The present study investigated how syllable structure differences between the first Language (L1) and the second language (L2) affect L2 consonant perception and production at syllable-initial and syllable-final positions. The participants were Mandarin-speaking college students who studied English as a second language. Monosyllabic English words were used in the perception test. Production was recorded from each Chinese subject and rated for accentedness by two native speakers of English. Consistent with previous studies, significant positional asymmetry effects were found across speech sound categories in terms of voicing, place of articulation, and manner of articulation. Furthermore, significant correlations between perception and accentedness ratings were found at the syllable onset position but not for the coda. Many exceptions were also found, which could not be solely accounted for by differences in L1–L2 syllabic structures. The results show a strong effect of language experience at the syllable level, which joins force with acoustic, phonetic, and phonemic properties of individual consonants in influencing positional asymmetry in both domains of L2 segmental perception and production. The complexities and exceptions call for further systematic studies on the interactions between syllable structure universals and native language interference with refined theoretical models to specify the links between perception and production in second language acquisition. Accentedness in speech refers the degree to which the pronunciation of an utterance sounds deviated from an expected version of its production . ForeignCritical Period account emphasizes age dependency, which postulates genetically guided maturation of domain-specific language learning mechanisms as the reason for the declining abilities to learn L2  model adds a neural-level specification and explanation from both developmental and cross-linguistic perspectives . There a/; It is noteworthy that the three models for speech learning draw heavily on data from perceptual tests of consonants at the syllable-initial position alone. Apart from what these segmental learning models can explain and predict, suprasegmental differences between L1 and L2 strongly influence L2 phonetic perception and production. The adult L2 perception and production literature indicates the existence of a positional asymmetry that is attributable to differences in L1 and L2 syllable structures . For insOne straightforward explanation is that the syllable-final difficulties in L2 consonantal perception and production may reflect a general pattern of universal structural asymmetry in favor of the onset in terms of accessibility, stability, and learnability . If the The relationship between perception and production has been an outstanding issue in speech science . In L2 aThe main purpose of the present study was to investigate positional asymmetry and the influences of Mandarin Chinese syllable structure on the relationship between perception and production of American English consonants. In one previous report, Mandarin speakers’ perceptual gains on a French /b-p/ contrast during perceptual training resulted in improved production . Importa/. In contrast, Mandarin has a richer set of affricates, namely, the alveolar // and //, the retroflex // and //, and the palatoalveolar // and //, each pair carrying the aspirated-unaspirated distinction. In English, there is only one pair of palatoalveolar affricates with the voicing distinction (/tʃ/ and //). In the approximant category, Mandarin has liquids and glides like English. But the Mandarin ‘r’ sound is often transcribed as // (a voiced retroflex fricative). The two languages also differ in phonotactic constraints in terms of combinatory and distributional restrictions. While consonants can form clusters in American English words, no consonant clusters are allowed in Mandarin. The inventory of coda structures in English is considerably richer than Chinese. For the current study, we take into account 18 consonants that could appear in both initial and final position of the syllable in English (see Table 1 for sample words). English also allows all consonants to appear in either syllable-initial or syllable-final position except /h/, /j/ and /w/. In Mandarin Chinese, only two nasal sounds, /n/ and //, are permissible in the syllable-final position. In both languages the velar nasal sound // cannot occur in the word-initial position.A comparison of Mandarin Chinese  and American English phonemes and syllable structures is necessary to help understand the syllable structure differences and the consonant systems of the two languages. There are approximately 400 syllables in Mandarin without tones and 1100 syllables with the tones added . In contIn the present study, an overall assessment of consonantal perception and production skills in adult ESL learners in China was attempted by examining effects for all the major individual classes of English consonants in terms of voicing, POA, and manner of articulation (MOA) in the CVC (consonant-vowel-consonant) syllabic context. Testing all the major classes of English consonants was partly motivated by the pedagogical need to identify general patterns and issues in perception and production among Chinese college students for whom English is part of their core curriculum. For comparison purpose, perception data were also collected from adult native speakers of English using the same set of speech stimuli to verify whether native English speakers would show a similar positional asymmetry to the Chinese subjects. The voicing subcategories in this study refer to the two-way distinction of voiced and voiceless consonants. The POA subcategories refer to the six-way distinction of bilabial, labiodental, dental , alveolar, palatal-alveolar, and velar consonants. The MOA subcategories refer to the five-way distinction of nasal, plosive, fricative, affricate, and approximant (including both liquids and glides) consonants.There were two specific hypotheses for our study motivated by the three models on L2 phonetic learning and the universal structural asymmetry theory. First, adult Chinese ESL learners would experience more difficulties in perceiving and producing English consonants at the syllable-final position relative to the syllable-initial position across all the voicing, POA, and MOA subcategories due to the limitations of Mandarin Chinese syllabic and phonotactic structures. We did not expect the native speakers of English would have the same perceptual issue although the universal structural asymmetry theory would predict otherwise. Second, the position-dependent difficulties would be reflected in stronger correlations between L2 perception and production at the syllable onset than at the coda./ contrast at the coda position, our expectation, in line with the three models of L2 phonetic learning, was that the Chinese ESL learners would not experience much difficulty in producing or perceiving this syllable-final nasal contrast in English. In other words, the nasal sounds might not show the positional asymmetry. As the POA has more subcategories tied to individual sounds  than voicing and the MOA, we might see a constellation of exceptions in the POA subcategories. In accordance with the SLM and PAM, English sounds such as the voiced stops, voiced fricatives/affricates, interdental fricatives, and palatoalveolar affricates that do not exist in Chinese would show different degrees of perception and production difficulties with some of these sounds demonstrating equal difficulties or reduced positional disparity between the syllable onset and coda.Considering the syllable structure of Mandarin Chinese and the complexity of the causes for L2 phonetic learning difficulties due to the relative importance of acoustic, phonetic, phonemic properties of the individual speech sounds in each subcategory, we expected to see category-dependent variations in the positional asymmetry phenomenon as well as exceptions to our two general hypotheses at the individual sound level. In particular, as the Chinese language allows /n/-/The reported study was conducted with approval from the institutional review boards for human subject protection at the two home institutions. Thirty-nine Chinese college students participated in this study. One Chinese female student did not complete all the tests in the study and was dropped in statistical analysis. The Chinese participants were between 20 and 21 years old . All of them were native speakers of Mandarin Chinese. When selecting participants, we excluded students who spoke Mandarin Chinese  with a noticeable accent. Our survey of language background indicated that all our Chinese participants grew up speaking standard Mandarin Chinese from the first year of age. While eight  of the 38 participants were raised in regions where the local dialects (Wu and Min) were very different from Putonghua , they alTo reduce possible confounds on the perception-production correlations due to insufficient input/learning as specified in the SLM, we were rather restrictive in recruiting the Chinese subjects with respect to their L2 background. The Chinese subjects had received at least 6 years of formal English education in junior and senior high school, in which reading and writing proficiency in English were emphasized rather than conversational skills. None had lived in an English-speaking community before joining the study. All the Chinese participants had passed the National Matriculation English Test in China for college admission, and all except one had passed the national standardized English proficiency test, Test for English Majors, TEM-4 , before Table 1 for examples and the target phonemes). To control stimulus familiarity, all word candidates were selected from the published vocabulary list required for College English Test (CET Band 4) in China (The perception data were collected from both subject groups with a revised Speech Assessment and Training software program (SAT) based on versions used in previous publications . In the in China . The worBefore the perception test, the subjects were familiarized with the visual phonetic symbols along with alphabetic letter spelling shown on a computer monitor with target sounds marked in each word. After ensuring that the subjects were confident about recognizing all the symbols for the consonants and verifying their symbol recognition accuracy, each phoneme in the perception test was presented 10 times using different words, respectively, in the syllable onset and coda positions. Listeners were explicitly instructed to pay attention to possible target consonant candidates as prompted on computer screen and make choices by clicking the proper symbol. The listeners were asked to rely on their immediate impression of the consonant in the target onset or coda position irrespective of word candidacy or meaning. The word stimuli were presented at 70 dB SPL in random order. The subjects were tested individually in a sound booth. The selected target responses were automatically registered in a Microsoft ACCESS database in the SAT program and sorted into syllable onset and coda positions for each subject.Production data were digitally recorded from each Chinese participant, featuring isolated words that contained the contexts for allophonic variations of the target English consonants. The order of perception and production tasks was counterbalanced among the subjects. Each word was presented on computer screen, the subjects were asked to pronounce it in isolation three times with approximately 1 s pause in between. The subjects were instructed to pronounce the words clearly each time. The spoken words were then normalized in RMS intensity and assessed by two native speakers of English, who had formal training in phonetics. The SONY Sound Forge 9 program and a Sennheiser HD280 Pro binaural headphone were used on a workstation installed with the Presonus Firebox sound card for the rating task.While production accuracy judgment only permits a binary choice, the accentedness rating measure is designed to allow more gradient reflection of the degrees of deviation from the target pattern of speech production as expected of a native speaker. For this reason, the accentedness rating measure was adopted in the present study. The ratings for the target consonants were in the range of 1 (wrong consonant or very strong foreign accent) and 5  following a foreign accent rating scale similar to Post hoc pair-wise t-tests were performed for the individual consonant subcategories to examine the effects of syllable structure on perception and production. To examine the overall positional effect on the perception-production links, correlational analysis was first performed on the overall pooled perception and production scores separately for syllable-initial and syllable-final positions. Correlational tests between perception and production as a function of syllabic position were also run for each class of speech sounds. To examine possible dialectal influences, we additionally performed statistical analyses with dialect as a between subjects factor using a multivariate analysis of variance (MANOVA) model. Given the heterogeneity of the dialectal background of the eight subjects who were from regions where the local dialects are very different from Putonghua, we also performed further analysis by removing these eight subjects from our data set to verify the statistical results.The raw scores for each subject were sorted, grouped, and averaged for syllable-initial and syllable-final positions based on the subcategories of voicing, POA, and MOA. The data for the glides (/w/ and /j/) and the glottal fricative /h/ were not included as they did not occur in the syllable-final position in English. Statistical analyses were performed using Systat12. For the perception and production scores, repeated-measures ANOVA tests were performed separately to examine the main effects of syllabic position (onset vs. coda), consonant classification , and possible interactions. As the raters used continuous rating scores, inter-rater and intra-rater reliability for the production data was assessed using Pearson’s correlation analysis. Figures 1 and 2 for the Chinese subjects. As expected, the native speakers of English showed ceiling-level perceptual performance for all the consonant categories tested . Repeated measures ANOVA results and paired t-tests for the grouped consonant categories showed no statistically significant positional asymmetry effects for the monolingual English speakers. As the focus of the study was on L2 perception and production in terms of positional asymmetry, the reported statistics in the remainder of the text would be on the Chinese speakers only. As expected, the Chinese subjects performed significantly better for consonants in syllable-initial position than for those in syllable-final position. There were also exceptions.The pooled perception data and average scores sorted in terms of voicing, POA and MOA categories are shown in the left panels of F = 49.2, p < 0.00001, η2 = 0.571] and an interaction between position and voicing . There was no main effect of voicing . Further tests of simple main effects showed that significant position effects (onset vs. coda differences) for both the voiced  and voiceless  consonants. A post hoc two-tailed paired t-test was run to compare the difference scores (onset minus coda) for voiced and voiceless consonants. The result indicated that the voiceless sounds in English had larger onset-coda perceptual difference than the voiced sounds for the Chinese subjects .In the two voicing subcategories (voiced vs. voiceless), significant effects were found for the main factor of syllabic position , place . There was also an interaction between position and place . Simple main effects tests showed significant differences among the POA subcategories at both the onset  and coda . Significant position effects were observed for the bilabial , labiodental , alveolar , and velar  sounds. Post hoc paired t-tests  were performed for each POA category, which confirmed significant syllabic position effects for the bilabial, labiodental, alveolar and velar sounds: bilabial , labiodental , alveolar , and velar . The interdental and palatoalveolar sounds, which were not part of the Mandarin Chinese phonemic inventory, were the exceptions: interdental , and palatoalveolar .In the six POA subcategories , significant effects were observed for the main factors of position , manner , interaction of position and manner . Simple main effects tests showed significant differences among the MOA subcategories at both the onset  and coda . In addition, significant position effects were observed for all the MOA subcategories, namely, the nasals , stops , fricatives , affricates , and approximants . Post hoc paired t-tests  confirmed significant syllabic position effects for each MOA subcategory: the nasals , stops , fricatives , affricates , and approximants .In the five MOA subcategories , the significant effects were as follows: position . Intra-rater correlations were further performed by half-splitting the individual ratings for the same consonants in each subject, and the results showed a high level of consistency for both raters . The scoring data indicated that the two native English speakers with training in phonetics were highly consistent in their accentedness judgment. The two raters’ scores were thus averaged for each sound tested for each subject. Overall, the subjects’ consonantal production was rated significantly better  for syllable-initial position than syllable-final position. There were also some exceptions in individual subcategories as reported below.The accentedness ratings for the Chinese subjects in terms of voicing, POA and MOA subcategories are summarized in the right panels of F = 37.5, p < 0.0001, η2 = 0.764], voicing , interaction of position and voicing . In tests of simple main effects, a significant position effect (onset vs. coda differences) was observed for the voiced consonants , and significant differences between the voiced and voiceless sounds were found at the coda . Post hoc paired t-tests showed a significant position effect for accentedness in voiced consonants  but not in the voiceless consonants .In the two voicing subcategories (voiced vs. voiceless), the significant effects were as follows: syllabic position  and place . There was also an interaction between position and place . Simple main effects tests showed significant differences among the POA subcategories at both the onset  and coda . Significant position effects were observed for the bilabial , interdental , alveolar , and velar  sounds. Post hoc paired t-tests were performed for each POA subcategory, which confirmed positional asymmetry in the same four POA subcategories: bilabial , interdental , alveolar , and velar . The two exceptions were labiodental , and palatoalveolar .In the six POA subcategories , significant effects in accentedness were found for the main factors of position , manner , interaction of position and manner . Simple main effects tests showed significant differences among the MOA subcategories at both the onset  and coda . In addition, significant position effects were observed for the nasals , stops , and approximants . Post hoc paired t-tests confirmed significant syllabic position effects for the nasals , stops , and approximants . There were two exceptions; namely, fricatives , and affricates .In the five MOA subcategories , the significant effects in accentedness were as follows: position  . In contrast, no significant correlational effect was observed between perception and production for the syllable-final position  .Pearson’s correlation results for the grand mean scores of the Chinese subjects showed significant positive links between perception and production in the syllable-initial position . In addition, in the production data for POA, there was one interaction effect  approaching the level of significance .Multivariate analysis of variance analyses showed that none of the main effects or interaction effects concerning the dialect factor reached the level of statistical significance (Supplementary Tables S3–S5). The perception data did not appear to be much affected by removing the eight subjects (Supplementary Table S3). In the production data (Supplementary Table S4), however, there was a significant position effect for the interdentals , which was not observed in the statistical results with all the 38 subjects . In the correlational analysis (Supplementary Table S5), the MOA affricate subcategory failed to reach the level of significance  at the syllable onset, but it was a very close miss.Further analysis by removing the eight subjects who grew up in the Wu and Min dialect regions essentially replicated the results reported above , the difference in the voiceless vs. voiced sounds could be due to disparity in transferring L1 experience with the voicing distinction to L2 learning. Due to the highly restrictive syllable structure of Mandarin, Mandarin speakers would have more perception and production experience with voiceless consonants in the onset position than voiced consonants, which could partly explain why their perception for the voiceless sounds showed larger onset-coda difference than the voiced sounds. Previous studies showed that Chinese ESL learners had difficulty in the use of vowel lengthening for word-final voiced stops in both perception and production  and L2 (English) jointly showed a direct impact on the perceptual accuracy of individual L2 consonants. Interestingly, we observed a lack of balance among the subcategories of each consonantal classification. The main effects and significant interaction of position and voicing indicate that the Chinese ESL learners’ lack of integration of acoustic cues in the vocalic context for perceiving English stop sounds not only depends on syllabic position but also differs between the voiced and voiceless sounds. For instance, syllabic position showed a stronger effect on perceptual accuracy of voiceless consonants than voiced consonants. This result is not unexpected, suggesting that both syllable structure universals and language-specific factors are at play here . As the oduction .The POA perception data suggest that L2 phonetic learning difficulties exist at multiple levels, among which structural differences at the syllable level may become a subordinate factor for certain sounds. In particular, the interdental and palatoalveolar sounds did not show a significant effect of syllabic position. As the palatoalveolar sounds happen to be fricatives that are relatively long in duration, the positional asymmetry effect could be partly offset by the presence of long-duration acoustic cues from the preceding vowels that may aid the perception of syllable-final fricative/affricate sounds . It was Consistent with the syllable structure universals theory , the ManThe significant interaction effects between position and consonant categories indicated that there were differences in the production of various consonantal classes. We observed some discrepancies between perception and production. First, the positional asymmetry effect in terms of voicing was found only for the voiced consonants in production. The overall production of voiceless English consonants by Mandarin Chinese speakers was rated to be more native-like than the voiced ones, reflecting the fact the most of the Chinese consonants are voiceless sounds. One theoretical challenge with the current data is to explain why L1 syllabic structure does not appear to influence L2 production as much as it does in the perceptual domain. Part of the answer may lie in the different scales of measurement we adopted for our study. The perceptual data used a percentage scale of 0–100 whereas the production data were in a much reduced range of 1–5 with no absolute zero involved. Another factor to consider is the relative strength of links between perception and production. The correlation analysis results indicate that there was hardly any significant correlation between perception and production at the syllable-final position. In the present design, the Chinese subjects were instructed to produce the words in isolation, which could have led to increased conscious efforts to articulate each sound in a word regardless of the position. As discussed earlier, phonemic inventory differences and allophonic variations likely play an important role here, too. For example, the English interdental fricatives were the most difficult for the subjects as Mandarin Chinese does not use the interdental POA. The interdentals were so difficult for the Mandarin ESL learners that syllabic position did not seem to matter - their performance for the interdentals was equally poor in the onset and coda for both perception and production. There are also other factors to be taken into account. For instance, successful L2 perceptual training and the perception-induced improvement in production are shown to be dependent on the variability of the input that require multiple talkers and multiple phonetic contexts . Corpus Despite the existence of large variances, overall perception and production scores were positively correlated in the syllable-initial position but not in the syllable-final position, which appear to conform to the universal syllable structure pattern in favor of CV over VC. Our data are consistent with previous studies that show a lack of direct correspondence between L2 speech perception and production at the syllable-final position. For instance, Figure 2 and Table 2; also see supplementary data) is not due to a lack of variance in either perception or production measures. One technical issue concerning the investigation of the perception-production relationship lies in the lack of commensurability in methodology in terms of experimental protocols and measures.As predicted, we saw a constellation of exceptions in the individual POA subcategories. Specifically, significant positive correlations between perception and production were found for palatoalveolar sounds in both onset and coda positions. No significant correlation was found for labiodentals and interdentals in either onset or coda. These exceptions cannot be solely explained with either syllable structure universals or the L1 syllable structure interference account. Given the range of scores, the existence of these exceptions . In the production data, there were some minor differences involving the dialect factor that approached the level of statistical significance, which also slightly affected the perception-production correlational test results when those eight subjects were removed in the analysis . As our subject sample did not include those who acquired Mandarin Chinese late and spoke Mandarin Chinese with a noticeable local accent, further studies can probe how dialectal influences  factor into the effects of native language interferences in perception and production of the second language.As native speakers of Chinese may represent geographically and linguistically diverse regions with distinct local dialects, it is important to control for dialectal influences in speech research studies. We selected our subject sample by excluding those who spoke Putonghua with an accent. But our sample included eight subjects who are early bilingual speakers of both Putonghua and local dialects that are very different from Putonghua. Statistical tests that specifically examined and removed the dialectal  influences provided verification of the perceptual test results  and external cues (heard on the neighboring sounds/syllables) contribute important perceptual information, and language experience may fundamentally change perceptual weighting of such cues e.g., . An alteA second limitation of the current study is that the results were obtained from English major students in one of the top universities with a highly selective admission rate in China. As perception and production may proceed at different time courses in L2 acquisition, it would be necessary to apply well-defined subject selection criteria for a proper investigation. While efforts were made to include a normally distributed sample size in terms of L2 ability using the standardized TEM-4 scores, the Mandarin-speaking ESL population would be expected to exhibit a much wider range of English proficiency. Further work would be needed to examine whether similar patterns of positional asymmetry in perception and production at the syllable level can be obtained from Mandarin-speaking subjects with lower and higher English proficiency levels as assessed by CET and TEM tests .A third limitation is that the reported results were pooled across consonants for the major classes of voicing, POA, and manner of articulation. While this allows us to see the general patterns of the major consonantal classes, refined studies at the individual sound level are needed to allow a detailed examination of the acoustic, phonetic, and phonological factors at play in the syllable-initial, intervocalic, and syllable-final positions. We currently do not have an exact model for explaining all the exceptions we reported. Existing theories and models including SLM, PAM, NLNC, the Automatic Selective Perception model , and theIn practice, ESL teachers are advised that articulatory training would be ineffective unless the problem of perception is overcome . This pe/ and /n/ vs. /l/; The segmental phonetic learning models such as SLM, PAM, and NLNC all posit that the perceived relationships between L1 and L2 categories play an important role in how accurately L2 segments are perceived or produced. But these models have not fully taken into account production measures such as accentedness rating and the role of syllable structure that interacts with acoustic, phonetic, and phonemic similarities between L1 and L2 speech sounds. The current data supplement these models by highlighting the role of syllable structure in learning L2 consonants. Further research efforts, including speech training, are needed to extend to the study of more complex syllable structure involving consonant clusters and the contribution of vowel contexts e.g.,  and refiThe present study investigated the role of native language syllable structure in second-language phonetic perception and production. The overall scores show a strong positional asymmetry effect  on L2 consonantal perception and production across the categories of voicing, place of articulation, and manner of articulation. Moreover, a significant positive correlation between L2 perception and production was found in the syllable-initial position but not in the syllable-final position. There are also exceptions to the overall positional asymmetry pattern, suggesting that syllable structure is not the sole determinant. The results highlight the complexity of L2 speech learning and the necessity to consider syllable structure universals and native language interference by including syllable structure and allophonic variations in a multi-factor model for speech learning, which have important implications for future behavioral and brain research.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.


Streptococcus agalactiae  is an important human pathogen that colonizes the urogenital and/or the lower gastro-intestinal tract of up to 40% of healthy women of reproductive age and is a leading cause of sepsis and meningitis in the neonates. GBS can also infect the elderly and immuno-compromised adults, and is responsible for mastitis in bovines. Like other Gram-positive bacteria, GBS can form biofilm-like three-dimensional structures that could enhance its ability to colonize and persist in the host. Biofilm formation by GBS has been investigated in vitro and appears tightly controlled by environmental conditions. Several adhesins have been shown to play a role in the formation of GBS biofilm-like structures, among which are the protein components of pili protruding outside the bacterial surface. Remarkably, antibodies directed against pilus proteins can prevent the formation of biofilms. The implications of biofilm formation in the context of GBS asymptomatic colonization and dissemination to cause invasive disease remain to be investigated in detail. Streptococcus agalactiae  is often encountered in the gastro-intestinal and the genital tract of healthy women as part of the normal flora. From this site, the bacteria can reach the newborn through the birth canal and cause sepsis and/or meningitis . Also in this case, a high variability among strains was observed both in pilus expression and in the capacity to form biofilms, even when they belonged to the same serotype or MLST phylogenetic lineage. A subset of serotype III strains belonging to the hyper virulent lineage ST-17 harboring both pilus 1 and 2b was shown to form stronger biofilms than all other tested strains, particularly at low pH (D'Urzo et al., In the more recent study by D'Urzo et al., the formation of biofilm-like structures Park et al. investigated the phenotype of the CsrRS two-component regulatory system knockout, and showed an increase capacity of CsrRS mutant bacteria to adhere to host cells and to form biofilm-like structures on plate (Park et al., Streptococcus can form multicellular communities that are expected to facilitate its persistence under environmental stress conditions. A number of in vitro studies have demonstrated that GBS forms biofilm-like structures on abiotic surfaces. Yet, the presence in these structures of the extracellular matrix typical of bacterial biofilms has not been investigated in this species. Additional studies are also needed to confirm the relevance of biofilm formation in vivo. If this would be the case, the involved virulence factors could constitute new therapeutic and preventive targets against this important human pathogen.Similar to other Gram-positive pathogens colonizing the human host, Group B Dr. Roberto Rosini and Dr. Immaculada Margarit are Novartis Vaccine employees. Dr. Immaculada Margarit holds Novartis stock options.


Sudanese folk medicine represents a unique blend of indigenous cultures with Islamic, Arabic and African traditions. In addition, Sudan encompasses different terrains and climatic zones, ranging from desert and semi-desert in the north to equatorial with a short rainy season (semi-aridand semi-humid) in the centre to equatorial with a long rainy season  in the south. This variation contributes to the immense diversity of vegetation in the region. The flora of Sudan consists of 3137 species of flowering plants belonging to 170 families and 1280 genera. It is estimated that 15% of these plants are endemic to Sudan. The intersection of diverse cultures and the unique geography holds great potential for Sudanese herbal medicine. Medicinal and aromatic plants and their derivatives represent an integral part of life in Sudan. Indigenous remedies are the only form of therapy available to the majority of poor people. It has been estimated that only 11% of the population has access to formal health care. Therefore, research on the desired pharmacological effects and possible unwanted side effects or toxicity is required to improve efficacy and safety of Sudanese herbal medicine. In the future, it would be preferable to promote the use of traditional herbal remedies by conversion of raw plant material into more sophisticated products instead of completely replacing the traditional remedies with synthetic products from industrialized countries. The present review gives an overview of traditional Sudanese medicinal and aromatic herbs and their habitats, traditional uses, and phytochemical constituents.Supplementary material is available for this article at 10.1007/s13659-012-0015-2 and is accessible for authorized users. Supplementary material, approximately 2.03 MB.


Background: There is a critical need for precision phenotyping across neurodevelopmental disorders, especially in individuals who receive a clinical diagnosis of autism spectrum disorder (ASD). Phelan-McDermid deletion syndrome (PMS) is one such example, as it has a high penetrance of ASD. At present, no biometric characterization of the behavioral phenotype within PMS exists.Methods: We introduce a data-type and statistical framework that permits the personalized profiling of naturalistic behaviors. Walking patterns were assessed in 30 participants . Each individual's micro-movement signatures were recorded at 240 Hz. We empirically estimated the parameters of the continuous Gamma family of probability distributions and calculated their ranges. These estimated stochastic signatures were then mapped on the Gamma plane to obtain several statistical indexes for each child. To help visualize complex patterns across the cohort, we introduce new tools that enable the assessment of connectivity and modularity indexes across the peripheral network of rotational joints.Results: Typical walking signatures are absent in all children with PMS as well as in the children with idiopathic-ASD (iASD). Underlying these patterns are atypical leg rotational acceleration signatures that render participants with PMS unstable with rotations that are much faster than controls. The median values of the estimated Gamma parameters serve as a cutoff to automatically separate children with PMS 5–7 years old from adolescents with PMS 12–16 years old, the former displaying more randomness and larger noise. The fluctuations in the arm's motions during the walking also have atypical statistics that separate males from females in PMS and show higher rates of noise accumulation in idiopathic ASD (iASD) children. Despite high heterogeneity, all iASD children have excess noise, a narrow range of probability-distribution shapes across the body joints and a distinct joint network connectivity pattern. Both PMS and iASD have systemic issues with noise in micro-motions across the body with specific signatures for each child that, as a cohort, selectively deviates from controls.Conclusions: We provide a new methodology for precision behavioral phenotyping with the potential to use micro-movement output noise as a natural classifier of neurodevelopmental disorders of known etiology. This approach may help us better understand idiopathic neurodevelopmental disorders and personalize the assessments of natural movements in these populations. SHANK3 gene. SHANK3 codes for a scaffold protein located at the post-synaptic density (PSD) of glutamatergic synapses. Specifically, they are important for the formation and stabilization of synapses, as they assemble glutamate receptors with their intracellular signaling apparatus and cytoskeleton at the PSD  is a complex neurodevelopmental disorder associated with efferent and afferent neurological abnormalities, believed to emerge from underlying impairments in synaptic transmission and synaptic plasticity  that may also serve as an additional source of peripheral afferent feedback. This putative source-component of afferent feedback can be statistically estimated (non-invasively), with millisecond time precision at the motor output level  shares with others. Overt movements are defined by explicit goals and are deliberately performed, whereas covert movements are driven by less obvious implicit goals and are highly automatic. Both movement classes coexist within a gradient of intentionality and contribute to the flow of motions along a continuum , a recent initiative of the National Institutes of Mental Health (NIMH), to “d Insel, . Specifid Insel, . In thisd Insel, .In the specific context of neurodevelopment, this new methodology could equally benefit disorders that result in social deficits and those that do not. We illustrate this framework using the gait patterns of 16 children with PMS in relation to 11 age- and sex-matched controls. Together, with novel analytical methods presented in this study, we provide new visualization tools to examine synchronous patterns of peripheral joints' coordination automatically detecting self-emerging synergies of co-articulated joints across the body. Since there is high penetrance of ASD in PMS . The entire study protocol was approved by the Rutgers University IRB. Clinical records were obtained in compliance with the Health Insurance Portability and Accountability Act (HIPAA). The study conforms to the guidelines of the Helsinki Act for the use of human subjects in research.There were 16 participants with PMS in this study, 9 females and 7 males, ranging from 5 to 15 years old. Eleven of the 16 children were previously described in the literature  and subjects with iASD (3) also participated in the study. Controls included 5 females and 6 males, ranging from 5 to 19 years old, including one 19 year old professional athlete. The three male participants with iASD ranged from 10 to 12 years old. In addition to a diagnosis of ASD, one participant also had a diagnosis of ADHD and Tourette's syndrome. His inclusion served as an interesting point of comparison. Specifically, as there have been reports of comorbid ASD and Tourette's syndrome  and neurological abnormalities.Neurological examinations were conducted by a pediatric neurologist to evaluate gross motor skills and gait, fine motor coordination, cranial nerves and deep tendon reflexes.Autism Diagnostic Observation Schedule-Toddler Module  or Sanger sequencing was used to confirm Since participants with PMS were unable to follow precise verbal instructions and perform decision-making tasks and/or experiments with a variety of cognitive loads, this study examined a naturalistic behavior that they were all able to perform—natural gait. All walking took place on a raised platform to cover the proper distances defining the weak electro-magnetic field created by the sensing system  recording at 240 Hz. The platform also ensures a systematic walking pattern, requiring turns and back-and-forth pacing, across all subjects  period of walking was recorded for each child, which was repeated across a number of sessions, including pre- and post-treatment in a clinical trial with Insulin-Like Growth Factor-1 . This paper focuses on the first (baseline) session.We first analyzed the kinematics layer of raw positional and orientation data along with their inherent variability unique to each individual. The raw displacement and angular rotational data are the outputs of the 15 sensors , 14 attached to the body and one used for calibration and digitization purposes Figure . Data weNmaxV values. Lower values of this normalized parameter thus indicate faster angular speed on average. Likewise joint rotations that are on average slower will produce higher values of the normalized peak angular velocity. Figure Specific trajectory parameters of interest included the time series of joint angular velocities (the rate of change of joint orientations over time) and the joint angular acceleration (the rate of change of angular velocity). Figure n Figure . The norp-value is p < 0.01. Maximum likelihood estimation (MLE) is used to estimate the shape and the scale parameters of the continuous Gamma family of probability distributions with 95% confidence intervals for the motions of each joint. The empirically estimated stochastic signatures of the whole body motions can then be examined as they distribute by individual body segments or as they integrate across the body , to unveil patterns of the peripheral network of rotational joints.The parameters of interest are gathered into a frequency histogram. Here we chose the normalized peak angular velocities and peak angular accelerations to extract the micro-movements waveform. Unimodality of the resulting histogram of micro-movements' peaks is assessed using the Hartigan's dip test  and quantify the magnitude of the shift on the Gamma parameter plane, i.e., the changes in the PDF that arise as a function of context, treatment, etc. These shifts build a stochastic trajectory that is unique to each person under the conditions of choice. These statistical rates of change constitute yet another layer of analyses that provides useful information about the evolution of the statistical patterns of the person and their unique a = 1, the memoryless exponential distribution) to values of a > 10 ranging from skewed to symmetric distributions. In this previous work, shifts to the right of the Gamma parameter plane move the patterns away from randomness  of the motor output signals Torres, . These lss Ross, , toward ss Ross, . These rss Ross, , 2013. Ta) and estimated scale (b) parameters whereby the mean FF is the empirically estimated scale parameter b. Therefore, along the scale axis, higher values of b denote higher noise-to-signal ratio, and lower values of b denote shifts toward more reliable regimes of the continuous random process under study. It should be noted that the term “noise” here has a very precise statistical meaning, in contrast to the negative connotation implied in the motor control literature  Fano, , was als14 joints x 14 joints PLV matrix every 240 frames (240Hz sampling resolution of the sensors). We used a high threshold of synchronization value (0.85) to create a binary matrix. Entries in the original PLV frame that were above or equal to the threshold were set to 1 and those below the threshold were set to 0 . PLV is a statistic used to quantify the phase coupling between two biological nonlinear signals in time-series, such as time-series of electroencephalographic signals , that is, the number of links connecting the node to other nodes in the network. In this case , we provide a simplified representation to illustrate densely vs. sparsely interconnected nodes across the network so as to identify critical differences between controls and PMS-ASD cases.The modularity index provides a sense of the subdivision of the network into non-overlapping groups of nodes that work together within a “community.” This metric assesses self-emerging structuring of the network by maximizing the number of within-group edges, and minimizing the number of between-group edges. Thus, modularity is a statistic that quantifies the degree to which the network may be subdivided into such clearly delineated groups. For example, Figure The clustering coefficient another metric that we can use is the clustering coefficient, i.e., the fraction of triangles around a node, or equivalently, the fraction of node's neighbors that are neighbors of each other. For example, in Figure The This is an arbitrary choice of metrics for visualization and analytical purposes. They are tools that we have adapted (for the first time) from the analyses of central networks of brain nodes  to the peripheral network of joints from bodily rhythms. These modified methods help examine the self-structuring of highly complex motions spanned by the many degrees of freedom (DoF) of the body. They complement our previous work on detection of synergies and co-articulation in goal directed behavior . By examining synchronous sub-networks we can uncover self-emerging synergies and co-articulation patterns at the joint angles level that may inform individual self-regulatory motor control strategies. The motivation here is that examination of a coping neurobiological system -such as that of PMS children- may reveal self-emerging / self-discovered over-compensatory strategies by the nervous systems of some of the children that could help us guide treatment in others with iASD. More importantly the personalized treatment of the problem can help us tailor interventions involving sensory substitution and sensory augmentation therapies well suited to the unique bodily characteristics of each child as the brain tries to control its peripheral joint network dynamics.We refer the reader to Figure In Figure Notice the marked contrast captured by these personalized metrics between the representative control and the representative PMS participant who shows very low connectivity, and very homogeneous modularity distributions. This outcome suggests that the body of the child with PMS does not coordinate synergies as the typical control does. Instead a larger number of independent modules emerge with homogeneous distributions of joint participation across all modules and no synergistic patterns efficiently co-articulating the joints. This is a sign of very atypical motor control requiring far more physical energy to manage many independent modules than to manage a few synergies.We examined the statistical patterns of fluctuations in motor performance (micro-movements) across the body. First we characterized the normative patterns of angular velocity in the feet and identified fundamental statistical differences in the PMS and iASD children with respect to the normative data from controls of various age groups. We then examined the underlying patterns of angular acceleration of the lower body, specifically the legs, and characterized the noise levels of their micro-motions. We then moved up to the upper limbs and examined patterns of the arms' micro-motions during their overall body movements when walking back and forth in the platform of Figure p < 0.01) as all children manifested multimodal distributions  for one foot or for both feet  but the other does not. In subsequent analysis of whole body connectivity patterns, it is evident that these are children whose upper body joint network patterns approach those of typical controls. Figure p > 0.1) stand in marked contrast with the neurotypical controls .All PMS children display unimodal patterns  according to the Hartigan's dip test of unimodality, , with higher noise to signal ratio than other controls are 5–6 years old. At this age the gait patterns are still maturing in the typically developing children  in Figure Finally, we examined connectivity and modularity patterns of the peripheral network of joints. A controllable system must have a good balance between highly interconnected nodes and independence in self-emerging modules that appropriately exploit the abundant degrees of freedom of the body through efficient synergies and patterns of co-articulation. We tested several indexes related to coordination.Figure Figure Notice that in Figure p < 0.01). The PMS group has mean noise values comparable to mean noise found in controls (due to pooling across the different ages) but has an overall broader range, particularly in the higher-noise end .The distributions of the noise-to-signal ratio  empirically estimated from the angular acceleration across all body joints were also found to differ across subjects .Supplementary Figures While the PMS group suffers from the systemic excess rotational acceleration issue, the iASD group suffers from systemically higher noise levels in their micro-movements. This is consistent with the faster rate of accumulation in the iASD empirically estimated cumulative distribution functions (eCDF), see Figures Building on the differences in upper- and lower- body synergies between controls and children with PMS and iASD, we investigated variations in upper body extremities during the walking. To this end we empirically estimated the Gamma parameters from the data of each of the female and male subjects and generated 1000 points per group by randomly choosing from the empirical parameter values of the normalized peak acceleration index.p-value color coded according to significance level (see color bar). Notice that all p-values are extremely small. Even the non-significant entries are very close to 0.05. The most striking feature of the pooled data is the clear separation between males and females in PMS. The differences are also appreciated in the individual eCDFs shown in Figures p-value matrices shown in Figures Figures This work characterizes the stochastic signatures of the patterns of micro-movements across the body in children of different ages with PMS. This statistical characterization was performed in relation to controls and also compared to three male individuals with iASD. The latter small group was used to illustrate a highly heterogeneous disorder with three very different individuals with similar clinical diagnoses with the prospect of identifying some statistical pattern common to all three. The results of this characterization underscore the need for individualized assessments of various layers of data to provide a comprehensive phenotype of the person affected by a neurodevelopmental disorder (in this particular case PMS) and better integrate the knowledge from various layers of basic research and clinical practice Figure .14x3 individuals, 42 different distributions with similar shape and high dispersion).In all atypical cases, we found excess noise and randomness according to the Fano Factor and other statistical indexes. By examining the stochastic signatures of the moment-by-moment fluctuations in motor performance during walking, we were able to separate levels of spontaneous random noise present in most PMS and iASD participants from well-structured, systematic noise with predictive power in neurotypical controls. In addition to the characterization of signatures of motor noise, we found excess rotational acceleration in PMS. Our interpretation of this feature is that it most likely interferes with their volitional motor control. Excessively accelerated rotations were particularly prevalent in the young 5–7 year old subgroup, and in the adolescents, albeit to a lesser extent. In the iASD individuals, the common hallmark was excess noise and the narrow range of shapes of probability distributions across all 14 joints  are descriptive, based on observation, interpretation of the observed behaviors and at best using computerized assessments from hand coded descriptions that are then built into the heuristics of a computer program. Whether by hand or computerized, human heuristics defines discrete aspects of behavior a priori, thus skewing the research to focus on issues that are unambiguous to the naked eye, at the expense of leaving out important spontaneous aspects of behavior that occur largely beneath awareness. Automatic biometric assessment from high grade instrumentation combined with analytics that spontaneously uncover self-emerging patterns from the inherent variability of the data have a chance to accelerate progress toward target treatments and the longitudinal tracking of their effectiveness or risks over different time scales.systemic micro-movement problem in this population, quantifiable in non-invasive and systematic ways. We have proposed that, paired with this excess sensory-motor noise problem, are issues of sensory-motor integration and sensory-motor transformations that can have a direct impact on socio-motor behavior, deficits that may define the phenotype. For example, lack of proper synergies across the body, such as those revealed here in PMS and iASD, would impede efficient body entrainment during dyadic interactions that take place in social exchange during clinical testing. This could be misinterpreted as lack of joint attention. Yet, in reality, under persistent and systemic random noise across the body, it would be challenging to entrain with any external biological rhythms, such as those present in the social scene during clinical testing. Furthermore, the continuous presence of systemic random noise would prevent any type of proper integration of kinesthetic reafferent (movement-based) feedback with external inputs from biological and non-biological motions coexisting in the environment. In this regard, previous work indicates that typical controls are capable of unambiguously differentiating their own stochastic patterns of walking movements from those of others (Johnson et al., The present results speak of a systemic noise problem in disorders that result in a diagnosis of ASD. They extend our previous results in iASD (Torres et al., Further investigations into motor sensing patterns may be important in general to advance our understanding of sensory issues in iASD and other neurodevelopmental disorders. Sensory issues have been previously reported (Dinstein et al., As these minute fluctuations or signatures of motor noise are invisible to the naked eye, the ASD phenomena have been conceptualized as devoid of sensory-motor issues (Lord et al., Central structures participating in the brain networks for forward prediction, such as those in the cerebellum, are likely to be compromised in PMS (Aldinger et al., We propose that the persistently corrupted kinesthetic motor reafference may have origins at the synapse, with different sub-classes of molecular pathways selectively outputting different motor-noise patterns characterized by specific statistical signatures. This is a testable hypothesis that paired with the tools provided here would guide a new type of precision phenotyping in neurodevelopmental research.This study offers a new unifying statistical framework for the personalized analyses of naturalistic behaviors with unprecedented level of detail. We were able to capture and characterize motor phenotypic features of PMS relative to normative data, identify areas of commonality and differences with iASD, and propose a new general statistical platform with the potential to eventually establish a bridge between behavior and genetics at an individualized level Figures . There iET designed the study, analyzed the data and wrote paper; ET, JN, SM, CW, VK, participated in data collection and manuscript preparation; AK provided subject recruitment, clinical supervision and manuscript editing. All authors read and approved the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Rutgers The State University of New Jersey and ET hold three provisional US-international patents for the biometrics presented in the paper.


This is the first attempt to compile a comprehensive and updated species list for Hydrozoa in the Arctic, encompassing both hydroid and medusa stages and including Siphonophorae. We address the hypothesis that the presence of a pelagic stage (holo- or meroplanktonic) was not necessary to successfully recolonize the Arctic by Hydrozoa after the Last Glacial Maximum. Presence-absence data of Hydrozoa in the Arctic were prepared on the basis of historical and present-day literature. The Arctic was divided into ecoregions. Species were grouped into distributional categories according to their worldwide occurrences. Each species was classified according to life history strategy. The similarity of species composition among regions was calculated with the Bray-Curtis index. Average and variation in taxonomic distinctness were used to measure diversity at the taxonomic level. A total of 268 species were recorded. Arctic-boreal species were the most common and dominated each studied region. Nineteen percent of species were restricted to the Arctic. There was a predominance of benthic species over holo- and meroplanktonic species. Arctic, Arctic-Boreal and Boreal species were mostly benthic, while widely distributed species more frequently possessed a pelagic stage. Our results support hypothesis that the presence of a pelagic stage (holo- or meroplanktonic) was not necessary to successfully recolonize the Arctic. The predominance of benthic Hydrozoa suggests that the Arctic could have been colonised after the Last Glacial Maximum by hydroids rafting on floating substrata or recolonising from glacial refugia. The class Hydrozoa is a monophyletic group in the phylum Cnidaria, consisting of approximately 3500 currently described species . The basThe Hydrozoa are a potentially good model for testing hypotheses about dispersal and the colonization of new regions because they have different dispersal strategies related to different life histories. Many Hydrozoa with circumglobal distributions are benthic  which maThe Arctic region is a geologically young system and provides an opportunity for examination of dispersal. In recent geological history (back to Quaternary glaciations), the global sea level has fluctuated approximately 100 m between glacial lowstands and inter-glacial highstands ,13. The Despite extensive records of Hydrozoa in the Arctic from the end of XIX century ,17 to reThe main aims of this study are: (1) to compile an up-to-date list of Hydrozoa occurring in Arctic waters, with their zoogeographic affinities and life cycle strategies; (2) to explore patterns of Hydrozoa distribution and diversity within the Arctic region and (3) to analyse the effect of dispersal ability on distribution. This is the first attempt to create a comprehensive Arctic species register that covers the whole class Hydrozoa, encompassing both polypoid and medusa stages and including Siphonophorae.We address the hypothesis that the presence of a pelagic stage (holo- and meroplanktonic) is not relevant to dispersal capabilities of Hydrozoa and colonization of the Arctic.We use the Arctic Circle (66° 33.5' N) as the boundary of the Arctic, with some extensions. Thus, our area comprises the nearly landlocked Arctic Ocean, and adjacent shelf seas , the Nordic Seas (Greenland and Norwegian seas with southern Greenland and Iceland included), the Labrador Sea, Baffin Bay, Hudson Bay, the High Arctic Archipelago (HAA) . The BerWarm waters of the Atlantic and Pacific Oceans flow northward to the Arctic. Atlantic waters flow into the Arctic Ocean over the 2500 m deep, 500 km wide Fram Strait and the Nordic seas. Pacific waters flow through the shallow and narrow Bering Strait .An Arctic Hydrozoa list, including the zoogeographical affinity and reproductive strategy, is based on data extracted from the literature –21,27–87The study area was divided into regions following Spalding’s ecoregions  with somSpecies were classified into zoogeographical groups in relation to worldwide occurrence, as follows: 1) Arctic—noted only in high polar regions; 2) Arctic-boreal—occurring in both arctic and boreal waters; 3) boreal—found in temperate waters of the North Atlantic and North Pacific, in the present study found only in the sub-Arctic region, i.e. Iceland or/and the Bering Sea; 4) subtropical-Arctic—occurring from the Arctic to subtropical waters, with the Mediterranean region included; 5) cosmopolitan—distributed widely, and extending to tropical regions.The species were categorised into three groups based on their life history strategy: 1) holoplanktonic species, spend their whole life as pelagic forms, 2) meroplanktonic species, have both a benthic and a pelagic stage, 3) benthic species, those that reproduce by means of fixed gonophores and those that produce short-lived, reduced medusae (eumedusoids and cryptomedusoids). For the purpose of the analyses, species that produce medusoids are grouped with benthic species because medusoids are short-lived and have limited dispersal ability .Two diversity measures independent of sampling effort and sample size were employed to compare diversity at different taxonomic levels in different Arctic regions. Average taxonomic distinctness (AvTD) is the average taxonomic path length between all pairs of species . VariatiMultivariate analysis was used to identify patterns of hydroid species distribution. The similarity of species composition between Arctic regions was calculated with the Bray-Curtis index. These regions were then classified into groups by hierarchical agglomerative clustering using group-average linking, and the resulting classification presented as a dendrogram. Cluster and diversity analyses were performed with Primer package v. 6 .Pearson's chi-square test was used to test for differences in the occurrence of hydrozoan species with medusa or polyp stage between the zoogeographical categories and to measure whether the proportions of the groups differed between polar regions.In the Arctic, the class Hydrozoa is represented by two subclasses, six orders, 54 families, 140 genera and 305 species , Table 1The fauna was dominated by the family Sertulariidae with 62 species (21% of the hydrozoan species known for the Arctic region). Sertulariidae was the most species-rich family in each studied Arctic region (from seven species in the Beaufort & High Arctic Archipelago (HAA) to 44 species in Alaska & Bering Sea). The next most species-rich families were Haleciidae (7%), and Campanulariidae (5%).Highest species richness was noted in the Barents Sea, and lowest in the Hudson Complex, Beaufort Sea & HAA and Central Polar Basin (CPB) .The AvTD values for the studied regions generally fell within the 95% probability funnel. However, the value for most of the regions lay below the expected mean . Two regCluster analysis was used to examine the similarity of species occurrence in different Arctic regions, and clustered regions into three groups. The first group comprised the CPB and the Beaufort Sea & HAA; the second group included Alaska & Bering Sea; the third group was split into four subgroups: (a) East Canada and Hudson Complex, (b) Norwegian Sea, Iceland, the Barents Sea and Western Greenland, (c) White and Kara Seas, East Siberian and Laptev Seas and Chukchi Sea, and (d) Eastern Greenland .The zoogeographical affinity of each species is presented in the The proportions of zoogeographical groups were similar among the studied polar regions . Each re2 = 10.5, df = 2, p = 0.005). While benthic species represented a similar ratio in both pools, the number of holoplanktonic species was proportionally greater in the Arctic and the number of meroplanktonic species lower.Most of the species in the studied region was benthic . Twenty percent of species (54 species) displayed a holoplanktonic life history, while 16% (43 species) possessed both benthic and planktonic stages. The number of species with various life cycle strategies differed between the Arctic species pool and the global species pool   . BenthicThe CPB and Beaufort Sea & HAA had a higher proportion of species with a pelagic stage (mostly holoplanktonic taxa) during their life history (i.e. more than 50%), compared to the other regions where, in contrary, benthic species constituted more than 60% .The species list compiled from the literature revealed an overall hydrozoan species richness for the Arctic of 268. Species in the order Leptothecata dominate (55%), with Anthoathecata forming the second largest group (29%). Such proportion almost mirrors that of the global species pool, where the global ratio between these two orders is 59% to 32% . SlightlThe most species rich families in the Arctic are Sertulariidae 21%) which dominated in each studied region, Haleciidae (7%) and Campanulariidae (5%). These families are the most specious in many areas in the world, including, for example, the Indian Ocean , Bay of 1% which Species richness (S) and other diversity indices  are heavily dependent on sampling effort . When saMost of the Arctic regions (except the White Sea and Iceland) fall into the probability funnel for simulated average taxonomic distinctness (AvTD) and variation in taxonomic distinctness (VarTD), revealing that they involve good representatives of Arctic taxonomic diversity. The Iceland species list is not complete because boreal species that were only present in Iceland were not included in the Arctic master list . The speSome regions share patterns of taxonomic relatedness of species. For instance, Alaska & Bering Sea and the Barents Sea are characterized by high species richness and a VarTD value also above the expected level, while AvTD is at the lower limit of the funnel. Low AvTD and high VarTD values can be attributed to the relatively lower number of higher taxonomic ranks (compared to the number of species) and uneven species distribution across the hierarchical taxonomic tree.In the Beaufort Sea & High Arctic Archipelago (HAA) and the Central Polar Basin (CPB) both AvTD and VarTD reached their highest values, even though species richness was low in these regions. This indicates that these groups of species were taxonomically very distinct (about every second species in a different family). These results confirm the independence of both taxonomic distinctness indices from the sampling effort and species richness. Increased taxonomic distinctness of assemblages has been attributed to greater stability of environmental conditions both in an evolutionary and an ecological context . The BeaCluster analysis was used to analyze the similarity of species occurrence in different Arctic regions. Regions separated into two main clusters: firstly, the CPB and Beaufort Sea & HAA, at 55% similarity. As mentioned above, both regions shared similar trends in diversity indices: low species richness but taxonomically very distinct (high AvTD and VarTD) and in species composition: lack of boreal species, lower percentage of benthic taxa and higher percentage of taxa having a pelagic phase (mostly holoplanktonic).Secondly, a more diverse assemblage, consisting of three groups and two regions split off from the rest. The distinction of Alaska & Bering Sea is clearly noticeable. This region is geographically the most isolated from the Arctic Ocean. The Bering Strait is a shallow (50 m deep) and narrow (82 km wide at its narrowest point) connection between the Bering Sea and the Chukchi Sea. Thirty six species were found exclusively in Alaska & Bering Sea and did not enter the Bering Strait and Arctic Ocean. Of them, 21 species are boreal and the Bering Sea is the northernmost limit of their distribution. Fourteen species of the family Sertulariidae are absent from other Arctic regions.Heteropyramis crystallina, H. maculata and Muggiaea kochi) and the hydromedusa (Hebella scandens) were most likely occasional visitors. Single records of Lafoea symmetrica and Hydractinia arctica are known only from deep waters. When these species are excluded from the analysis the grouping is totally different, with E Greenland combining with W Greenland, E Canada, Iceland, the Barents and Norwegian Seas. Analyses with a presence/absence database introduce bias resulting from giving equal weight to all species, regardless of whether they are rare or common [E Greenland is another region separated from the remaining groups. This is due to the single occurrence of six rare species that were exclusively noted in this region. Cosmopolitan siphonophores  than to the Alaska & Bering Sea fauna. The majority of species in the Chukchi Sea have a circumpolar distribution. Only 4 species were restricted to Pacific Arctic waters: y Dunton  who obsey Dunton , who notThe next group, in which the Norwegian and Barents seas, W Greenland and Iceland are clustered together, is under the direct influence of Atlantic waters, which may explain the similarity in species composition in these regions. Relatively warm and saline Atlantic water flows northward with the main inflow along the Norwegian and Barents seas and west Svalbard continental margins . Anotherin situ survival of macrofauna in these areas [The hydrozoan fauna in the Arctic is dominated by Arctic-boreal species and includes a small fraction of exclusively Arctic species (19%). The dominance by Arctic-boreal forms, the lack of endemism of higher taxa and the very low level of species endemism is typical of Arctic fauna and flora ,100,101.se areas . The Chuse areas ,105. Somse areas , the latse areas .The Arctic is influenced by both Pacific and Atlantic waters, but more so by the Atlantic . The conObelia geniculata, Lafoea dumosa, Nemertesia antennina, Plumularia setacea) could in fact be cryptic species complexes [Predominance of benthic species over holo- and meroplanktonic species is a common attribute of Hydrozoa worldwide. In the Arctic, 64% of species are benthic and have only a planula larva for their dispersal stage. Even in the CPB and Beaufort & HAA, benthic species constitute a high proportion of the community. The largest number of more widespread species in the Arctic (present in most ecoregions) belong to families that completely lack the medusa stage, including Sertulariidae and Haleciidae. Moreover, many cosmopolitan hydrozoans both in the Arctic (present study) and globally lack a pelagic stage . TherefoEudendrium album and Sertularia argentea [Clava multicornis [Gonothyraea loveni [The traditional view of Hydrozoa is that holo- and meroplanktonic species will have a better dispersal potential and a more extensive distribution than benthic species, whose only means of dispersal is a rather short-lived, lecithotrophic planula larva ,111. Thiargentea , Clava mticornis , Gonothya loveni ).A totally different strategy is employed by holoplanktonic siphonophores, most of which are hermaphrodite, or monoecious (both sexes present on the same colony)  to reducData collected and analysed in the present study are subject to bias resulting from variation in the sampling effort undertaken through historical time in particular regions, extension of ecoregions and their accessibility. There is also a strong imbalance in the literature which underestimates the pelagic community of Hydrozoa in favour of higher sampling effort of benthic habitats; this imbalance is further exacerbated by the destructive nature of net sampling which destroys delicate jellyfish zooplankton into unrecognizable blobs. Another potential limitation of the present study  results from integration of data through time and space when and where different people identified species in different time and regional scales. We tried to eliminate this issue by checking all possible synonyms .The total species richness of Hydrozoa in the Arctic was 268 with Sertulariide being the most speciose family. The hypothesis that the presence of a pelagic stage (holo- or meroplanktonic) was not necessary for successful recolonization of the Arctic is supported by our analyses. The predominance of benthic Hydrozoa suggests that the Arctic could have been colonised after the Last Glacial Maximum by hydroids rafting on floating substrata, or recolonizing from glacial refuges. Nevertheless, as holoplanktonic or meroplanktonic species outweigh the benthic species in widely distributed categories such as cosmopolitan, subtropical-Arctic and bipolar, we cannot deny that having the medusa or pelagic stage (e.g. as in the case for Siphonophora) is also an important mean of dispersal. Most Arctic hydrozoan species have Arctic-boreal distributions. The hydrozoan fauna shows a very low level of endemism, a common phenomenon in other Arctic macrofaunal groups.We acknowledge the severe problem of imbalance in knowledge of particular regions in the Arctic as well as in sampling effort between pelagic versus benthic domains. The results of our comparative analyses may therefore change with time, when more data are available.S1 Table(DOC)Click here for additional data file.S2 Table(DOC)Click here for additional data file.


Patients admitted to the intensive care unit with critical illness often experience significant physical impairments, which typically persist for many years following resolution of the original illness. Physical rehabilitation interventions that enhance restoration of physical function have been evaluated across the continuum of recovery following critical illness including within the intensive care unit, following discharge to the ward and beyond hospital discharge. Multiple systematic reviews have been published appraising the expanding evidence investigating these physical rehabilitation interventions, although there appears to be variability in review methodology and quality. We aim to conduct an overview of existing systematic reviews of physical rehabilitation interventions for adult intensive care patients across the continuum of recovery.This protocol has been developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) guidelines. We will search the Cochrane Systematic Review Database, Database of Abstracts of Reviews of Effectiveness, Cochrane Central Register of Controlled Trials, MEDLINE, Excerpta Medica Database and Cumulative Index to Nursing and Allied Health Literature databases. We will include systematic reviews of randomised controlled trials of adult patients, admitted to the intensive care unit and who have received physical rehabilitation interventions at any time point during their recovery. Data extraction will include systematic review aims and rationale, study types, populations, interventions, comparators, outcomes and quality appraisal method. Primary outcomes of interest will focus on findings reflecting recovery of physical function. Quality of reporting and methodological quality will be appraised using the PRISMA checklist and the Assessment of Multiple Systematic Reviews tool.We anticipate the findings from this novel overview of systematic reviews will contribute to the synthesis and interpretation of existing evidence regarding physical rehabilitation interventions and physical recovery in post-critical illness patients across the continuum of recovery.CRD42015001068.PROSPERO  Admission to the intensive care unit (ICU) with critical illness is typically associated with significant morbidity for survivors, including profound impairment in physical strength and functional performance. These symptoms contribute to the ‘post-intensive care syndrome’ evident in survivors of critical illness  and havePhysical rehabilitation interventions are advocated to address physical and functional deficits associated with ICU-AW, and delivery is advocated across the continuum of the patient pathway commencing in the ICU, following transfer to the ward and beyond hospital discharge into the community . TypicalAs the profile of physical rehabilitation for critical illness patients has increased and the volume of published data exploring the effectiveness of interventions has grown, multiple systematic reviews have been reported aiming to synthesise available evidence and draw conclusions on the most beneficial therapeutic options. A number of these have focused on interventions delivered within the ICU, e.g. Kayambu et al. , Calvo-AWe will carry out an overview of existing Systematic review (SR) evaluating physical rehabilitation interventions for adult patients with critical illness patients across the continuum of recovery. Variability in the review question and population, intervention, comparator and outcome components across the large body of currently available reviews is a limiting factor to the overall synthesis of their findings and translation into clinical practice. An overview of SR offers a logical and appropriate step allowing comparison and contrast of individual reviews to be made and providing a precis of evidence at these different levels .At which stage of the post-critical illness recovery continuum  do physical rehabilitation interventions have the most effect?Do particular patient populations gain more benefit from post-critical illness physical rehabilitation interventions than others?Which type of physical rehabilitation interventions produce benefits (short- and long-term) for post-critical illness patients?What adverse events or harmful effects are experienced from receipt of any physical rehabilitation interventions?Undertaking an overview of existing reviews is a novel approach within the field of physical rehabilitation following critical illness. Adopting this strategy, our aim is to summarise and appraise the best available evidence for the use of physical rehabilitation interventions across the continuum of recovery following critical illness, to address the following questions:CRD42015001068).Our protocol has been written using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P)  and is rWe will search the Cochrane Systematic Review Database, Database of Abstracts of Reviews of Effectiveness, Cochrane Central Register of Controlled Trials (CENTRAL), Ovid SP MEDLINE, Ovid SP Excerpta Medica Database (EMBASE) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) via EBSCO host. All authors contributed to devising the search strategies for each database using a combination of subject headings and free-text keywords to describe critical illness, physical rehabilitation interventions and the different stages of the recovery continuum. Table Following initial removal of duplicate and non-relevant material, two review authors will independently screen search results (based on abstract and title) against inclusion criteria (see below) for full-text review . Full-text papers will then be further screened for eligibility. A bespoke assessment of study eligibility form will be used for documentation. In the absence of consensus, arbitration by a third author (KM) will be sought. References will be managed in Endnote v7.0 (Thomson Reuters).We will include systematic reviews of randomised controlled trials (RCTs) investigating the effect of any physical rehabilitation interventions following critical illness at any stage of the recovery continuum. If a review includes quasi-RCTs in addition to RCTs, we will also include these. Where non-RCTS are included in the review, the review will be included only if the RCTs are reported separately.Participants will be adult patients who have been admitted to the ICU with critical illness, irrespective of causal diagnosis. We will exclude systematic reviews that only include studies of short-stay post-operative management (less than 48-h length of stay in the ICU). This is to focus the review content on patients considered most likely to develop intensive care unit-acquired weakness and go on to experience the physical consequences of critical illness and require physical rehabilitation interventions. Data extraction will include details of the populations included in each eligible systematic review, and these can be discussed and interpreted accordingly.We will include all types of physical rehabilitation interventions including exercise-based treatments and adjunctive strategies such as electrical muscle stimulation or cycling. These interventions can either be compared to control interventions  or an alternative physical rehabilitation. We will exclude reviews including studies of composite interventions such as combined physical and cognitive rehabilitation and reviews including studies where the comparator was the same intervention but delivered at a different level of intensity.Primary outcomes of interest are findings reflecting the recovery of any aspect of physical function, long-term measures of physical function or its surrogates. Where applicable, these outcomes will be summarised according to type of physical rehabilitation intervention, e.g. exercise-based rehabilitation programmes or electrical stimulation, and time point of assessment and duration of follow-up .Secondary outcomes will include the following: structure, content and format of physical rehabilitation interventions according to recovery continuum stage; details on specific patient populations examined in each included review; reported rates of adverse events or harmful effects associated with interventions; and effect on other domains of outcome such as health-related quality of life where examined and reported.Data extraction and analysis will be conducted in line with guidance from the Cochrane Handbook of Systematic Reviews of Interventions. Full texts of included reviews will be retrieved. Two review authors (LS and BO’N) will independently extract descriptive and outcome data from each included review. A third review author (KM) will arbitrate in the event that discrepancies cannot be resolved by consensus. A bespoke data extraction form will be designed, piloted and used to record review features including the aims and rationale, types of studies included, population(s), intervention(s), comparator(s), outcomes  and date of last search and methods of assessing quality of studies. In the event that we include more than one review containing the same studies, we will examine the review question and comparisons explored, the date of the last search and key aspects of methodological quality (e.g. types of studies included and risk of bias assessment) and will list the individual studies included in each of the review. In this way, we will enable identification of trials included in one review but not another. Using these data, we will determine which of the reviews should contribute data to the results based on the review with the more current search strategy and more recent trials.Two review authors (BC and BB) will independently assess the quality of reporting and the methodological quality of included reviews using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)  checklisWe will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach  to assesReasons for missing data will be recorded as reported by the original reviews. If the original reviews included this detail, we will report the number of studies that performed intention-to-treat or per protocol analyses.I2 statistic for heterogeneity [Data will be presented as a narrative synthesis, with textual commentary supplemented with use of summary tables and figures to enhance clarity of reporting . We willogeneity . We willogeneity , 29. FloIf applicable, we will conduct sensitivity analysis in relation to studies of differing methodological quality.Depending on sufficiency of reviews, we plan to analyse the main functional outcomes according to patient population , intervention  and setting .The findings of this overview of systematic reviews of physical rehabilitation for adult patients with critical illness across the continuum of recovery will potentially have implications for clinical practice, research and future guideline development and update. It is intended that our results provide greater clarity and synthesis of available evidence on the most effective physical rehabilitation interventions to deliver according to the stage of recovery following critical illness. This is likely to have impact on existing and planned resource allocation in the clinical environment, inform the direction of future research including randomised controlled trials of intervention effectiveness and underpin guideline recommendations. Conclusions from this overview will highlight which, if any, physical rehabilitation interventions demonstrate clear benefit and those for which there is no clear evidence at which, if any, stage in the continuum of recovery. If sufficient data are available, our findings may also add clarity to the ‘dose’ of physical rehabilitation intervention, i.e. type, timing, intensity, duration and also circumstances under which any adverse effects of harm was caused as a result of the intervention.We plan to follow the approach outlined by the Cochrane Collaboration for undertaking an overview . As suchIt is intended that this overview will provide insight regarding considerations for the design and conduct of future interventional trials of physical rehabilitation intervention in the post-critical illness population, acknowledged to be complex studies .