Following a single seizure, or recent epilepsy diagnosis, it is difficult to balance risk of medication side effects with the potential to prevent seizure recurrence. A prediction model was developed and validated enabling risk stratification which in turn informs treatment decisions and individualises counselling.Data from a randomised controlled trial was used to develop a prediction model for risk of seizure recurrence following a first seizure or diagnosis of epilepsy. Time-to-event data was modelled via Cox's proportional hazards regression. Model validity was assessed via discrimination and calibration using the original dataset and also using three external datasets – National General Practice Survey of Epilepsy (NGPSE), Western Australian first seizure database (WA) and FIRST .People with neurological deficit, focal seizures, abnormal EEG, not indicated for CT/MRI scan, or not immediately treated have a significantly higher risk of seizure recurrence. Discrimination was fair and consistent across the datasets (c-statistics: 0.555 (NGPSE); 0.558 (WA); 0.597 (FIRST)). Calibration plots showed good agreement between observed and predicted probabilities in NGPSE at one and three years. Plots for WA and FIRST showed poorer agreement with the model underpredicting risk in WA, and over-predicting in FIRST. This was resolved following model recalibration.The model performs well in independent data especially when recalibrated. It should now be used in clinical practice as it can improve the lives of people with single seizures and early epilepsy by enabling targeted treatment choices and more informed patient counselling. Exclusion criteria included previous treatment with ASMs or the presence of a progressive neurological disease.Participants were randomly allocated to treatment policy, by phone or fax, using the minimisation method, balanced across centre or region and number of seizures at randomisation. For participants assigned to immediate treatment, the clinician selected the optimum ASM, based on their usual practice and started treatment as early as possible. Participants assigned to deferred treatment received no drugs until the clinician and individual agreed that it was necessary, mainly after a seizure recurrence.MESS remains the largest reported study of people with single seizures and early epilepsy. While the study's primary purpose was to compare treatment policies, it also provided an important opportunity to examine seizure recurrence risks and factors that modify those risks.2.1.2National general practice study of epilepsy and epileptic seizures (NGPSE): The NGPSE Western Australian study (WA): The WA [: The WA ,12 obserPeople with status epilepticus, prior seizures of any nature except febrile convulsions, and non-epileptic events such as convulsive syncope were excluded FIRST seizure trial group (FIRST): The FIRST Participant consents: This was a re-analysis of randomised controlled trial and observational study data not requiring ethical approval.2.2The outcome, time to seizure recurrence, was estimated for each individual with observations censored at date of last follow-up if no recurrence had occurred or if an individual was lost to follow-up, including death. Acute symptomatic and provoked seizures were not considered as a seizure recurrence. Analysis used Cox proportional hazards modelling on a time since entry timescale. Further details of the statistical methodology can be found in the Supplementary Material.The list of eleven prognostic factors for potential inclusion in the model was: age at first seizure, gender, cause of seizure (remote symptomatic or not), neurological deficit, previous acute symptomatic seizure(s), epilepsy in first degree relative, seizure type, seizures only while asleep, electroencephalogram (EEG) result, computerised tomography (CT) or magnetic resonance imaging (MRI) scan result, and treatment policy. These were chosen based on clinical consensus and knowledge from previous predictive studies in epilepsy ,17.Individuals were classified as remote symptomatic if on entry to MESS the clinician considered that their seizure was caused by a past condition or event such as a head injury; meningitis or encephalitis; intracranial surgery; or other. Investigations (EEG and CT/MRI) were only undertaken if considered clinically indicated. Neurological deficit included hemiparesis and learning difficulty. An abnormal EEG was defined as focal or generalised slowing, or epileptiform abnormalities. CT/MRI scans were classified as abnormal or not. The continuous variable for age was investigated using fractional polynomial transformations The performance of the model was evaluated in terms of discrimination and calibration. Discrimination was measured using Harrell's c-statistic 2.3For assessment of model transportability, the final optimism-adjusted model was externally validated in the NGPSE, WA and FIRST datasets. Validation was approached on a case-by-case basis to account for differences in predictor specification across the external datasets. In particular, when a predictor in the final model was not available in the external dataset see , a reduc2.3.1Where calibration plots showed systematic under- or over-prediction of risk of recurrence in the external validation, recalibration via baseline hazard updating was undertaken to account for the different risk profile of the external dataset 33.1The parsimonious multivariable model (after backwards selection) for risk of seizure recurrence after study entry included covariates for neurological deficit, seizure type, EEG result, CT/MRI scan result and treatment policy. The optimism-adjusted c-statistic for the model was 0.575 and the calibration slope, adjusted for model fitting optimism, was 0.827. Optimism adjusted results for the predictors can be seen in p-values for Schoenfeld residual test – neurological deficit: 0.470, focal seizures: 0.049, other seizure types: 0.212, abnormal EEG: 0.714, EEG not clinically indicated: 0.971, abnormal CT: 0.838, CT not clinically indicated: 0.796, treatment policy: 0.019, overall: 0.141). The p-value for treatment of 0.02 provides some evidence that the effect of baseline treatment allocation changes over time. With the evidence being borderline, however, it is preferable to fit a common time effect for treatment for simplicity.The baseline estimates of seizure recurrence at one and three years were 0.351 and 0.462 once adjusted for shrinkage. Unadjusted estimates for all analyses can be found in the Supplementary Material. There was no evidence to doubt the proportional hazards assumption, except for treatment  included covariates for cause of seizure, seizure type, EEG result, CT/MRI scan result and treatment policy. The optimism-adjusted c-statistic and slope were 0.351 and 0.462, respectively. Results, adjusted for optimism, can be seen in The c-statistic for the external validation of the MESS1 model in NGPSE data was 0.555. Calibration plots at one and three years can be seen in 3.2.2The parsimonious multivariable model for the matched MESS data (MESS2) included covariates for neurological deficit, seizure type, EEG result, CT/MRI scan result and treatment policy. The optimism-adjusted c-statistic and slope were 0.576 and 0.825, respectively. Results, adjusted for optimism, can be seen in The c-statistic for the external validation of the MESS2 model in WA data was 0.558. Calibration plots at one and three years can be seen in 3.2.3The parsimonious multivariable model for the matched MESS data (MESS3) included covariates for neurological deficit, seizure type, EEG result, and treatment policy. The optimism-adjusted c-statistic and slope were 0.574 and 0.834, respectively. Results, adjusted for optimism, can be seen in The c-statistic for the external validation was 0.597. Calibration plots at one and three years can be seen in 3.3The baseline estimates of seizure recurrence at one and three years in WA were 0.448 and 0.531, and 0.267 and 0.407 in FIRST, after adjusting for model-optimism. Calibration plots at one and three years for the recalibrated models can be seen in 4People with neurological deficit, focal seizures, abnormal EEG results, not indicated for a CT/MRI scan result, or randomised to delayed treatment have a significantly higher risk of seizure recurrence. Not indicated for a CT/MRI scan maybe because of correlation with age, EEG or other factors. Indeed, in MESS, it is likely that age influenced whether someone had a scan. This may also reflect clinical practice specific to the UK.The model was validated in three independent datasets from across the world. Variations to the original MESS model were required for all external datasets, so it is impossible to compare agreement between the datasets directly. Discrimination was fairly similar across all three external datasets, and close to 0.50, the value of no predictive value. It is, however, within keeping with other models in epilepsy and is indicative of the challenge of predicting seizures Many studies have evaluated risk of a second seizure after a first, and there have been several attempts to provide narrative summaries and meta-analyses of them ,29. MethA prediction model for risk of seizure recurrence in people with a single seizure only, using MESS, has previously been developed and externally validated ,6. That The current study has limitations. The MESS dataset is over 10-years old but the prognosis of epilepsy has not changed over time. While the population of people with epilepsy has increased in age with more people who are elderly presenting, and these are under-represented in the MESS dataset, age was found not to be a predictor of outcome. MESS and FIRST were randomised trials and thus recruited people from unknown source populations. NGPSE is a population sample and WA is a tertiary hospital clinic-based sample. These different sources can have marked effects on the risk of recurrence, and on the models too as shown by the need to recalibrate the model for use in WA and FIRST. Additionally, no interaction terms were included in the model as it can be challenging to interpret interactions between continuous and categorical variables when a model is used within clinical practice. Also, information regarding adherence was not collected and therefore modelled. Medication adherence can interfere with outcome of seizures however we feel that our pragmatic approach of not modelling adherence reflects clinical practice where adherence can be challenging to measure.Following the development and external validation of a model it is important to work with expert clinicians and patient and participant involvement groups to determine the most appropriate presentation method 5Use of a clinical prediction model for risk of seizure recurrence after a single seizure or diagnosis of epilepsy can guide treatment decisions and counselling thus improving personalised management of people with seizures. The model developed here has been shown to perform well in independent data especially when recalibrated to account for differences in the underlying risk profile in two of the external datasets. The next steps include discussing the most appropriate presentation method for this model with end-users, testing the clinical utility of the model within clinical practice, and ultimately ensuring that this model is adopted as part of routine clinical practice to improve the lives of people with single seizures and early epilepsy.https://www.nihr.ac.uk/). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, or the Department of Health.This article is independent research arising from a Post-Doctoral Fellowship (Dr Laura Bonnett - PDF-2015-08-044) supported by the National Institute for Health Research (


Purpose: Because older adults are at elevated risk of COVID-19-related adverse health outcomes, and staying at home is an effective strategy to avoid unnecessary exposures, the current formative study used the Reasoned Action Approach (RAA) to identify the beliefs underlying older adults' decision to stay home for the next month.Methods: The participants  for the current study were selected from a nationally representative online survey of US adults from April 10-20, 2020. We used multiple linear regression to estimate the relative contribution of the four RAA global constructs  in explaining intention to stay home after controlling for demographic covariates. We also conducted a content analysis to identify beliefs about advantages, disadvantages, and facilitators of staying home.Results: After controlling for demographic characteristics, injunctive norms  and self-efficacy  showed statistically significant independent associations with intention to stay home. The specific beliefs underlying the decision to stay home spanned across health and wellness dimensions and suggested interpersonal, mental health, and leisure/recreational facilitators.Conclusions: These findings suggest three public health intervention targets. First, self-efficacy building interventions could enhance older adults' perceptions of their ability to stay home to avoid unnecessary exposures. Second, health communication messages to address injunctive norms could emphasize that people important to older adults think they should stay home. Third, for the youngest of the older adults, health communication messages could emphasize the advantages of staying home. In response to the coronavirus disease 2019 (COVID-19) outbreak in the spring of 2020, governors across the US issued stay-at-home executive orders to prevent the spread of the virus and protect the health care infrastructure from becoming overwhelmed. Stay-at-home orders have been shown to be effective at preventing COVID-19 infections , and lowStrategies to promote engagement in a behavior such as staying home are more effective if they are based on evidence and theory . TherefoAccording to the RAA , intentivia a qualitative elicitation. Of relevance here, beliefs about the advantages and disadvantages perceived about engaging in the action underly the attitude toward the act of staying home, and beliefs about the circumstances that might facilitate the behavior underly perceived behavior control related to staying home. However, not all beliefs listed by a priority group operate as salient. Thus, an important step in applying the RAA is to conduct a salient belief elicitation to identify the outcomes and circumstances that are at the top-of-the-mind of the specific priority group . This is particularly important when a priority group is at elevated risk for serious outcomes, as is the case with older adults and COVID-19.via the US Postal Service's Delivery Sequence File. These surveys have been shown to generate high-quality and generalizable results  from April 10-20, 2020. Participants were recruited into the larger study using the Ipsos Knowledge Panel, a nationally representative, probability-based sample established using address-based sampling  results . Ipsos pn = 273). We excluded 13 (4.8%) participants who were missing data resulting in a final unweighted sample of 260 eligible for analyses. A general population weight  was applied to the data to minimize bias and variance due to non-response error. Weighting was calculated based on the latest March supplement of the Current Population Survey (CPS) with variables such as gender, race/ethnicity, age, education, census region, and household income. The final weighted sample size was 206.Of the 1,632 Knowledge Panel members invited to participate in the larger study, 1,010 (61.9%) completed the survey. For this study, we selected participants age 65 and over ] and 72-94 [n = 97 (47.0%)]. The values for age and the four global constructs were mean-centered before computing the interaction terms.Analyses were conducted using SPSS version 25.0 . We usedTo identify the underlying beliefs, we conducted a multi-step inductive content analysis . The resAs shown in r = 0.935, p < 0.01), next for injunctive norms , next for instrumental attitude , and lowest for descriptive norms .In terms of the RAA global constructs, the mean values were 4.12 (SD = 0.96) for intention, 4.19 (SD = 0.94) for attitude, 4.10 (SD = 0.98) for injunctive norms, 3.88 (SD = 0.91) for descriptive norms, and 4.13 (SD = 0.97) for self-efficacy. All constructs were measured on 1-5 scale. All four global constructs were significantly correlated with intention. The correlation with intention was highest for self-efficacy . Participants who were more conservative had lower levels of intention to stay home than those who identified as liberal. After the RAA global constructs were added in the second block, there was a statistically significant increase in the adjusted R2, and political ideology was no longer significantly associated with intention. After controlling for demographic characteristics, injunctive norms  and self-efficacy  showed significant independent associations with intention to stay home. Neither attitude nor descriptive norms had significant weights.Results from the regression analysis testing factors associated with intention to stay home are displayed in b = −0.253; SE = 0.122; B = −0.122, p = 0.04). To probe this significant interaction, we split the file into two groups, those age 65-71 and those age 72-94, and used multiple linear regression to test the association between attitude and intention controlling for demographics and the remaining RAA global constructs. These analyses showed that for the 65-71 year old group, attitude was significantly associated with intention to stay home . However, attitude was not associated with intention for the 72-94 year old group .We also tested age by attitude, age by injunctive norms, age by descriptive norms, and age by self-efficacy by adding these interaction terms to the third block of the regression model. Only age by attitude was statistically significant , was that staying home might allow me to catch up on things at home. This included responses such as catching up on chores and cleaning, doing home projects, and reading. The third most commonly cited advantage of staying home (10.6%) was the population health benefit that my staying might slow or stop the spread of COVID-19.temporary effects on mental or emotional well-being. This included responses such as I might get bored, go stir crazy, or experience cabin fever. An additional 7.6% were concerned about more serious mental health disadvantages, including believing that staying home might lead to depression, anxiety, loneliness, or stress. The second most frequently mentioned disadvantage, mentioned by 15.3% of the older adults, involved physical health problems, such as gaining weight and exercising less. Our participants also saw interpersonal disadvantages of staying home. More specifically, 12.2% reported they might miss interaction with friends and family, including their own children and their grandchildren. Finally, 7.3% indicated they miss getting out of the house to attend social events. This included response about being confined to the house and not being able to attend recurring events like going out to dinner and one-time events like weddings.Having things to do was the most commonly elicited circumstance that might make it easier for participants to stay home (25.7%). This included things like watching movies/TV shows and doing yard work/other outside activities. Related to this, 6.5% mentioned having the right weather might make staying home easier. One in ten participants (10.8%) expressed that having food and supplies delivered to them might make it easier to stay home, and 5.5% mentioned having access supplies would help. In terms of interpersonal facilitators, 5.3% mentioned living with someone and 4.4% mentioned being able to chat virtually. An additional 4.0% mentioned access to technology as a facilitator.The percent of older adults mentioning each of 11 categories of facilitating circumstances is presented in This formative study tested factors associated with older adults' intention to stay home during the early part of the COVID-19 pandemic in the US. The means for intention and the four global constructs were positive, around four- on a five-point scale. Thus, for the most part, early in the epidemic, US older adults intended to stay home, saw it as a good thing to do, and believed they could stay home. However, there is room for improvement. Public health strategies are needed to help people continue to follow guidelines, particularly as we are required to stay home for longer periods.The next finding of note was that when only demographic factors were included in the model, political ideology was the only demographic characteristic significantly associated with intention to stay home. Specifically, participants who were more conservative on the political spectrum reported lower intention to stay home. This is consistent with research  that als2 of 0.732 in our model is higher than what was found in a study . This finding suggests providing younger old adults with opportunities to exercise in and around their residences, grocery delivery of healthy foods, and other weight control programs might help them to stay home. Second, more older participants listed missing interacting with family and friends than young-old participants (15.5 and 9.2%). Because older adults may have limited opportunities to freely interact with family/friends, providing these individuals with technology to virtually connect with others and providing them with safe ways to talk with family/friends in-person  might address this potential disadvantage. Because this was an exploratory analysis, future research is needed to further examine these potential interactions.A strength of this study is that the data are drawn from a nationally representative, probability sample resulting in generalizable findings. Furthermore, we were able to gather open-ended data about beliefs that elaborated on perceived advantages and disadvantages of staying home, as well as perceived facilitators of staying home. However, there are limitations that should be taken into account when interpreting the findings. First, this study used a cross-sectional design. It was designed to suggest potential factors and cannot be used to come to causal conclusions. Longitudinal and experimental studies are needed to assess the effects of COVID-19 mitigation interventions like stay-at-home orders on global constructs, intention, and behavior. Second, only five RAA items and three open-ended questions were included in the online survey due to resource constraints . We assessed one of the two components of attitude  and one of the two components of perceived control . We asked only three of the six recommended open-ended questions. Thus, we could not draw conclusions based on the complete RAA theory. Third, on a related note, we used only one item per RAA construct. This limited our ability to assess the reliability of the measures. Fourth, the outcome assessed in this study was intention to engage in the desired behavior as opposed to the actual behavior of staying home. Thus, we did not test the intention-behavior relationship, a key part of the RAA. Finally, although it corresponded to guidelines, the behavior “stay in my house or apartment except to get food, care for a relative or friend, get necessary health care, go to an essential job, or exercise separated from others” is a complex one. It is possible that different participants interpreted the behavior differently. Future research with samples of older adults of color, for example, is needed to investigate and address health equity .Older adults are a priority population for increasing COVID protective behaviors. The current study provides insights into the global constructs associated with intention and the underlying beliefs of staying at home for older adults. Based on the findings in this study, we suggest three possible directions for public health interventions. The first is to develop interventions that enhance the self-efficacy of older adults to stay home to avoid unnecessary exposures. A second strategy supported by the current study's findings is to develop health communication messages that emphasize that people important to older adults think they should stay home. Third, for the youngest of the older adults, communication messages should emphasize the advantages of staying home. All of these strategies should keep in mind that the epidemic has wide ranging effects and that older adults are concerned with interpersonal, social, leisure, and mental health issues. These lessons can be applied to other behaviors, such as being vaccinated, as the COVID-19 pandemic persists, and we face future public health crises.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 Indiana University Institutional Review Board. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.JM and CO analyzed the data and JM, CO, and SM drafted the manuscript. JM, CO, KM, and SM contributed to conceptualization, investigation, methodology, and writing review and editing. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The oral squamous cell carcinoma (OSCC) is detrimental to patients’ physical and mental health. The prognosis of OSCC depends on the early diagnosis of OSCC in large populations.Here, the present study aimed to develop an early diagnostic model based on the relationship between OSCC and oral microbiota.Overall, 164 samples were collected from 47 OSCC patients and 48 healthy individuals as controls, including saliva, subgingival plaque, the tumor surface, the control side , and tumor tissue. Based on 16S rDNA sequencing, data from all the five sites, and salivary samples only, two machine learning models were developed to diagnose OSCC.Actinobacteria, Fusobacterium, Moraxella, Bacillus, and Veillonella species exhibited strong correlations with OSCC.The average diagnostic accuracy rates of five sites and saliva were 98.17% and 95.70%, respectively. Cross-validations showed estimated external prediction accuracies of 96.67% and 93.58%, respectively. The false-negative rate was 0%. Besides, it was shown that OSCC could be diagnosed on any one of the five sites. In this model, This study provided a noninvasive and inexpensive way to diagnose malignancy based on oral microbiota without radiation. Applying machine learning methods in microbiota data to diagnose OSCC constitutes an example of a microbial assistant diagnostic model for other malignancies. Oral cancer is a significant threat to patients’ physical and mental health. According to the Global Cancer Statistics , an estiTherefore, it is essential to diagnose OSCC at an early stage, especially in large populations, and the prognosis of the treatment could benefit from the early detection of OSCC. In the diagnosis of OSCC and many other tumors, pathologic diagnosis is the gold standard, and radiologic examinations provide useful supplementary data. However, it is difficult to apply these traditional methods as primary diagnostic methods for OSCC in large populations due to their invasive, radioactive, and expensive nature. Therefore, an effective, convenient, and noninvasive method is necessary as a screening tool for OSCC in large populations.Porphyromonas gingivalis , and intratumoral tissue were useful for OSCC diagnosis. What is more, this diagnostic model can effectively avoid missed diagnoses; therefore, it is a potential early OSCC diagnostic method for large populations.post hoc analyses were carried out to evaluate the different aspects of the performance of the diagnostic model developed in stage II, i.e., external discrimination capacity and its reliability on the sample size of the random forest prediction model based on the oral microbiome.This study consisted of three stages. In stage I, the demographic data and microbiome were characterized using descriptive methods to provide a clear profile of both internal and external samples and the whole study data. Also, the microbiome and demographic data were analyzed using exploratory methods to test the study assumption, i.e., whether OSCC patients have microbiome patterns different from those of healthy people. In stage II, random forests were developed to determine the different patterns and further analyze the specified operational taxonomic unit (OTU) role in the differences between microbiome patterns of healthy and OSCC individuals. In stage III, The institutional review board of the West China Hospital Stomatology of Sichuan University approved the study . All the patients provided written informed consent forms before sample collection.The sample collection protocol conformed to the Manual of Procedure for Human Microbiome Project Core Microbiome Sampling Protocol A HMP Protocol #07-001 . There wAll patients were sampled before treatment to ensure that the microbiome was not affected by chemotherapy, radiotherapy, and oral prophylaxis. Of the 47 OSCC patients, 47 salivary samples , 18 subgingival plaque samples (the pla group), 21 surfaces of tumor samples (the tum–muc group), 16 control side of healthy mucosa samples (the con–muc group), and 16 tumor tissue samples (the tum group) were collected , in Beij3 cubes on a sterile platform; the tumor samples were then steeped in sterile povidone-iodine for 3 min and vortexed several times using 500 µl of PBS. The tumor samples were divided into two parts, with one being steeped in Tris-EDTA buffer (pH = 7.4) stored at −80°C and with the other one being used for cultivation  . The partivation .® soil DNA Kit  according to the manufacturer’s protocols  according to the manufacturer’s instructions, and quantified using QuantiFluor™-ST  . AccordiRaw FASTQ files were demultiplexed and quality-filtered using QIIME (Version 1.9.1) with the following criteria : i) the http://drive5.com/uparse/), and chimeric sequences were identified and removed using UCHIME. The taxonomy of each 16S rRNA gene sequence was analyzed by RDP Classifier (http://rdp.cme.msu.edu/) against the silva (SSU123) 16S rRNA database using a confidence threshold of 70%  showed that healthy individuals’ microbial community was concentrated, while the microbial community of patients was relatively discrete. Besides, the microbiome in samples from both OSCC and healthy individuals from the same center (West China College of Stomatology), i.e., OSCC and healthy control group, was similar. In contrast, those from the external center  exhibited a different pattern  were sampled to investigate the frequencies of oral microbial communities in OSCC patients. All the results are presented in the These exploratory results implied that the microbiome pattern between the healthy and OSCC subjects was significantly different. The significant differences suggested that the oral microbiome does have the potential capacity to discriminate the OSCC patients from all the individuals.We examined the similarities and differences of genera present in the healthy group and as depicted in Streptococcus (22.73%), followed by Neisseria (18.23%), Prevotella (14.56%), Porphyromonas (7.33%), Haemophilus (6.72%), and Veillonella (4.05%). The OSCC group was found to contain Streptococcus (11.09%), followed by Neisseria (12.88%), Prevotella (12.03%), Porphyromonas (4.18%), Haemophilus (3.35%), and Veillonella (6.01%).The OTUs representing different phyla were not similar between the two groups. The healthy group was observed to contain Streptococcus, Neisseria, and Prevotella and more Veillonella and Fusobacterium in the OSCC group. On the species level, there were less Haemophilus and more Veillonella in the OSCC group.The stacked column plots also showed the differences between the two groups in terms of phylum , and pairwise comparisons revealed a significant difference between control subjects who remained healthy and those with OSCC. Although the coefficient of determination is very low, there is a difference between the two groups. On the one hand, it is suggested that there can be a clear difference between the two, which can be used as an auxiliary diagnosis of OSCC; on the other hand, this mode difference may not be large and may lack discrimination in particular cases. Meanwhile, considering the number of OTUs, the samples size is relatively small, so a special method is needed to identify such slight differences. This is the machine learning diagnostic model mentioned later.Analysis of similarities (ANOSIM) , we sampled microbiota in these five locations.The Simpson index and Shannon index reflected the diversity of microorganisms in saliva, subgingival plaque, surface of tumor, normal mucosa, and intratumoral tissue. According to It can be seen from the Venn diagram , 70% (65), 80% (75), and 90% (83) of all the 93 salivary samples. For each sample size, the random forest model was tested different times of a test sample size of 10,000 to obtain accuracy with comparable variations. The average accuracies of the tests with different sample sizes provided the association of the training sample sizes and the performance of OSCC identification models using the salivary microbiome.Cross-validations showed that as the training sample size increased, the random forests based on salivary samples became more accurate. Seventy-five samples could supply significantly high performance, while more training samples could give rise to even greater accuracy; i.e., with all the 93 samples in training set at 95.70% accuracy, another 1.20% improvement could be obtained over 94.50% with 83 samples in the training set  exhibited sensitivities of 100%; therefore, no OSCC would be misclassified. However, as the training sample size decreased, false-negative predictions were found, i.e., 15 patients in 5,130 OSCC patients with a training sample size of 56 and three patients in 4,998 OSCC patients with a training sample size of 65. An interesting finding is that all the 18 false-negative predictions happened in one same sample. This sample was found from an OSCC patient having early invasive carcinoma on the oral cavity floor. At the early stages of cancer development, the characteristics of the oral microbiome were close to those of healthy individuals compared with other OSCC patients. Such samples from early cancer development stages might be misclassified as from healthy individuals due to the partly changed microbial profiles, which would be identified correctly by the models with larger training sets.This suggested the strategy of screening model development; the prediction random forest can first be built based on small sample sizes, such as those >50, and then the accuracy can be improved as the new samples are added to the training set to renew the basic model.Also, the difference between groups of healthy individuals from different centers suggested that a continuous and dynamic renewal of the prediction model using new samples would be of necessity for a potential change in population applied. It is recommended for each center to address the differences between microbial profiles in different populations when building its own prediction random forest.The human microbiome, a dynamic, interconnected ecosystem reflecting the locating environments, plays a central role in the process of development, health, and disease . AlthougSalivary samples would be an optimal choice for the OSCC preliminary diagnosis due to their advantages in the sample collection process. Early diagnosis plays a critical role in the treatment of OSCC, and many methods have been used in the diagnosis of OSCC. Compared with the traditional methods , our novel model, based on oral microbiota, exhibited apparent advantages. First, compared with CT and PET, no radiation is involved during sample collection and examination. Second, the cost of 16S rRNA gene sequences is 20%–50% of CT/MRI for every patient and <20% of PET. Third, the examination is more convenient for patients than CT, MRI, and PET. This method only requires the collection of saliva and sequencing, without the need for professionals to purchase or learn other examination equipment, and can be easily implemented in oral medical clinics or hospitals. Fourth, the diagnosis of histopathological analysis usually takes about 3–5 days, because the preparation of tissue samples and the interpretation by the diagnostic physician are quite complex and rigorous. This method only requires sequencing and machine data processing, which will provide quick help for diagnosis. Besides, some studies have indicated that oral microbiota could provide a potential risk assessment for several other diseases, like dental caries . Our inv18F-FDG PET has been recommended in the diagnosis of OSCC patients  can be found below: The institutional review board of the West China Hospital Stomatology of Sichuan University approved the study . The patients/participants provided their written informed consent to participate in this study.XXZ: validation, methodology, formal analysis, data curation, writing—original draft, and writing—review and editing. YH: validation, methodology, data curation, writing—original draft, and writing—review and editing. XP: methodology, data curation, and writing—original draft. BL: methodology, data curation, and writing—original draft. QH: methodology and data curation. BR: supervision. ML: supervision. LL: resources. YL: supervision. GC: formal analysis and supervision. JL: funding acquisition and supervision. YM: conceptualization, methodology, formal analysis, writing—review and editing, and funding acquisition. XDZ: conceptualization, methodology, and funding acquisition. LC: conceptualization, methodology, writing—review and editing, and funding acquisition. All authors contributed to the article and approved the submitted version.This study was supported by the National Natural Science Foundation of China, 81870759 and 82071106 (LC), 81803332 (YM), and 81991500 and 81991501 (JL); the Sichuan Science & Technology Program 2018SZ0284 (YM); Innovative Research Team Program of Sichuan Province (LC); and the Chengdu Science & Technology Bureau 2018-YF05-01265-SN (YM).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.


Nurse managers (NMs) expect support to carry out their ethical activities in a complex health care environment. In this study, the Ethics Quarter (EQ) is suggested as a new educational ethics e-learning intervention for nurse managers. The aim of this study was to evaluate the usability, feasibility and fidelity of the EQ. The goal was to create a new way to support NMs’ ethical activity profile  for the use of healthcare organizations.ClinicalTrials.gov with the identifier: 04234503). The participants were NM members of the Union of Health and Social Care Professionals in Finland (n = 95).The EQ was developed under guidance of the criteria for complex interventions in health care (CReDECI2) guideline. A cross-sectional survey was conducted within the intervention group after a randomized controlled trial (the main study is registered in ) and recommendations for further development  were highlighted. Fidelity, measured with Google Analytics, reported shorter time used by NMs on the EQ education than estimated.A system usability scale (SUS) assessed the overall usability of EQ as good (a mean SUS score of 85.40 out of 100). Positive feedback about the EQ’s feasibility was reported in structured and open questions (a good, necessary and practical research knowledge-based e-learning intervention for all nurse managersThe findings support the high usability, feasibility and average fidelity of the EQ intervention and its potential while also providing evidence for the development of future ethics education. Health care organizations would benefit from adopting the EQ to support the ethical activities and ethical activity profile of NMs. Additionally, this study provides an example of ethics intervention development and evaluation in nursing research. Ethics is a fundamentally central, everyday basis of the work of nurse managers (=NMs), referring to all responsible for leadership, management and administrative positions and working as a part of the health care administration at unit, middle, and strategic level management. NMs have a wide impact on their staff, organizations and patients in health care. Thus, it is crucial that NMs fulfill their various ethical responsibilities by performing ethical activities. In this study, these ethical activities of NMs, based on previous literature, have been theoretically outlined, and using deductive reasoning summarized into a new construct, the ethical activity profile of NMs , consistNMs havethe responsibility to develop their own ethics knowledge. NMs should develop their own skills, competence and knowledge base in ethics throughout their career [NMs have a responsibility to influence ethical issues. NMs should work as ethics spokespersons and political strategists [NMs have the responsibility to conduct or implement ethics research. NMs should support research [NMs have the responsibility to identify ethical problems [NMs have the responsibility to solve ethical problems [Firstly, r career . In addir career , 3. Secoategists , articulategists , 6, by vategists . NMs shoategists , create ategists , 10 and ategists . Influenresearch , 4, set problems , 13. Thuproblems . Ethicalproblems . Finallyproblems , 13, 16.problems . ProperlAll five above-mentioned dimensions of the ethical activity profile require different types of ethical activities from NMs, are equally important, and can be summarized together. To have a high ethical activity profile, NMs have to perform activities from all dimensions. However, based on earlier studies, only a limited number of NMs develop their own ethics knowledge , 12, infEarlier studies point out that NMs are in need but lack support for ethics issues from their superiors and organizations . CurrentDeveloping of an intervention is a systematic process consisting of several phases and components. When developing new interventions, scientific user evaluations are crucial  and thusFidelity analysis, why or how the intervention works, could be included in each stage of the EQ intervention: design, delivery, receipt and enactment . HoweverThis study evaluated the developed ethics educational e-learning intervention, the Ethics Quarter, from user perspective. The purpose was to evaluate the usability, feasibility and fidelity of the intervention, tested for the first time in this study in clinical environment after a randomized controlled trial (results of the effectiveness of the intervention have been reported elsewhere) . The ultA descriptive, cross-sectional design was used to evaluate the usability, feasibility and fidelity of the EQ intervention.n=2) who used the EQ as planned and thus, no changes were made. In addition, the usability and feasibility of the EQ was pilot-tested (n=8): all master and postgraduate students of the Department of Nursing Science at the University of Turku working as nurse managers were invited to participate. Based on the pilot study results, an educational video about using the EQ educational area was added and some language corrections were made.The EQ educational e-learning intervention for NMs was developed according to the criteria for complex interventions in the health care (CReDECI2) guideline . Based oDuring the development phases, the structure of the EQ was clarified; two quarters comprise one dimension of NMs’ ethical activity profile. The EQ has five dimensions, 12 evidence-based educational quarters, including introduction and summary  after participating in the EQ intervention among the intervention group of a randomized controlled trial in 2020. The study is registered in ClinicalTrials.gov with the identifier: 04234503. NMs were recruited via the membership register of the Union of Health and Social Care Professionals in Finland (Tehy) trade union (https://www.tehy.fi/en) by e-mail. The union is a national professional interest group for registered nurses, NMs and advanced consultants/specialists in the social and healthcare sector who have a master’s degree (nursing science or related) or registered nurse’s degree. Inclusion criteria for the participants were: current work as a nurse manager and a sufficient command of the Finnish language. The introductory information e-mail included a short description of the study and the intervention and the link to the http://etiikanvartti.fi/?tutkimus website. The website featured complete information about the study; if the NM wanted to participate, s/he gave informed consent and filled in all the study measurements, including background factors.Evaluation of the EQ was carried out by Finnish NMs (n=119) had very strong commitment to the EQ: (n=95) 79.8% completed it and the final response rate was 56.2% (95/169). The baseline background factors (n=169) were statistically compared between the NMs who 1) completed the EQ and participated in measurements (n=95), 2) got the password, but did not sign in to the EQ (n=50), and 3) signed in, but did not participate in measurements (n=24) (Table p<0.005) than those who received the password, but did not sign in to the EQ and those who signed in, but did not participate in measurements. There were no other statistically significant differences  in the demographic characteristics between the groups.For the main trial, 169 NMs were randomly allocated to the intervention group and received a password to log in to the learning environment. However, 50 users 29.5%) never signed in. The NMs who signed in  ; FinnishFeasibility was measured with structured independent 5-point Likert  questions, created for this study, concerning the EQ as a learning method, EQ duration and EQ contents , position in organization, length of work experience, number of subordinates, participation in continuing ethical education, participation in an ethical work group or committee, having an official ethics-related post, participating in an ethics research project, participating in an ethics development project, and having some kind of ethics organizational structure in work organization, e.g., a clinical ethics committee Table .p-value 0.05 (two-tailed).In the usability evaluation, the SUS items were scored before the analysis according to the Brooke system , leadingIn the feasibility evaluation, similar statistical analyses as above were conducted for feasibility item scores. Furthermore, inductive content analysis  and quanIn the fidelity evaluation, it was calculated how much time on average NMs spent on one dimension (two quarters). The intervention was planned to take 15 minutes per quarter, 30 minutes per dimension; this was the basis for comparison.The study was approved by the University Ethics Committee in February 2020 and by the (Tehy) trade union in January 2020. Responsible conduct of research  was follThe usability of the EQ was reportedly high . The mean = 71) of the 95 responses. The responses were positive in 99% (n = 70) of cases and negative in 1% (n = 1). Of the responses, 11% (n = 8) also included development propositions. To summarize, positive feedback considered that the EQ contents were good, necessary, time-saving, practical and research knowledge-based, suitable for all nurse managers to perform. Negative feedback considered the contents self-evident and too scattered. Developmental feedback suggested that contents should be more challenging and interactive and more exercise contents were hoped for (Table Open feedback about content of EQ was obtained in 75% (or Table .A lot of new and usable knowledge” (29), “The contents were based on research knowledge” (30), “Contents were clear and vigorous. The issues were summarized very well into an understandable and plain language format. I could have studied more ethics this way.” Managers considered that the contents of the EQ increased their knowledge in nursing management ethics; the mean score was 4.59 . NMs described the increased knowledge as follows: “Really good study set and so clear that it increased my own understanding of ethics issues” (86), “Good content, gave me tools to implement ethical activities into practice” (46), “I got a lot of where to lean on” (50), “The course got me thinking more about ethical issues and to take them into consideration; I believe it’s also going to continue in the future” (69). (58). The NMs considered the contents of the EQ to be sufficiently challenging, 4.15 : “The contents were sufficient in relation to the time reserved” (21), “the exercises led me to reflect on the issue more accurately” (139).NMs reported that the contents of the EQ were interesting; the mean score was 4.68 : “The fidelity of the EQ was average based on the time used for one dimension. According to Google Analytics, NMs spent on average 18.57 minutes to complete one dimension.This study produced valuable user perspective evaluation of the new ethics e-learning intervention. The EQ intervention was tested for the first time in a clinical environment for nurse managers and evaluated from the perspective of usability, feasibility and fidelity. Managers perceived the feasibility and usability of the EQ intervention as good: the EQ offered a feasible and usable way to support their ethical activity profile. Furthermore, the fidelity was average. There are only a few earlier ethics interventions for NMs even though previous literature has pointed out NMs’ needs to be supported in ethics issues , 20, 21.There is little earlier empirical knowledge on how to impart ethical skills to NMs in practice , 6. In tIn this study, the e-learning method was considered to be a feasible, possible and practical way of learning ethics and ethical activities conveniently , and NMsThe EQ intervention’s developmental areas were also identified in this study. The time used by the NMs in the educational area was shorter than estimated. On average, NMs used only 18.57 minutes per dimension, not 30 minutes as planned. According to a previous Cochrane review, it seems that healthcare professionals have quite low engagement with e-learning interventions . FurtherThe EQ intervention seems to be valuable for all health care organizations, which currently provide suboptimal levels of support for ethics for NMs , 18. AlsThe strength of this study lies in its evidence-based intervention development: by following the (CReDECI2) guideline criteria  we aimedThis study also has some limitations. Feasibility was measured with independent structured questions created for this study, never validated; thus, conclusions have been made with caution and strengthened by open question responses. The fidelity of this study was measured only relying on Google Analytics statistics. A multi-perspective, comprehensive multi-method approach would have offered better insight into fidelity, e.g. into enactment : did NMsOur findings suggest that an ethics educational e-learning intervention, the Ethics Quarter, is a usable, feasible and not too burdensome option for supporting NMs’ ethical activity profile in health care organizations. The results of this user perspective study advance the understanding about educating NMs in ethics issues with the e-learning method and the main concern seems to be lack of engagement. Thus, in future studies, easily added, more extensive user logs could give insight into what elements of e-learning interventions increase the level of participation or make NMs return to the e-learning environment. Furthermore, it would be crucial to investigate enactment, i.e. whether the strengthened ethical activity profile of NMs also translates into actual ethical activities of NMs in healthcare organizations. A further step in developing the EQ intervention itself would be increasing the challenge of the EQ and implementing some interactivity into the educational area; for example, through common discussions or other participants’ readable responses as a possible option. The contents of the intervention must also be constantly updated based on the latest knowledge of ethical activities. Furthermore, contents of the EQ could be revised in the future for the whole multi-professional management team.


In this paper, we have aimed to elucidate the therapeutic effect of intramedullary nailing (IMN) in treating comminuted proximal humeral fractures (CPHFs) and its influence on the recovery of shoulder joint function. For this purpose, 60 cases with CPHFs were selected, particularly from January 2020 to October 2021. In these cases, 28 cases were treated with a locking proximal humeral plate (LPHP) and assigned to the control (Con) group and the remaining 32 patients were treated with IMN and included in the research (Res) group. The therapeutic effect, surgical indicators, total complications, visual analogue scale (VAS) score, and postoperative shoulder joint function score were compared between the two arms. We observed that compared with the Con group, the effective rate in the Res group was higher while the operation time, intraoperative blood loss, and fracture healing time were shorter, the overall complication rate and VAS score were lower, and the postoperative shoulder joint function score was higher, all with statistical significance. The above results indicate that IMN is effective and safe in the treatment of CPHFs, which can validly reduce the discomfort of patients and facilitate the recovery of shoulder joint function. Comminuted proximal humeral fracture (CPHF) is a common and serious fracture type, which is susceptible to the elderly with osteoporosis or osteopenia , 2. AccoLocking proximal humeral plate (LPHP) fixation is a common internal fixation method for the treatment of CPHFs, which can provide reliable and effective internal fixation for patients with type II, III, and IV fractures , 8. LPHPIn this paper, we have aimed to elucidate the therapeutic effect of intramedullary nailing (IMN) in treating comminuted proximal humeral fractures (CPHFs) and its influence on the recovery of shoulder joint function. For this purpose, 60 cases with CPHFs were selected, particularly from January 2020 to October 2021. In these cases, 28 cases were treated with a locking proximal humeral plate (LPHP) and assigned to the control (Con) group and the remaining 32 patients were treated with IMN and included in the research (Res) group. The therapeutic effect, surgical indicators, total complications, visual analogue scale (VAS) score, and postoperative shoulder joint function score were compared between the two arms. We observed that compared with the Con group, the effective rate in the Res group was higher while the operation time, intraoperative blood loss, and fracture healing time were shorter, the overall complication rate and VAS score were lower, and the postoperative shoulder joint function score was higher, all with statistical significance.The remaining paper is arranged according to the following agenda items, where a brief introduction or description of every section is provided to improve the understandability of the underlined manuscript.In the subsequent section, the proposed methodology is explained with detailed information about its various steps and proper selection and rejection criteria. In n = 32), which comprised 14 males and 18 females with a mean age of 68.91 ± 9.42 years, was treated with IMN. This retrospective study was ethically ratified by the Ethics Committee of our hospital, and all the participants and their guardians provided signed informed consent.Sixty patients with CPHFs admitted, particularly from January 2020 to October 2021, were enrolled. Among those cases, 28 cases treated by LPHP were included in the Con group, including 12 males and 16 females, with an average age of 66.62 ± 8.41 years. The Res group ; humerus surgical neck fracture or fracture of tibial anatomical neck; hematological diseases or infectious diseases; women during pregnancy or lactation.LPHP fixation was applied to the Con group. The patient was placed supine under general anesthesia. The fracture site was repaired first, and the fracture fragments were immobilized with temporary Kirschner-wire and reduction forceps. The proximal humerus locking plate was placed 8 mm below the greater tuberosity peak, and the correct position of the steel plate was confirmed by anteroposterior and axillary fluoroscopy. Finally, the incision was closed without negative pressure drainage.IMN was applied to the Res group. An appropriate type of intramedullary nail was prepared before surgery. The patient under general anesthesia was placed in the supine position with a shoulder pad height of 40, and the affected limb was placed on the fluoroscopic operating table. The skin was cut lengthways about 2.0–3.0 cm in front of the midpoint of the acromion, and the superficial and deep fascia were separated. Then, a small portion of deltoid muscle along the muscle fibers was separated to expose the greater tuberosity and rotator cuff. The nail entry point was determined to be the junction between the medial articular surface of the top of the greater tuberosity and the greater tuberosity. Subsequently, surgical reduction of the fracture was completed under fluoroscopy. The guide pin was inserted and reaming was performed, with the reaming size being more than 1 mm larger than the actual selected intramedullary nail. The nail was inserted approximately 5 mm below the cartilage surface of the humeral head, and the distal and proximal screws were placed with the aid of the auxiliary system. Finally, the patient's rotator cuff was repaired, and the incision was closed without negative pressure drainage .Efficacy.Surgical Indicators. This study compared the OT, intraoperative blood loss (IBL), and fracture healing time between the two cohorts of subjects.Total Complications. We observed and recorded the number of cases of infection, acromion impingement, humeral head necrosis, arthrodynia, and limitation of shoulder mobility, and calculated the total incidence of complications.Visual Analogue Scale (VAS) [le (VAS) . PatientScoring of Postoperative Shoulder Joint Function. The Constant Murley (C-M) shoulder function score was used for evaluation [aluation , includiT-test and paired T-test were utilized for intergroup (before and after treatment) and intragroup comparisons, respectively. A significance level of P < 0.05 was used in all analyses.Data processing and image rendering employed SPSS 22.0 and GraphPad Prism 6, respectively. The number of cases/percentage (n/%) was used to represent the categorical data, and the chi-square test was used to compare the data between groups. Mean ± SEM was used to represent the quantitative data, and independent sample P > 0.05)  .P < 0.05)  .P < 0.05)  .P < 0.05)  .P > 0.05) (Pain levels were assessed by VAS scores in both arms. A notably lower VAS score was determined in the Res group than in the Con group ( > 0.05) .P > 0.05)  .CPHFs are clinically complex fractures, mostly of the Neer III or IV type . Such frThis study included 60 patients with CPHFs. The comparison of efficacy revealed a statistically higher overall response rate in the Res group than in the Con group (90.63% vs 67.86%), indicating that IMN was better than LPHP fixation with definite efficacy. The reason may be related to the large range of soft tissue dissection in LPHP, which has a relatively great influence on local bone and muscle soft tissue, resulting in poor postoperative rehabilitation effect . When coAlthough our research has proved that IMN contributes to significantly superior clinical outcomes in terms of curative effect, surgical indicators, safety, pain, and shoulder joint function recovery, there are still some deficiencies to be addressed. For example, we can expand the patient sample to improve the accuracy of experimental results and increase patient follow-up to analyze the long-term effects of the two procedures.In conclusion, our research confirms that IMN is more feasible for the treatment of CPHFs, with definite efficacy and safety, as well as has more significant effects on pain relief and rehabilitation of shoulder function.In this paper, we have aimed to elucidate the therapeutic effect of intramedullary nailing (IMN) in treating comminuted proximal humeral fractures (CPHFs) and its influence on the recovery of shoulder joint function. For this purpose, 60 cases with CPHFs were selected, particularly from January 2020 to October 2021. In these cases, 28 cases were treated with a locking proximal humeral plate (LPHP) and assigned to the control (Con) group and the remaining 32 patients were treated with IMN and included into the research (Res) group. The therapeutic effect, surgical indicators, total complications, visual analogue scale (VAS) score, and postoperative shoulder joint function score were compared between the two arms. We observed that compared with the Con group, the effective rate in the Res group was higher, the operation time, intraoperative blood loss, and fracture healing time were shorter, the overall complication rate and VAS score were lower, and the postoperative shoulder joint function score was higher, all with statistical significance. The above results indicate that IMN is effective and safe in the treatment of CPHFs, which can validly reduce the discomfort of patients and facilitate the recovery of shoulder joint function.


Existing knowledge has established the connection between maternal education and child survival, but little is known about how educational assortative mating (EAM), relates to childhood mortality. We attempt to examine this association in the context of Nigeria.Data was obtained from the 2008, 2013, and 2018 waves of the Nigeria Demographic and Health Survey, which is a cross-sectional study. The sample includes the analysis of 72,527 newborns within the 5 years preceding each survey. The dependent variables include the risk of a newborn dying before 12 months of age , or between the age of 12–59 months . From the perspective of the mother, the independent variable, EAM, includes four categories . The Cox proportional hazard regression was employed for multivariate analyses, while the estimation of mortality rates across the spectrum of EAM was obtained through the synthetic cohort technique.p < 0.05. Both infant and child mortality rates were highest in low-education homogamy, as expected, lowest in high-education homogamy, and lower in hypogamy than in hypergamy. Furthermore, the trends in the rate declined between 2008 and 2018, and were higher in 2018 than in 2013.The risk of childhood mortality varied across the spectrum of EAM and was particularly lowest among those with high-education homogamy. Compared to children of mothers in low-education homogamy, children of mothers in high-education homogamy had 25, 31 to 19% significantly less likelihood of infant mortality, and 34, 41, and 57% significantly less likelihood of child mortality in 2008, 2013 and 2018 survey data, respectively. Also, compared to children of mothers in hypergamy, children of mothers in hypogamous unions had 20, 12, and 11% less likelihood of infant mortality, and 27, 36, and 1% less likelihood of child mortality across 2008, 2013 and 2018 surveys, respectively, although not significant at This indicates that, beyond the absolute level of education, the similarities or dissimilarities in partners’ education may have consequences for child survival, alluding to the family system theory. Future studies could investigate how this association varies when marital status is put into consideration.The online version contains supplementary material available at 10.1186/s12889-021-11568-0. The indicators of mortality, including infant and child mortality, are important indices for assessing community health status and human capital development , 2. InfaA large body of literature has reported that increased maternal education offers protection from childhood mortality , 6. EvenThe theoretical basis of the association between EAM and child survival is engrained in the family system theory. Family system theory suggests that families operate as a unit, with complex interaction and independencies –11. AccoSecondly, parents’ educational similarities could encourage better consensus and consistency in prenatal healthcare choices and behavior, including abstaining from unhealthy practices that have implications for infant health outcomes during the prenatal stages . Also, iThirdly, according to the Andersen behavioral model of healthcare utilization, financial resources could act as an enabling factor in healthcare utilization . As educStudies from high-income countries concerning the nexus between EAM and child health outcomes are limited. However, evidence from the United States suggests that parents’ educational homogamy is beneficial for child health while hypergamy is detrimental . In low-When under-5 mortality is decomposed, the findings from the 21-cross-country study may not be a complete reflection of infant mortality in particular. While morbidities of preventable diseases such as malaria, diarrhea, chronic malnutrition, and so on are common causes of child deaths , 25, deaThis study analyzed data obtained from three waves of the Nigeria Demographic and Health Survey (DHS). It includes the surveys of 2008, 2013, and 2018, collected from June to October 2008, February to July 2013, and August to December 2018, respectively. Nigeria is located in West Africa, and the survey was conducted by the National Population Commission (NPC) in collaboration with ICF International. The study protocols followed the Helsinki guidelines, and also received approval from the National Health Research Ethics Committee of Nigeria. The sample for the survey was selected using a stratified two-stage cluster design. This consisted of the selection of primary sampling units (PSUs) across both rural and urban strata. A nationally representative sample of 36,269; 40,680; and 41,668 households were selected across the PSUs in 2008, 2013 and 2018, respectively. All women aged 15 to 49 years old in households were eligible for interviews. Out of the 34,596; 39,902; and 42,121 eligible women in 2008, 2013 and 2018, respectively, between 97 to 99% were successfully interviewed in each of the years. Questions related to household socio-demography, reproductive health, and fertility, among others. No financial compensation was attached to the respondent’s participation. More information about the survey setting and data collection is available in the final reports –33.Sample selection focused on children who had complete information about their survival status and the educational attainment of both parents. Children of mothers who are either separated, widowed, not cohabitating, or not in a marital union were excluded from the analysis. This was done because the direct or indirect input of the father into childcare could be limited or non-existent . In addition, mothers who have been married more than once were also excluded because elements from the previous union(s) may have unexplained residuals in the current union. This reduced the sample to a total of 72,527 out of 94,053 births across the three surveys. Analysis of infant mortality included all 72,527 children , and child mortality included 53,595 children . However, analysis varied slightly across models, depending on the number of missing values among covariates, varying up to 5.3%.The outcome variables in this study were the risk of infant and child mortality. During the survey, the women were asked about the number of births they had in the 5 years preceding the date of the survey, and the survival status of the child. Where a child was reported dead, the age at death was inquired. We combined the children’s survival status and the current age, or age at death, to generate the outcome variables for the survival analysis. Children who had died (i.e. non-censored) were regarded as cases, whereas children who were still alive at the time of the survey were treated as right-censored.The independent variable in this study was EAM, generated from information on the level of education of both the mother and the father. During the survey, the mother responded to questions about her highest level of educational attainment, as well as that of her partner. For both the mother and the partner, the responses were in four variants, (1) no education, (2) primary education, (3) secondary education, and (4) tertiary education.Although, most studies on EAM have used a single construct of the homogamy category. However, given that child health outcomes are strongly associated with parents’ level of educational attainment, we sub-divided homogamy into low and high education. Relative to the mother, we generated four categories. (1) Low-education homogamy–both parents have at most primary school education, (2) High-education homogamy–both parents have at least secondary education, (3) Hypergamy –the father has at least secondary and the mother has at most primary, (4) Hypogamy – the father has at most primary and the mother has at least secondary education. This pattern follows the perception that people who have primary education and no education tend to have similar child health outcomes, while those having secondary education and above equally share similar child health outcomes , 34. Forgender, birth order, birth interval, perceived birth weight, type of birth (singleton vs. multiple births), and the place of delivery .Several variables at the child, maternal, household, and community levels which have been described as possible determinants of infant and child mortality were included as covariates –29, 35. chronological age, the number of surviving children, and employment status. Household-related variables include the source of drinking water, distance to a medical facility (a problem vs. not a problem), religion, and family wealth. The family wealth index was derived through principal component analysis based on the number and kinds of assets each household owns, ranging from a television to a bicycle or car, and housing characteristics such as toilet facilities and flooring materials. The index was already available as part of the Nigeria DHS dataset. Community-level covariates include the geopolitical zone of residency and rural/urban residency.Maternal-related variables include For multivariate analysis, we used the Cox proportional hazard regression with the frailty model. This was done for two reasons. First, Cox regression analysis allows for the inclusion of censored data and it models censored time-until-event data as a dependent variable. Secondly, the frailty model considers the hierarchical structure of the data. Children are nested within households, and, as such, have shared frailty, which may make subjects within households correlate .αi, the hazard function hij(t) for the failure time of the jth child in the ith household  is expressed asConditioned on frailty h0(t) is an unspecified baseline hazard function, αi is the group-level (household) frailty and βx denotes the vector of the regression coefficient for a set of covariates . The subinterval probabilities of death are calculated by dividing the number of deaths occurring in the relevant age interval for children who were exposed to death in a specific calendar period by the number of children exposed in the calendar period. See the DHS statistics guide for a more detailed explanation of this methodology  is quotient from the subinterval probabilities of dying.Only cohort B is completely included, while cohorts A and C are only partially exposed to mortality in the time-period [thodology , 41. TheThe strength of the approach is rooted in the fact that it allows the full use of the most recent data.syncmrate” in STATA. All analyses were done using STATA software version 13.0 , and results were reported at a 95% significance threshold.The procedure was implemented using the command “The socio-demographic characteristics of the pooled sample are presented in Table p-values > 0.05). Also, the graphed plot of the log) of the main predictor variable against survival time showed roughly parallel lines for all categories of EAM (particularly after the neonate period), an indication of proportional hazard  less likelihood of infant mortality (see Table p > 0.1) for children of mothers in hypergamous union and by 11%  for children of mothers in hypogamous union, although these were not significant at p < 0.05  less likelihood of infant mortality, though the result was not statistically significant at p < 0.05  lower likelihood of child mortality compared to children of mothers in low-education homogamy (see Table p < 0.05) for children of mothers in hypergamy and also by 27%  for children of mothers in hypogamy  less likelihood of child mortality, but the result was also not statistically significant, similar to infant mortality , and increasing mother age. On the other hand, factors such as female gender, longer birth intervals, higher birthweight, and higher parity indicate protectiveness.The results of the sensitivity analyses where EAM was re-segmented into at most secondary vs. tertiary showed a near-perfect similarity with the main analysis  to examine trends in the association between EAM and childhood mortality in the context of Nigeria. The Cox proportional hazard regression was employed for multivariate analyses, while estimates of mortality rates across the spectrum of EAM were obtained through the synthetic cohort technique. The findings showed that 1) compared to children of couples in low-education homogamy, the risk of both infant and child mortality is lower in any other combination of EAM, and particularly lowest among those of high-education homogamy. 2) Compared to children of mothers in hypergamous unions, those of mothers in hypogamous unions had a seemingly lower likelihood of both infant and child mortality, although not statistically significant. These findings were consistent across the three waves.Furthermore, the mortality rates were mostly highest in low-education homogamy, lowest in high-education homogamy, and lower in hypogamy compared to hypergamy. While these mortality trends decreased between 2008 and 2018, they were higher in 2018 than in 2013. The current study is significant because it suggests that, in addition to the absolute level of education, the similarity of parents’ education may be related to child survival, alluding to the family system theory.The finding is partly consistent with another study from SSA  but diffIn the current study, high-education homogamy had a strong association with reduced infant and child mortality, while low-education homogamy had the highest risk of childhood mortality. Parents who both have high education are more likely to understand the importance of maternal and child healthcare (MCH), thereby more likely to have a consensus in its utilization. Forms of MCH such as antenatal care or birth delivery in a health facility are associated with reduced childhood mortality , 42. AlsSecondly, improved education could translate into better job opportunities and, by implication, better financial income, thereby offering affordability for medical costs or insurance. By contrast, low education attainment may be attributed to poor household income, accompanied by poor nutritional intake, making infants and young children more susceptible to sickness , 46.In the multivariate, sensitivity, and mortality rates analyses, childhood mortality showed a lower likelihood in hypogamy compared to hypergamy, consistent with similar studies , 48. WomThe findings from this study reiterate the fact that parents’ education is important for infant and child survival. Therefore, policy measures should include promoting a policy of “education for all” and, particularly, female education, which is already in tandem with the 4th agenda of sustainable development goals (SDGs). While women’s education in Nigeria has attracted some policy attention and some marked improvements have been observed over the years, regional variation still exists. As also indicated by the results in the geopolitical zone in the multivariate analysis, regional-specific policies may be more relevant. In regards to child health outcomes, the mother’s education may likely compensate where the father’s education falls short.Secondly, in addition to women’s empowerment, paternal involvement in prenatal care should also be used as a strategy for better feto-natal health outcomes. Paternal involvement is associated with better prenatal care , and theAdditionally, most studies on educational assortative mating have mostly considered homogamy as a single construct without further dichotomization into low or high education. However, the findings in this study show that significant differences exist between both, particularly regarding child health outcomes. Therefore, the findings in this study may offer some implications for theory.The limitations associated with this study include the use of cross-sectional data, which does not allow for the inference of a causal relationship. Second, there may be instances of under-reporting of mortality due to cultural reasons that forbid speaking of the dead or the emotional pain associated with recalling a lost child. Third, due to the few samples of neonatal mortality, we analyzed neonatal mortality together with infant mortality. Lastly, the educational attainment of the father was as reported by the mother. There is the possibility of error, particularly in the sensitivity analysis in supplemental Table This study has shown that beyond the absolute level of education, the similarity of parental education, conceptualized as EAM, is associated with child survival, alluding to the family system theory. Findings from this study have social, health, and theoretical implications. First, basic and compulsory educational attainment should be made a statutory provision and freely accessible. Secondly, campaigns relating to both reproductive and pediatric health should be targeted at the population group most susceptible to infant and child mortality, and content should be regional-specific. Third, since education is relevant to health behaviors and by extension, health outcomes, it may be important to conceptualize EAM a bit differently in public health studies than in a pure sociological context. Future studies could investigate how EAM is associated with other aspects of child wellbeing or could show how the magnitude of the association varies when marital status is put into consideration.Additional file 1: Figure S1. Test of proportional hazards assumption for EAM.Additional file 2: Table S1. Cox proportional regression showing the unadjusted hazard ratio between educational assortative mating (EAM), infant and child mortality: 2008-2018 Nigeria DHS.Additional file 3: Table S2. Cox proportional regression comparing the adjusted hazard ratio of infant and child mortality between hypergamy and hypogamy: 2008-2018 Nigeria DHS.Additional file 4: Table S3. Cox proportional regression showing the adjusted hazard ratio between the alternative measure of educational assortative mating, infant and child mortality: 2008-2018 Nigeria DHS.Additional file 5: Table S4. Cox proportional regression showing the adjusted hazard ratio of infant and child mortality between the alternative measure of hypergamy and hypogamy: 2008-2018 Nigeria DHS.Additional file 6: Table S5. Cox proportional regression showing the adjusted hazard ratio between difference in years of education (DYE), infant and child mortality: 2008-2018 Nigeria DHS.


The results showed direct effects from fearlessness to interpersonal and behavioral psychopathic traits. Parental warmth, fearless temperament, and their interaction, predicted CD, which, in turn, showed a negative effect on psychopathic traits. The indirect effects indicated significant negative mediation effects of warmth through CD on psychopathic traits, which seem to be stronger when children present lower levels of fearlessness. Overall, these results contribute to better understand the development of child psychopathic traits and provide additional insight on effective strategies that will help to restrain the potential development of a high-risk profile in early childhood.The role of psychopathic traits in predicting more serious and persistent patterns of child conduct problems has been well documented. The jointly presence of interpersonal (grandiose–deceitful), affective , and behavioral psychopathic traits (impulsive–need of stimulation) identifies a group of children at increased risk of psychosocial maladjustment. The present study aims to disentangle the underlying mechanisms by examining how early parenting  and child temperament  predict later psychopathic traits, via conscience development (CD). Data were collected in a large sample of children ( Child conduct problems, involving a heterogeneous pattern of deviant behaviors such as aggression, rule-breaking, and oppositional or destructive behavior ,2, have Psychopathic personality has been defined as a developmental disorder with its roots in early childhood ,20. The Comprehensive developmental models on the etiology and later development of psychopathic traits have suggested that certain temperamental styles, such as behavioral disinhibition or fearlessness, are linked with problems in conscience development (CD), these associations being critical for understanding the emergence of psychopathic traits (see ). The coNotwithstanding the importance of temperamental factors in the development of psychopathic traits, it should be noted that they are supposed to be largely due to biological deficits and, therefore, might be difficult to avoid or prevent. When practical implications are prioritized, the identification, assessment, and management of those factors able to enhance, maintain, or restrain such developmental process gain more prominence. In this regard, the role of parenting practices in the development of psychopathic traits has been evidenced as particularly influential (see ), with pIn this context, after evidencing that not all children showing a fearless and uninhibited temperament will invariable manifest deficits in moral emotions, most theories of CD have also considered the role of parenting, which interacts with a child’s temperament in a complex dynamic process . In thisBased on the foregoing, it can be suggested that child temperament interacts with parental practices to increase or buffer the risk for later psychopathic traits , with thThe main purpose of the current study was, therefore, to unravel the etiological mechanisms leading to psychopathic traits in childhood by testing a developmental model where parenting practices and fearless temperament interact to predict psychopathic traits, via CD. Since guilt and empathy can be identified early in life, and because they play an important role in the development of psychopathic traits ,35, the Mage = 4.25; SD = 0.91). A total of 72 public (79.2%), charter (18.1%), and private (2.8%) schools participated in the study, which were located in predominantly working-class communities, with no diversity in terms of ethnicity (93.9% of children were Spanish). Regarding children’s family background, 23.7% of mothers and 39.8% of fathers completed compulsory education, 47.4% and 31.2% completed higher education, and 28.9% and 29% completed vocational training studies.The Estudio Longitudinal para una Infancia Saludable ) is a prospective longitudinal study conducted in Galicia (NW Spain) with the aim of better understanding the behavioral, emotional, personality, and psychosocial development from early childhood to adolescence. For the purposes of the current study, parent-reported information collected in the first three waves of study were included in the analyses. Data collection started when children were in preschool , encompassing children born in 2011–2013. Only children with available data in some of the main study variables, namely fearlessness, parental warmth, guilt and empathy, and psychopathic traits, were included in the present study, resulting in an initial sample of 2266 children (48.5% girls), who were on average 4 years old (F(2248) = 2.51, p = 0.082, and initial (T1) levels of conduct problems F(2227) = 0.30, p = 0.741. However, differences in terms of gender and SES were found between groups. Specifically, there was a higher proportion of boys in families who dropped out of one wave of the study (χ2(2) = 11.88, p < 0.01); whereas higher levels of SES were found in families who participated in all three waves of the study (F(2249) = 16.27, p < 0.001), a result consistently found in previous longitudinal research [Two follow-ups were conducted within one-year intervals. Thus, the first follow-up (T2) was conducted one year after the initial wave of data collection and the second follow-up (T3) was conducted two years after the first wave of the study. The level of attrition is considered adequate, since 88.6% of respondents who participated in T1 participated in T2, and 76.3% of respondents who participated in T1 also participated in T3. As commonly observed in longitudinal studies, attrition was derived from death or frailty, withdrawal, lack of success in additional contacts for a follow-up survey, or by non-returning a survey by some participants . Compariresearch . Even thresearch .To assess the intended constructs, measures specifically developed for being used with preschool children were selected. Moreover, the use of validated measures with a Spanish version were prioritized. In case it was not available at the time of data collection, items were adapted and translated by the research group, according to the standard guidelines for translation and adaptation of instruments .Covariates. In addition to the gender of the child , we accounted for the socioeconomic status (SES) of the family in the first wave of study. The SES variable was created by combining the scores on a set of items related to the socioeconomic background of the family .Parental warmth. A parent-reported scale based on the Warmth subscale from the Child Rearing Scale (CRS) [never to 5 = very often).le (CRS) ,62, inclle (CRS) , was useFearlessness. The level of child’s fearlessness was reported by parents through a scale consisting of six items , developed for being used from age three, and used in previous studies, including the ELISA project [Does not apply at all) to 4 (Applies very well). project ,16. PareA latent variable of CD was defined by the composite score of two observed variables, namely guilt and empathy.Guilt. A parent-reported scale composed of 5 items  was used to measure the level of guilt displayed by the child. The items were scored in a 7-point scale from 1  to 7 (Definitely true). This scale was adapted from the guilt/shame scale that was developed and included in the long form of the Children’s Behavior Questionnaire (CBQ) [re (CBQ)  as an adEmpathy. A parent-reported scale adapted from the Griffith Empathy Measure (GEM) [Totally disagree) to 3 . The global empathy score was used in the present study (α = 0.67).re (GEM) , a measuPsychopathic traits. The parent-reported version of the Spanish Child Problematic Traits Inventory (CPTI) [Does not apply at all) to 4 (Applies very well).y (CPTI) ,67 was uThis study was approved by the Bioethics Committee at the Universidade de Santiago de Compostela, and the Spanish Ministry of Economy and Competitiveness. A total of 126 public, charter and private schools were initially contacted in order to ask for potential collaboration. The contacts were initially conducted by phone, and information letters were subsequently sent by email. If a school accepted to take part in the study, families were contacted and invited to participate via information letters and group meetings in the schools. An active consent form was filled out by families  for each child who participate in the study. The informed consents were collected by preschool teachers, who handed out the information to the parents. In all the waves of study, participants were given a month to fill out the questionnaires. After that period, some reminders were sent to those who were late, firstly by the preschool teacher and then directly by the ELISA staff via email. Families did not receive any monetary compensation for their participation in the study. Nonetheless, as a reward for their participation, all the schools received a set of educational games for preschoolers in T1, whilst both families and schools participated in a draw of several sets of books and educational games, valued between EUR 50 and 100, at the end of the third wave data collection (T3).Firstly, descriptive statistics and zero-order correlations among all the study variables were analyzed. To test the conditional indirect effects of parental warmth, fearlessness, and CD on psychopathic traits, an SEM model was conducted in Mplus 7.4 . The modDescriptive statistics and bivariate correlations among all the study variables are displayed in p < 0.001) and guilt , both measured at T2. This model showed an adequate model fit, χ2(6) = 48.381, p < 0.001; CFI = 0.98; TLI = 0.90; RMSEA = 0.06; SRMR = 0.01. All the psychopathic traits are significantly correlated in the SEM .The standardized results regarding the direct relationships modeled in The conditional indirect effects computed in the model can help to interpret all these associations, which can be summarized in the following terms. Warmth directly predicted CD (mediator) which directly predicted all psychopathic traits , while the relationship between warmth and CD was moderated by fearlessness . Because the direct effects of warmth on psychopathic traits were not moderated by the level of fearlessness, mediated moderation effects were discarded; i.e., regardless of the level of fearlessness, parental warmth is not directly related to GD, CU, and INS. As shown in β = −0.33, p < 0.001; path a), which, in turn, significantly predicted GD , CU , and INS . These relationships might be indicative of mediation effects (a * bi) of fearlessness through CD on GD (β = 0.13), CU (β = 0.21), and INS (β = 0.11). The Sobel test indicated that all these mediation effects were statistically significant .Lastly, because fearlessness has been traditionally related with both CD and psychopathic traits ,47, and Psychopathic personality has emerged as an important construct for better understanding child conduct problems . ThroughFrom a developmental model that posits the effect of temperamental variables  and parenting practices  in the development of psychopathic traits, the current study intended to account for person-by-context interactions that are supposed to interplay in a dynamic process that could influence the basis of both CD  and, subInterestingly, our results evidenced the same conditional effects for all psychopathy dimensions, suggesting that previous findings linked to CU traits could be expanded, at least as pertaining to this model, to all three psychopathy dimensions. Although preliminary, this is an important result since most of previous research has examined the effects of both fearlessness and parental warmth on CU traits, without accounting for the potential shared effects with both GD and INS traits. It should be noted that current results showed direct effects of fearlessness on GD and INS traits, but not the expected direct effects on CU traits ,34. Althequifinality is likely to be pertinent in the etiological mechanisms involved in psychopathic personality. Thus, it is not expected that a single factor—at the genetic, neurobiological, neurocognitive, developmental or environmental level—would act in an isolated way in the etiology and developmental pathway of psychopathic traits [From a developmental psychopathology perspective, the development of a psychopathic personality is usually viewed as a dynamic, changing, and ongoing process . Which fc traits . Dynamicc traits ,63. Morec traits , with psc traits , whereasc traits . Even coc traits  have proc traits . AssuminFinally, current results would also derive some practical implications. Since psychopathic traits seem to be identifiers of youths within serious and long-standing pathways of problematic behavior, they should be primarily identified in clinical settings. To maximize results, these programs should be tailored to the unique characteristics that define this specific group , and should include those factors that have been proven to be potential mechanisms of change in psychopathic personality . Some promising results from the applied context have shown that focusing on improving parental warmth, whilst declining inconsistent and coercive parenting, may have clinical value not only in reducing problematic behavior in children with high psychopathic traits, but also in favoring a significant reduction in all affective, interpersonal, and behavioral features of psychopathic personality ,57. BaseTo our knowledge, this is one of the first studies linking the developmental model of CD to psychopathic personality, accounting for all its dimensions. It involves a large sample of children from a prospective longitudinal study, conducted across two years, and starting at the preschool years, which is considered a key stage in the development of empathy and conscience . Even thCurrent results allow strengthening developmental models of psychopathic traits, with parenting practices based on warmth and affection emerging as environmental mechanisms able to prompt changes in psychopathic traits across development , particu