Presence of ducks, and in particular of free-grazing ducks, has consistently been shown to be one of the most important risk factors for highly pathogenic avian influenza outbreaks which has compromised poultry production in South-East Asia since the early 2000s and continues to threaten public health, farmers’ livelihood and food security. Although free-grazing duck production has been practised for decades in South-East Asia, there are few published studies describing this production system, which is suspected to play an important role in the maintenance of avian influenza viruses. This study aimed at describing quantitatively the long-distance free-grazing duck production system in South Vietnam, characterising the movement and contact patterns of the duck flocks, and identifying potential associations between farming practices, movement and contact patterns and the circulation of avian influenza viruses. We conducted interviews among stakeholders involved in the free-grazing duck production system  in combination with a virological cross-sectional survey in South Vietnam. Results show that both direct and indirect contacts between free-grazing duck flocks were frequent and diverse. The flocks were transported extensively across district and province boundaries, mainly by boat but also by truck or on foot. A third of the investigated flocks had a positive influenza A virology test, indicating current circulation of avian influenza viruses, but none were positive for H5 subtypes. The age and size of the flock as well as its location at the time of sampling were associated with the risk of influenza A circulation in the flocks. These findings should be considered when developing risk assessment models of influenza virus spread aimed at informing the development of improved biosecurity practices leading to enhanced animal health, sustainable animal production and reliable income for farmers. For over a decade, regular outbreaks of highly pathogenic avian influenza (HPAI) have occurred in poultry throughout South-East Asia, in spite of large-scale vaccination campaigns, as implemented in Vietnam and Indonesia, and stamping-out interventions , 2. In V2 [short-distance  FGDs are herded within the commune boundaries and return to the farm premises at night, while long-distance  FGDs leave the farm for an extended period of time, often several weeks, and are transported across administrative boundaries. According to a survey conducted in 2010 in the An Giang province of the MRD, long-distance FGDs, short-distance FGDs and confined ducks accounted for 55%, 43% and 2% of the number of ducks, respectively [In Vietnam, poultry production in general, and duck production in particular, is concentrated in the Red River delta and the Mekong River delta (MRD), with a density of ducks in the MRD of about 507 heads per km2 . Free-gr2 . In such2 : short-dectively . In Nortectively .It has recently been suggested that long-distance FGDs are likely to play an important role in the maintenance and spread of the avian influenza (AI) viruses . First, This study has been approved by the Clinical Research and Ethical Review Board of the Royal Veterinary College (project number 3597).The study was conducted in An Giang province, in South Vietnam. Two districts (Chau Phu and Tri Ton) were selected on the basis of the importance of the integrated rice-duck production system and the presence of FGD flocks at the time of the field work, which took place between October and December 2015. There are no official records of the location and movements of FGD flocks, so the only way to identify farmers to be interviewed was to use the most up-to-date local knowledge of communal veterinarians . Using tThree questionnaires, one for each type of stakeholder , were developed and tested in the field during a two-day pilot study (the questionnaires are available as supporting information files). The farmer questionnaire included questions related to the socio-economics of the farm, duck production, flock movements and poultry health. For the purpose of this study, a flock was defined as a group of birds of the same age purchased, managed and sold as a whole. Some farmers owned two or more groups of birds of different ages, which were kept separate during grazing, transport and in enclosures; these groups were defined as distinct flocks. Farmers were also asked to locate all sites that they had visited with their current flock. Subsequently, further aspects about each site  were investigated. The location of each site specified by the farmers was approximated by the coordinates of the centroid of the commune were the site was located. The distance between sites was calculated as the Euclidean distance between two sites visited consecutively by a farmer. The transporter questionnaire included questions related to the socio-economics of the household, the characteristics of the duck transport activity and the biosecurity practices. The paddy owner questionnaire included questions related to the socio-economics of the household, the characteristics of the paddy management in terms of rice culture and post-harvest renting as well as the observed contacts between FGD flocks. Informed consent was obtained in writing prior to each interview. The questions were asked in Vietnamese by a previously trained interpreter, and the answers were translated into English by the interpreter directly to the primary investigator (AM) who recorded the answers and asked for clarification when necessary.Concurrently with the questionnaire study, biological samples were taken both from interviewed farmers’ duck flocks and interviewed transporters’ vehicles (boats or trucks). Oropharyngeal swabs were collected by the local veterinary services from 60 birds per flock and 20 samples of fresh faeces were taken from each transport vehicle. Oropharyngeal swabs were collected rather than cloacal swabs, as it was previously suggested that they are more sensitive to detect the presence of HPAI H5N1 virus in ducks , 24, 25.2 test and Fisher’s Exact test). A logistic regression analysis was performed to identify the variables that were associated with an increased risk of influenza A infection of the duck flocks. The outcome variable was the influenza A infection status of the flock. A flock was considered positive if at least one sample out of 60 tested positive for influenza A. Explanatory variables included a total of 51 farm-level variables derived from the data collected via the questionnaires. First, potential risk factors were screened for statistically significant association with influenza A infection status using univariable logistic regression based on the likelihood ratio test. Variables significant at p < 0.2 were retained for the multivariable analysis. They were manually added to a logistic regression model using a stepwise forward selection procedure. We used the Akaike Information Criterion (AIC) to select the model best fitting the data. The best model was considered to be the most parsimonious model whose AIC was less than two points greater than that of the model associated with the smallest AIC [Questionnaire results were summarised using descriptive statistical indicators  and differences between groups were tested using standard statistical tests appropriate for the type of variables  in order to increase the egg production while keeping the scavenging capacity and disease resistance. All farmers kept ducks for egg production only. Thirty-one farmers (70%) sourced their flocks as day-old ducklings from a hatchery, while the remainder purchased adult ducks from another duck farmer or a trader . All duck flocks had been vaccinated against HPAI subtype H5N1 virus at least once, using either a vaccine produced by a Vietnamese company  or a vacEach of the three stakeholder groups  had specific sources of income, as presented in While all paddy owners reported letting their paddies to FGD farmers after most harvests, 65% (15/23) rated this income as “not important” and none rated it as “very important”. The sale of rice was the main source of income for most of the paddy owners . Around 39% (9/23) reported that they systematically give the money received from the farmers to “charities”, which refers to communal associations who take care of disadvantaged people, run ambulance services or maintain infrastructures such as roads and bridges. Twelve paddy owners provided detailed data on the income obtained from their rice paddies. The annual income per hectare from the sale of the rice and from the rice paddy rental ranged from 30 to 80 million VND  and from 0.45 to 1.5 million VND (20 to 70 USD), respectively. On average, the latter represented 2.5% of the income generated by the former.The location of the 219 unique sites reported by the 44 farmers during the interviews is shown on Figs Four types of contacts between FGD flocks were identified by the stakeholders: (i) direct outdoors: two flocks accidentally mix during scavenging, on the waterways or in the night enclosures; (ii) indirect outdoors: two flocks use the same paddy sequentially during the same harvest season with a maximum of two days between the departure of the first flock and the arrival of the second; (iii) direct during transport: two or more flocks are transported together in the same vehicle to reduce the cost associated with the journey; and (iv) indirect during transport: two flocks are transported sequentially in the same vehicle without cleaning and disinfection of the vehicle between the two journeys. The nature and frequency of the contacts between FGD flocks, as reported by farmers and paddy owners, are summarised in 2 test, p-value < 0.01). Indirect contacts between FGD flocks were very frequent as transport vehicles are rarely cleaned and disinfected. Only three transporters (18%) reported washing the inside of their vehicle with water after each journey, while half of the interviewees reported cleaning their vehicle every six months or less often. Three transporters (18%) reported disinfecting their vehicle, using a commercial combination of glutaraldehyde and benzalkonium. The frequency of disinfection ranged from “after each journey” for one of them to “every other month” for the two others.The perception in relation to shared use of vehicles by at least two flocks differed between farmers and transporters, in that the former reported sharing vehicles during 10% (16/162) of the journeys and the latter 31% (500/1600)  had at least one pooled sample positive for the influenza A virus matrix gene. All samples (duck flocks and vehicles) were negative for H5 virus subtype.Eight explanatory variables were associated with the influenza A status of the flock in the univariable analysis . FollowiAlthough the use of the free-grazing duck production system has been on the decline in South-East Asia for the last three decades as a result of intensification of agricultural production, increasing cost of labour and increasing pesticide use , the FGDGenerally, the description of the system revealed a number of flaws related to biosecurity practices in the free grazing duck production, which represent opportunities for the circulation of pathogens between FGD flocks. The long duration of the production cycle (up to two years according to our results) and the complexity of the production system are also likely to be important factors in the epidemiology of avian diseases in general, and HPAI in particular. The analysis of the flocks’ movements showed that these flocks are very mobile within the MRD, as indicated in previous studies , 36. TraBy boat was the most common transport means used by duck farmers due to the well-developed canal network, in contrast to the poor road network in our study area. Contacts between duck flocks during transport were reported to happen regularly. In addition, cleaning and disinfection of the vehicles was found to be insufficient, increasing the risk of pathogen transmission between flocks, as previously suggested , 40, 41.Overall, the interviews with the stakeholders showed that the long-distance FGD production system is characterised by a highly connected contact network, where the connections of a farmer to rice paddy owners, transporters, traders and other farmers are critical for the success of their business. For instance, familiarity with the paddy owners accounted for a third of the reasons influencing farmers’ choice of scavenging sites. Annual variation in rainfall and floods, intensification of rice cultivation, increasing urbanisation as well as competition between duck farmers limit the availability of post-harvest rice paddies for duck scavenging. In this respect, farmers with established experience and those who were well connected appeared more successful at obtaining sufficient access to rice paddies all year round and thereby being able to reduce the costs of long-distance journeys across the river delta. From the paddy owners’ point of view, two thirds of the interviewees reported that the income from the paddy rental was not important for their business. The benefits of renting out the paddies are mainly in kind from ducks feeding on a range of rice pests such as golden snails  and fertIn our study, 31% of the flocks tested positive for influenza A viruses, indicating a high level of circulation of these viruses. Significant predictors of the influenza A status of the flocks were the age and size of the flocks as well as the location at the time of sampling relative to the home location. No flocks tested positive for H5 subtype viruses. Analyses of outbreak data have highlighted the seasonality of H5N1 outbreaks in the South of Vietnam, with a marked high-risk season between December and February , 46. HowPoultry vaccination programmes against HPAI viruses have been implemented in Vietnam since 2005. In our study, all free-grazing duck flocks were vaccinated, as previously reported in other provinces of the MRD , 36. It According to the multivariable analysis, flocks which were not in their home commune at the time of sampling were more likely to be positive for influenza A infection than flocks which were at home. Also, influenza A positive flocks had travelled more recently than negative flocks as shown by the univariable analysis. Visiting flocks and flocks which had travelled recently have experienced stressful transport conditions, which may have affected the immunity of the birds and therefore explain the increased odds of influenza A infection, as reported elsewhere . FarmersAvian species present on the rice fields at the time of the survey included egret, heron and pond heron species which have been reported to be susceptible to HPAI infection  but therThe main difficulty when working on long-distance FGD flocks is their recruitment. Some previous studies based their sampling on local poultry flock registers from local veterinary services ). However, such an approach does not allow for the recruitment of visiting duck flocks, which would mean preventing the sample to fully represent the long-distance FGD population present within the study area at the time of a survey. As described in other recent publications , the conIt is difficult to assess whether the long-distance FGD population that was present at the time of the study was representative of the whole region as no large-scale study has tried to describe the spatio-temporal distribution of the long-distance FGD flocks so far. The province of An Giang has a duck density of 12 heads per hectare of rice fields which is comparable to the average density in the MRD  and the production system described in our study presents many common features with those reported for other provinces of the MRD, as discussed above. Therefore, the province of An Giang can be considered as a rice and duck producing region representative of the MRD. However, it has to be kept in mind that the province has a proportionally higher surface of rice fields than the rest of the MRD , which cThe use of questionnaires probably introduced some bias to the data collected from the different stakeholders: recall bias as well as bias due to social acceptability of the answers might have occurred. Even though the questions related to past journeys and activities focused on those performed with the current flock, some parts of the journey will have been already several months old, potentially leading to recall biases regarding different parameters such as duration of the transport and occurrence of contacts with other flocks for instance. Last, technical constraints limited the number of stakeholders recruited in the biological study . Indeed, long-distance FGD flocks are often transported to different districts and provinces see  to folloThe free-grazing duck production system is characterised by intense and diverse contacts between duck flocks as well as long-distance journeys potentially leading to the spread of pathogens. However, it provides a major source of income for a large number of stakeholders in many countries in South-East Asia. It is therefore paramount to examine this system carefully, assess its contribution to the maintenance of influenza viruses and generate realistic and acceptable recommendations for risk management without threatening the livelihood of thousands of farmers. This work provides a detailed description of the stakeholders involved in this system and of factors that contribute to sustaining local and regional circulation of influenza viruses. The findings can be used to develop risk assessment models of influenza virus spread to develop better biosecurity practices ultimately leading to better animal health, sustainable animal production and reliable income for the farmers involved.S1 File(PDF)Click here for additional data file.S2 File(PDF)Click here for additional data file.S3 File(PDF)Click here for additional data file.S4 File(TXT)Click here for additional data file.S5 File(TXT)Click here for additional data file.S6 File(TXT)Click here for additional data file.S7 File(TXT)Click here for additional data file.


The first hypothesis claims that morphology organizes whole words into morphological families and series, while the second sets morphology at a pre-lexical level, with morphemes standing as access units to the mental lexicon. The present paper examines more deeply the notion of morphological salience and its implications for theories and models of morphological processing.This paper deals with the impact of the salience of complex words and their constituent parts on lexical access. While almost 40 years of psycholinguistic studies have focused on the relevance of morphological structure for word recognition, little attention has been devoted to the relationship between the word as a whole unit and its constituent morphemes. Depending on the theoretical approach adopted, complex words have been seen either in the light of their paradigmatic environment , or in terms of their internal structure . These two competing views have strongly determined the choice of experimental factors manipulated in studies on morphological processing . Moreover, work on various kinds of more or less segmentable items (from genuinely morphologically complex words like  In linguistics, the semiotic notion of salience has been applied to inflectional and derivational morphology from the 1980s onward, mainly in the framework of ‘Natural Morphology’  approach, salience is one of the factors that contribute to the ‘naturalness’ of a linguistic item or structure, which in turn determines how easily it can be processed by the human brain , p. 11. Two kinds of factors are supposed to determine the salience of the components of a morphologically complex word, thereby affecting the recognition of its morphological structure. The first group of factors relates to the strength of the mental representation of the whole complex word and its components, which is thought to be modulated by the following variables: (i) (token and type) frequency; (ii) numerosity  and morpho-semantic transparency , coded at a sublexical level and processing complex words implies passing through a decomposition mechanism that strips off the affix in order to isolate the stem, so that the morphemic nature of the remaining letters can be checked by the system. Access to word representations  thus operates via the pre-activation of their constituent morphemes. This mechanism is exemplified in the interactive activation model developed by morphomic level and have the function of organizing the lexicon in terms of morphological families. In processing terms, the recognition of any complex word initially triggers the activation of all word forms that can match with it, and a competition is then engaged between the pre-activated forms until the right lexical representation reaches its recognition threshold (determined by its surface frequency). During this competition phase, competitors send positive activation to their respective base lexemes, which send positive activation back to them. According to this account, exemplified in the supralexical model of According to the second view, called the “whole-word perspective,” morphology is represented at the interface of word and semantic representations and derives from lexemes as introduced by Both sublexical and supralexical approaches to morphological processing integrate a morphological level of processing, however, they differ with respect to the location of morphological units within the architecture of the mental lexicon, as well as the content of these units, both of which properties define their role of such units in word processing. According to the sublexical view, morphemic units stand as access units, situated between the letter/syllable level and the word level: consequently, these units can only correspond to concrete letter clusters that constitute words  and are insensitive to any semantic characteristics of words  or to their lexical environment (in terms of orthographic neighborhood or family size). On the other hand, the supralexical view situates morphological units above the word-forms and before the semantic units. These intermediate units are supposed to be abstract enough to tolerate form variations induced by the processes of derivation and inflection. This implies that a morphemic unit does not need to exist in the real world in order to be coded in long-term memory, but that its existence/emergence depends on the interactions between the word-form and the semantic levels; it also implies that all morphemes of a given language are not necessarily represented within the mental lexicon: unknown words, neologisms, hapaxes, and nonce words are not necessarily connected with morphemic units.However, determining which factors are involved in lexical access and which factors influence the organization of the mental lexicon are issues that have not been sufficiently explored so far, although they are highly relevant to lexical modeling. We suggest that it is crucial to keep these issues apart: the factors driving the early stages of processing are likely to be different from those coded in long-term memory. In our view, observing sensitivity to the internal structure of complex words can be interpreted as reflecting a central role of morphemes in lexical access, but the factors influencing lexical access  are likely to be different from those organizing the mental lexicon properly .Numerous psycholinguistic studies have addressed the issue of morphological processing during word recognition. Using the lexical decision task (in which participants must make a decision about whether combinations of letters are words or not), these studies explore the factors influencing the processing of complex words as well as their internal structure. Among these factors, surface frequency  and base frequency (the token or lemma frequency of a root), which measure the statistical occurrence of complex words, have been extensively studied in languages for which lexical databases are available e.g., . These shunter facilitating the recognition of its morphologically related target hunt) differing significantly from formal  and meaning relationships , have led the authors to conclude that independent morphological representations are coded somewhere within the mental lexicon in a similar way to orthographic, phonological, and semantic representations. Therefore, until the beginning of the 21st century, experimental studies considered morphological effects to result from systematic form-meaning correlations.Many studies have lent further support to the decompositional approach to complex word recognition, using priming, and, more recently, masked priming . In maskHowever, between 2000 and 2005, many masked priming studies started to focus exclusively on formal aspects of complex words, that is on their so-called ‘morphological surface structure’ e.g., , p. 1091corner, which cannot be decomposed into the morphemes corn- and -er). Using the masked priming paradigm, it was shown that pseudo-derived word primes  as well as pseudo-derived non-word primes  were able to produce significant priming effects on the recognition times of their pseudo-base . Moreover, the studies found both the quality and the magnitude of these priming effects to be comparable to the priming effects produced by genuinely derived words . Finally, the systematic use of orthographic control primes  in these studies showed that these surface morphological effects could not be assimilated to mere formal overlap. Consequently, these effects were taken to result exclusively from the surface morphological structure of the primes.While the priming study carried out by sport- combined with the suffix -ation to produce sport-ation) were used as primes. The data revealed that pseudo-word primes like sportation facilitate the recognition of their base  with no difference from the facilitation effects obtained using transparent primes .Further masked priming studies have tested the effect of pseudo-derived non-words primes, and systematically found facilitation effects, lending strong support to the notion of an early mechanism of form decomposition that is applied to all morphologically structured stimuli . In gene1; Finnish: Studies showing masked morphological priming effects without semantic relationships have been broadly replicated in various languages  in order to test the flexibility of the morpho-orthographic segmentation process described by decompositional models. Once again, their results were interpreted as demonstrating the robustness of the decomposition process in the case of various orthographic alterations in semantically related  as well as unrelated prime-target pairs .All these studies led the authors to conclude that the morphological decomposition mechanism transcends stimuli and languages. A review by The results reported in the previous section have largely been taken to support a decompositional approach. However, in our view, there are also studies that are inconsistent with this interpretation.artist-artist) in order to enhance semantic facilitation  than for opaque pairs . prénom ‘name’) and non-words  in French. They showed that when compared to unrelated primes, both prefixed words and prefixed non-words facilitate target recognition. However, when compared to an orthographic non-word condition , pseudoprefixed primes do not differ from orthographic primes, suggesting a strong formal component in surface morphological priming with semantics. Finally, Some masked priming studies have indeed demonstrated very early semantic influences in word recognition. on e.g., . They foamitié - ami ‘friendship-friend’; Low SF amiable - ami ‘friendly friend’) and found an interaction between priming effects and the prime SF (Experiment1), but no effect for the BF. Experiments 1 and 3 demonstrated that the SF of morphological primes affects the degree of morphological priming: high SF derived primes show significant facilitation relative to orthographic control primes , whereas low SF primes do not. The results of Experiment 4 revealed, by contrast, that BF does not influence the size of morphological priming on free root targets. Suffixed word primes facilitate the processing of free root targets with low and high BF. These data support the relevance of the whole word form (as reflected by SF) over its parts, since the BF does not interact with priming. More recently, brutal – brute vs. adorable – adore vs. agitatal – agitate, respectively). They found facilitation effects on all three conditions relative to each of the three unrelated baselines . In our view, the lack of orthographic controls that could separate formal from morphological effects constitutes a serious obstacle for the interpretation of their data, which thus only show that related primes facilitate target recognition. Furthermore, it is very surprising to see that despite an interpretation in favor of the decompositional hypothesis, these authors did not test BF effects, which should strongly determine decomposition and therefore the magnitude of priming effects.Other studies have explored the interaction of frequency effects with paradigmatic factors such as affix type and suffix productivity. In a series of lexical decision task experiments, cleaner, hunter, biker).Further evidence against the decompositional hypothesis comes from the studies conducted by etr-paintpain) to effects of primes with TL outside the morpheme boundary . Although priming effects were obtained independently of the position of the TL (at the morpheme boundary or not), this has not lead researchers to call the decompositional approach into question  that disrupt the morpho-orthographic structure. Masked priming experiments have compared the effects of complex non-word primes with TL at a morpheme boundary , no morphemic units should be activated and therefore no priming is expected. And even if a sublexical mechanism was able to recode letter position (as suggested by niter – paintpa) than those with disrupted morpheme boundaries (as in etr – paintpain). Moreover, the mechanism of letter recoding must depend on a match between the prime and a whole-word representation coded at the word form level, which implies that the whole word guides access rather than its parts. In our view, rather than supporting decomposition, the data obtained with non-words constitute strong evidence in favor of holistic processing of the primes and, by extension, of all the stimuli, whatever their surface structure. We take the fact that words with jumbled letters can induce priming effects to provide sufficient grounds to reject the claim by Amenta and Crepaldi, according to which non-word effects cannot result from lexical activation. We interpret these data obtained with non-words in the opposite way: the pattern of systematic form-meaning correspondences that we call morphology . By contrast, the second experiment took as targets less frequent inflected forms , thus reversing the typical design in which the target corresponds to the base, i.e., the member of the morphological family that already has the greatest residual activation because of its frequency. Under the conditions of the second experiment, only small pseudo-family-size verbs induce repetition and morphological priming, for both frequent and infrequent inflections, whereas large pseudo-family-size verbs fail to induce repetition or morphological priming. Moreover, inflectional priming for small pseudo-families verbs does not differ for the two types of primes, i.e., frequent or not frequent inflections. These data added new evidence to the view that both the lexical frequency of word-forms and relative frequencies between primes and targets influence morphological processing.Talking about morphological links implies taking into account another factor whose impact on complex word recognition has been demonstrated and replicated in various languages: morphological family size , the later is determined by qualitative variables  resulting from morphological relationships shared by words.As mentioned above, the empirical data from the psycholinguistic literature so far have mostly been interpreted in favor of a decompositional view, which reduces morphological effects to formal effects. But if morphological salience only relates to the surface structure of words, this salience, which seems to guide the early stages of word recognition, cannot be called ‘morphological’ since morphological relationships are, by definition, pairings of form, and meaning . On the The present review has presented and discussed the factors which guide the processing and the lexical representation of morphologically complex words, and has given an overview of the highly controversial debate on possible interpretations of the results obtained so far. More specifically, we have shown that the issue of the relative prominence of the whole word and its morphological components has been overshadowed by the fact that psycholinguistic research has progressively focused on purely formal and superficial features of words, drawing researchers’ attention away from what morphology really is: systematic mappings between form and meaning. While we do not deny that formal features can play a role in word processing, an account of the general mechanisms of lexical access also needs to consider the perceptual and functional salience of lexical and morphological items.We hold that results obtained on the basis of masked priming are in line with holistic models of lexical architecture or models in which morphology emerges from the systematic overlap between forms and meanings . In suchCertainly, the notion of salience refers primarily to formal aspects, because the perceptual body of the morpheme is necessarily the starting point of the processing mechanism. However, the notion of salience makes sense for complex word processing only if the form it refers to is associated with a meaning or function. Salience, in other words, is a property of the morpheme , not simply of a phonetic or graphemic chain. We suggest that re-focusing attention on salience, rather than on purely formal aspects, could lead to more interesting interpretations of the data observed so far in the psycholinguistic literature.HG: Psycholinguistic contribution; SD: Linguistic contribution.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.


When using the conventional two-coil inductive link for the simultaneous wireless power and data transmissions in implantable biomedical sensor devices, the strong power carrier could overwhelm the uplink data signal and even saturate the external uplink receiver. To address this problem, we propose a new magnetic-balanced inductive link for our implantable glaucoma treatment device. In this inductive link, an extra coil is specially added for the uplink receiving. The strong power carrier interference is minimized to approach zero by balanced canceling of the magnetic field of the external power coil. The implant coil is shared by the wireless power harvesting and the uplink data transmitting. Two carriers  are used for the wireless power transmission and the uplink data transmission separately. In the experiments, the prototype of this link achieves as high as 65.72 dB improvement of the signal-to-interference ratio (SIR) compared with the conventional two-coil inductive link. Benefiting from the significant improvement of SIR, the implant transmitter costs only 0.2 mW of power carrying 50 kbps of binary phase shift keying data and gets a bit error rate of 1 × 10 Implantable biomedical sensor systems will play an important role in future medical diagnoses and treatments ,2. The bk = 0.5∼0.2) and can hardly achieve reliable transmission under weak coupling. To achieve reliable uplink data transmission under weak coupling, a new modulation method was recently proposed in [Conventionally, by using load-shift keying (LSK) in the uplink, power and uplink data are simultaneously transmitted through a closely-coupled coil pair for implantable biomedical sensor systems ,6,7. Theposed in , named pTo both enhance the reliability under ultra-weak coupling and reduce the impact of the uplink data transmission on WPT, a dual-carrier inductive link scheme is proposed in . In thisIn this paper, to address the aforementioned problems, we propose a magnetic-balanced inductive link for our intraocular biomedical sensor device, as seen in The rest of the paper is organized as follows.  tissues . The uplAs seen in d) denotes the distance between the external power coil and the implant coil. The distance (The positions of the three coils and their notations are demonstrated in d) could vary from 15 mm to 40 mm due to the different facial forms and different ways of wearing glasses, which is considered as the operating range of our system.In our intraocular biomedical sensor device, the coil sizes are limited by the application requirements, and the size of the implant coil is decided by the doctors from our cooperative hospital. To avoid blocking the eyesight, the implant coil is designed to surround the periphery of the cornea hidden behind the eyelid. The external power coil will be embedded inside the glasses frame in front of and around one eye. The equivalent circuit model of the coupling circuit is shown in s is the Laplacian.By applying the mesh-current approach on the equivalent circuit model, Equations –4) are  are 4) aEquations –4) can  can 4) cSince the external receiver acquires the uplink signal from the coil Equation . EquatioEquation  could beEquation  is omittInstead of fully expanding Equation , we explEquation  could beEquation . Since LEquation  can be rEquation . AccordiEquation , the uplEquation , the upld) is small. In addition, we optimize the turn number  versus different skew distance (d) is small as seen for the red line  in our operating range. It shows that higher resistance of Through calculating and comparing Equation , where VThe evaluation of coil misalignment effects is important in the design of inductive links for implantable sensor devices. In our intraocular sensor device, the implant coil could also be moved due to the movement of the eyeball and the displacement of the glasses.d) is 20 mm. The directions of the X axis and Y axis are illustrated in We implemented our prototype using discrete components and off-the-shelf chips to prove the feasibility of the future integrated circuit (IC) design, as shown in duced in . As seend), as d). The SIR and SNR are measured before the uplink receiving filter by using a spectrum analyzer . When measuring the SIR and SNR, the power delivered to the load (PDL) is kept as constant as 5 mW by adjusting the transmitting power of the class-E power amplifier (PA). When the coil separation (d) is 20 mm, the SIR before the uplink receiving filter is as large as d) is as large as 60 mm (the maximum coil separation of our prototype to supply 5 mW of power to the load wirelessly), the SNR is about 14 dB, which is still adequate to achieve BPSK demodulation, and the SIR is about −38 dB, which can be improved by a fourth-order Butterworth low-pass filter. In addition, the SNR decreases when ous work , the SIRd) is within the operating range (15–40 mm); thus, the BER is below d is enlarged to 60 mm, the uplink is still reliable, and the measured BER is about To measure the bit error rate (BER), a pseudo-random data sequence is transmitted continuously at a data rate of 50 kbps in half an hour for each measurement. When measuring the BER, the PDL is kept as constant as 5 mW by adjusting the transmitting power of the class-E PA. In the experiments, no bit error occurs in half an hour when the coil separation  through using the method in . To provIn order to assess the impacts of tissue on the inductive link, the implant coil is wrapped in 10 mm-thick beef tissue as seen in d). The simulated coupling coefficients are in good agreement with the measured results. In order to assess the radio frequency (RF) exposure safety on the human body, we used the ANSYS HFSS electromagnetic simulation suite to calculate the specific absorption rate (SAR). The simulation results show that the maximal local SAR in tissues is about three orders lower than the basic restriction of 2 W/kg .In addition, there could be temperature increase in the human body due to the power consumed by the implant coil and implant circuits. According to the comprehensive thermal analysis on an intraocular implant , our devA comparison of the proposed inductive link system with other published works is shown in Compared with the conventional LSK method ,33, the Compared with the multiple coil pair method , our worThe work in  is our pThis paper proposes a new magnetically-balanced inductive link for the simultaneous power and uplink data transmissions under ultra-weak coupling. An extra external coil is specially added for the uplink receiving. The power carrier interference is minimized to approach zero by balanced canceling of the magnetic field of the power carrier. We optimize the coil parameters to achieve higher SIR based on the modeling of the mutual inductance. We also optimize the circuit parameter to minimize the impact of the uplink data transmission on the PTE. We use our intraocular sensor device as an application example to present the modeling and the optimization procedure in detail. The prototype achieves as high as a 65.72-dB improvement of the SIR compared with the conventional two-coil inductive link. Benefiting from this substantial improvement of SIR, the inductive link achieves a 1 × 10


Two-dimensional gel electrophoresis (2DE) is a well-developed, high-resolution technology to separate complex mixtures of proteins. This technique has been widely used for the past four decades, and has played a vital part in the developmental history of proteomics. The advantages and limitations of 2DE in proteomics research have been reviewed  in the protein sample , and that after-IEF equilibration coats all proteins with SDS, thereby improving protein migration in SDS-PAGE  in the 2DE patterns cannot be avoided owing to the change in molecular masses of reduced protein spots. Optimizing the sample preparation protocol to contain a reduction and alkylation step is a better option. For example, the Bio-Rad Laboratory showed that reduction alkylation treatment during sample preparation led to improved 2DE maps, significantly reducing horizontal streaking , and the results will be more reproducible.In summary, it is debatable whether the reduction and alkylation of proteins between the two dimensions of 2DE is necessary. Based on its widespread use in laboratories, the routine 2DE workflow still needs to be optimized regarding this step. We strongly suggest performing reduction and alkylation prior to IEF. Currently, protein sample preparation is usually conducted at reducing conditions in the presence of DTT; therefore, adding protein alkylation step to the sample preparation process will not increase the complexity or duration of the protocol. The application of reducing and alkylating reagents (working in concert in the extraction medium) or commercial kits should be optimized according to protein samples, especially the efficiency of protein alkylation during sample preparation. We also recommend that the additional equilibration step between the two dimensions is omitted if the reduction and alkylation of proteins has been incorporated in sample preparation, and that sample preparation protocols are optimized to ensure that the disulfide reduction is completed. This modification would reduce the potential loss of proteins and the “blurring” of focused spots that often occurs in 2DE gels.WW: Conceived the paper. WW, XW, and CX: Wrote the paper.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.


A breakthrough in the high-pressure structures of Ba based on a full exploitation of aperiodic symmetry is discussed in the general context of the ‘complex structures of simple metals’. Crystal structures of elements at high pressure (HP) are crucial for understanding the fundamental physics of condensed matter under extreme conditions and the basics of chemical bonding  periodicity. Finding true regularity in the n-dimensional arrangement of atoms can be done reliably using modern computing algorithms, avoiding groundless speculation and misleading interpretations of phenomena.Understanding complex phenomena requires high-precision data, resolving the finest details of the experimental picture. High-pressure crystallography has now reached a level where diffraction data allow the solution of HP structures to a similar accuracy as under ambient conditions. The resulting HP data are very robust and even sufficient to solve structures with et al.  model and an incommensurately modulated (IM) model. Normally, experimental diffraction data allow one to directly recognize a composite structure, which is characterized by periodicity of both the host and guest components. One can immediately recognize a fit to the COMP model from the full experimental diffraction data set, if two separate groups of reflections, which belong to the host and guest components, can be found. In contrast, aperiodicity originates from the irrational ratio of one or more of their unit cell parameters. If the two groups of reflections have an intersection, then both IM and COMP models must be considered and refined accurately, in order to select the correct model. Such an analysis is presented by Arakcheeva  al. 2017 for the  al. 2017.i.e. the disappearance of any interaction between both host/guest and guest/guest atoms. If, however, the IM model is adopted, this phenomenon is instead interpreted as the disappearance of satellite reflections, i.e. the crystal structure becomes periodic with a new equilibrium in the interactions between host and guest atoms. Hence different models lead to completely opposite conclusions. This shows once again how critically important the reliability of crystallographic data and their careful evaluation are for obtaining correct insight into the physical and chemical properties of compounds and materials.The authors mention one more intriguing consequence of selecting the correct model for host–guest structures. If the COMP model is assumed, the temperature/pressure-dependent vanishing of reflections related to the guest component leads to the conclusion that there is one-dimensional melting of this chain component, et al. (2017The article additionally presents the solution of two slightly different Ba IVb phases and gives some hints for the critical review of the solution of previously published structures of the same compound at higher and lower pressures. One could expect that the model developed by Arakcheeva  al. 2017 can also


To solve the navigation accuracy problems of multi-Unmanned Underwater Vehicles (multi-UUVs) in the polar region, a polar cooperative navigation algorithm for multi-UUVs considering communication delays is proposed in this paper. UUVs are important pieces of equipment in ocean engineering for marine development. For UUVs to complete missions, precise navigation is necessary. It is difficult for UUVs to establish true headings because of the rapid convergence of Earth meridians and the severe polar environment. Based on the polar grid navigation algorithm, UUV navigation in the polar region can be accomplished with the Strapdown Inertial Navigation System (SINS) in the grid frame. To save costs, a leader-follower type of system is introduced in this paper. The leader UUV helps the follower UUVs to achieve high navigation accuracy. Follower UUVs correct their own states based on the information sent by the leader UUV and the relative position measured by ultra-short baseline (USBL) acoustic positioning. The underwater acoustic communication delay is quantized by the model. In this paper, considering underwater acoustic communication delay, the conventional adaptive Kalman filter (AKF) is modified to adapt to polar cooperative navigation. The results demonstrate that the polar cooperative navigation algorithm for multi-UUVs that considers communication delays can effectively navigate the sailing of multi-UUVs in the polar region. Unmanned Underwater Vehicles (UUV) are important pieces of equipment used in ocean engineering for marine development and have made great technological progress in recent years. UUVs can accomplish important missions, such as marine surveying, plane crash searches, etc. ,2,3,4. TThe severe natural environment and extreme navigation environment have caused many challenges to UUV missions in the polar region. Strapdown Inertial Navigation Systems (SINS) are the most widely used navigation device among the UUVs, since the SINS navigate UUVs autonomously. Multi-UUVs are faced with the same problems as single UUVs in the polar region, such as calculation overflow and error magnification, which cause the conventional north-oriented SINS to be invalid in the polar region . The dirTeamwork is an essential part of work and school activities. It can improve work efficiency greatly, which is also true for UUVs. The intelligence development of a single UUV is limited, but it can be solved by multi-UUV cooperation. Multi-UUVs have a great advantage over a single UUV, especially in terms of time and efficiency. In general, there are two cooperative multi-UUV navigation types: the parallel type and the leader-follower type .The cooperative navigation system, developed by the Virginia Tech research team, is a typical parallel UUV cooperative navigation system, in which the UUV sends information to its surrounding neighbors in the form of an acoustic broadcast . The mobMany novel algorithms have been proposed to achieve the cooperative navigation of multi-robots in non-polar regions ,13,14, bTo solve navigation problems of multi-UUVs in the polar region, a polar cooperative navigation algorithm for multi-UUVs that considers communication delays is proposed in this paper. The development of the polar cooperative navigation algorithm and modification of the adaptive Kalman filter (AKF) based on communication delays are the two main contributions of this paper. Based on this algorithm, cooperative navigation is achieved among the leader-follower UUVs team in the polar region. Although the follower UUVs are equipped with low-precision navigation devices, they can achieve high navigation accuracy with this algorithm. The following sections are arranged as follows. The formation configuration, acoustic communication delay and overall process of the polar cooperative navigation algorithm are discussed in Different formation configurations and acoustic communication modes will have different effects on the polar cooperative navigation system of multi-UUVs. Under the premise of ensuring navigation accuracy, it is our goal to reduce costs and improve efficiency as much as possible. This section will focus on the formation configuration, underwater acoustic communication and overall process of the polar cooperative navigation system.Typical formation configurations of multi-UUVs mainly include the parallel type and the leader-follower type. In the parallel type, all the UUVs are required to have the same configuration. This means that all the UUVs should be equipped with high-precision navigation devices, and each UUV communicates with its neighbor UUVs. The number of multi-UUVs in a parallel, polar cooperative navigation system is limited by the underwater acoustic communication bandwidth. A parallel cooperative navigation system of multi-UUVs is shown in L is the leader UUV, and UUVF1, UUVF2, UUVF3, UUVF4 are the follower UUVs.Unlike the parallel type, the configuration of each UUV in the leader-follower type can be different. The leader UUV is equipped with high-precision navigation devices, and the follower UUVs are equipped with low-precision navigation devices, which can reduce costs. In addition, the underwater acoustic communication is only required between the leader UUV and follower UUVs. There is no need for follower UUVs to communicate with each other. The limitations caused by underwater acoustic communication bandwidth are greatly reduced. A typical leader-follower cooperative navigation system usually includes a single leader or double leaders. A leader-follower cooperative navigation system of multi-UUVs is shown in From the viewpoint of the underwater acoustic communication bandwidth and navigation equipment costs, the leader-follower type is superior to the parallel type. The leader UUV is equipped with high-precision navigation devices, including SINS, OCTANS , Doppler Velocity Log (DVL), depth meters and USBL. The follower UUVs are equipped with low-precision navigation devices only, including SINS, DVL, depth meters and USBL, to reduce costs.Due to the extreme natural and navigation environment underwater in the polar region, communication becomes one of the difficulties in polar cooperative navigation of multi-UUVs. As the radio signal cannot transmit under deep water, underwater acoustic communication becomes the first choice for polar cooperative navigation systems. Underwater acoustic transducers are most widely used in underwater acoustic communication. Information is transmitted through sound waves rather than radio waves. Thus, underwater acoustic communication is less efficient than radio communication.The working principles of underwater acoustic communication can be described as follows: First, information is converted into an electrical signal by an electrical transmitter. Second, after digital processing by an encoder, the transducer converts the electrical signal into an acoustic signal. Third, the acoustic signal propagates through the medium of water and propagates the information to the receiving transducer. In this case, the acoustic signal is converted into an electrical signal. Finally, after the digital signal is deciphered by the decoder, the information is converted to sound, text or picture by the electrical receiver.According to the characters of underwater acoustic communication, there will be underwater acoustic delays in the propagation of underwater acoustics. These underwater acoustic delays usually consist of an underwater acoustic detection delay and an underwater communication delay. The underwater acoustic detection delay mainly depends on the detection equipment itself, and its value is relatively fixed and small. The underwater acoustic communication delay is caused by the high complexity of signal processing and the limitations from underwater bandwidth and low transmission rate. There will be a communication delay when the leader UUV sends its information to the follower UUVs in the polar cooperative navigation of multi-UUVs. As the efficiency of the underwater acoustic equipment varies with time and the distance between the leader UUV and the follower UUVs, the underwater acoustic communication delay is a random value . AccordiBased on the above analysis, the leader-follower type is superior to the parallel type of navigation system. Like the formation configuration shown in Both the leader UUV and the follower UUVs are equipped with high-precision timing clocks. The clock synchronization is achieved before the multi-UUVs start their mission. The leader UUV sends information to the follower UUV through underwater acoustic communication, including the time, attitude, velocity, position of the leader UUV and the relative position between the leader UUV and follower UUV. The relative distance and orientation information between the leader UUV and follower UUV can be measured by the leader UUV through USBL. Through the combination of the information sent by the leader UUV, and information from its own navigation devices, the motion states of a follower UUV can be estimated accurately.In the leader-follower polar cooperative navigation system, the leader UUV is equipped with high-precision navigation devices, including a high-precision SINS, OCTANS, DVL, USBL and depth meter. Based on the polar grid navigation algorithm proposed in ref. , the leaIn the polar region, there will be calculation overflow and error magnification of the navigation in conventional north-oriented SINS. The direction information and the orientation information cannot be distinguished in conventional wander-oriented SINS. Therefore, conventional SINS is invalid in the polar region. The polar grid navigation algorithm proposed in  can solvInertial frame—Navigation frame—Body frame of UUV—Geographic frame—Earth centered earth fixed frame—Grid frame—Body frame of DVL—Acoustic array frame of USBL—The relationships among the frames are important parts of the SINS. To simplify the description, the frames involved in this paper are briefly represented by the following symbols: Based on the polar grid navigation algorithm proposed in ref.  and in tSubtracting Equation (2) from Equation (3), the attitude error equation of the follower UUV in the Based on the Subtracting Equation (8) from Equation (9) and ignoring the second-order small terms, the velocity error equation of the follower UUV can be expressed as follows:te noise .Due to the rapid convergence of the Earth’s meridians and the meridians converging in the poles, the conventional latitude and longitude representation is no longer applicable in the polar region. In the polar grid navigation algorithm, the coordinates in the Based on the By subtracting Equation (11) from Equation (12), the position error equation of the follower UUV can be described as follows:Because of the accumulative errors in the SINS and the low-precision navigation devices, there will be cumulative errors in the follower UUV. According to the Doppler Effect, the DVL can measure the velocity of the UUV. With the help of the DVL, the follower UUV can correct its velocity to improve the navigation accuracy. However, there are installation errors, scale factor errors, and random measurement errors affecting the accuracy of the DVL, because of the characteristics of the DVL. The output of the DVL can be described in the The USBL can obtain the relative position between the leader UUV and a follower UUV through the time that the acoustic signal arrives at the acoustic element. Since the size of the USBL acoustic array is particularly small, it is easy to choose a position on the carrier with low noise. Therefore, the application of the USBL is flexible and convenient.The USBL is mainly composed of a transducer, an acoustic emission array, a transponder and an acoustic receiving array. The acoustic emission array and acoustic receiving array are fixed in the transducer to form the acoustic array. The mutual positions between the acoustic elements constituting the acoustic array have been precisely determined. The transponder is installed on the follower UUV. The phase comparison method is used in this system. The orientation of the transponder in the acoustic array frame is obtained by measuring the phase difference of the acoustic element. The relative distance between the leader UUV and the follower UUV is calculated by the propagation time of the acoustic signal in water. According to the above information, the relative position between the leader UUV and follower UUV can be determined.From Equations (18)–(20), The main factors that affect the accuracy of the USBL are the error of the system, a measurement error for the marine environmental parameters and an acoustic array installation error. To simplify the analysis and highlight the subject of this paper, these errors are regarded as zero-mean Gaussian white noise. The error equation of the USBL in the Filter models of the follower UUV can be established based on the analysis in The states in the follower UUV are SINS states, DVL states and USBL states, which can be described as:Based on the attitude error equation, velocity error equation, and position error equation of the SINS (Equations (4), (10) and (13)) and the error models of the DVL and USBL (Equations (17) and (23)), the dynamic model of the follower UUV can be described as follows:This dynamic model can be expressed in the form of a vector as:The SINS equipped in the follower UUV has low precision. There are accumulated errors in the follower UUV, which cannot be ignored. Because the leader UUV is equipped with high-precision navigation devices, the information from the leader UUV can be used to correct the errors of the follower UUV. Based on the information sent from the leader UUV and the measurement results from the USBL, accurate position information for the follower UUV can be obtained. Therefore, the position error is chosen as one of the observation states. In addition, the accurate velocity information regarding the follower UUV can be provided by the DVL. Therefore, the velocity of the follower UUV calculated from the SINS can be corrected by the DVL. The other observation state is the velocity error. Based on the analysis above, the observation states can be expressed as:The observation model can be described as follows:According to the characteristics of polar cooperative navigation, there is a communication delay in the process of multi-source information fusion. Based on the acoustic communication delay’s characteristics and the role of underwater acoustic communication in the whole system, a system model of underwater acoustic delay can be constructed. In conventional AKF, the estimation results of the states are corrected according to real-time measurement information. Thus, conventional AKF which does not consider communication delay is not suitable for polar cooperative navigation of multi-UUVs. The schematic diagram of polar cooperative navigation of multi-UUVs considering communication delays is expressed in The estimation processes of attitude, velocity and position in the follower UUV are described in The discrete expressions of the filter model and observation model can be expressed as follows:Conventional AKF mainly consists of state updates (prediction) and measurement updates (correction) ,22. The Due to the underwater acoustic communication delay, the states of the follower UUV cannot be corrected by the measurement results at the current time. To meet the needs of the multi-UUVs cooperative navigation algorithm considering communication delays for use in the polar region, the conventional AKF needs to be modified. The underwater acoustic communication delay is a major factor in improving the accuracy of the conventional AKF. The analysis and special representation of underwater acoustic communication delays are discussed in the following text.According to the analysis in t0, is also the initial time of the follower UUV. The leader UUV sends a detection signal through USBL to the follower UUV at t1. At the same time, information about the states of the leader UUV is self-recorded. Because of the underwater acoustic communication delay, this detection signal will be received by the follower UUV at t2. After a short reaction time, the follower UUV sends a confirming signal to the leader UUV through USBL at t3. This confirming signal is received by the leader UUV at t4. The leader UUV calculates the relative positions of the leader UUV and the follower UUV. Then, the relative position and the information of the leader UUV at t1 are sent to the follower UUV at t5. After broadcasting through the water, this information is received by the follower UUV at t6. The underwater acoustic delay can be described as follows [As shown in  follows ,15.(39)The underwater acoustic delay consists of the underwater acoustic detection delay and the underwater acoustic communication delay. During the measurement cycle, both To describe the underwater acoustic communication delay better, it can be quantified. Since time synchronization is achieved between the leader UUV and the follower UUV and the underwater acoustic communication delay is a limited value, the underwater acoustic communication delay can be expressed versus time. Thus, the acoustic communication delay can be quantized. After quantification, the underwater acoustic communication delay can be expressed as follows:For example, Considering the existence of underwater acoustic communication delays, the information that the follower UUV receives from the leader UUV at time time k−i ,15. Therk − i can be described as follows:Based on Equation (47), the states at time By substituting Equation (49) into (28), the observation model can be modified as follows:Therefore, the system model and observation model of the modified AKF adapted to polar cooperative navigation of multi-UUVs considering communication delays can be expressed as follows:To maintain the positive definiteness of the covariance of system noise matrix and measurement noise matrix as well as to simplify the system, Equations (36) and (38) in the conventional AKF are modified as follows:The complete formula of the modified AKF considering communication delays and is adapted for the polar cooperative navigation of multi-UUVs can be expressed as follows:To clearly express the modified AKF, the filter flow chart of the modified AKF used for the polar cooperative navigation of multi-UUVs considering communication delays is shown in To verify the advantages of the proposed algorithm, a simulation and experiment were performed using the polar cooperative navigation algorithm of multi-UUVs considering communication delays. By comparing the results in different situations, the advantages of the proposed algorithm can be obtained. To simplify the analysis, the simulations and experiments met the limitations proposed in According to the conditions proposed above and the UUV characteristics, a simulation of the polar cooperative navigation algorithm of multi-UUVs considering communication delays was designed. The initial conditions and limitations were as follows:System simulation conditions: the simulation time was 12 h; the filtering period was 0.1 s. Initial conditions of UUV: the initial position of UUV consisted of latitude, According to the conditions set above, the simulation results of the follower UUV, including attitude errors, velocity errors and position errors, can be expressed as described in the following text. There were two comparison simulations. In the first comparison simulation, different random communication delay ranges were set in the conventional AKF. The impact of communication delay on the conventional AKF is clearly expressed as In this simulation, the simulation time was 1 h and As shown in In the second comparison simulation, Algorithm 1 was compared with Algorithm 2. Algorithm 1 represents the polar cooperative navigation algorithm of multi-UUVs considering communication delays that is proposed in this paper. Algorithm 2 represents the polar cooperative navigation algorithm of multi-UUVs based on conventional AKF that does not consider communication delays. The estimation errors of the follower UUV, including attitude errors, velocity errors and position errors, are shown as For a clearer description of the results obtained from the simulation, the RMS errors from attitude errors, velocity errors and position errors are shown in As shown in The polar cooperative navigation algorithm of multi-UUVs considering communication delays has been discussed in this paper. Due to geographical constraints, the current experiment could be conducted in the polar region. Therefore, a semi-physical simulation experiment was performed, which means that the experiment was conducted in a non-polar region and the data measured during the experiment is used for the semi-physical simulation. According to the UUV characteristics, gyro drifts and accelerometer bias are natural characteristics of UUVs. They do not change in different locations. Therefore, the gyro drifts and accelerometer bias can be obtained from an experiment in the non-polar region. Practically-measured data and the simulated data comprise the experimental data. The experimental data is composed of the angular velocity, No matter whether gained from simulation or experiment, the true values of Inertial Measurement Unit (IMU) The experiment was conducted in a rectangular pool at our institute in a non-polar region (N45°73′ E127°41′). The follower UUV accomplished a uniform liner motion. The gyro drifts and the accelerometer bias of the follower UUV were extracted from the following UUV that was produced by our laboratory. The follower UUV, called White Dolphin-100 UUV, is shown in The gyro drifts measured in the non-polar region included gyro constant drifts and gyro random drifts. The gyro constant drifts were The experimental results of the follower UUV, including attitude errors, velocity errors and position errors, are expressed in To describe the experimental results clearly, the RMS errors of attitude errors, velocity errors and position errors are expressed in Comparing the experimental results and the RMS errors, it can be seen that the proposed polar cooperative navigation algorithm of multi-UUVs considering communication delays can be used to estimate states effectively. More accurate information regarding the states can be obtained from the proposed algorithm compared with the conventional algorithm.Conventional SINS is difficult to apply in the polar region. Therefore, the cooperative navigation algorithm based on conventional SINS is not suitable for multi-UUVs in the polar region. Using the grid frame and the UUV characteristics, error equations for the follower UUV that are suitable for the polar environment were established. Using the polar grid algorithm proposed in paper , the polAccording to the first comparison simulation (results in Both the second comparison simulation (results in A polar cooperative navigation algorithm for multi-UUVs considering communication delays was proposed in this paper. We mainly focused on the construction of the polar cooperative navigation algorithm and only the communication delays were considered in this paper. To simplify the analysis and for the purposes of this paper, some hypothetical ideal situations were included in this paper. For example, the underwater acoustic communication was assumed to be well-performing and reliable. In addition, only communication delays were considered in this paper. There are substantially more complex situations in practical application, including communication interruption, communication lost-packets, communication drop-outs and so on. These situations will influence the accuracy of the cooperative navigation. We believe these problems will be solved with further improvement in underwater acoustic communication and navigation algorithms, which will be our future job.A polar cooperative navigation algorithm for multi-UUVs considering communication delays was proposed in this paper. Using UUV characteristics and the environment of the polar region, a polar grid navigation algorithm for a leader UUV and follower UUV was established. The acoustic communication delay was analyzed, and a discretization model for the acoustic communication delay was established. Due to the existence of acoustic communication delays, there are large errors when conventional AKF is used in the polar cooperative navigation of multi-UUVs which consider communication delay. Therefore, the conventional AKF method was modified to consider underwater acoustic communication delays. The simulation and experimental results show that the proposed algorithm can be effectively used for cooperative navigation of multi-UUVs in the polar region.


The aim of this study is to characterize in resting-state conditions the cerebral blood flow velocity (CBFV) signals of fibromyalgia patients. The anterior and middle cerebral arteries of both hemispheres from 15 women with fibromyalgia and 15 healthy women were monitored using Transcranial Doppler (TCD) during a 5-minute eyes-closed resting period. Several signal processing methods based on time, information theory, frequency and time-frequency analyses were used in order to extract different features to characterize the CBFV signals in the different vessels. Main results indicated that, in comparison with control subjects, fibromyalgia patients showed a higher complexity of the envelope CBFV and a different distribution of the power spectral density. In addition, it has been observed that complexity and spectral features show correlations with clinical pain parameters and emotional factors. The characterization features were used in a lineal model to discriminate between fibromyalgia patients and healthy controls, providing a high accuracy. These findings indicate that CBFV signals, specifically their complexity and spectral characteristics, contain information that may be relevant for the assessment of fibromyalgia patients in resting-state conditions. Fibromyalgia syndrome (FMS) is a chronic disease  characteThere are several brain areas that are activated in response to painful stimuli, including the primary and secondary somatosensory cortices, the insula, the anterior cingulate and the thalamus, as well as prefrontal and parietal regions, which compose the neuromatrix of nociception –6. In thOne of the techniques that has been recently proposed to evaluate the dynamics of brain activation associated to painful stimuli is Transcranial Doppler (TCD) monitoring –15. It iThe aforementioned TCD studies have found that there are measurable variations in CBFV of anterior cerebral arteries (ACA) and middle cerebral arteries (MCA) in response to different kinds of painful stimuli, being these changes more pronounced in FMS patients than in general population –15. FurtStudies with TCD in the psychophysiological field have commonly based their analysis on the evaluation of the temporal evolution of the mean CBFV  ,17,20, aThe studies about resting-state categorization of CBFV in general population –24 have Although previous studies that have applied TCD to evaluate CBFV characteristics of FMS patients have been based on temporal analyses of the signals, the described methodology based on frequency, time-frequency and information theory features is worth to consider in order to assess the resting-state characteristics of CBFV of FMS patients.As previously described, TCD has started to be applied for evaluating differences in cerebral hemodynamics between patients and controls during pain processing. The current work will advance in this kind of analysis by evaluating other kinds of signal processing and feature extraction methods that can help to differentiate between FMS patients and controls.Specifically, the main goal of the present work is to characterize the CBFV signals from FMS population in resting-state conditions in comparison with healthy population. Taking into account studies with general population , we propOur first hypothesis is that there will be significant differences between FMS patients and the control group in frequency, time-frequency and information theory parameters obtained from the CBFV signal. This first hypothesis is supported by the evidence from previous studies that have applied this kind of analyses in general population and by the fact that other neuroimaging techniques have observed that resting-state networks of chronic pain patients show alterations in comparison with healthy subjects –12.Furthermore, our second hypothesis is that we expect to find an association between these TCD parameters and psychological and clinical measures related to depression, anxiety and pain. Previous studies ,27 have Fifteen females with FMS aged between 36 and 67 years  and fifteen pain-free females aged between 33 and 53 years  with comparable sociodemographic data were recruited for the study. Patients were recruited via the Valencian Fibromyalgia Association (AVAFI). Exclusion criteria included neurological disorders, major psychiatric diseases, and migraines during the day of the experimental session, strokes or inflammatory causes of pain. The control group was recruited by means of announcements in notice boards of universities and sport associations. The exclusion criteria for the control group were the same applied to patients, and the presence of any kind of chronic pain disorder. All participants were right-handed based on Edinburgh Handedness Inventory responses . All the participants gave their informed written consent prior to their inclusion in the study. The study was approved by the ethics committees of the Universitat Politècnica de València and of the Hospital Universitari and Politècnic La Fe.In order to evaluate the mood, manual preference and the impact of pain on participants’ lives, they had to complete several questionnaires before the experimental session: several visual-analog scales for assessing daily and worst pain intensity during the last week, and also the pain laterality , the State-Trait Anxiety Inventory questionnaire (STAI ), the EdAn additional questionnaire had to be answered at the end of the experimental session: a reduced version of the resting state questionnaire (RQ) . It consIn order to measure the cerebral hemodynamic of participants, a commercial transcranial Doppler sonography device  was used. Blood flow velocities (in cm/s) in ACA and MCA from both hemispheres were simultaneously monitored using two 2-MHz probes. Each probe was capable of conducting the exploration at two different depths at the same time. The probes were placed in the temporal bone window and fixed using a headset provided with the Doppler Box. The insonation depth of each probe varied between 50 and 55 mm to register MCA blood flow velocity, and between 65 and 70 mm to monitor ACA blood flow velocity.QL software (provided with the system) was used to register the signals from the Doppler Box and export them to text files for later analyses. The CBFV signals were stored with a sampling rate of 100 Hz while the raw signal was extracted as a binary file sampled at 7042 Hz.Blood pressure was measured using a wrist blood pressure monitor . Mean arterial pressure was calculated from systolic and diastolic pressures.Before starting the experiment, participants had to fill out all the questionnaires described above except from the RQ questionnaire. They also received information about the experiment prior to data acquisition.Thereafter, the Doppler sonography probes with the headset were placed on the participant’s head by an experienced neurologist.Once the probes were correctly located, participants received instructions to remain awake, in silence and to avoid any thought during a 5-minute resting period. After this period, the participants had to complete the RQ questionnaire. Finally, they had to complete other tasks, which are not considered in this study.Blood pressure was measured before and after the resting period.The envelope and raw signals obtained by Transcranial Doppler were analyzed offline using MATLAB R2015b  and its toolboxes with custom MATLAB scripts. Only the measurements with a signal quality enough to allow their analyses were considered.The preprocessing of the envelope and raw signals was applied to the 5-minute data corresponding to the resting period. The first step was a detection and correction of outliers caused by artifacts. In the case of the envelope signals, this was followed by a linear low-pass filter (with a 10 Hz cut-off frequency) that removed the effect of higher frequency artifacts. Finally, in order to avoid the dependence with the incidence angle between the ultrasound probe and the artery, the envelope signal was normalized dividing it by its mean during the resting period and multiplying by 100, in a similar way to other studies . On the Several parameters were calculated to characterize the hemodynamic signals from different perspectives: time, frequency, time-frequency and information theory ,24. The Finally, heart rate was calculated from the intervals between the peaks of the normalized envelop signal, also known as inter-systolic intervals .Five statistical features widely used were calculated to characterize the signals from each vessel. These statistical features included mean, standard deviation (StD), variance, kurtosis and skewness. They were calculated both to the signals before normalizing and after normalizing.The goal of information-theoretic analysis is to assess the complexity (or predictability) and the regularity of signals and it is often applied in the analysis of biomedical signals ,36. The The LZC is a non-parametric feature that evaluates the randomness of finite sequences in a one-dimension signal . It is rThe entropy rate measures the regularity by means of the evaluation of repetitive sequence of patterns in a signal . EntropyFinally, the MSE method evaluates the regularity of complex signals by applying a consecutive coarse-graining process to the signal by averaging a successively increasing number of data points  in non-overlapping windows . The samThe frequency features that were calculated included peak frequency (PeakFreq), centroid frequency (CentFreq), bandwidth (BW) ,24,43 anThe peak frequency and the centroid frequency are measures that can be used to evaluate spectral changes in the signals, while the BW is used to measure the spectral spread . In addiThe peak frequency, the centroid frequency and the BW were calculated from the preprocessed signal and also after applying a more restrictive low-pass filter (cut-off frequency of 0.6 Hz), in order to remove the effect on these parameters of the cardiac cycle.On the other hand, the spectral power in frequency bands described in previous TCD studies  was calcFinally, an additional band (0.12–0.25 Hz) (B012-015) that has shown accentuated fluctuations in the brain metabolism of chronic pain patients in resting-state was also analyzed . The speA time-frequency analysis based on the wavelet transform was made in order to examine how spectral components change over time. In this analysis, two parameters were calculated: the relative energy from the approximation coefficients (RWEa10) in different time-frequency bands and the wavelet entropy (Wentropy). The discrete Meyer wavelet was used to obtain a 10-level discrete wavelet decomposition ,45.In order to explore the differences between the FMS and the control group regarding the questionnaire data and the extracted features from the cerebral hemodynamic responses, several statistical data analyses were applied. All the analyses were conducted using SPSS 16.0  with a 0.05 significance level.An analysis of variance (ANOVA) was applied. The between-subject factor was the experimental group (FMS vs. control). Dependent variables included the extracted features from bilateral ACA and MCA, the data from questionnaires and the heart rate. Prior to applying the ANOVA, Kolmogorov-Smirnov and Levene tests were used to check the different dependent variables for normality and homoscedasticity, respectively. If a specific variable did not follow normality criteria, a non-parametric test was applied instead (Mann-Whitney U).Spearman correlations were calculated between the variables from questionnaires and the CBFV features to analyze possible relations between pain-related variables  and cerebral blood flow. Furthermore, Pearson correlations were calculated between the information-theoretic features and the heart rate in order to evaluate the effects of heart rate in the complexity and the regularity parameters.Finally, a Linear Discriminant Analysis (LDA)  was applThe clinical data are summarized in Focusing on clinical questionnaires, the FMS group showed significantly higher levels of pain intensity than the control group in the Pain Intensity/Laterality questionnaire.Regarding anxiety measures (STAI questionnaire), significant differences were observed for the STAI-state and STAI-trait, with higher levels of anxiety for the FMS group. Regarding depression (BDI questionnaire), significantly higher values were obtained in the FMS group for overall depression scores.Finally, the results obtained for the different scales and subscales of the WHYMPI questionnaire showed statistically significant differences for sections I and II. Section I is related to “pain experience”, and significant effects were found in the following subscales: negative mood, pain interference, activity interference and pain severity. In Section II (“response by significant others”), significant differences were found in the following subscales: distracting responses, solicitous responses and punishing responses. FMS patients perceived a lower psychological and instrumental support and a higher negative support by significant others than the control group. The subscales from section III (daily activity) did not reveal any significant effect.No significant differences were found between the mean arterial pressure before and after the resting period, neither for the control group nor for the FMS group.Finally, the resting questionnaire responses did not show any behavior that was considered sufficient to exclude any participant from the experiment.Some vessels were discarded because the quality of the signal was not enough to allow their analysis, giving a total number of 25 subjects for L-MCA (12 FMS group), 25 subjects for R-MCA (12 FMS group), 23 subjects for L-ACA (11 FMS group) and 24 subjects for R-ACA (11 FMS group).For the envelope signals, Tables The envelope signals from the FMS group in the left hemisphere were less predictable than those of the control group as measured by different information-theoric features. Mean MSE values for the different scales, arteries and groups can be observed in Regarding the frequency analysis, results show a lower LF/HF ratio in different vessels of the FMS group and a higher spectral power in the frequency band between 0.12 Hz and 0.25 Hz in the L-MCA of this group. Besides, the centroid frequency in the lower frequencies spectrum (0–0.6 Hz) in the L-MCA and L-ACA and the peak frequency in the L-MCA were higher in the FMS group.The grand average power spectral density for each group in the different arteries can be observed in The heart rate did not show any significant difference between the Control (68.568 ± 8.768) and the FMS (72.224 ± 11.37) groups  = 0.855; p = 0.364; partial η2 = 0.034).Regarding raw data, no significant differences were found in any calculated parameter between the control group and the FMS group. The analyses described in following sections (correlation and LDA) were applied only to the envelope CBFV features.Correlations were found between BDI questionnaire results, STAI-state, STAI-trait, pain severity factor (WHYMPI) and different envelope CBFV features. Significant correlations are shown in in In the case of the data set composed by all the features from the four vessels , the selected features by the model were: LZC, LF, MSE factor 1 and the normalized power in the 0.12–0.25 Hz band for L-MCA; MSE factors 3 and 13 for R-ACA and MSE factor 14 for R-MCA. Initially, the classification model used all the features from all the samples as the training set to assess the LDA model. The classification achieved an accuracy of 91.30%. On the other hand, the classification results of the leave-one-out cross-validation (CV) approach achieved an accuracy of 100%.Regarding the data set composed by ACA vessels features, the selected feature was the centroid frequency in the lower frequency band in the left hemisphere. The classification results using this feature from all the samples as the training set achieved an accuracy of 65.20% and the leave-one-out CV approach achieved an accuracy of 65.20%.Finally, in the data set composed by MCA vessels features, the selected features were: LF/HF ratio and MSE1 for the left hemisphere and Entropy Rate and LF for the right hemisphere. The classification results using MCA vessels features from all the samples as the training set showed 91.7% of accuracy. The same accuracy was obtained with the leave-one-out CV approach.The confusion matrices of the different classification models are shown in This study has characterized the CBFV features obtained by TCD from FMS patients and healthy population. Results have shown that there exist significant differences in CBFV parameters of the TCD envelope signals of these groups in resting-state conditions.The analyses of clinical pain measures showed results that are in line with previous studies . More spRegarding the analyses of the registered TCD signals, we analyzed the envelope and raw CBFV signals, both for the FMS patients and the healthy population. Even though the raw CBFV analysis did not show any significant differences between the parameters from both groups, the envelope CBFV analysis showed differences in some of the parameters. The raw CBFV signal had been used previously as a valuable signal that can provide complementary information to the envelop CBFV analysis in resting-state conditions  and duriFocusing on the envelope signal, the information-theoretic analysis showed significant differences for the LZC features in the two vessels of the left hemisphere. Although previous evidence indicates that several forms of pain are characterized by bilateral cerebral activations , there iLZC measures the possibilities of finding new patterns in a temporal series, so a larger LZC implies a more complex dynamical behavior . Our resThe correlation results show an association of complexity measures such as LZC and MSE  of the L-MCA with current anxiety (STAI State) and, in the case of LZC, with current pain level. Besides, the MSE values  of the L-ACA are positively correlated with current anxiety (STAI State). The regularity (Entropy rate) of the CBFV signals in the R-MCA is negatively linked with the depression level (BDI measure).Finally, the correlation analysis also shows the absence of relation between heart rate and information-theoretic parameters. Taking into account that the number of participants in the present study is rather small, this is a result that should be confirmed in future studies, as a larger sample size may be required to detect significant correlations between the studied parameters. However, it should be noted that this result is consistent with previous studies. Aboy et al.  had alreAll these results seem to indicate that the complexity of the CBFV is influenced by different factors such as the depression, pain and anxiety levels of the participants in the study.Although the bases of the observed differences in CBFV are unknown, there are evidences that have found a link between higher complexity in neuronal electrical activity and depression. Li et al.  describeOn the other hand, we have also found significant differences between the experimental groups in parameters from the frequency analysis. As can be observed in The global peak frequency is significantly higher in the FMS patients than in healthy participants . The CBFV component that has the biggest influence on the power spectrum is the cardiac cycle, which determines the position of the global peak frequency. Although the analyses with the current sample have not been able to detect significant differences between groups in the heart rate calculated from the intervals between the peaks of the normalized envelop signal, the higher values in the global peak frequency that have been obtained in the present study are coherent with the already known observation that FMS patients have higher heart rates than healthy population ,57. TherWhen focusing on lower frequency bands, patients seem to have a decreased spectral power in the LF band in comparison with controls, and an increased spectral power in higher frequencies . The LF/The correlation analyses show that the lower values the LF/HF ratio observed in the FMS group, for example in the L-MCA, are associated with higher values of both depression and anxiety (STAI trait). On the other hand, the LF spectral power of the L-MCA, which is also lower in the FMS group, is associated with pain indicators (Pain severity factor of the WHYMPI). Finally, the centroid frequency in the lower frequency band is associated with depression and anxiety (STAI state).Our results also show that the fluctuations in the frequency band between 0.12 and 0.25 Hz are accentuated, in accordance to Malinen et al. , who hadAll the obtained results are in accordance with previous studies that have demonstrated the relationship between negative emotional factors and activation of brain areas that are related to pain ,61. TherFinally, results from the LDA classification show that features extracted from CBFV could be useful to discriminate between FMS patients and healthy population by means of lineal models. The best accuracy was achieved when using all the calculated parameters from MCA and ACA, confirming the importance of characterizing the four arteries (MCA and ACA) in order to classify between FMS patients and healthy population. In addition, the stepwise features selection showed the high influence of the information-theoretic and frequency features in the LDA models, which would be in line with the previous results.There are other studies with TCD that are applying classifiers to automatically detect cognitive states, i.e., –65. AlthThe present study has some limitations that should be taken into account. Firstly, the number of participants in this work is reduced. The results should be confirmed with a large population of different age ranges and ethnicities, making possible to analyze the influence on the results of other related factors such as medication. Due to this limitation, the correlation analyses between the TCD parameters and questionnaire scores have been conducted globally with the whole sample, and not separately for each group. This has to be taken into account when interpreting the correlation results. Most of the participants on the FMS group take prescription drugs, mainly analgesics, antidepressant and anxiolytic drugs. Therefore, the influence of drugs in our results cannot be completely discarded. Secondly, other physiological parameters were not continuously monitored during the procedure because the work did not have the goal of studying phenomena such as vasomotor activity or cerebral autoregulation. Consequently, we do not have direct indicators of the influence of those phenomena in the obtained results. Thirdly, the participants in this work were women. The results should be confirmed using also a sample with FMS male patients. Finally, the TCD technique has some limitations. It measures CBFV, which is just an indirect estimation of cerebral blood flow. Besides, its spatial resolution is rather low , being rThe main goal of this study was to characterize the resting-state TCD in fibromyalgia patients. Therefore, we acquired raw and envelop CBFV signals in the main cerebral vessels (ACA and MCA). We observed that the fibromyalgia patients were characterized by a higher complexity of the envelope CBFV signal, as well as by a higher peak frequency, a higher 0.12–0.25 Hz band power, a lower LF/HF ratio and a higher centroid frequency in the lower frequency band in resting-state. In addition, these results showed a significant association with clinical pain parameters and emotional factors. Finally, we were able to classify with a high accuracy between FMS patients and healthy participants using the characterization features from the envelope CBFV signal.