would be advisable to reinforce the training in the field of literacy of pre-service teachers, both generalists and specialists.Throughout the study, it was found that early childhood education professionals attribute a high importance to the learning of literacy in children at this stage and that the use of digital resources would increase the effectiveness of educational action in this regard. There is, among the respondents, the perception that the COVID-19 pandemic has slowed down the acquisition of literacy acquisition objectives. In this sense, the use of opaque facemasks is seen as a negative element for the development of the corresponding skills, both visually and phonologically. In the above perceptions, specialist teachers  value the importance of literacy learning less than generalists. However, those who attribute the greatest negative impact to the use of facemasks are the bilingualism specialists. Regarding the method  that the participants used to learn to read, those who used the analytical method  give more importance to literacy learning, but those who learned with the synthetic method identify a greater impact of the use of facemasks.


This commentary acknowledges that the evidence-based practice (EBP) movement did not automatically or initially understand the impact of context on successful implementation (SI). The subsequent work of research teams, such as the PARIHS  team, and the Ottawa team led by Squires, have contributed to the ongoing refinement of the concept. However, still under discussion is whether having a more comprehensive set of contextual attributes will necessarily lead to more implementation success. Just as the strength of the evidence does not automatically lead to implementation success, so having a comprehensive understanding of contextual factors will not necessarily improve implementation uptake. It is now rather surprising to consider that when the evidence-based practice (EBP) movement hit the world stage in the early 1990s, context was not even considered to be an important variable in the quest to get evidence into practice. Dominating the discourse was the pursuit of research excellence, as demonstrated by the adherence to rigorous systematic review training and level of evidence. As a young researcher working in Oxford in the 1990s, I had the privilege of being at the epicentre of this movement, motivated by leaders such as Iain Chalmers, Muir Gray and Dave Sackett. Theirs was the voice of pure epidemiological reason and they generated a way of thinking about EBP that has arguably changed healthcare practice. My job at that time was to lead the setting up of a clinical practice research unit for nursing. This entity, called the National Institute for Nursing, was co-funded by the Royal College of Nursing of the United Kingdom, Oxford District and Regional Health Authorities and a philanthropic organisation called the Sainsbury’s Monument Trust. The Institute was also supported by Oxford University via Green (Templeton) College and Oxford Brooks University Nursing Department. Our job was to start the journey of generating the evidence base for clinical nursing practice and to get it into practice. Interesting to note also was the attention paid to aligning key organisations to a new initiative in order to optimise the success of the venture. This was probably my first lesson in understanding the importance of  context at a macro level.1  was developed in response to the challenges we were experiencing in our attempts to get clinical guidelines and other pieces of evidence into practice. The pure logic of the EBP movement just was not working for us. So, this was when we generated the formula that successful implementation (SI) was a function (f) of the interplay of the type of evidence (E), the context (C), and the way the evidence was helped, enabled or facilitated to get into practice (F). The PARIHS framework was one of the first implementation science or knowledge translation frameworks to make this bold statement that factors other than the quality of evidence could influence effective uptake. It must also be noted that in other disciplines , context was a well-recognised construct known to shape processes and outcomes. The PARIHS framework2 have indicated the early PARIHS framework identified three key elements to context, namely leadership, culture and feedback. These dimensions were not conceived as being inclusive of all contextual factors, but reflective of the priority elements that were generated inductively from an analysis of four case studies that helped to test the early PARIHS framework. Concept analyses of the three core elements5 of PARIHS followed . As a result of the context concept analysis, we further refined the framework to include resources as a core context element and expanded audit and feedback to the broader concept of evaluation. These refinements were presented as part of our work on developing and refining ways to operationalise the framework.6 As Squires et al7 when, in response to feedback from users, we refined the original PARIHS framework and called it the integrated or i-PARIHS framework. Facilitation became the active ingredient moderating the other key elements: evidence was extended to embrace wider notions of new ideas and was termed innovation; we took account of the fact that the individuals or teams that were going to use the new evidence were invisible in the original framework, hence the addition of a construct called ‘recipients.’ But the biggest refinement was to our representation of context. From a linear representation of items located at (implicitly) at unit or ward level, we argued that context was a multi-level  and multidimensional construct. The facilitator’s (or whomever was enabling the process of the uptake of new knowledge) job was to work with the recipients and stakeholders to diagnose what was necessary to do in relation to the innovation, recipients and the inner , inner  and outer contexts. Such diagnostic activity is common with other frameworks, some concentrating on behavioural characteristics of individuals8; others providing data about contextual or organisational readiness for change data.9 A further refinement of the framework took place in 20152 painstaking work on identifying characteristics of context is whether having a comprehensive list will in fact lead to improvements in facilitators’ ability to improve the uptake of evidence into practice. Implicit in their argument is that continued under-achievement of successful evidence implementation is related to this failure to describe and hence measure, modify, and control context. I am not convinced that there is such a clear correlation. Indeed, the crux of Squires and colleagues’2 argument seems to rest on the premise that if contextual factors are thoroughly described and accounted for, that implementation will become easier or more successful. This line of argument is reminiscent of the early EBP days when it was assumed that the strength of the evidence would be an advantage to SI. We now know this is not the case, hence the move towards multidimensional approaches to understanding the science of implementation. Having a list and providing a context assessment to a team of clinicians who have not had any experience in implementation could be a daunting experience, so the facilitator or knowledge broker needs to actively engage with stakeholders in the immediate context to help them work out what to prioritise as they go forward with their change activity. Implementation is a profoundly social enterprise. The primary question regarding Squires and colleagues’11 we have constantly had to work out the balance between providing a comprehensive view of the constructs  context, inner  context and outer context) and keeping the tools sufficiently clear, short and simple so that everyone gets a sense of the key issues. Also, given the inherent worldview of our approach to knowledge translation10 and implementation which is that it is multidimensional, contingent, and more characteristic of a complex adaptive system, the challenge then becomes one of not being prescriptive but rather the tools are used to inform, shed light and help tailor multiple small actions to work towards the goal of implementation. In our research on developing a set of tools to help clinicians and researchers use the i-PARIHS framework,2 have moved the conversation on in terms of outlining a comprehensive list of contextual factors that could influence SI. How they are operationalised and whether they have increased impact because of their specificity across health areas are still to be tested. Squires et al Not applicable. AK is one of the originators of the PARIHS framework. AK is the single author of the paper.


The light yield obtained with the 241Am source is 3600 ± 600 photons per MeV, which is much smaller than the maximum attainable light yield obtained from the bandgap. Temperature dependent radioluminescence measurements confirm the presence of thermal quenching at room temperature with the activation energy and the ratio between the attempt and the radiative transition rates of 61 meV and 129, respectively. Although thermal quenching affects light yield at room temperature, this green light-emitting perovskite opens an avenue for new lead-free scintillating materials.We report the optical and scintillation properties of (C A new tin perovskite material with green emission is investigated as a new scintillator for imaging readout. Temperature dependent measurements were studied to understand the mechanism and to improve the future lead-free scintillator. X-ray, nevertheless recently they were shown to be effective for gamma-ray and neutron spectroscopy with good energy resolution.6,7 Although larger effective atomic number and mass density should favor AIP lead halide quantum dots and nanosheets for stopping high-energy radiation applications, their radiation absorption lengths are in fact much smaller than those in bulks. The short actual lengths are due to the presences of the ligands and/or adhesives making the packing fractions much lower than those in bulks.2,8,9 Also, small Stokes shift generates some problems with the reabsorption.10 For HOIP lead halide crystals, the bromide crystals are more stable and having larger light yields than iodide ones.7 However, the blue emission of bromide crystals is less attractive due to the lower quantum efficiencies for typical photodiodes used for X-ray imaging display panels.11 Finally, both HOIP and AIP lead halide materials share the same disadvantage as the lead cation (Pb) is toxic and can cause severe health hazard.Lead halide perovskite materials gain lots of interest as a new generation of scintillating materials.12 copper (Cu),13,14 tin (Sn),15 antimony (Sb),16 bismuth (Bi),17 and europium (Eu).18 With the cation replacement, beside decreasing the toxicity, we also can tune the emission wavelength from blue to green. However, all of them, except Bi, have effective atomic numbers and atomic masses lower than Pb reducing the radiation absorption. Despite that scintillation efficiency for most lead free perovskite materials has been estimated to be lower than for Pb compounds,19,20 it has to be verified by means of pulse height spectra and radioluminescence measurements. In this work, we report optical and scintillation properties of green-light-emitting (C6H5CH2NH3)2SnBr4 crystals as a new potential candidate of lead free scintillator. The photoluminescence (PL) peak is at 498.14 nm while time-resolved PL (TRPL) decay curve exhibits the lifetime of 1.05 μs. For scintillation, we compare its properties to the previous sibling, (CH3(CH2)7NH3)2SnBr4 (ref. 6H5CH2NH3)2SnBr4 are much shorter than those in (CH3(CH2)7NH3)2SnBr4, we obtain that the respective absorption length at 20 keV of 0.016 cm is slightly shorter than that of 0.017 cm. The bandgap of (C6H5CH2NH3)2SnBr4 is found to be 2.51 and 2.12 eV for experimental and theoretical values, respectively. For the empirical light yield calculation considering unity photoluminescence quantum yields (PLQY) and transfer efficiencies,4 the maximal attainable light yield is inversely proportional to the bandgap and therefore, the value for (C6H5CH2NH3)2SnBr4 is expected to be between 160 000 and 190 000 photons per MeV. However, the light yield at room temperature (RT) is relatively low (3600 ± 600 photons per MeV) and we associate this low yield due to low PLQY and thermal quenching of the exciton as it is a common observation in HOIP crystals.4 For parameters in quenching, we compare both activation energy and the ratio between thermal quenching and radiative transition rates in other HOIP crystals.12 This should lead to more in-depth understanding of scintillation processes in lead-free HOIP.The possible cation replacement for lead is manganese (Mn),3PO2, 50 wt% in H2O), benzylamine  and tin(ii) bromide (SnBr2) used for synthesis, were purchased from Sigma-Aldrich. The synthesis method of (C6H5CH2NH3)2SnBr4 was adopted and modified from the reference reported by Cao et al.15 The compound was prepared from aqueous solution of 2 ml C6H5CH2NH2 and 3 ml of 48% HBr in 5 ml distilled water mixed with a solution of 0.5 g SnBr2 in 7 ml of 48% HBr and 20 ml of H3PO2. The solution mixture was stirred vigorously and heated to 60 °C for three hours to achieve a homogeneous solution. The crystals were grown after the mixture was left over few days at room temperature. The crystals were filtered from the solution mixture, and dried in aeration. For microcrystals, we kept the crystals in the solution mixture  and put them in the ultrasonic bath operating at 80 kHz for 15 minutes. All samples were kept in the dry box and only to be exposed with air directly prior and after measurements.Hydrobromic acid , hypophosphorous acid (Hλ = 1.54178 Å). The data acquisition was employed at RT under Bragg–Brentano geometry with the speed of scanning of 10 s per step and step size of 0.02.Powder X-ray diffraction (XRD) data were recorded on a Bruker D8 Advance AXS diffractometer with a graphite-monochromatized Cu Kα radiation  with an accelerating voltage of 5 kV and a commercial atomic force microscope . A standard cantilever with spring constant of 40 N mX-ray photoelectron spectroscopy (XPS) experiments were carried out by using X-ray source of magnesium Kα with typical excitation energy output of 1254 eV. The impinged spot size on the sample is about 1 mm in diameter.via a 30 kHz picosecond pulsed diode laser . The PL measurement was based on epifluorescence method. PL spectra were detected using AvaSpec-HERO spectrometer . The emission was then selected by a band filter at 500 ± 25 nm and detected by a single-photon avalanche photodiode (APD) connected to a time-correlated single-photon counting acquisition module . Absorption spectra of perovskite crystals were obtained using ultraviolet-visible (UV-vis) spectrometer . PLQY measurements were carried out by placing the sample inside a Labsphere integrating sphere coupled to a Newton 920 Charge Coupled Device (Andor) through an optical fibre for photon counting. Cobolt 320 nm continuous-wave diode laser was used as an excitation source.PL measurements were performed at room temperature (RT) using free-space excitation and collection through a visible-near-infrared microscope objective . The sample was excited −1. For imaging, X-ray source was PHYWE XR 4.0 expert unit  operated at 35 kV voltage and 1 mA current while the camera was a commercial color camera with 1 s exposure time. The card with the chip was just put in front of the scintillator while its back side was put close to the aperture of the X-ray tube where the uncollimated X-ray came out. They were placed as close as possible to reduce light scattering.For all those measurements, we used one integrated setup. It consists of an Inel XRG3500 X-ray generator Cu-anode tube, 45 kV/10 mA, an Acton Research Corporation SpectraPro-500i monochromator, a Hamamatsu R928 photomultiplier tube (PMT), and an APD Cryogenic Inc. closed-cycle helium cooler. First, we measured the radioluminescence (RL) at different temperatures between 10 and 350 K starting from the highest to lowest temperatures in order to avoid the possible contributions from thermal release of charge carriers to the emission yield. After RL measurements, we recorded low temperature afterglow and thermoluminescence (TL) glow curves. Prior TL measurements, the crystals were exposed to X-rays for 10 minutes at 10 K and the monochromator was set to the zeroth order. The glow curves were recorded at temperatures between 10 and 350 K with a heating rate of about 0.14 K sFor the pulse height measurements, the crystal was mounted on the window of a Hamamatsu R9880U-20 PMT, with a thin layer of silicone grease to provide optical coupling. The PMT was operated at a voltage of −750 V for these measurements. The PMT anode signal was input directly to a Caen DT5720D digital pulse processing unit.3(CH2)7NH3)2SnBr4 retrieved from Cao et al.15 and the triclinic unit cell of (C6H5(CH2)2NH3)2SnBr4 retrieved from Xu et al.21 were used for the (CH3(CH2)7NH3)2SnBr4 and (C6H5CH2NH3)2SnBr4 calculations, respectively. The Kohn–Sham formulation22,23 as implemented in the Vienna Ab initio Simulation Package (VASP)24,25 was used for the calculations. The Projector Augmented Wave (PAW) method26,27 was employed to describe the interaction between ion cores and electrons. The electron exchange–correlation was treated by the generalized gradient approximation (GGA) based on the Perdew–Burke–Ernzerhof (PBE) functional.28 A rotationally invariant GGA+U approach introduced by Dudarev et al.29 was used with an effective Hubbard parameter Ueff being 9.0 eV for the Sn p orbital. The plane wave basis sets with a cut-off energy of 500 eV were employed for all calculations. The Brillouin zone was sampled with 3 × 3 × 1, 3 × 3 × 3, 3 × 3 × 3 k-point grids for (CH3(CH2)7NH3)2SnBr4, (C6H5(CH2)2NH3)2SnBr4, and (C6H5CH2NH3)2SnBr4, respectively, according to the Monkhorst–Pack scheme.30 DFT-D3 method was adopted to account for the dispersion correction.31 The conjugate gradient method was employed for cell optimizations, and the calculations were considered to converge when the maximum forces on each atom were less than 0.01 eV/1 Å. During calculations, all atoms were allowed to be fully relaxed.The orthorhombic unit cell of (CH6H5CH2NH3)2SnBr4 crystals. The appearance of the single crystal and the X-ray diffraction (XRD) pattern are shown in 6H5(CH2)2NH3)2SnBr4 structure21,32 with the removal of one [CH2] moiety in its ligand, see Fig. S1 and Table S1 of ESI.6H5CH2NH3)2SnBr4 are 5.52°, 12.68°, 18.54°, 24.84°, 27.08°, 31.05°, and 37.34° which could be assigned to the (001), (002), (003), (004), (005), (006), and (007) lattice planes, respectively, comparable to the previous reported of 2D layered metal halide perovskite.33–36 For the complete calculated lattice and geometrical parameters comparing to those of (CH3(CH2)7NH3)2SnBr4 and (C6H5(CH2)2NH3)2SnBr4, we enlist them in Table S2 of ESI.P1. This phase still belongs to the general class of A2SnX4  HOIP crystals and consists of the stack of 〈100〉-oriented perovskite inorganic layers, forming a two-dimensional (2D) Sn-X octahedra network in alternation with the organic sheets of C6H5CH2NH3+ cations. The structure has a deficit of [CH2] chain in the cation of (C6H5(CH2)2NH3)2SnBr4 2SnBr4 while those for (C6H5(CH2)2NH3)2SnBr4 (ref. 3(CH2)7NH3)2SnBr4 (ref. 6H5CH2NH3)2SnBr4 has the smallest Eg, it has the highest estimated maximum light yield of approximately 190 000 photons per MeV.1,4Br4 ref.  are 2.406H5CH2NH3)2SnBr4 as shown in 3/2 and 3d5/2 core levels. Those binding energies are only 0.5 eV lower than those of (C6H5(CH2)2NH3)2SnBr4 reported by Xu et al.21 The chemical states of Sn2+ of (C6H5CH2NH3)2SnBr4 remains the same throughout the prolonged observation. We monitored the progression changes from the Sn2+ into Sn4+ oxidation states after three-month duration kept at ambient conditions. The rest of XPS signals can be found in Fig. S3 of ESI.−1, one peak at 484.35 cm−1 due to SiO2 substrate, and three other peaks at frequencies around 1000 cm−1. The first two low frequency peaks at 87.66 and 101.84 cm−1 are attributed to two external modes of C6H5CH2NH3+.37 The peak centered at 181.11 cm−1 is attributed to the internal asymmetric stretching mode of Sn–Br vibration. Finally, the peaks above 500 cm−1 only arise from the internal modes of the organic cations.37,38Furthermore, the investigation on the quality of the crystals also involves the surface characteristics and elements inside (C6H5CH2NH3)2SnBr4 are shown in 3(CH2)7NH3)2SnBr4 (ref. 6H5(CH2)2NH3)2SnBr4.21 For five days, the peak and the width of the PL almost remain constant while the intensity decreases by 23%, see Fig. S4 of ESI.3(CH2)7NH3)2SnBr4 can be related with the completely different structure while the difference with (C6H5(CH2)2NH3)2SnBr4 is consistent with previously observed in Mn-based HOIP.12 For the latter, the longer emission wavelength is related to the lower exciton binding energy in (C6H5CH2NH3)2SnBr4 in comparison with the energy in (C6H5(CH2)2NH3)2SnBr4 due to the absence of one [CH2] chain in the cation. From the absorption spectra, we can derive the optical bandgap as it is shown in the Tauc plot of Fig. S5 from ESI.6H5(CH2)2NH3)2SnBr4 which the experimental and theoretical values are 2.67 eV and 2.40 eV, respectively.21,32 The experimental bandgap in (C6H5CH2NH3)2SnBr4 is still lower than those in (C6H5(CH2)2NH3)2SnBr4 and (CH3(CH2)7NH3)2SnBr4, which is expected from the shortest organic chain in (C6H5CH2NH3)2SnBr4. For Stokes shift, the values for (C6H5CH2NH3)2SnBr4 and (C6H5(CH2)2NH3)2SnBr4 are similar of 0.02 eV and 0.03 eV, respectively. Time resolved PL (TRPL) decay curve in 3(CH2)7NH3)2SnBr4 (ref. 6H5(CH2)2NH3)2SnBr4,21 respectively.Absorption and PL spectra of (CBr4 ref.  and ∼30 Br4 ref.  and (C6H6H5CH2NH3)2SnBr4. The absence of traps is related with very short chain of (C6H5CH2NH3)2SnBr4 in comparison with other 2D HOIP crystals.12 Thus, for scintillation mechanism, most excitons are free and therefore this material has the fastest lifetimes among other Sn HOIP crystals.15,21 These are the advantages of (C6H5CH2NH3)2SnBr4 for scintillator applications.Radioluminescence (RL) and thermoluminescence (TL) properties are shown in 39 The characteristics from the thermal quenching are presented as Arrhenius plot in I) with Arrhenius equation can be summarized as following:IT, ΔEq, Γ0/Γv, and kB are the intensity at low temperature of around 10 K, the thermal quenching activation energy, the ratio between thermal quenching rate at T = ∞ (attempt rate) and the radiative transition rate, and Boltzmann constant, respectively. 6H5CH2NH3)2SnBr4 crystal. As it is only related to one mechanism without any assumption of the phase transitions, the smooth behavior of intensities reflects that the crystals have no phase transition. For (C6H5CH2NH3)2SnBr4, ΔEq and Γ0/Γv are 61 meV and 129, respectively. Γ0/Γv of (C6H5CH2NH3)2SnBr4 is much smaller than those for (C6H5(CH2)2NH3)2MnCl4 (ref. 6H5CH2NH3)2SnBr4 happens at higher temperatures. We also note that the thermal quenching maybe responsible for 1.05 μs fast lifetime of (C6H5CH2NH3)2SnBr4 as it was previously observed in lanthanide trihalides.40Temperature dependent RL spectra mapping at different temperatures from 10 K to 350 K are shown in 6H5CH2NH3)2SnBr4.21 Moreover, PLQY value is consistent with both temperature-dependent PL and TRPL measurements in Fig. S6 of ESI.1 Pulse height measurement with 241Am at RT in Fig. S8 of ESI1 The light yield at 10 K is still consistent with the previous measurements on HOIP crystals at 10 K.4 With this light yield, we still can perform X-ray imaging as shown in the inset of 6H5(CH2)2NH3)2SnBr4.15It was shown at 6H5CH2NH3)2SnBr4 crystals prepared by solution process. The crystal shows bandgap of 2.51 eV, green emission with PL peak at 498.14 nm and fast PL lifetime at 500 nm of 1.05 μs. For scintillation, the observed short absorption length at 20 keV of 0.016 cm unexpectedly results the low light yield at RT (3600 ± 600 photons per MeV). From temperature dependent RL observation, the thermal quenching activation energy and the ratio between thermal quenching and radiative transition rates are 61 meV and 129, respectively. Compared to other HOIP crystals, the small ratio indicates the occurrence of thermal quenching at high temperature thus affecting the light yield. Although we still could perform X-ray imaging, the quenching effect should be minimized to increase the sensitivity. Another method to increase the light output is through the fabrication of the nanostructures as it was already demonstrated in perovskite materials.41 With these findings, (C6H5CH2NH3)2SnBr4 may be considered to open possibilities for new candidates of green-emitting lead-free perovskite scintillator.In this work, we reported optical and X-ray scintillation properties of , scanning electron microscope (SEM) and X-ray imaging, F. M., S. A. B., and M. D. B.; XPS and Raman characterization, A.; DFT characterization, M. H. M.; RL and TL characterization, M. E. W., M. M., and W. D.; data analysis and writing, L. J. D. and S. K.; supervision, W. D. and M. D. B. All authors have read and agreed to the published version of the manuscript.There are no conflicts to declare.RA-011-D1RA01123E-s001