The role of human mobility in the epidemiology of emerging Aedes-transmitted viral diseases is recognized but not fully understood. The objective of this systematic review and meta-analysis was to examine how human mobility patterns are driving chikungunya outbreaks.Literature was systematically reviewed for studies on chikungunya prevalence in countries/territories with high-level evidence of human mobility-driven outbreaks, based on: (1) emergence of chikungunya outbreaks with epidemic chikungunya virus genotypes among displaced/migrant populations and their hosting communities; and (2) identification of imported index case(s) with epidemic genotypes phylogenetically related to the genotypes circulating during emerging or subsequent outbreaks.The meta-analysis of extracted prevalence data revealed that a large proportion of the population in countries/territories afflicted by outbreaks is still at risk of infection during future outbreaks. On the other hand, approximately one-half of suspected chikungunya cases could be infected with other co-circulating acute febrile illnesses.We discussed in this paper how human mobility-driven chikungunya outbreaks can be addressed, and how the involvement of several sectors in addition to the health sector in multisectoral approaches (MSAs) is important for prevention and control of chikungunya and other Aedes-transmitted arboviral outbreaks. The rapid spread of the chikungunya virus (CHIKV) among populations with no prior immunity is an epidemiologic feature of its current emergence as an epidemic disease . On a glAedes aegypti and Aedes albopictus. The latter species is widely distributed and can adapt to a wide range of climates in both rural and urban environments, and can act as an epidemic vector in some settings  and “outbreak” in [all fields] were used to search PubMed and Scopus for journal articles [publication type] published from 1 January 2004 to 31 December 2017, with no language restrictions. Because the emergence of the new East/Central/South African genotype of the virus on Lamu Island of Kenya in 2004 was the takeoff point of the recent CHIKV circulation and outbreaks around the world [High-level evidence on the role of human mobility as a driver for chikungunya outbreaks in afflicted countries  was deteFull-text publications on cross-sectional studies reporting chikungunya IgG seroprevalence or prevalence of laboratory-confirmed recent infections  in countries with chikungunya outbreaks linked to human mobility with high-level evidence were selected . StudiesI2 statistic [I2 > 50% indicates high heterogeneity. In addition, forest plots were used to show the random effects of pooled outcomes.Prevalence data were extracted from the full-text articles of eligible studies . Extracttatistic , where IThe risk of bias in the selection of cross-sectional studies was assessed using the appraisal checklist of the Joanna Briggs Institute for studies reporting prevalence data , with slSearching using PubMed and Scopus yielded 1867 records . Of thesI2 = 99.0%) based on the random-effects meta-analysis of 4 studies  based on a random-effects meta-analysis of 12 studies [I2 value  to the prevention and control of this disease. The lessons learned from the reviewed publications on earlier outbreaks show some interesting approaches. In La Réunion, during the campaign against chikungunya from 2005 to 2006 , 40, theAedes management framework was also developed to improve control of Aedes-borne arboviral diseases [MSAs are recommended by the WHO Global Strategic Framework on Integrated Vector Management (IVM) and the Global Vector Control Response 2017–2030 (GVCR) , and pubdiseases . Moreovediseases  providesdiseases  and an Idiseases , particuWithin the context of emerging chikungunya outbreaks due to people displacement, and according to the IVM framework , the majRisk assessment of vector-borne diseases outbreaks and communication in situations of people displacement into new environments following conflicts or disasters should involve not only the health sector but also the education and environment sectors. This assessment can be performed according to the standard WHO guidelines for the rapid risk assessment of acute public health events . Risk peA robust coordination pathway and the institutionalization of coordination mechanisms will ensure the meaningful and effective participation of all relevant stakeholders . The secAlthough this study is limited by the retrieval of peer-reviewed data from 2 databases, it provides high-level evidence on human mobility-driven chikungunya outbreaks, showing that a high proportion of nonimmune people are exposed to the risk of future outbreaks and that case reporting is not optimal in many countries unless laboratory-confirmed. Further studies are thus required to assess the impact of human mobility on chikungunya outbreaks on morbidity and mortality. It would also be very interesting to investigate how much of the chikungunya transmission is not only due to human mobility but also to local emergence. Moreover, the criteria used for assessing the level of evidence may not address all possible risks of bias. Therefore, the findings of this study should be interpreted cautiously in the context of the criteria used for selecting the studies.Aedes-transmitted arboviral outbreaks. Some lessons learned from successful MSAs should be evaluated for replication in situations of potential emergence of outbreaks due to human mobility patterns such as people displacement. Furthermore, evidence should be derived from a wider range of socioeconomic, cultural, and geographic contexts involving different countries and regions.This study demonstrates the impact of human mobility on the emergence of chikungunya outbreaks, with pooled anti-CHIKV IgG seroprevalence of approximately 15% across different countries/territories with outbreaks linked to human mobility with high-level evidence. Accordingly, most populations in countries/territories afflicted with such outbreaks are still at high risk of infections and human mobility is still a potential driver for future outbreaks. These results also probably provide an indication of the status of other arboviral diseases transmitted by the same mosquito species. On the other hand, chikungunya is not the only cause of febrile episodes during the emergence of chikungunya outbreaks, as revealed by the prevalence of laboratory-confirmed recent infections among about half of suspected patients. To address the challenge of human-mobility driven emergence of outbreaks, there is a need for MSAs involving partnerships and collaborations at national, regional, and global levels. The huge amount of human movement becomes increasingly demanding for the containment of The Journal of Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.Supplementary materials are available at Notesjiaa500_suppl_Supplementary_Table_1Click here for additional data file.jiaa500_suppl_Supplementary_Table_2Click here for additional data file.jiaa500_suppl_Supplementary_Table_3Click here for additional data file.


Electroencephalogram (EEG) signals contain vital information on the electrical activities of the brain and are widely used to aid epilepsy analysis. A challenging element of epilepsy diagnosis, accurate classification of different epileptic states, is of particular interest and has been extensively investigated. A new deep learning-based classification methodology, namely epileptic EEG signal classification (EESC), is proposed in this paper. This methodology first transforms epileptic EEG signals to power spectrum density energy diagrams (PSDEDs), then applies deep convolutional neural networks (DCNNs) and transfer learning to automatically extract features from the PSDED, and finally classifies four categories of epileptic states . It outperforms the existing epilepsy classification methods in terms of accuracy and efficiency. For instance, it achieves an average classification accuracy of over 90% in a case study with CHB-MIT epileptic EEG data. Epilepsy is a chronic disease involving sudden and repeated seizures of brain dysfunction. Due to different starting locations and transmission modes of abnormal electrical activities in brains, there are various complex clinical manifestations of epilepsy, including transient sensory disorders, limb convulsions, loss of consciousness, behavioral disorders, etc. Such clinical manifestations of epilepsy can cause severe physical damage and mental trauma to patients . MonitorThe electroencephalogram (EEG) has been a prevalent approach for examining brain activities in epilepsy. For patients with epilepsy, the EEG signals of their brain activities can be categorized into interictal, preictal, and seizure states. When a seizure occurs, the EEG signals exhibit certain unusual patterns. Moreover, the EEG signals of the preictal state and the interictal state also show distinctive patterns. Therefore, these patterns in the EEG signals can be used to differentiate epileptic states, enabling the identification of the progress and the potential occurrence of a seizure and the mitigation of damaging impacts on the patients.Seizure detection by using EEG signals has been investigated for decades –5. For iIn recent years, deep learning has started to gain popularity for medical image analysis and bioelectric signal processing. With a large amount of data, it outperforms traditional feature extraction and machine learning methods in pattern detection and image recognition in terms of classification accuracy . Deep leHowever, most of these studies applied domain knowledge to select a specific channel from multichannel EEG signals for analysis, while the data-driven analysis with multichannel epileptic EEG signals remains unexplored. Moreover, there is still room left to further improve the accuracy and efficiency of seizure classification from EEG signals with advanced signal processing and deep learning algorithms. This paper focuses on enhancing the accuracy of classification by analyzing EEG signals of different epileptic states in the brain, which would be helpful for the potential detection of seizures in future study. The epileptic states include an interictal state, a preictal state, and a seizure state. The preictal state can be further divided into two durations: preictal duration to 30 min  and preictal duration to 10 min . These four categories of epileptic states can be determined from EEG signals. Usually, the small differences in the features of EEG signals between the interictal and preictal states and between the “preictal I” and “preictal II” states are hardly visible or not discernable by eye. However, the dissimilarity in these epileptic states can be captured by deep learning with superior computational power. Therefore, we aim to achieve accurate epileptic state classification by proposing a deep learning-based classification methodology for multichannel EEG signals, named “epileptic EEG signal classification (EESC).” It adopts wavelet transform and power spectrum density (PSD) to preprocess the multichannel EEG signals and incorporates three deep convolutional neural network (DCNN) models for feature extraction and epileptic state classification.Epileptic EEG signal data in the CHB-MIT database (an open-source public database) are used to verify the effectiveness of the proposed EESC methodology in the case study. Extensive comparisons with the existing epilepsy classification algorithms are implemented. The CHB-MIT database contains child scalp electroencephalogram (sEEG) data from 23 cases  that werAs mentioned in the Introduction, the EEG signals can be divided into interictal, preictal, and seizure states. Moreover, classifying epileptic seizures 10 to 30 min in advance can help prevent and mitigate the adverse effects of possible seizure occurrence. Up to now, there is no consensus on the earliest detection time before the seizure occurrences. In our analysis, we choose the latest detection time as 10 min, since the EEG signals can show certain peculiar signals when close to the occurrence of seizure . It is of use to further divide the preictal state into two durations: preictal duration to 30 min  and preictal duration to 10 min  for differentiating the importance of duration to the epilepsy progress. Therefore, the EEG signals are divided into four categories: interictal, preictal I, preictal II, and seizure state.The final dataset for the analysis includes the EEG signals from 11 patients with a total of 56 min of EEG signals in the seizure state and 110 min in the preictal I, preictal II, and interictal states respectively for classification. The EEG signals are divided into frames, with a length of 4 s. Since the EEG signals in the seizure state are shorter than other states, we overlap the consecutive frames of the EEG signals in the seizure state by 2 s. For the classification algorithm, we hold out 70% of the data as the training set and use the remaining 30% as the testing set.In this paper, an epileptic EEG signal classification (EESC) methodology based on deep convolutional neural networks is proposed to classify four critical epileptic states with multichannel EEG signals. The overall framework of the proposed methodology is summarized in Multichannel epileptic EEG signals are used to classify four categories of epileptic states, namely the interictal state, preictal I, preictal II, and seizure state. The features of these multichannel EEG signals are represented by characterizing the energy variation of the signals in the frequency domain. To obtain the effective characteristics of multichannel EEG signals, they are first denoised by wavelet transform and then analyzed by power spectrum density (PSD). The two-dimensional images generated from PSD, called power spectrum density energy diagrams (PSDEDs), reflect the energy information of different frequency bands of the EEG signals. PSDEDs are used as features for the subsequent classification since they reveal the differences among the four categories of epileptic states.The original EEG signals are collected on human scalps, so they are inevitably full of noise  and have a low signal-to-noise ratio. In order to reveal the characteristics of EEG signals, they first undergo a denoising procedure . For thiPower spectrum density (PSD) analysis is used on the denoised multichannel EEG signals for feature extraction. The main idea here is to extract the corresponding EEG features by characterizing the energy variation of the signal in the frequency domain . PSD canFurthermore, the EEG signals can be transformed into two-dimensional images called power spectrum density energy diagrams (PSDEDs). For instance, when multichannel EEG signals have n channels, the periodogram is obtained for each channel of the EEG signals. If the EEG signals are divided into 32 frequency bands, and PSD functions of different frequency bands can be integrated. A two-dimensional matrix with n rows and 32 columns is then formed and is then normalized to generate a PSDED. The power spectrum densities in the interictal, preictal I, preictal II, and seizure state for one of the patients are shown in Here, epileptic EEG signal classification (EESC) is used for classifying four different epileptic states by using deep convolutional neural networks (DCNNs) and transfer learning with the PSDEDs from the original multichannel EEG signals. The proposed method is shown in The architecture of Inception-v3  has beenResNet can alleviate the problem of gradient vanishing in the training of DCNN by adjusting the traditional network structure. Its key structure is to propose the basic network unit, the residual block, by adding a shortcut connection. Residual blocks are used in the whole network as the basic units of ResNet asx,y,f represent the input, output, and residual mapping of the block, respectively. By transforming the output y into the residual f, the network is more sensitive to the small fluctuations between output y and input x than a plain network structure like VGGNet. In the proposed EESC, ResNet152 transforms the input image with a size of 224 × 224 × 3 into a feature vector of 2,048-dimensions.where Inception-ResNet-v2  combinesFor each image, the feature vectors extracted from three network features are concatenated into a 5,632-dimensional feature vector. Two fully connected layers with 1,024 and 512 neurons are added to reduce the dimensions, and a dropout layer (0.5) is set behind each fully connected layer to prevent over-fitting. The softmax of the output layer is expressed as:k represents the number of categories, i represents a category in k, gi represents the calculated value of that category, and softmax converts the calculated values into the output probability for each category.where Training the three DCNNs in the proposed EESC requires large amounts of data and time. Transfer learning  can be uWhen the current datasets differ greatly from the datasets used in pre-trained weight training, the second approach above is usually adopted. Transfer learning with the pre-training model facilitates the training of classification networks and enables a superior fine-tuning effect. First, the pre-trained weights of ImageNet are loaded to the proposed EESC deep neural networks, and then the weights are updated by the PSDED images from the original multichannel EEG signals. The PSDED images share similar basic features, such as lines, edges, etc., with images from ImageNet. Therefore, transfer learning can still learn important information on the weights of the EECS networks from networks trained with ImageNet data. For the classification algorithm, we hold out 70% of the data as the training set and use the remaining 30% as the testing set.The cross-entropy loss function is widely used in classification problems. Its formula is shown in Equation (3).yi is the label and ŷi is the predicted probability. During training, samples of a batch are fed to the network each time, and the mean value of the loss of samples in the batch is considered as the loss of the batch. Despite its simplicity, it cannot differentiate the losses from different samples in a batch during training and further improve the training accuracy.where topk) values are averaged as the final loss. It prioritizes ambiguous samples with large loss values during training and improves the classification accuracy on those.An online hard example mining (OHEM)  loss funAccuracy, sensitivity, and specificity are the metrics most widely used in the literature for evaluating model performance. They are derived from the correctness of prediction, including true positive (TP: correctly predicts the positive class), true negative (TN: correctly predicts the negative class), false positive (FP: incorrectly predicts the negative class as positive), and false negative (FN: incorrectly predicts the positive class as negative). They can be calculated as follows:Besides, the confusion matrix is a systematic way to illustrate the classification accuracy for the four categories of epileptic states in the case study. The classification rate displayed in the diagonal of the confusion matrix represents the accuracy of each category, while other values represent the percentage of misclassified samples. This paper focuses on the analysis of four epileptic states in EEG signals of patients to classify the four epileptic states accurately. We can classify the preictal, interictal, and seizure states, and this could potentially help detection.Epileptic EEG signals are first used by the three individual deep convolutional neural networks  for epileptic state classification. Four states can be classified and heat maps can be generated, as shown in Epileptic EEG signals are then used by the proposed EESC methodology. The confusion matrix of EESC is shown in When integrating the OHEM loss function mentioned in section 3.2 into the EESC methodology, the classification accuracy of preictal I and preictal II is increased by 3 and 4%, respectively, as shown in We summarize the classification accuracy of all the aforementioned models for epileptic EEG signal classification in Furthermore, we compare the classification results from the aforementioned models in terms of sensitivity and specificity. In this case study, sensitivity is the percentage of correct classification of a particular epileptic state, while specificity is the percentage of correct classification for other epileptic states. They are summarized in Finally, state-of-the-art research in epileptic EEG signal classification is applied to the dataset from the CHB-MIT database to implement a comparison with the proposed EESC methodology. The results are summarized in The PSDED obtained from PSD analysis can represent the energy level at each frequency of the epilepsy EEG signals. It is noted from The heat map of PSDEDs in Essentially, this proposed EESC methodology is a multi-classification algorithm, mainly for four categories of epileptic EEG classification. The purpose of this study is to accurately classify EEG signals of different states.Conventional models for epileptic seizure classification use wavelet transform (WT), short-time Fourier (STF), and other methods to extract features from EEG signals and then use machine learning to classify them. For comparison, three popular machine learning algorithms, i.e., support vector machine (SVM) , extremeThe results of these conventional models with different machine learning algorithms are summarized in confusion matrices in We augment the feature extraction in those conventional models with the proposed ensemble of DCNNs on the power spectrum density energy diagram (PSDED) obtained from original EEG signals. With the PSDED images, the three machine learning classifiers  are still used to classify epileptic states. The performance metrics obtained are represented by the confusion matrices in Furthermore, by comparing the classification results with the proposed EESC methodology in Accuracy, sensitivity, and specificity are used in this paper to evaluate the performance of the classification of epileptic states. For instance, as illustrated in Accurate classification could potentially reduce damage caused by seizure occurrence. In this paper, we propose a novel epileptic EEG signal classification (EESC) methodology using DCNNs based on transfer learning and the power spectrum density energy diagrams (PSDED) to classify different epileptic states . The methodology is verified by the multichannel EEG signals in the CHB-MIT database. It can be concluded through the study that (1) the proposed EESC methodology outperforms other benchmark models in classifying different epileptic states; (2) DCNNs have excellent feature extraction ability from the power spectrum density energy diagram (PSDED) of multichannel EEG signals; (3) the model trained with an OHEM loss function prioritizes samples with large loss and achieves high classification accuracy. In medical practice, the proposed EESC methodology could have important practical impacts on epilepsy diagnosis and treatment. For instance, to patients, the high classification accuracy of preictal states  of EESC can enable reliable and timely warning; to doctors, the high classification accuracy of EESC can facilitate their understanding of the categories of epilepsy in patients, enabling effective epilepsy prevention and treatment.Consequently, this work addresses one of the significant challenges for accurate epileptic state classification with multichannel EEG signals. As part of our future research, we aim to improve the EESC methodology in the following ways in order to better serve epilepsy prevention and treatment: (1) to design precise tags for EEG signals in the preictal state to further improve the classification performance; (2) to utilize the proposed classification of EEG to detect and/or predict seizures; (3) to further reduce the false detection of seizure occurrence, for instance, by incorporating temporal correlation among frames of EEG signals; (4) to enable the diagnosis of different categories of epilepsy by locating the focus of epileptic seizures.http://physionet.mit.edu/physiobank/database/chbmit/.Publicly available datasets were analyzed in this study. This data can be found here: YG: substantial contributions to the conception or design of the work. YZ: provide approval for publication of the content. JL: revising it critically for important intellectual content. QC and BG: analysis and interpretation of data for the work.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 healthcare system in Mozambique is striving to reduce the high maternal and child mortality rates and stay on par with the Sustainable Development Goals (SDG 3.1). A key strategy to curb maternal and child mortality is to promote the use of professional childbirth services proven to be highly effective in averting maternal deaths. Currently, little is known about the use of childbirth services in Mozambique. The present study investigated the prevalence of professional healthcare delivery services and identified their sociodemographic correlates.This study used cross-sectional data on 7080 women aged 15–49 years who reported having a child during the past 5 years. The data were collected from the 2011Mozambique Demographic and Health Survey. The outcome variables were the choice of childbirth services that included 1) place of delivery , and mode of delivery . Data were analyzed using descriptive and multivariate regression methods.The prevalence of health facility and C-section delivery was 70.7 and 5.6%, respectively. There was a difference in the use of professional birthing services between urban and rural areas. Having better educational status and living in households of higher wealth quintiles showed a positive association with the use of facility delivery services among both urban and rural residents. Regarding ethnicity, women of Portugais , Cindau  and Xichangana  had relatively higher odds of using facility delivery services than others. Antenatal care (ANC) visits were a significant predictor of facility delivery services both in urban  and rural  areas. Among rural women, ANC visit was a significant predictor of C-section delivery .More than a quarter of the women in Mozambique were not using health facility delivery services, with the prevalence being noticeably lower in the rural areas. The Republic of Mozambique is one of the least developed countries in Southern Africa with a large portion of the population living below the poverty line. Characterized by high fertility rates and plagued by high maternal and child mortality rates, preventative maternity services are underutilized or may be inaccessible. Approximately 30% of births in the region are attended by family members while 23–40% are attended by insufficiently trained traditional birth attendants. Access to skilled birth assistance and health facility delivery services requires financial resources and many women in Mozambique cannot afford necessary expensive procedures and services.Currently, little is known about the use of childbirth services in Mozambique. Using the well-established Andersen’s Behavioural Model of Health Service, the present study investigated maternal healthcare service utilization and identified correlated sociodemographic variables. The study used the 2011 Mozambique Demographic and Health Survey cross-sectional data on 7080 women aged 15–49 years who reported having a child during the past 5 yrs.Findings revealed more than a quarter of women in Mozambique were not using health facility delivery services, particularly in the rural areas. Women with higher educational status and those living in more affluent households were more likely to use health facility delivery services in both rural and urban regions. Furthermore, antenatal care (ANC) visits were a predictor of C-section delivery in rural regions.The Republic of Mozambique is located in Southern Africa and is one of the least developed countries in the region , 2. SincAccording to available estimates, the under-five mortality rate was 72 (per 1000 live births as of 2017) and that of maternal mortality was 480  . ApproxiReproductive health services in Mozambique are inadequate to meet the needs of a growing population. This is particularly the case for services such as the availability of skilled birth assistance as well as equipment for providing sophisticated procedures such as C-sections , 15 whichttps://dhsprogram.com/publications/publication-FR266-DHS-Final-Reports.cfm.Data for this study were collected from the sixth round of Mozambique Demographic and Health Survey. The survey was conducted by the National Statistical Institute  and the Ministry of Health (MISAU). The work was finally supported by United States Agency for International Development of the United America (USAID) with Inner City Fund (ICF) International providing technical assistance. Sample population included eligible men (15–54 years) and women (15–49 years) residing in households in urban and rural areas, excluding institutions such as hospitals, hotels, dorms. Data collection was done through direct interviews using a tablet-type computer  system and this process lasted from June 2011 to November 2011. Sampling was done using multistage cluster technique which involves stratifying the provinces into primary sampling units (PSUs), and then selecting of households each PSUs. Of the 13,964 households initially selected, a total of 13,718 women were finally interviewed, resulting in a 99% response rate. These details are available from the final report of Mozambique 2011 DHS and available here: The outcome variables of interest were: 1) place of delivery: home versus health facility, 2) use of c-section: yes versus no.The selection of explanatory variables was guided by Andersen’s Behavioural Model of Health Service utilization which postulates that healthcare utilization is a function of three major factors: 1) predisposing factors, 2) enabling factors and 3) need factors . For thisvy command  and higher education only . Women from the middle , richer  and richest  wealth quintile households had significantly higher odds of using facility delivery compared with those in the lowest quintile. Women of Portugais , Cindau  and Xichangana  ethnicity had relatively higher odds of using facility delivery services than others. Rural women in the female headed households had higher odds of using facility delivery services . Using adequate ANC visits was a significant predictor of facility delivery services both in urban  and rural  areas.Regarding the use of c-section services, the most notable predictors were similar to that of facility delivery: rural residence, higher education, higher wealth, and adequate ANC visits. Having higher education showed positive association with the use of c-section among urban  and rural residents with secondary education . Cindau women in the urban areas  had higher odds of using c-section. Among rural women, using adequate ANC visits was a significant predictor of choosing c-section delivery .Using the data from Mozambique Demographic and Health Survey, findings from this study revealed that little less than one-third of the women in Mozambique were not using health facility delivery services. In the region-specific analysis, the disparity was more evident among rural women, with the prevalence being two-fifth compared with about 90% among urban women. Urban-rural disparity in the use of maternal and reproductive services is common in Sub-Saharan African countries –28. The There were sociodemographic disparities in the utilization of facility delivery and c-section services. Women with higher education were significantly more likely to use facility delivery services compared with those who had no education. The positive effect of education on health service seeking behaviour can function in two ways. Firstly, educated women are more likely to be aware of the danger signs of pregnancy and the risk factors of pregnancy complications; hence, they are more likely to avail themselves of the services , 32. SecWomen’s ethnic background was an important predictor of using facility delivery services as well. The racial/ethnic differences in maternal health service use and health outcomes have been a subject of growing interest in many countries –37. The Lastly, we found an association between the use of ANC visits and professional birthing services. ANC programs are generally educational and serve as the preparatory stage for safe delivery and successful termination of a pregnancy. Women who contact care-providers during the ANC stage are more likely to learn about and plan the place of delivery . PromotiThis study provided relevant insights regarding the prevalence and use of facility delivery and c-section services use in a nationally-representative sample in Mozambique. Findings contribute to an existing gap in the literature and generate potential areas of investigation for future research. Significant differences were found in the use of facility delivery services among certain ethnicities. While these findings provide a general idea regarding the nature of ethnic inequality, it did not allow the investigation of underlying mechanisms contributing to the trend. Further qualitative studies should be carried out to explore the sources of disparity and potential areas of intervention.Several limitations should be noted for this study. The data were cross-sectional and hence no causality can be inferred from the associations. Authors used a secondary database and, therefore, have no influence over the selection and measurement of the variables. As the data were self-reported, the chances of recall and reporting bias cannot be ignored. The factors that influence healthcare service utilization are diverse and multifaceted, but the choice of the explanatory factors was limited to what existed in the Mozambique 2011 DHS survey. Factors such as geographical distance, transportation facilities, quality of services in local healthcare settings, availability of female care provider have also been found to be important in primary studies; we were not able to adjust for these factors in the current analysis. The use of C-section services is also a complex outcome that can be driven by various personal and medical factors; no such data were collected in the Mozambique DHS. The survey was conducted in 2011, and therefore may not represent the current scenario. Lastly, due to the nature of the survey and analyses, causality cannot be inferred for the relationship between the outcomes (place of delivery and use of c-section services) and associated explanatory factors.This was a secondary analysis of the 2011 Mozambique Demographic and Health Survey data on the use of professional childbirth services among community dwelling women. The findings indicate that approximately 30% of the women were not using health facility delivery services, with the difference denoting a considerable urban-rural gap. Significant differences were also observed for women’s education, household wealth, and ethnic background.


Thoracic endometriosis (TE) is a rare type of endometriosis, where endometrial tissue is found in or around the lungs and is frequent among extra-pelvic endometriosis patients. Catamenial pneumothorax (CP) is the most common form of TE and is characterized by recurrent lung collapses around menstruation. In addition to histology, immunohistochemical evaluation of endometrial implants is used more frequently. In this review, we compared immunohistochemical (CPE) with histological (CPH) characterizations of TE/CP and reevaluated arguments in favor of the implantation theory of Sampson. A summary since the first immunohistochemical description in 1998 until 2019 is provided. The emphasis was on classification of endometrial implants into glands, stroma, and both together. The most remarkable finding is the very high percentage of stromal endometriosis of 52.7% (CPE) compared to 10.2% (CPH). Chest pain, dyspnea, right-sided preference, and diaphragmatic endometrial implants showed the highest percentages in both groups. No significant association was found between the recurrence rate and the various appearances of endometriosis. Sometimes in CPE (6.8%) and CPH (30.6%) no endometrial implants were identified underlining the importance of sensitive detection of endometriosis during and after surgery. We suggest that immunohistochemical evaluation should become mandatory and will improve diagnosis and classification of the disease. Endometriosis is characterized by implantation and growth of endometrial glands and stroma outside the uterine cavity . Of noteThe greatest enigma in pathogenesis of endometriosis is still the unanswered question of why, despite a high rate of retrograde menstruation, only approximately 1–10% of women in their reproductive age acquire endometriosis , disturbBesides elucidation of these risk factors that favor initiation of endometriosis, the question whether or not the endometrium is the main if not the only source for ectopic endometrial cells needs to be answered as it impacts also strongly the therapy of the disease.Therapeutically, the decision whether it is sufficient to eliminate only the ectopic implant(s) or whether endometrium or uterus must also be examined carefully, is crucial. As clearly shown, the overall recurrence rates were lowest for patients who underwent hysterectomy together with laparoscopy compared to laparoscopy alone . These dSince many arguments have been put forward to criticize the implantation hypothesis such as the occurrence of extra-pelvic endometriosis , the thon = 628 TE patients . In. In22]. Treatment of hemoptysis very often results in complete remission or partial response in all patients treated with hormonal or conservative treatment, which is in strong contrast to the high recurrence rate observed for CP/TE . This doIn summary, the origin of thoracic endometriosis appears to be almost exclusively in the endometrium as already described for pelvic endometriosis although not all causative factors contributing to the initiation and progression of the disease are known. We suggest that the diagnosis of stromal endometriosis with or without immunohistochemical confirmation should become mandatory for pelvic and thoracic endometriosis, and possibly for other extra-pelvic sites. Furthermore, there is an urgent need for more sensitive and effective detection methods to assess endometrial implants during surgery in the pelvis and in extra-pelvic sites. Especially detection of ectopic endometrial implants at extra-pelvic sites should always be accompanied by a careful examination of the pelvis.


Ovarian cancer (OV) is a considerable threat to the health of women due to its complex mechanisms and atypical symptoms. Various currently available treatments fail to substantially increase the survival rate of OV patients. The tumor microenvironment (TME) is gaining attention due to its role in tumorigenesis and tumor progression. This study mainly investigated the immune characteristics of OV by CIBERSORT and MCP-counter. We reclassified OV into four TME cell subtypes with different prognoses and evaluated the infiltration of the cells in each subtype. The immune risk of diverse subtypes was evaluated based on the immunoscore calculated by Cox regression analysis. The molecular mechanisms and hallmark pathways of the four subtypes were analyzed. The results indicate that the immune procancer cell subtype is associated with the worst prognosis, closely related to the high immune risk group, and characterized by low expression of checkpoints and MHC class I and II molecules, high expression of hypoxia-related genes, high enrichment of the EMT and hypoxia pathways, and low enrichment of the DNA repair and interferon α response pathways. This study contributes to the investigation of immune mechanisms and identifies more effective targets for immunotherapy of OV. Ovarian cancer is a highly lethal malignancy that ranks as the seventh leading cause of female cancer worldwide; there will be approximately 21,750 new cases of OV in 2020 . TherefoThe tumor microenvironment (TME) is the complex environment of a tumor that is mainly composed of the vasculature, cells, and extracellular matrix . FibroblTherefore, we aimed to analyze the immune characteristics and roles of TME cells in OV in detail. An important step in our study was to link the RNA-seq data to TME cells by CIBERSORT  and MCP-1. The format of the TCGA RNA-seq data was fragments per kilobase million (FPKM). The primary solid tumor samples with the detailed FIGO stage, histological grade, and overall survival (OS) were selected. To validate the results, two additional raw datasets GSE26193 and GSE9891 were downloaded from the Gene Expression Omnibus (GEO)2.The Cancer Genome Atlas (TCGA) RNA-seq data and clinical characteristics of OV were obtained from UCSC Xena3, and the probe IDs in the GEO data were processed using the relevant platform dataset. If multiple Ensembl or probe IDs matched a gene name, the average of all IDs was used to calculate the expression value of a gene. The FPKM OV data of TCGA were transformed to the transcripts per million (TPM) data format because TPM can be used to transform the RNA-seq expression data similar to the gene expression data . The MCP-counter R package was used to evaluate the expression of two additional TME cell types, fibroblasts and endothelial cells. Then, the z-score was used to normalize the data acquired by two separate methods, and the results were combined to finally obtain the proportion of 23 TME cell types in 172 OV samples.CIBERSORT and MCP-counter were used to transform the RNA-seq data into the proportion of TME cells. The TCGA data were reformatted as required for CIBERSORTk = 4) of the elbow plot was used to define the best cluster number of OV samples. Finally, four new OV subtypes were defined based on TME cells; these subtypes were different from the stage or grade. Additionally, 23 TME cell types were also clustered into four groups by hierarchical clustering based on Euclidean distance and Ward’s linkage.To determine a better classification method for investigating OV, consensus clustering of 172 OV data samples was performed by the ConsensusClusterPlus R package . The optp-value of the Cox regression results to generate an immune risk model based on linear regression Exp was performed by the GSVA R package , which wt-test, and multivariate groups were compared by Kruskal-Wallis test. The receiver operating characteristic curve (ROC curve) was used to evaluate the sensitivity and specificity of the immunoscore-based prediction of OS. The area under the curve (AUC) was calculated by the timeROC R package . Detailed clinical characteristics and cell proportions are listed in A total of 359 primary solid tumor samples of OV with detailed clinical information were downloaded from the TCGA dataset . The genn = 52) (n = 62) (n = 24) (n = 34)  , immune (n = 62) , immune (n = 24) , and imm(n = 34) . The OS + T cells was found. IKCS was characterized by a high proportion of activated NK cells, CD8+ T cells, and regulatory T cells (Tregs). IPACS included a high number of naïve B cells and plasma cells. Activated dendritic cells, follicular helper T cells, and resting memory CD4+ T cells demonstrated high infiltration in IHCS, and Tregs were characterized by low infiltration.Significant discrepancies in IPCCS and the other three subtypes were identified in the case of 20 out of 23 TME cell types . M0 macrp-values corresponding to M2 macrophages were significant; however, the expression of M2 macrophages was high in IPCCS similar to that of M0 macrophages  are important TME cells that release factors and boost angiogenesis leading to poor tumor outcome and resistance to treatment  was investigated. The results indicated that neutrophils and fibroblasts were distributed in stages II, III, and IV of OV . These tP < 0.05 according to the results of the analysis. These six TME cell types were used to establish an immune risk model of OV, and the results are shown as a forest plot  with est plot . The risest plot . The Kapest plot .Comparison of the immunoscores of four subtypes indicated that IPCCS had the highest immunoscore and that the immunoscore of the four subtypes was gradually and slightly decreased . This reTo analyze the molecular mechanisms corresponding to various subtypes, current literatures were searched for data on chemokines and chemokine receptors , immune The majority of immune checkpoints were expressed at low levels in IPCCS and the high immune risk group , especiaMost hypoxia-related genes were expressed at high levels in IPCCS and the high immune risk group indicated a certain degree of hypoxia in the environment of OV cells . BhandarTo determine the differences in the enrichment of hallmark pathways between various subtypes and immune risk groups, GSVA of the hallmark pathways was performed using 172 TCGA OV data. The GSVA score of the hallmark pathways demonstrated that certain pathways  were highly enriched in IPCCS and the high immune risk group . These wn = 359). The same six TME cell types were used to compute the immunoscore of each sample in the GEO and TCGA cohorts, and each cohort was divided into the high and low immune risk groups according to the median immunoscore  and the entire TCGA cohort  to construct an immune risk model. The model was used to calculate the immunoscore and evaluate the immune risk in each OV sample. The results indicated that different cell subtypes of OV are associated with variable immune risk. IPCCS was associated with high immune risk and the worst prognosis. In contrast, IPACS and IHCS were associated with low immune risk and better prognosis. The data indicated that the model can reliably distinguish differences in the survival time of the patients in the high and low immune risk groups; the high immune risk group was associated with poor prognosis. Consistent results were obtained by validating the model using the GEO database. The ROC curve analysis also showed that the immunoscore had higher sensitivity and specificity in the prediction of prognosis compared with that of other clinical features.CIBERSORT and MCP-counter analyses of the TCGA OV data yielded the proportions of 23 TME cell types of OV. A classification diagram was used to divide all OV data into four subtypes based on the proportion of 23 TME cell types indicating that TME of OV has four main categories. These subtypes were different from the routine stage and grade characteristics, and each subtype had unique cell types that may account for different prognosis of OV. The Cox regression analysis of these cell types was used to select six TME cell types  according to TME cell types and demonstrated infiltration of exclusive cell types in each subtype of OV. Then, six TME cell types were selected by Cox regression analysis to calculate the immunoscore that could assess the immune risk and predict the prognosis of OV. The results showed that IPCCS was associated with high immune risk and poor prognosis. Finally, the analysis of the mechanisms of various subtypes of OV was performed, and the results may assist in identifying effective therapeutic targets for OV.http://xena.ucsc.edu; https://www.ncbi.nlm.nih.gov/geo.Publicly available datasets were analyzed in this study. This data can be found here: GZ and SN designed and directed all research. SC, QG, YC, YH, XZ, and CK performed the data processing and experimental analyses. GZ, SN, SC, and QG drafted the manuscript. All authors reviewed and approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The COVID-19 pandemic is a severe global health crisis. Wearing a mask is a straightforward action that can be taken, but shortage of stock and equity of allocation were important issues in Taiwan. Furthermore, increased anxiety leading to the stockpiling of masks has been common during the pandemic.We aim to summarize the name-based mask rationing plan implemented in Taiwan and explore the public’s perceived anxiety about mask shortages.The government of Taiwan took action to control the supply and allocation of face masks. We summarize the timeline and important components of the mask rationing plan. A survey that aimed to investigate the overall response to the mask rationing plan was answered by 44 participants.The mask rationing plan was implemented in late January 2020. Daily production capacity was increased from 2 million masks to 16 million masks in April 2020. People could buy 9 masks in 14 days by verification via their National Health Insurance card. Digital face mask availability maps were created. Moreover, the mask plan safeguarded the purchase of masks and resulted in decreased anxiety about a mask shortage . The majority of people felt that the mask plan was satisfactory .We found that the unique name-based mask rationing plan allowed for control of the production and supply of masks, and contributed to the appropriate allocation of masks. The mask rationing plan not only provided the public with physical protection, but also resulted in reduced anxiety about mask shortages during the pandemic. The COVID-19 pandemic has become a severe global crisis and there were more than 20 million cases as of late August 2020 . The TaiWearing masks to protect against viral transmission is straightforward but attitudes toward mask use varied across countries . The recWearing a mask is common in Asian countries; prior to the COVID-19 pandemic, people wore masks in public places to prevent infection. Due to the sudden, unexpected, and overwhelming pandemic, people panic-bought masks in Taiwan. Increased anxiety about mask shortages led to people stockpiling masks. Thus, the shortage of mask storage, soaring prices, and equity of allocation were important issues in the early phase of the COVID-19 pandemic. The government of Taiwan took action to control the supply and allocation of face masks; this unique mask plan was believed to have greatly contributed to the success of the battle against COVID-19 in Taiwan ,9,12. FuOur study was approved by the ethical committee of MacKay Memorial Hospital, Taipei, Taiwan (registration number 20MMHIS140e). We summarize here the strategies undertaken by the government of Taiwan, as well as details of the name-based mask rationing plan, taken from the website of the Centers for Disease Control, Taiwan (CDC) . As the To investigate the potentially psychogenic impacts of the mask plan, we also conducted a simple survey with a 5-point scale questionnaire that aimed to investigate the overall response to the mask rationing plan. Taiwanese residents aged >18 years were freely recruited at the entrance of our hospital. They were able to read and write Mandarin. The questionnaire was anonymous and not related to medical services. There were 10 simple questions using plain language and it took approximately 1-2 minutes to finish the questionnaire . QuestioThe questionnaire was administered to 44 adults residing in Taiwan. In Taiwan, several strategies were implemented to reduce the spread of COVID-19 and the unique name-based mask rationing plan was believed to play a crucial role in Taiwan’s success in the battle against the virus . This maThere have been controversies about the protective effectiveness of masks. In addition, attitudes toward wearing masks have varied across countries. Wearing a face mask is a straightforward and simple measure that the general public can use to prevent the spread of contaminated droplets and limit virus transmission. Specialized medical masks are a critical component of personal protective equipment in clinical settings. However, the effectiveness of mask use among those in the general community remains controversial ,10,20. WThe pandemic can cause stress and approximately 1 in 5 COVID-19 survivors experienced mental health problems within 90 days of their COVID-19 diagnosis . The useWhile controversy regarding the effectiveness of mask use remains and our study was limited to a small group of responders, the results from this pilot study suggest that the nationwide strategy of mask rationing contributed to the appropriate allocation of masks and a reduction in anxiety about mask shortages. The diagnosis of psychiatric conditions is rigorous and based on the Diagnostic and Statistical Manual of Mental Disorders. We did not aim to confirm a causal relationship between the mask shortage and mental illness; rather, we conducted this preliminary study to indicate whether there is a potential relationship between the mask plan and the public’s perceived anxiety during the pandemic. Further large-scale population-based studies are required to draw stronger conclusions.In conclusion, the disease burden of the COVID-19 pandemic was still increasing when the name-based mask plan was implemented and the mask plan contributed to the success of Taiwan’s battle against COVID-19. In this study, we highlighted the important timeline dates and components of this mask plan; this may serve as a reference for policy makers. The mask plan safeguarded mask allocation and may also have decreased perceived anxiety during the pandemic. Further studies are required.


Medial migration is the paradoxical migration of the femoral neck element (FNE) superomedially against gravity with respect to the intramedullary component of the cephalomedullary device, increasingly seen in the management of pertrochanteric hip fractures with the intramedullary nail. We postulate that the peculiar anti-gravity movement of the FNE in the medial migration phenomenon stems from a ratcheting mechanism at the intramedullary nail-FNE interface, which should inadvertently produce unique wear patterns on the FNE that can be seen with high-powered microscopy. By examining the wear patterns on retrieved implants from patients with medial migration, our study aims to draw clinical correlations to the ratcheting mechanism hypothesis.Four FNEs were retrieved from revision surgeries of four patients with prior intramedullary nail fixation of their pertrochanteric hip fractures complicated by femoral head perforation. The FNEs were divided into two groups based on whether or not there was radiographic evidence of medial migration prior to the revisions. Wear patterns on the FNEs were then assessed using both scanning electron microscopy and light microscopy.Repetitive, linearly-arranged, regularly-spaced, unique transverse scratch marks were found only in the group with medial migration, corresponding to the specific segment of the FNE that passed through the intramedullary component of the PFNA during medial migration. These scratch marks were absent in the group without medial migration.Our findings are in support of a ratcheting mechanism behind the medial migration phenomenon with repetitive toggling at the intramedullary nail-FNE interface and progressive propagation of the FNE against gravity. These cephalomedulary devices offer advantages such as a more efficient load transfer with the shorter lever arm, significantly less soft tissue disruption, shorter operative time, and have been shown to have superior outcomes when compared to the traditional extramedullary sliding screw devices particularly in unstable, multifragmentary fractures (AO type A2/A3)7.In recent years, load sharing devices such as fixation with intramedullary nails have gained popularity in the management of pertrochanteric hip fractureset al in their series of 70 proximal femur fractures managed with the Proximal Femoral Nail (PFN)8. Medial migration leads to complications with considerable morbidity including femoral head perforation, penetration into the acetabulum, destruction of the hip joint, and in some cases, migration into the pelvic cavity  were retrieved from revision surgeries of four patients with prior fixation of their pertrochanteric hip fractures with the Synthes Proximal Femoral Nail Antirotation (PFNA), complicated by FNE perforation of the femoral head. Radiographic analysis of plain radiographs were performed and the FNEs were divided into two groups based on whether or not there was medial migration prior to the revisions (n=2 per group). Wear patterns on the FNEs were assessed using both scanning electron microscopy (SEM) and light microscopy. Correlations of the FNE wear patterns with findings from their corresponding radiographic analysis was then performed and compared.10.The use of the SEM was made in view of its potential for higher magnification and its ability to create an all-in-focus image in the viewing of a 3-dimensional specimen with significant variations in the Z-axis with postprocessing of recorded stacks of through-focus imaging to overcome the depth of field limitExtraction of the FNEs during the revision surgeries were performed in accordance to the manufacturer’s recommendations for FNE removal. All FNE were extracted uneventfully using the Synthes PFNA Blade Extraction Set.Markings were made on the FNEs at regular intervals using a marker pen and numbered to facilitate orientation and localisation of specific scratch marks on the FNE. Standard preparation with application of a 15nm gold coating using a sputter coater to the surface of the FNEs was performed to facilitate visualisation and surface analysis with the SEM [FEI Quanta 650 FEG]. Viewing was performed at 10kV for all magnifications. A montage of 5x magnification was created to facilitate spatial orientation and the FNEs were reviewed systematically in segments at 40x, 80x, 160x and 300x magnification, respectively.Radiographic analysis was performed using plain radiographs with anterior-posterior (AP) and lateral views. Measurements of the medial migration distance, tip-apex distance (TAD) and identification of the specific segment of the FNE that passed through the intramedullary component of the PFNA during medial migration were made using software tools [CARESTREAM Vue Motion]. Assessment of fracture configuration and position of the tip of FNE within the nine Cleveland zones in the femoral head were also performed.The light microscope [Olympus SZX12] was used to facilitate pinpointing of the exact location of specific scratch marks on the FNEs to aid correlation with the specific segment of the FNE that passed through the intramedullary component of the PFNA during medial migration. This was performed systematically in segments at 63x and 90x magnification, respectively.Similar longitudinal scratch marks on both the superior and inferior ridges of the FNE were seen in the retrieval specimens from all four patients. There were however, unique wear patterns present only on the FNEs from the group with medial migration corresponding to the segment of the FNE that has passed through the intramedullary component of the PFNA during medial migration . These wRepetitive, linearly-arranged, regularly-spaced transverse scratch marks were seen on the apex of the inferior ridge of the FNE in both patients with medial migration -8. TheseThe angle that these transverse scratch marks made with respect to the longitudinal axis of the FNE was consistent with the angle that the FNE made with respect to the opening of the intramedullary component of the PFNA at the intramedullary nail–FNE interface at the apex of the inferior ridge .These findings were suggestive of (i) repetitive toggling at the intramedullary nail-FNE interface with scratch marks made as a result of a pivoting process at the intramedullary nail–FNE interface when the implant is under load, and (ii) progressive propagation of the FNE superomedially driven by an underlying cyclical process.No transverse scratch marks or scratch patterns unique to a particular part of the FNE was seen on both FNEs in the group without medial migration. Longitudinal scratch marks similar to those found on the FNEs in the patients with medial migration were seen on both the superior and inferior ridges extending through the whole length of the FNE. An example of these longitudinal scratch marks .The medial migration distances seen on radiographs for our patients with medial migration were 22.3mm and 12.8mm seen at 2.6 months and 12.3 months, respectively. The timing of revision surgery were similar in both groups, with one early failure (3-4 months post index surgery) and one late failure (12 months post index surgery).The indication for revision surgery was FNE perforation of the femoral head in all cases, with penetration into the acetabulum in three of the four cases. The pattern of femoral head perforation however was different between the two groups. In the group without medial migration, superior cutout was seen in both cases with varus collapse of the proximal fracture fragment. In the group with medial migration, cut-out occurred medially in both cases in line with the axis of the femoral neck element, without rotational displacement or varus collapse of the proximal fracture fragment. Unstable fracture configurations were seen in both cases in the group with medial migration and only one case in the group without medial migration (AO/OTA 31A2.3). Comminution at the greater trochanter and an unstable medial calcar pattern were seen in these cases of unstable pertrochanteric fractures.TAD were 18.9mm and 39.8mm in the group with medial migration, 15.2mm and 32.9mm in the group without medial migration. The position of the FNE tip within the femoral head were center-center and inferior-anterior in the group with medial migration, superior-center and superior-anterior in the group with medial migration.et al proposed that toggling is required for medial migration of the femoral neck element in the cephalomedullary device to occur based on the consistent fracture pattern involving the medial calcar and the greater trochanter seen in their case series of eight pertrochanteric hip fractures where medial migration occurred9. In our group with medial migration, consistent findings of an unstable pertrochanteric fracture configuration (AO/OTA 31A2.3) were found in all patients with deficits seen in both the medial calcar and the greater trochanter similar to Weil et al’s case series of patients.Weil et al’s toggling theory was supported by their biomechanical study where they were successful in recreating the medial migration phenomenon in all five different nail designs tested  with a biomechanical model specifically engineered for toggling to occur. No medial migration was seen when toggling was intentionally restricted in all of the cephalomedullary nail designs with a single femoral neck element tested. In our study with the Synthes PFNA which has a single femoral neck element, we found repetitive, linearly-arranged, regularly-spaced transverse scratch marks only on the FNEs from the group with medial migration, corresponding to the segment of the FNE that has passed through the intramedullary component of the PFNA during medial migration. These characteristic wear patterns were indentations made by the pivoting action of the FNE on the intramedullary component of the PFNA at the intramedullary nail-FNE interface, suggestive of repetitive FNE toggling and progressive migration of the FNE driven by an underlying cyclical process, in support of Weil et al’s toggling theory. The longitudinal scratch marks found common to all retrieval FNEs may have been made during the insertion of the FNE with the hammer or during the removal of the FNE with the slotted hammer.Weil 8. Interestingly, preventing nail toggle did not prevent medial migration of the distal FNE when two femoral neck implants [Synthes PFN] were used in Weil et al’s study, suggesting that the mechanism of migration in two-screw devices may be different9. Migration was prevented only with clamping of the nail and removal of the superior neck element9.Medial migration was also observed in dual lag screw intramedullary nail systems, in the Z-effect phenomenon17. This is supported by Sommer et al’s biomechanical study showing higher cut-out resistance in the intramedullary constructs versus extramedullary constructs when implants with similar FNE designs were tested 18.Cephalomedullary nail fixation devices have a significantly lower primary cut-out rate compared to extramedullary devices12. Medial migration occurs in a subset of these cut-outs and has an increasing number of cases reported in the literature in the last decade. With wear patterns demonstrated on retrieved implants clearly different from other cut-outs suggesting different underlying mechanisms leading to failure, further studies may be beneficial in investigating whether the subset of cut-outs due to medial migration are different from the regular femoral head cut-outs well described in the literature.Despite being more resistant to cut-out, femoral head cut-out remains as the most common complication of cephalomedullary nail fixation in the management of pertrochanteric hip fractures of which the majority is believed to be the result of biomechanical failureet al’s study also showed that the FNE blade designs  outperformed the FNE screw designs  in terms of overall cut-out resistance, suggesting that the FNE blade is a superior design compared to the FNE screw irrespective of whether of whether it is an intramedullary or extramedullary construct18. In Nikoloski et al’s study of 6 cut-outs in 97 patients managed with the Synthes PFNA which has a FNE with a helical blade design, a bimodal distribution of TAD leading to failure was seen19. All cut-outs occurred had TAD either less than 20mm or more than 30mm. No cut-outs occurred with TAD between 20-30mm. Nikoloski et al proposed that the helical blade behaves differently to a screw, and that placement too close to the subchondral bone may lead to penetration through the head. Our study findings were similar to Nikoloski’s study with all cut-outs occurring either less than 20mm or more than 30mm in both groups.Interestingly, Sommer Based on the wear patterns seen in our study unique to the group with medial migration, we postulate that medial migration requires two criteria to occur: (i) toggling, and (ii) propagation of the femoral neck element medially with respect to the proximal fracture fragment. This is a progressive process where perforation of the femoral head and acetabulum occurs during the compression phase (e.g. single leg stance), and propagation of the femoral neck element medially occurs during the tension phase (e.g. when the lower limb is lifted off the ground). 26. Cleveland et al divided the femoral head into nine zones with good reliability in the reporting of FNE tip positioning27. Caruso et al in their retrospective analysis of 571 patients for cut-out risk predictors in cephalomedullary nailing of pertrochanteric fractures showed the highest rates of cut-out occurring with superior FNE tip placement within the femoral head26. Interestingly, this pattern of FNE tip placement resulting in cut-outs was seen only in the group without medial migration in our study. In the group with medial migration, cut-outs occurred despite FNE tip placement in low risk positions. This is especially significant as it includes the center-center position, commonly thought to convey the highest resistance to cut-outs26. Larger studies will be useful in the assessment of whether the cutout risk with respect to FNE tip positioning in medial migration follows the regular pattern seen in cut-outs given the unique underlying pathophysiology in medial migration. Our study is the first retrieval study in the literature investigating the medial migration phenomenon. With high-powered magnification and the scanning electron microscopy’s ability to create an all-in-focus image in the analysis of the 3-dimensional FNE specimen, we were able to perform a detailed and comprehensive examination of the wear patterns on the FNE specimens to verify the toggling mechanism hypothesis. The consistent, unique wear patterns found on the retrieved FNE specimens exclusive to the medial migration phenomenon serves as strong evidence in support of Weil et al’s toggling mechanism hypothesis, in line with the radiological and biomechanical findings from their study.The risk of cut-out has been associated with FNE tip positioning within the femoral headOne limitation in our study is our small sample size. Despite the increasing number of cases reported in the last decade, medial migration remains poorly recognised to date and retrieval specimens are difficult to acquire. Although our study findings are convincing of repetitive toggling occurring at the intramedullary nail-FNE interface with progressive migration of the FNE in the medial migration phenomenon, evidenced by unique, consistent wear patterns present only in the specific segment of the FNE that passed through the intramedullary component of the PFNA during medial migration, retrieval studies with larger sample sizes will be useful in confirming our findings. With toggling being a bi-directional process predisposed by an unstable pertrochanteric fracture configuration, and progressive FNE migration likely driven by an underlying cyclical process, biomechanical studies with bi-directional cyclic loading at the hip joint may be useful in investigating the role of loading-unloading at the hip in the medial migration phenomenon, particularly in unstable pertrochanteric fractures.The wear patterns found on the FNE with medial migration are in support of repetitive FNE toggling and progressive migration of the FNE, driven by an underlying cyclical process. Coupled with radiological findings of a one-direction motion of the FNE superomedially against gravity, our study findings are suggestive of a ratcheting mechanism exclusive to the medial migration phenomenon.


The stress corrosion cracking is the central issue for high-strength wires under high tensile stress used in civil engineering. This paper explores the resistance of stress corrosion cracking of three typical steel wires of high-strength carbon through a laboratory test, combining the actions of tensile stress and corrosive solution. Besides, the impact of tensile stress and immersion time are also investigated. During the tests, the wires were subject to electrochemical measurements of potentiodynamic polarization and electrochemical impedance spectroscopy, and the microstructure analysis was performed on the fractured cross sections. The obtained results show the following: the high-strength wire, conforming to GB/T 5224, has higher resistance to the combined actions of tensile stress and corrosive solution; tensile stress of 70% fracture strength and longer loading-immersion time make the film of corrosion products on steel surface unstable and weaken the corrosion resistance; the surface film consisted of the iron oxide film and the corrosion products film whose components are mainly iron thiocyanate and iron sulphide. Due to the high bearing capacity and stiffness, the prestressed concrete (PC) structures are widely used in large-span building, bridge and hydraulic structures . The PC Walter  reportedfib), using ammonium thiocyanate (NH4SCN) solution as the corrosive environment for SCC test. This method has been standardized by ISO 15630 3−x. The ferro-thiocyanate compounds form on the steel surface and will promote the anodic dissolution of steel [Some ferric iron formed in the anodic dissolution process, and the reaction of ferric iron in solution containing thiocyanate produces ferro-thiocyanate compound, i.e., Feof steel . From th4SCN solution, respectively. The surface film consisted of the original iron oxide film and the corrosion products film whose components are mainly iron thiocyanate and iron sulphide. The original iron oxide film was dense while the corrosion products film was rough and loose. The steel wires with similar chemical composition were selected to study the stress corrosion behavior in this paper. The results showed that they had different corrosion resistance in the same corrosion environment. It indicated that even if the contents of Cr, Ni and Cu increased slightly, the performance of corrosion product film on the wires surface would be affected. Meanwhile, stress corrosion is the result of multiple factors synergy, such as composition and microstructure. Thus, in order to improve the stress corrosion resistance of steel, it is necessary to improve many aspects.The electrochemical measurements show that, with loading duration, the corrosion current density increases, and the corrosion resistance is weakened. The results from polarization curves and EIS are consistent with those from corrosion morphologies.The tensile stress leads to a more unstable corrosion products film formed on the steel, which means worse flatness and compactness. The stress substantially decreased the surface electron transfer resistance, thus promoting the corrosion of the high strength wires.The surface film consisted of the original iron oxide film and the corrosion products film, whose components are mainly iron thiocyanate and iron sulphide.The corrosion-resistance performance of the wires, conforming to GB/T 5224, is better than the selected wire conforming to BS 5896.The corrosion resistance of steel wire will be affected by the change of chemical composition. Stress corrosion is the result of multiple factors synergy, such as composition and microstructure.


The latest advancements in DNA sequencing technologies have facilitated the resolution of the phylogeny of insects, yet parts of the tree of Holometabola remain unresolved. The phylogeny of Neuropterida has been extensively studied, but no strong consensus exists concerning the phylogenetic relationships within the order Neuroptera. Here, we assembled a novel transcriptomic dataset to address previously unresolved issues in the phylogeny of Neuropterida and to infer divergence times within the group. We tested the robustness of our phylogenetic estimates by comparing summary coalescent and concatenation-based phylogenetic approaches and by employing different quartet-based measures of phylogenomic incongruence, combined with data permutations.Our results suggest that the order Raphidioptera is sister to Neuroptera + Megaloptera. Coniopterygidae is inferred as sister to all remaining neuropteran families suggesting that larval cryptonephry could be a ground plan feature of Neuroptera. A clade that includes Nevrorthidae, Osmylidae, and Sisyridae (i.e. Osmyloidea) is inferred as sister to all other Neuroptera except Coniopterygidae, and Dilaridae is placed as sister to all remaining neuropteran families. Ithonidae is inferred as the sister group of monophyletic Myrmeleontiformia. The phylogenetic affinities of Chrysopidae and Hemerobiidae were dependent on the data type analyzed, and quartet-based analyses showed only weak support for the placement of Hemerobiidae as sister to Ithonidae + Myrmeleontiformia. Our molecular dating analyses suggest that most families of Neuropterida started to diversify in the Jurassic and our ancestral character state reconstructions suggest a primarily terrestrial environment of the larvae of Neuropterida and Neuroptera.Our extensive phylogenomic analyses consolidate several key aspects in the backbone phylogeny of Neuropterida, such as the basal placement of Coniopterygidae within Neuroptera and the monophyly of Osmyloidea. Furthermore, they provide new insights into the timing of diversification of Neuropterida. Despite the vast amount of analyzed molecular data, we found that certain nodes in the tree of Neuroptera are not robustly resolved. Therefore, we emphasize the importance of integrating the results of morphological analyses with those of sequence-based phylogenomics. We also suggest that comparative analyses of genomic meta-characters should be incorporated into future phylogenomic studies of Neuropterida. The insect superorder Neuropterida contains more than 6500 described and extant species that are classified into three holometabolous insect orders: Megaloptera , Neuroptera  and Raphidioptera (snakeflies). Among these three, Neuroptera is by far the most species-rich order with 5917 species, in comparison to the much less diverse Megaloptera and Raphidioptera (386 and 253 species respectively) . OverallRecent phylogenetic investigations of Neuropterida have converged on the hypothesis that the order Raphidioptera is sister to a clade comprising Megaloptera and Neuroptera , 25–27. Oliarces) [The order Neuroptera comprises 16 extant families. In comparison to the adults, the larvae of Neuroptera have evolved a very broad spectrum of morphological adaptations to very different habitats and lifestyles , 20. Onlliarces) . The monliarces) . Howeverliarces) , 15 and liarces) , 20, 21,Concerning the phylogeny of neuropteran families, conflicting phylogenetic results have emerged both among different molecular studies , 21 as wDespite the above-outlined discrepancies among phylogenomic studies, some results seem to be robust across phylogenomic studies, but they are in conflict with the results of morphological studies. Such conflicts include the phylogenetic placement of Coniopterygidae as sister to the remaining families of Neuroptera, as suggested by previous analyses of genomic sequence data, but also by analyses of a small number of molecular markers , or by tPrevious molecular studies of the phylogeny of Neuropterida have mostly relied on conventional measures of branch support, such as the non-parametric bootstrap  and the The purpose of this study is to provide: 1) a phylogenomic framework and updated divergence time estimates of Neuropterida, 2) an evaluation of conflicting phylogenetic signals in the backbone phylogeny of the group, and 3) a discussion of the implications for morphological character evolution within Neuropterida based on the results of the present contribution and those of other studies. In an effort to resolve the existing incongruencies we assembled a novel transcriptomic dataset of Neuropterida and of suitable outgroup species, and assessed the robustness of our phylogenetic estimates with concatenation-based quartet approaches combined with data permutations and with gene tree-based quartet approaches. We additionally estimated divergence times of the major lineages of Neuropterida by using an approach that enables monitoring the effect of data selection on the Bayesian posterior divergence times of Neuropterida.On average, 3292 sequences per transcriptome or official gene set (OGS) passed the reciprocal best-hit criterion during the orthology assignment step . We excluded a total number of 21 transcriptomes and OGSs from our dataset because we found too few target genes (orthologs) within them  with those obtained when analyzing the second codon positions of the nucleotide sequence data Fig.  are topoAgulla as sister to a clade comprising all the Palearctic Raphidiidae. These relationships received maximum bootstrap and maximum bootstrap by transfer (TBE) support  suggest different topologies concerning the inter-familiar phylogenetic relationships of Neuroptera  approach delivered strong statistical support for most inferred phylogenetic relationships  on the divergence times of Neuropterida Fig. , except Agulla and all remaining Raphidiidae in the dataset was estimated to have occurred in the middle of the Eocene . The split of crown Megaloptera was estimated to have occurred at the beginning of the Triassic period , while crown Neuroptera started to diversify much earlier at the beginning of the Permian . The crown group of Osmyloidea started to diversify at the beginning of the Jurassic . Many consecutive deep splits in the phylogeny of Neuroptera  were estimated to have occurred at the end of the Triassic or the beginning of the Jurassic , whereas all concatenated analyses of amino-acid sequence data suggested a clade of Osmylidae + (Nevrorthidae + Sisyridae). This incongruence between methods was only present when analyzing amino-acid sequence alignments. The analyses of the codon-based nucleotide sequence alignments  resulted in phylogenetic relationships congruent to the summary coalescent approach. Despite the high bootstrap and high TBE support from the concatenated analyses of amino-acid sequence data for a sister group relationship of Sisyridae and Nevrorthidae, our FcLM analyses do not unequivocally support the inferred phylogenetic relationships within Osmyloidea. Specifically, quartet support calculated with ASTRAL and FcLM analyses show almost equal proportions of quartets supporting each of the two above-mentioned prevalent phylogenetic hypotheses. Moreover, the FcLM analyses suggest substantial influence from taxon sampling and possibly from non-random distribution of missing data for this particular phylogenetic relationship. Putting the results of the concatenation-based, summary coalescent and FcLM analyses together, we conclude that the phylogenetic relationships of the three families in Osmyloidea should be considered for now unresolved.Our analyses of amino-acid sequence data and those of second codon positions of the nucleotide sequence data, suggest Hemerobiidae as sister to Ithonidae + monophyletic Myrmeleontiformia, whereas analyses of the complete codon-based nucleotide sequence alignments suggest Chrysopidae as sister to Ithonidae + paraphyletic Myrmeleontiformia. These incongruencies again warrant a detailed examination of potentially confounding signals. The FcLM analyses do not unequivocally support Hemerobiidae as sister to Ithonidae + Myrmeleontiformia (72.40 and 36.60% of quartets), despite the maximum bootstrap and maximum TBE support for this relationship (100%). The FcLM analyses also show some weak putatively misleading signal in support of this relationship that possibly originates from non-random distribution of missing data. Since the FcLM and ASTRAL quartet analyses do not unequivocally support Hemerobiidae as sister to Ithonidae + Myrmeleontiformia, we consider this part of the neuropteran tree as statistically not robustly resolved.Although many previous phylogenomic studies have focused on the biological causes of incongruence that results from analyzing the data with coalescent-based or concatenation-based phylogenetic methods , 74–76, Within holometabolous insects, Neuropterida is inferred as the sister group to Coleopterida, a phylogenetic hypothesis that is in accordance with the latest views on the phylogeny of Holometabola , 4. The In our study, the order Raphidioptera is placed as sister to Megaloptera + Neuroptera, in agreement with the results of most previous molecular studies –21, 82. Agulla as sister to the Palearctic Raphidiidae. Although the Nearctic genus Alena is not included in our analyses, the above-mentioned relationship suggests the monophyly of the Palearctic Raphidiidae and corroborates previous molecular phylogenetic analyses of Raphidiidae [Mongoloraphidia clade) and a Western Palearctic  radiation [Within Raphidioptera, both Raphidiidae and Inocelliidae are recovered as monophyletic in all of our analyses and with high statistical support. We estimated the common ancestor of extant Raphidioptera to have lived during the early Cretaceous (~ 136 Mya), although it is evident from the fossil record that stem lineages of Raphidioptera were distinctly diverse much earlier in the Mesozoic . Our reshidiidae . Furtheradiation . Biogeogadiation .The order Megaloptera is inferred as monophyletic in all analyses and the family Corydalidae is also inferred as monophyletic. These results are congruent with the results of target DNA enrichment-based phylogenomic analyses of Neuropterida . In addiThe order Neuroptera is inferred as monophyletic and our divergence time estimates suggest that its members started to diverge in the end of the Carboniferous (~ 301 Mya), while the common ancestor of the extant Neuroptera is estimated to have lived in the early Permian (~ 281 Mya). Our inferred phylogenetic trees corroborate the results of previous phylogenomic studies that suggested the family Coniopterygidae as sister to all remaining neuropteran families –22. The Nevrorthus all Malpighian tubules are free, while the aquatic larvae of Sisyridae have one cryptonephric tubule. The phenomenon of cryptonephry results in an improved water re-absorption mechanism and is apparently an adaptation to terrestrial environment, especially to a more exposed lifestyle and life in drier habitats. The original idea concerning the evolution of cryptonephry within Neuroptera is in contrast with the herewith presented phylogenetic relationships and with other molecular phylogenies [The phylogenetic placement of Coniopterygidae as sister to all remaining Neuroptera is in contrast with the majority of morphological analyses that have instead suggested Nevrorthidae as the most ancient lineage within the order , 11, 15.logenies , 20, 21,Nevrorthus and Osmylus [A clade of Nevrorthidae, Sisyridae and Osmylidae (i.e. Osmyloidea) is inferred as sister to all remaining neuropteran families except Coniopterygidae and this clade is stable across analyses of different datasets and methods. This clade was also strongly supported in all quartet analyses, which in turn suggests that the placement of these three families in a monophyletic group is robust. This result is also in agreement with the results of analyses of target DNA enrichment data . Potenti Osmylus  could co Osmylus . In the  Osmylus   has been traditionally considered to form a clade with the families Mantispidae, Berothidae and Rhachiberothidae. The unofficial term “dilarid clade” has been used to describe this phylogenetic assemblage , 15, 47.Mantispidae and Berothidae were recovered as sister taxa with strong statistical branch support in all phylogenetic analyses, but the placement of this clade within Neuroptera is not robustly resolved. Concatenation-based and summary coalescent phylogenetic analyses of amino-acid sequences suggest a sister group relationship of Mantispoidea with Chysopidae. However, the different quartet analyses did not unequivocally support this sister group relationship. Our results corroborate previous views suggesting a close phylogenetic affinity of Berothidae and Mantispidae , 47. DesA clade Chrysopidae + Hemerobiidae, suggested by analyses of mitochondrial genomes , 22 and The family Ithonidae is inferred as monophyletic and sister to monophyletic Myrmeleontiformia. The monophyly of Myrmeleontiformia is also strongly supported by our FcLM analyses and by previous analyses of morphological characters , 48. TheWithin Myrmeleontiformia (excluding Psychopsidae), Nymphidae is inferred as the earliest diverging lineage. Larval synapomorphies of Myrmeleontiformia excluding Psychopsidae are the conspicuously raised ocular region, a sensory pit on the apical labial palpomere, a strongly developed mid-dorsal cervical apodeme, a distinctly widened body posterior to the prothorax, and a compact and laterally rounded abdomen , 47. TheIt is essential to mention that the different phylogenetic relationships of neuropteran families presented here corroborate previous results on the evolution of the larval gula-like sclerite within Neuroptera . WintertWe draw four major conclusions from our analyses: (1) Part of the backbone tree of Neuropterida receives strong statistical support in several independent phylogenetic analyses and should be considered for now the most likely scenario of neuropterid evolution. One such scenario is the early split between Raphidioptera and Megaloptera + Neuroptera. Within Neuroptera, all analyses support an early split between Coniopterygidae and the remaining Neuroptera which cannot be corroborated with morphological analyses. The families Nevrorthidae, Sisyridae and Osmylidae form a monophyletic group sister to all other Neuroptera except Coniopterygidae. The family Dilaridae is the sister group to all remaining Neuroptera except Coniopterygidae and Osmyloidea. Despite these seemingly robust phylogenetic results, the phylogenetic relationships between the most species rich groups of Neuroptera  are still not robustly resolved. For several branches in the neuropteran tree, the seemingly high branch support appears to be inflated and should be taken with caution. (2) Comparing concatenation versus summary coalescent approaches, and additional quartet-based measures of phylogenomic incongruence such as the FcLM approach, illustrates the potential of inflated branch support particularly derived from non-parametric resampling methods. Scientists are therefore advised to critically evaluate branch support in phylogenomic analyses and assume a conservative position. (3) The analyses of neuropterid relationships have received a lot of attention in the past and an extensive amount of phylogenomic data has been generated. However, parts of the backbone tree of Neuropterida can still not be robustly resolved which is disappointing, but reflecting a picture seen in other analyses of ancient phylogenetic splits as well. It will be necessary to invest molecular data beyond primary gene sequence information, for example structural genomic data , 102.  at the hierarchical level “Endopterygota” (i.e. Holometabola), based on a custom profile query in OrthoDB7  . The filtered dataset consisted of 124 species (92 neuropterid species and 32 outgroup species) including the four reference species of the ortholog set.Mapping of putative orthologous transcripts to each COG, at the translational  and at the transcriptional level , was performed with the software package Orthograph v. 0.5  see Add. SubsequOrthologous amino-acid sequences were aligned with MAFFT v. 7.123  and by ahttps://github.com/thomaskf/AliStat) [https://github.com/ottmi/symtest, see Misof et al. 2014 [We combined the results of alignment masking and protein-domain identification (see Suppl. Text AliStat) . OverallAliStat)  was measAliStat)  and by gWe selected the amino-acid supermatrix E Table  for downBased on the best ML tree, we calculated branch support from 100 non-parametric bootstrap replicates as well as from 10,000 replicates of the SH-like approximate likelihood ratio test (SH-aLRT)  with IQ-Modeling site-heterogeneous processes of amino-acid substitutions by incorporating site specific amino-acid profiles into phylogenetic reconstruction can potentially alleviate phylogenetic artifacts due to model miss-specification –135. We Heterogeneous amino-acid composition among species in the dataset can severely bias phylogenetic reconstructions due to violation of substitution model assumptions , 137–140We studied the effect of potentially confounding signal, like non-random distribution of data coverage and violations of SRH conditions, on our phylogenetic reconstructions with the FcLM approach  as descrk-means algorithm [We compared the results of tree reconstructions based on data at the amino-acid and nucleotide sequence levels. Substitutions at the nucleotide sequence level follow different processes than substitutions at the amino-acid sequence level, and thus the analyses at the nucleotide level can be considered an independent test of the results based on the amino-acid sequence data. Published investigations have consistently demonstrated that the base composition of second codon positions of protein-coding nucleotide sequences are the most homogeneous across taxa and thus least violate assumptions of the applied nucleotide substitution models , 80, 146lgorithm  in PartiThe concatenation approach has been criticized for being ignorant against gene tree discordance due to ILS and thus for being susceptible to tree reconstruction biases caused by these effects , 149. CuWe used 129 meta-partitions of the decisive amino-acid supermatrix  with the same calibrations and diffuse rate priors (α = 2) to check for repeatability of the analyses  to assess whether or not the results without data were significantly different, implying that the data harbor sufficient information for reliably estimating divergence times.Calculation of the Hessian matrices followed the standard procedure, applying the fitted substitution models (+ G with four rate categories) for each meta-partition  parameter outputs of the separate analyses of the meta-partitions were combined in a single MCMC summarized file. We mapped the posterior mean node ages and 95% confident intervals  on the overall best ML tree Fig. . The braIn addition to the informal discussion of implications of the proposed phylogeny for our understanding of the evolution of neuropterid insects in general, we also formally analyzed character transformations Fig.  with MesPrevious ACSRs of the larval ecologies of Neuropterida have suggested that ancestral Neuropterida most likely had an aquatic larva , 21. HowAdditional file 1: Supplementary Tables S1–S20. The supplementary tables include: 1) descriptive statistics of the results of orthology assignment, 2) results of FcLM analyses, 3) summarized results of the divergence times estimates as resulted from the different runs (MCMC chains) and fossil calibrations  all phylogenetic trees inferred from the analyses of different datasets and tree-inference methods, 2) results of additional ACSR analyses under different parameters, 3) heatmaps visualizing the pairwise alignment completeness scores of all analyzed supermatrices, 4) heatmaps visualizing the pairwise deviation from SRH conditions in each analyzed supermatrix, 5) scatter plot of the mean posterior node-age estimates from run 1 plotted against the mean posterior node-age estimates from run 2 when using all fossil calibrations, 6) beanplots of median posterior node-age estimates from run 1 and from run 2 when using all fossil calibrations, 7) scatter plots of the mean posterior node-age estimates plotted against the 95% higher posterior density CI-width of each node when running the dating analyses with or without data.Additional file 4. Character matrix with coded states for 86 larval characters of Neuroptera. This is the nexus-formatted character matrix that was used for the parsimony-based analysis of the evolution of larval characters. Taxon sampling is the same as in Jandausch et al.  [8, 2019) , 95.