Edmontosaurus, a member of the sub-clade Hadrosaurinae, they were recently assigned to a newly-erected taxon, Ugrunaaluk kuukpikensis. However, taxonomic status of the new taxon is ambiguous largely due to the immature nature of the specimens upon which it was based. Here we reexamine cranial elements of the Prince Creek Formation hadrosaurine in order to solve its taxonomic uncertainties. The Prince Creek Formation hadrosaurine possesses a short dorsolateral process of the laterosphenoid, one of the diagnostic characters of Edmontosaurus. The Prince Creek Formation hadrosaurine also shows affinity to Edmontosaurus regalis in the presence of a horizontal shelf of the jugal. Our morphological comparisons with other North American Edmontosaurus specimens and our phylogenetic analyses demonstrate that the Prince Creek Formation hadrosaurine should be re-assigned to Edmontosaurus. Because the Prince Creek Formation Edmontosaurus shows differences with lower latitude Edmontosaurus in a dorsoventrally short maxilla, presence of a secondary ridge on the dentary teeth, and the absence of the transverse ridge between basipterygoid processes of the basisphenoid, we consider that the Prince Creek Formation Edmontosaurus should be regarded as Edmontosaurus sp. until further discoveries of mature hadrosaurines from the Prince Creek Formation Bonebed and/or equivalently juvenile Edmontosaurus specimens from the lower latitudes allow direct comparisons. The retention of the Prince Creek Formation hadrosaurine as Edmontosaurus re-establishes a significant latitudinal distribution for this taxon. Despite the large latitudinal distribution of the taxon, the morphological disparity of Edmontosaurus is small within Hadrosaurinae. The small morphological disparity may be related to the relatively low latitudinal temperature gradient during the latest Cretaceous compared to present day, a gradient which might not have imposed significant pressure for much morphological adaptations across a broad latitudinal range.Hadrosaurid fossils from the Liscomb Bonebed  were the first dinosaur bones discovered from the Arctic. While the Prince Creek Formation hadrosaurids were long identified as  Increasing work in the Late Cretaceous deposits of the palaeo- Arctic is revealing higher dinosaur diversity in the region than had been previously recognized –3. The m2 [Edmontosaurus saskachewanensis, which is now a junior synonym of Edmontosaurus annectens [Edmontosaurus [Ugrunaaluk kuukpikensis. However, the taxonomic status of the PCF hadrosaurid remains ambiguous. Xing et al. [Ugrunaaluk kuukpikensis is not a valid taxon, because it is based upon disarticulated and disassociated parts from multiple, immature individuals that are not ontogenetically comparable to known specimens of Edmontosaurus annectens and Edmontosaurus regalis. Furthermore, the recent discovery of lambeosaurine material from the Liscomb Bonebed demonstrated that the PCF bears at least two different kinds of hadrosaurids [Ugrunaaluk kuukpikensis could be chimeric. Therefore, reexamination of the PCF hadrosaurine material is mandatory in order to either uphold or refute the taxonomic validity of Ugrunaaluk kuukpikensis.Among the most abundant dinosaurs collected in Alaska are the bones attributable to members of the large herbivorous group, the Hadrosauridae. Almost all of the hadrosaurid body fossils in Alaska come from the Upper Cretaceous Prince Creek Formation (PCF), which crops out along the Colville River, North Slope, Alaska. The Liscomb Bonebed in the PCF is especially rich in hadrosaurid fossils (up to 220 elements/m2 ). The do2 , but Nel2  later idnnectens . Althougtosaurus , 30–35, tosaurus  recentlyg et al.  and Wosig et al.  both proosaurids , raisingEdmontosaurus may resolve the taxonomic uncertainty of the PCF hadrosaurine. Reexamination of the PCF hadrosaurine from the Arctic also offers the opportunity to understand how latitudinal environmental differences might have influenced hadrosaurid evolution.Here we present the first full description of the cranial elements of the PCF hadrosaurine. We focus on cranial material due to the difficulties in distinguishing immature hadrosaurine postcranial elements from those of lambeosaurines –42, emphAMNH FARB, American Museum of Natural History, New York, USA; CMN, Canadian Museum of Nature, Ottawa, Canada; DMNH, Perot Museum of Nature and Science, Dallas, USA; DMNH EPV, Denver Museum of Nature and Science, Denver, USA; NMMNH P, New Mexico Museum of Natural History and Science, Albuquerque, USA; ROM, Royal Ontario Museum, Toronto, Canada; TMP, Royal Tyrrell Museum of Paleontology, Drumheller, Canada; UAMES, University of Alaska Museum, Fairbanks, USA; USNM, United States National Museum, Smithsonian Institution, Washington, DC, USA.As travel funds were a limiting factor for RT during this study, for the purposes of fiscal efficiency, high-quality casts of UAMES specimens that are housed at CMN were included in this study.Edmontosaurus annectens , Edmontosaurus regalis , Laiyangosaurus youngi [Shantungosaurus [Brachylophosaurus canadensis  Edmontosaurus regalis , Gryposaurus notabilis , and immature Edmontosaurus annectens . The short prenarial region may either represent the immature state in Edmontosaurini [Edmontosaurus regalis [Edmontosaurus annectens  and Edmontosaurus regalis  specimens, but resembles those of Acristavus gagslarsoni [Brachylophosaurus canadensis [Naashoibitosaurus ostromi (NMMNH P-16106). The apex of the dorsal process is located slightly anterior to the midline of the maxilla as in other immature hadrosauroids [Laiyangosaurus youngi [The maxilla bears an anterodorsal process and lacks a wide premaxillary shelf as in typical hadrosaurines . This dinadensis  and Acrislarsoni  which arslarsoni , Brachylnadensis , and Naasauroids , 56, 57.sauroids , 57. As sauroids  pointed s youngi .Gryposaurus notabilis . The medial surface of the anterodorsal process is flat or slightly concave dorsoventrally for contact with its counterpart proximally and with the premaxilla distally. The lateral surface of the anterodorsal process bears a distinct posterodorsal ridge that defines the posterodorsal margin of the circumnarial fossa. The posterodorsal ridge is well-developed as in Edmontosaurus annectens , Edmontosaurus regalis , Kerberosaurus manakini [Shantungosaurus giganteus [Kerberosaurus manakini [Edmontosaurus annectens  and Edmontosaurus regalis [Edmontosaurus annectens .The nasal (UAMES 4271) is composed of the elongated anterodorsal process, the main body, and a triangular anteroventral process  as in otmanakini , 60 and manakini , 60 but  regalis  in whichThe triangular anteroventral process projects anteroventrally from the main body of the nasal and is partly covered by the premaxilla laterally. The contact surface with the premaxilla is defined dorsally by the ventral ridge of the main body. The main body of the nasal is trapezoidal and its flat dorsal surface bears a shallow depression posterolaterally for contact with the prefrontal.Edmontosaurus annectens and Edmontosaurus regalis [Edmontosaurus annectens  and Edmontosaurus regalis . Since the anterior margins of the prefrontal of relatively immature Edmontosaurus annectens are bifurcated , the feature in the PCF hadrosaurine may vary ontogenetically, although it is currently untestable. The lateral surface of the preorbital region is smooth in DMNH 22972 but is penetrated by several foramina in some other specimens . The orbital margin forms a smooth right-angle anterodorsally, unlike the gently arcuate anterodorsal orbital margins of Brachylophosaurus canadensis (CMN 8893), Maiasaura peeblesorum [Saurolophus osborni , but similar to Edmontosaurus annectens and Edmontosaurus regalis [Edmontosaurus annectens specimens  and Kerberosaurus manakini [Edmontosaurus [The prefrontal lacks a posterodorsal process  and Edmontosaurus regalis [Edmontosaurus regalis [Probrachylophosaurus [Edmontosaurus annectens in which the duct is open medially  are much longer anteroposteriorly than its dorsoventral height , unlike blesorum  and Bracnadensis , 63. Unl regalis , contact regalis  and Probhosaurus , but unlmedially . The venEdmontosaurus annectens of comparable size, and they proposed that a hypothetical ontogenetic trajectory of this feature would be distinct from that of Edmontosaurus. However, additional observations of Edmontosaurus annectens jugals demonstrate a high degree of intraspecific variation in this angle regardless of size .A right jugal UAMES 4187 is nearly complete . Its ant of size . Further process , 60. The regalis . The venEdmontosaurus regalis [Edmontosaurus annectens , Edmontosaurus regalis , Kamuysaurus japonicus [Kerberosaurus manakini [The postorbital process of the jugal is inclined ~73 degrees posterodorsally relative to the line connecting the ventral apices of the infratemporal fenestra and the orbit. The postorbital process bears the horizontal shelf on the postorbital process of the jugal as in  regalis . The venaponicus , and Kermanakini , 60. TheEdmontosaurus regalis , but is different from the strongly hooked posteroventral corners of Brachylophosaurus canadensis  and Maiasaura peeblesorum . The anterior half of the lateral surface is slightly depressed, forming the jugal contact. The quadrate contact faces posteriorly in some  and posteromedially in other specimens , demonstrating some morphological variation within the sample, which may represent the unintended inclusion of lambeosaurine quadratojugals in the studied sample.The quadratojugal is flat and slightly bowed laterally . Its posEdmontosaurus annectens , Saurolophus angustirostris [Gryposaurus notabilis (TMP 1980.022.0001) and Brachylophosaurus canadensis (CMN 8893). A symmetrical, arcuate quadratojugal notch is located well below mid-height of the quadrate, unlike in lambeosaurines. The quadratojugal notch is shallow and barely reaches half of the anteroposterior depth of the lateral flange. The quadratojugal notch is dorsoventrally asymmetrical, being deeper ventrally than dorsally. The posterodorsal margin of the quadratojugal notch is shallowly grooved. The lateral surface of the quadrate dorsal to the quadratojugal notch lacks a large depression for the lateral scarf joint connection with the quadratojugal, as seen in nestling Edmontosaurus annectens [Edmontosaurus annectens . The posterolateral spur is located slightly dorsal to the posterior apex of the quadratojugal notch. A groove for contact with the posteroventral projection of the quadrate ramus of the pterygoid is present anterior to the posterolateral spur. Ventrally, the medial condyle is reduced and positioned dorsal to the lateral condyle as in other hadrosaurids. The lateral condyle is slightly longer anteroposteriorly than mediolateral width of the ventral end of the quadrate in some specimens (e.g. DMNH 2014-12-567), resembling to nestling Edmontosaurus annectens [The quadrate  is bowed . The precotyloid fossa is triangular in lateral aspect and terminates anterior to the dorsal apex of the quadrate cotylus. The postcotyloid process is massive and its posteroventral surface is striated for contact with the exoccipital paroccipital process. The medial ramus is straight and defines the posterior margin of the supratemporal fenestra. Its medial surface is extremely rugose for contact with the parietal.The squamosal is dorsoventrally short  and especially of Edmontosaurus regalis . Although Mori et al. [Edmontosaurus, this feature changes drastically through ontogeny in Edmontosaurus [Edmontosaurus annectens (ROM 53513) [Edmontosaurus annectens. Since postorbital pocket of Edmontosaurus regalis is much wider than that of Edmontosaurus annectens [Edmontosaurus regalis, although the absence of an equivalently-immature Edmontosaurus regalis postorbital hinders further comparisons. As a result, it is impossible to confirm either the presence or absence of this character in Edmontosaurus regalis, and hence renders its utility as a diagnostic character of the PCF taxon highly suspect.The postorbital is a triradiate bone composed of anteromedial, squamosal, and jugal processes . The doriganteus  and is si et al.  emphasiztosaurus , 37. TheM 53513) . HoweverEdmontosaurus and Shantungosaurus giganteus [The anterior half of the parietal is known . The doriganteus , 37. TheEdmontosaurus annectens, Edmontosaurus regalis, and Shantungosaurus giganteus [Kamuysaurus japonicus [Kerberosaurus manakini and Shantungosaurus giganteus [The frontal of the PCF hadrosaurine is nearly twice as long as it is mediolaterally wide . The eniganteus , 60. TheEdmontosaurus regalis [The palatine process and the distal half of the dorsal quadrate process are missing in the available pterygoid . The posteroventral process is recurved ventrally to overlap the posterodorsal surface of the maxilla. Medially, the triangular process, a feature present in members of Hadrosaurinae [The anterior process of the ectopterygoid  is dorsoventrally thin . The possaurinae , is locaEdmontosaurus regalis [The dorsal process of the palatine is robust . The wide horizontal groove for the ophthalmic branch (CN V1) extends anteriorly from the foramen for the trigeminal nerve. The region between the anterior margin of the trigeminal nerve and the anteroventral ridge is short, and associated with the anteroposteriorly short contact with the basisphenoid. The region is anteroposteriorly as long or shorter than the dorsoventral height of the trigeminal nerve as in Edmontosaurus annectens , Edmontosaurus regalis (CMN 2288), and Saurolophus osborni (AMNH FARB 5221), but unlike in Brachylophosaurus canadensis (CMN 8893), Gryposaurus notabilis (AMNH FARB 5350), and Maiasaura peeblesorum (ROM 66181) in which the region is much longer. The passage for the mandibular branch (CN V3) is absent in the available laterosphenoids of the PCF hadrosaurines.The laterosphenoid  is a subtriangular bone composed of the dorsolateral process, the orbital flange, and the temporal plate . The dorthan 90%   and resembles those of Edmontosaurus annectens (CMN 8509) and Edmontosaurus regalis (CMN 2289). The lateral surface ventral to the trigeminal foramen is excavated to form a scarf joint with the alar process of the basisphenoid. The mediolaterally thin posterodorsal process of the prootic contacts the exoccipital medially and the parietal dorsally.The main body of the prootic defines the dorsal, posterior, and ventral margins of the trigeminal foramen , but shallower in smaller specimens . The ascending process is wide and low in small specimens and becomes narrower and taller in large specimens, occupying much less than the maximum mediolateral width of the supraoccipital. The posterior surface of the ascending process is markedly inclined anterodorsally. The anteromedial surface of the supraoccipital defines the smooth posterior surface of the endocranial cavity. The ventrolateral surface of the anterior process is triangular and contacts with the posterodorsal process of the prootic [Prosaurolophus maximus [Prosaurolophus maximus [Gryposaurus notabilis [The hadrosaurine supraoccipitals  lack squamosal bosses and are anteroposteriorly elongated , unlike  prootic . Whether maximus , is uncl maximus  and GrypBrachylophosaurus canadensis (CMN 8893), Edmontosaurus annectens , Edmontosaurus regalis [Prosaurolophus maximus [Corythosaurus casuarius, ROM 776; Parasaurolophus tubicen, NMMNH P25100) [Hypacrosaurus altispinus), suggesting that UAMES 34723 could possibly belong to a member of Lambeosaurinae. This feature could also be individually variable, as in some Edmontosaurus annectens . The posterior surface for contact with the basioccipital is extremely rugose. The bulbous posterior region of the basisphenoid forms the anterior parts of the paired sphenooccipital tubera, which are less developed than those of other hadrosaurines such as Brachylophosaurus canadensis (CMN 8893) and larger Edmontosaurus annectens (CMN 8509). The sphenooccipital tubera are likely to develop ontogenetically as they fuse with the basioccipital. The sphenooccipital tubera are separated ventrally by a shallow groove at the midline. Two parallel grooves run anteroposteriorly along the dorsal surface of the sphenooccipital tubera for the oculomotor nerve (CN III) [The basipterygoid processes of the basisphenoid  . Each ba(CN III) .Prosaurolophus maximus [Edmontosaurus annectens (ROM 53538) but is less angled than in larger Edmontosaurus annectens .In dorsal aspect, the basioccipital is a sub-circular bone that is slightly longer anteroposteriorly than mediolaterally wide . The median dorsal process is not preserved. The bi-lobed ventral process at the posteroventral margin of the predentary diverges at its base and is much less developed compared to the predentary of larger Edmontosaurus annectens .The right half of the anterior ramus of the predentary is preserved , but resembles immature specimens of Edmontosaurus annectens . The symphyseal process of the dentary is gently curved lingually and is generally 1.5 times as mediolaterally wide as the minimum mediolateral width of the dentary immediately posterior to it, unlike in lambeosaurines which have wider symphyseal process [Brachylophosaurus canadensis (CMN 8893) which is strongly concave. The lengths of the proximal edentulous margins vary from 12% to 17% of the length from the anterior end of the alveoli to the posterior margin of the coronoid process in the available specimens. These values are lower than those of larger but still immature individuals of Edmontosaurus annectens  as Mori et al. [Brachylophosaurus canadensis (CMN 8893) and some specimens of Edmontosaurus annectens . The anteroposterior expansion of the coronoid process is more developed anteriorly than posteriorly as in immature Edmontosaurus annectens . The base of the coronoid process is widely separated from the dentary dental battery by a deep depression unlike in a nestling Edmontosaurus annectens [Multiple nearly complete dentaries are preserved  demonstrates a maximum of two functional maxillary teeth per alveolus . One proEdmontosaurus regalis (present in a few teeth of CMN 2289) and lambeosaurines [Edmontosaurus [Kamuysaurus japonicus [Gryposaurus notabilis (AMNH FARB 8526) and Corythosaurus casuarius (AMNH FARB 3971) that are formed of multiple small protrusions. In an isolated teeth (DMNH 22338), the root is angled more than 140° from the tooth crown in distal/mesial aspect.Left and right hadrosaurine dentaries compressed against each other (DMNH 22851) demonstrate at least two functional teeth are present in each of the dentary’s anterior tooth rows , althougsaurines , 75. Thetosaurus , 73 and aponicus , but unlEdmontosaurus annectens and Edmontosaurus regalis.Two phylogenetic analyses were conducted in this study see . The firShantungosaurus giganteus + Edmontosaurus: a finger-shaped anterior process of the parietal (204–1), and a weakly deflected occipital condyle (234–1). Although the PCF hadrosaurine does not share three synapomorphies of the clade , jugal process of the postorbital wide anteroposteriorly (181–2), and short squamosal process of the postorbital (183–1)) which are ontogenetically variable [Edmontosaurus share a reduced postorbital process of the laterosphenoid (221–1). Among the other six synapomorphies of the unresolved PCF hadrosaurine and Edmontosaurus clade, the analysis indicates that the short edentulous slope of the dentary (38–0), the moderate anterior inclination of the coronoid process (48–1), the absence of the deep pocket of the postorbital (182–0) of the PCF hadrosaurines are all characters that are ontogenetically variable in their expression. Their presence or absence cannot be objectively assessed or considered phylogenetically informative in the absence of equivalent ontogenetic exemplars of each of the pertinent taxa.Among the four synapomorphies recovered for Edmontosaurini, the PCF hadrosaurine shares the marginal denticle of dentary teeth composed of one rounded knob (12–1), the thick lip-like structure of the premaxillary oral rim (74–4), and the absence of the specialized development of the nasal (163–0). The PCF hadrosaurine exhibits two of the six synapomorphies that define the clade consisting of variable , the firEdmontosaurus regalis (CMN 2289). The absence of the ventral transverse ridge could be intraspecific variation since expression of this structure is also present in Edmontosaurus annectens (ROM 59786). Alternatively, since a lambeosaurine is now recognized in the Prince Creek Formation [Corythosaurus and Hypacrosaurus may simply indicate that this element belongs to a member of Lambeosaurinae, although it also has a hadrosaurine feature (see description section). The anteroposteriorly long maxilla is unique to the PCF hadrosaurine and Laiyangosaurus youngi [The first analysis recovered a combination of three characters potentially unique to the PCF hadrosaurine: dentary teeth with a secondary ridge (6–2), basisphenoid without a ventral transverse ridge (217–1), and an anteroposteriorly elongated maxilla 110–0). The presence of a secondary ridge on the dentary teeth is shared with lambeosaurines and also with some teeth of –0. The ps youngi .Edmontosaurus in the strict consensus tree is a result of two conflicting topologies recovered in the 384 MPTs. In one topology, the PCF hadrosaurine is positioned as the sister taxon to the Edmontosaurus clade  because the two species of Edmontosaurus are united by a single character to the exclusion of the PCF taxon: a straight primary ridge on the dentary tooth crown . In the second recovered topology, the PCF hadrosaurine is the sister-taxon to Edmontosaurus regalis to the exclusion of Edmontosaurus annectens. The PCF hadrosaurine and Edmontosaurus regalis are united in this scenario by the shared presence of a horizontal shelf on the postorbital process of the jugal (354–1).The polytomy comprising the PCF hadrosaurine + Edmontosaurus annectens as separate OTUs recovered 576 MPTs of 1154 steps . The strict consensus tree recovered the PCF hadrosaurine within the polytomy of Edmontosaurus OUTs . Alternatively, the other topology positions PCF hadrosaurine as a sister taxon of the clade of adult Edmontosaurus annectens OTU + Edmontosaurus regalis, the clade supported by a straight primary ridge on the dentary tooth crown (8–0). It is important to note that the immature Edmontosaurus annectens OTUs and mature Edmontosaurus annectens OTU did not form a monophyletic clade with each other to the exclusion of Edmontosaurus regalis and the PCF hadrosaurine in two of the three topologies recovered.The second cladistic analysis which incorporated two immature rus OUTs . The polUgrunaaluk kuukpikensis. Among the eight characters, three were proposed to differentiate Ugrunaaluk kuukpikensis from Edmontosaurus, four from Edmontosaurus annectens, and one from Edmontosaurus regalis. However, the three characters proposed to differentiate Ugrunaaluk from Edmontosaurus are problematic. The first character, a posterolaterally projected circumnarial ridge without a premaxillary vestibular promontory, is present in at least one immature Edmontosaurus annectens specimen (ROM 53525). The second, an anterodorsally inclined posterior margin of the anterior process of the jugal, is also present in immature specimens of Edmontosaurus annectens  and the degree of inclination is variable intraspecifically in large, assumedly mature specimens as well  is one of the diagnostic characters of Edmontosaurus [Edmontosaurus clade, the absence of any unequivocally diagnostic characters differentiating the PCF hadrosaurine from Edmontosaurus, and the presence of at least one diagnostic character of Edmontosaurus in the PCF hadrosaurine, the present work assigns the PCF hadrosaurine to Edmontosaurus, and the name “Ugrunaaluk” is considered a junior synonym of Edmontosaurus.The unresolved clade of analyses  indicatennectens . In facttosaurus , 37. GivEdmontosaurus exhibits some differences from Edmontosaurus annectens and Edmontosaurus regalis as previously documented [Edmontosaurus. The maxilla is expected to elongate through ontogeny along with overall cranial elongation [Edmontosaurus is not a result of the relative immaturity of the specimens feature. Taxonomic significance of other features that may be different from Edmontosaurus annectens and Edmontosaurus regalis is ambiguous. The anteroposteriorly-elongated lacrimal in the small Alaskan specimens differs from that of adult Edmontosaurus regalis, but this could be a size and ontogeny-dependent feature and the lack of ontogenetically-equivalent specimens of Edmontosaurus regalis makes this hypothesis currently untestable. The large lateral exposure of the quadratojugal suggested by Mori et al. [E. regalis, but it is important to note that quadratojugal morphology is known to be variable intraspecifically (see description), thus it seems unlikely to be a taxonomically valid character. The absence of the transverse ridge between basipterygoid processes of the basisphenoid and the presence of the secondary ridge of the dentary teeth are recovered as unique combination to the PCF Edmontosaurus in the present phylogenetic analyses, but taxonomic importance of these characters are questionable due to their intraspecific variations (see description) and the multitaxic nature of PCF hadrosaurids [At the same time, the PCF cumented –38. The ongation , 56, 57,i et al.  may alsoosaurids .Edmontosaurus is the only feature that may be reasonably different from the other members of Edmontosaurus  [Edmontosaurus sp.), and Edmontosaurus regalis in between the two regions (present-day western Canada). However, in the modern ecosystems there are at least two genera of mammalian vertebrates that have ranges of comparable latitudinal magnitude, the wolf (Canis lupus) and the wild sheep of North America (Ovis sp.). Further, the cougar (Puma concolor) has arguably the widest range of any terrestrial mammal in the Western Hemisphere, ranging from northern Canada to extreme southern South America. Thus the latitudinal range seen in the fossil record for Edmontosaurus is not unprecedented, though deserved of elaboration.The reattribution of the PCF hadrosaurine to nectens) , 77 to nEdmontosaurus are also demonstrated with the small phylogenetic morphospace (Edmontosaurus (3.40%) is lower than the hadrosaurine average (4.41%), suggesting that the latitudinal habitat differences did not increase morphological disparity of Edmontosaurus. Gryposaurus, a genus with moderate latitudinal distribution from southern Utah  [Saurolophus, a genus which is expected to have a “ghost distribution” in the Arctic [Edmontosaurus, Gryposaurus, and Saurolophus are formed based on non-contemporaneous species. Although these possible artefacts must be treated with special cautions, the low partial disparity/OTU of Edmontosaurus, Gryposaurus, and Saurolophus may suggest that overall hadrosaurine morphological disparity is not strongly affected by their latitudinal geographic distribution. Small morphological disparities despite large latitudinal distributions may be related to the relatively low latitudinal temperature gradient during the latest Cretaceous compared to the present day [The significant morphological similarities within the genus phospace  and the phospace . The parpresent)  to southpresent) , and Saue Arctic , have one Arctic , and thasent day , which mS1 Data(NEX)Click here for additional data file.S1 Text(DOCX)Click here for additional data file.S1 Table(XLSX)Click here for additional data file.S2 Table(XLSX)Click here for additional data file.


Surface electromyography (sEMG) can be helpful for evaluating swallowing related muscle activity. Conventional recordings with disc electrodes suffer from significant crosstalk from adjacent muscles and electrode-to-muscle fiber orientation problems, while concentric ring electrodes (CREs) offer enhanced spatial selectivity and axial isotropy. The aim of this work was to evaluate CRE performance in sEMG recordings of the swallowing muscles. Bipolar recordings were taken from 21 healthy young volunteers when swallowing saliva, water and yogurt, first with a conventional disc and then with a CRE. The signals were characterized by the root-mean-square amplitude, signal-to-noise ratio, myopulse, zero-crossings, median frequency, bandwidth and bilateral muscle cross-correlations. The results showed that CREs have advantages in the sEMG analysis of swallowing muscles, including enhanced spatial selectivity and the associated reduction in crosstalk, the ability to pick up a wider range of EMG frequency components and easier electrode placement thanks to its radial symmetry. However, technical changes are recommended in the future to ensure that the lower CRE signal amplitude does not significantly affect its quality. CREs show great potential for improving the clinical monitoring and evaluation of swallowing muscle activity. Future work on pathological subjects will assess the possible advantages of CREs in dysphagia monitoring and diagnosis. Patients with dysphagia patients find it difficult or impossible to swallow food or liquids. Dysphagia affects millions of people every year  and is Swallowing is a complex process that involves the sequential voluntary and involuntary contraction of 26 muscles. Swallowing disorders (dysphagia) are highly prevalent in patients with neuromuscular or neurogenic diseases, for instance, between 27 and 50% of stroke patients and 75 to 97% of those with Parkinson’s disease develop dysphagia . It is pDysphagia is a potentially dangerous condition that can lead to various complications  includinSurface electromyography (sEMG) has been proposed as a promising diagnostic tool to evaluate the physiology of swallowing ,11. It eSurface EMG activity is usually recorded by disk electrodes in a bipolar configuration. Differential bipolar recording is better able to reject common noise compared to monopolar referential recording. The bipolar configuration also has an associated spatial filtering effect that, in addition to the low-pass filtering effect of the tissue volume conductor, smooths the sEMG signal . The pooConcentric ring electrodes (CREs) have been proposed to improve surface bipolar recordings of bioelectric signals as they can directly obtain an estimation of surface Laplacian potential, i.e., the second spatial derivative of the bioelectric potential on the body surface. CREs are made up of a series of concentric poles of conductive material including a central disc-shaped element and one (or more) larger outer rings. CREs act as a spatial filter that diminishes the contribution of distant bioelectric dipole sources and emphasizes the closest ones . They prRecent studies on using ultra-flexible electrodes  and elecThus, the aim of this study was to assess the performance of flexible disposable CREs in recording swallowing muscle myoelectric activity in the pharyngeal phase in healthy volunteers by comparing them with conventional bipolar recordings from disc electrodes to identify their possible advantages and disadvantages.Instituto Tecnológico Metropolitano  by an authorization issued on 5 September 2015.The recordings were taken from 21 healthy young volunteers  aged between 21 and 34 years old (24.3 ± 3.9). The exclusion criteria were: active inflammatory processes , congenital oral malformations, strange elements in the mouth (like piercing), history of head or neck cancer, plastic surgery in the oral, buccal or mental regions or diagnosed cognitive disorders . The subjects were informed about the nature of the study and signed an informed consent approved by the Ethics Committee of the The protocol used for signal acquisition was a modified version of the one proposed by Vaiman et al. . SurfaceThe myoelectrical activity of the muscle group was sensed by pairs of conventional disposable Ag/AgCl electrodes  that were 15 mm in diameter in the gel area with an inter-electrode distance of 25 mm, and CREs  made up of a central disc (16 mm diameter) and an external ring (28 mm and 42 mm inner and outer diameters). This disposable auto-adhesive and flexible pre-gelled Ag/Ag/Cl CRE was chosen because wet electrodes perform better than dry ones in short-term bioelectric recordings ,36. A diThe sEMG signals were differentially amplified (gain 1000), band-pass (1–1000 Hz) and power line (50 Hz) filtered with commercial bioamplifiers . Signals were acquired at a 5000 Hz sampling frequency with a DAQ device . A camera was positioned diagonal to each participant and every swallowing task was video-recorded frame by frame and synchronized with the sEMG recordings by means of a custom Labview program.The signals and video were recorded to characterize the activity while swallowing three different types of bolus: saliva, 10 mL of water and 10 mL of liquid yogurt. These three consistencies have been used by other authors to evaluate penetration/aspiration in dysphagia . Liquid As we were focused on the assessment of saliva and liquid boluses disregarding clenching or mastication, only the infrahyiod and suprahyiod muscle groups were evaluated. These groups are activated at the end of the oral phase and during the pharyngeal swallowing phase. The onset of the pharyngeal phase was verified on the recorded video.Muscular contraction (burst): is comprise of the onset and offset time of each muscular activation executed by the participant during the swallowing tasks. RIH in Background noise: refers to a 0.5 s signal segment without any muscle activity, such as the one shown in a green-dashed box in LIH in Correlation activity segment: refers to the bilateral muscular activity of the suprahyoid and infrahyoid muscles including approximately 0.5 s of basal activity prior to and after the swallowing process. The segments from each muscular group were saved in pairs for muscular correlation analysis. The red-dashed box in RSH and LSH in Offline analysis was performed on a custom program . Two filter setups were used: to compute frequency domain features and following the SENIAM (Surface ElectroMyoGraphy for the Non-Invasive Assessment of Muscles) recommendations, the signals were filtered by a fifth-order Butterworth filter with band-pass between 10 and 500 Hz ; a narroRoot mean square (RMS) is equivalent to the square root of the variance of the signal with zero mean and is a typical measure used to assess signal power in time domain.Signal-to-noise ratio (SNR) is computed as the ratio of the energy of the target signal (sEMG burst in this case) and background noise; it is usually given in decibels (dB) and gives information about signal quality.Signal-to-motion ratio (SMR) gives information about the level of the motion artifacts in the signal. It was computed using the whole recorded signal according to the description given by (3)SMR=1Th) was set to 3 times the standard deviation of the background noise segment.Zero-crossing (ZC) provides indirect information about the time domain of the signal frequency. It indicates the number of zero-crossings with amplitudes greater than a threshold to avoid low voltage fluctuations and background noise . In thisMedian frequency (MF) is the frequency below and above which 50% of the total power of the PSD lies.Bandwidth (BW) is the difference between the upper and lower frequencies of a signal where its spectral power is concentrated. In this work the upper and lower limits were computed considering a power tail of 5%.Three time domain and three frequency domain features were computed from every EMG contraction segment in order to analyze the differences in amplitude and frequency of the signals acquired by CREs and CDEs. Several previous studies used these features in sEMG recordings of the muscles used to swallow ,40,41.RTo mitigate the effects of noise, MF and BW were computed from the difference between the PSD of the burst and background noise segments. PSDs were obtained by the Welch method (window size of 1024 samples with 50% overlap).Crosstalk and synchronization between pairs of bilateral muscles were assessed by the Pearson correlation between sEMG signals from both sides.Two schemes were applied, first, the correlation was computed using the raw sEMG signals (after band-pass filtering), after which the correlation was computed from the sEMG envelope. The envelope was obtained by a moving average filter with 200 samples applied to the rectified sEMG signal. p < 0.05). As a two-sided Wilcoxon signed-rank test for pairwise comparison showed no statistically significant difference (p > 0.05) between sEMG parameters recorded from the left and right sides of any muscle, electrode configuration or bolus, the sEMG parameters from both sides were combined in the subsequent analyses to facilitate the comparison of electrode configurations and provide greater statistical power. A two-sided Wilcoxon signed-rank test was used to assess significant differences in the pairwise comparison of parameters between CDE vs. CRE (configuration comparison) and suprahyoid vs. infrahyoid (muscle comparison) for each type of bolus . A significance level of p = 0.05 was established for all the statistical tests performed on MATLAB .The results for the different features followed a non-normal distribution , which points to a greater relative reduction of noise. In fact, a statistical analysis of RMS from background noise segments (not shown) revealed that it was significantly smaller (p < 0.05) for CRE in all boluses for both supra and infrahyoid muscles. This led to no significant differences in SNR when swallowing saliva; however, the CRE SNR was still significantly smaller than those of CDEs for water and yogurt. CDEs and CRE obtained similar results for the presence of motion artifacts in sEMG recordings, with no significant differences in SMR except in the suprahyoid when swallowing water. Different factors affect signal quality and its characterization by SNR and SMR. In this study, SNR was estimated as the ratio of burst and basal segment power. This means that crosstalk from other muscles activated during swallowing would also be (incorrectly) considered as a contribution to “target signal” power. Similarly, greater power in the muscular bandwidth due to the contributions of other muscles would also affect SMR. Nonetheless, it is also clear that the electronic instrumentation in the signal conditioning and acquisition makes a “constant” contribution to noise that cannot be reduced by the electrode configuration. Other aspects such as muscle size, depth, thickness and composition of the layers between the electrode and target activity sources, etc., can affect the signal quality of both electrode configurations. No differences were obtained in forearm sEMG SNR [The smaller sensing volume means fewer recordings from the muscle cells, which was responsible for the lower power (RMS) of the swallowing signals recorded by CRE in this study. Similar results have been reported when comparing CRE and CDEs recordings of other bioelectrical signals such as the electrocardiogram , electrosEMG SNR  or from sEMG SNR , while tsEMG SNR  and bicesEMG SNR . No SMR With regard to the crosstalk issue, it is well known that sEMG measurements from swallowing muscle can be severely affected by the activity of the surrounding muscles ,14,31. RRegarding the blurring effect of the volume conductor, which affects the spectral content of original signals when detected on the body surface, concentric electrodes have been shown to reduce the spatial filtering effects of spectral components in other sEMG signals ,50. In tThe results of the muscle comparison (supra vs. infrahyoid) in healthy volunteers showed similar results for both electrode configurations including greater signal quality  for suprahyoid signals in general, similar frequency content  and coupling (cross-correlation) between the sides of the muscle. The only aspect that was noticeably different in the muscle comparison for both electrode configurations was in the signal amplitude (RMS), where significantly higher values for supra were recorded with CDEs, while no differences were found in the CRE recordings. These results are consistent with previous findings in the literature, which showed that using standard electrodes resulted in higher amplitude in suprahyoid signals during muscle activity  and signCertain limitations of the study should be noted, especially with regard to the composition of the database, there was only a small number of young and healthy subjects (21) and they were mostly women (76%). However, according to some authors ,56 no siThis work showed the feasibility of capturing the myoelectric activity of the swallowing muscles by a CRE and compared the results with sEMG recordings made with CDEs.sEMG analysis of the swallowing muscles and dysphagia diagnosis and characterization can benefit from the use of the concentric electrode configuration compared to conventional bipolar disc electrodes. The advantages include enhanced spatial selectivity, reduced crosstalk from adjacent muscles and a wider range of EMG components. Placing the CRE on the body is also easier since it does not have to be oriented with the muscle fibers, unlike the bipolar configuration with CDE. This is particularly relevant in swallowing muscles in which visually determining fiber orientation can be challenging. However, it is recommended that technical changes be adopted in the future to ensure that the CRE’s lower signal amplitude does not significantly affect its quality.CREs have great potential for improving clinical monitoring and evaluation of swallowing muscle activity. Further work on subjects with a wider range of ages and pathological cases will be necessary to further assess the advantages of CREs for sEMG recordings in dysphagia monitoring and diagnosis.


Magnetic skyrmions are spin swirling solitonic defects that can play a major role in information technology. Their future in applications and devices hinges on their efficient manipulation and detection. Here, we explore from ab-initio their nature as magnetic inhomongeities in an otherwise unperturbed magnetic material, Fe layer covered by a thin Pd film and deposited on top of Ir(111) surface. The presence of skyrmions triggers scattering processes, from which Friedel oscillations emerge. The latter mediate interactions among skyrmions or between skyrmions and other potential surrounding defects. In contrast to their wavelengths, the amplitude of the oscillations depends strongly on the size of the skyrmion. The analogy with the scattering-off atomic defects enables the assignment of an effective scattering potential and a phase shift to the skyrmionic particles, which can be useful to predict their behavior on the basis of simple scattering frameworks. The induced charge ripples can be utilized for a noninvasive all-electrical detection of skyrmions located on a surface or even if buried a few nanometers away from the detecting electrode. Materials’ hallmarks hinge on the propagation of electrons, which mediate the interaction among atoms and impact nontrivially on thermal, electrical, optical, magnetic and transport properties. After scattering at localized defects, Friedel oscillations arise, which lead to charge screening of the foreign atoms, as routinely observed with scanning tunneling spectroscopy (STS) Magnetic skyrmions ,23, i.e.Interestingly, model calculations indicated that skyrmion-like magnetic Friedel oscillations can be induced by an adatom deposited on a surface characterized by a finite spin-orbit interaction  with a mHere, we explore with a fully ab-initio framework the Friedel oscillations emanating from single magnetic skyrmions hosted in Fe covered by thin films of Pd deposited on Ir(111) surface see a. The laWe investigate the scattering properties of skyrmions as function of their size and depth underneath the surface once the spin-textures are buried below Pd films of various thicknesses. As a probing energy, we choose 2.15 eV, which is crossed by an interface state characterized by a wave vector 2 nmG. Our first-principles simulations are based on the full-potential Korringa-Kohn-Rostoker Green function (KKR) method ,62 inclu done in . The ato done in ,59,64 asl = 3 for the scattering wave functions and a grid of The self-consistent calculations are performed using an angular momentum cutoff of echnique ,66 to avWe have investigated three magnetic defects of different sizes as illustrated in As shown in , variousspersion a,b. At 2 channel .The local density of states (LDOS) depicted in A magnetic skyrmion created in the PdFe/Ir(111) surface generates the Friedel oscillations shown in r, away from the defect. The charge oscillations shown in As illustrated schematically in The proposed detection mechanism is thus based on a nonmagnetic electrode that can scan the surface of the nonmagnetic overlayer film prospecting for the XMR-signal emanating from the Friedel oscillations induced by buried skyrmions. We conjecture that besides XMR other detection schemes  can be uTo summarize, we performed ab-initio simulations on Friedel oscillations emanating from the scattering of electronic states at small magnetic skyrmions of different sizes. We explored the case of skyrmions hosted in an Fe layer deposited on Ir(111) surface all covered with Pd films with different thicknesses. We found that the wavelength and phase shift characterizing the induced charge ripples seem independent form the size of the skyrmions in strong contrast to their amplitude. This is intimately related to interference effects of constructive and destructive nature in conjunction with the complexity of the spin-texture configurations. Through the Friedel oscillations, the skyrmion can appear larger or smaller than their real true size. The skyrmions act as particles to which a phase shift can be assigned, which permits the use of simple scattering theory to explore scattering at, interaction and stability of complex configurations of skyrmions and other magnetic and atomic defects. The nature of the effective scattering potential characterizing the investigated skyrmions is found repulsive. We envisage that by tuning the skyrmion size, one can control the amplitude of the charge oscillations and therefore the interaction among skyrmions. This is not only important for the motion of skyrmions in racetrack devices but also in the detection and formation of lattices or superstructures made of confined spin-textures and defects. Finally, we demonstrated all-electrical detection of hidden skyrmions, or skyrmions buried below thick films, utilizing the XMR-signal characterizing the Friedel oscillations propagating through overlayers or spacers. Confinement effects can enhance the efficiency of the XMR signal and the overall appearance of the buried spin-textures.


Options to increase the ease of testing for SARS-CoV-2 infection and immune response are needed. Self-collection of diagnostic specimens at home offers an avenue to allow people to test for SARS-CoV-2 infection or immune response without traveling to a clinic or laboratory. Before this study, survey respondents indicated willingness to self-collect specimens for COVID-related tests, but hypothetical willingness can differ from post-collection acceptability after participants collect specimens.153 US adults were enrolled in a study of the willingness and feasibility of patients to self-collect three diagnostic specimens  and dried blood spot (DBS) card) while observed by a clinician through a telehealth session. After the specimens were collected, 148 participants participated in a survey about the acceptability of the collection, packing and shipping process, and their confidence in the samples collected for COVID-related laboratory testing.A large majority of participants (>84%) reported that collecting, packing and shipping of saliva, OPS, and DBS specimens were acceptable. Nearly nine in 10 (87%) reported being confident or very confident that the specimens they collected were sufficient for laboratory analysis.There were no differences in acceptability for any specimen type, packing and shipping, or confidence in samples, by gender, age, race/ethnicity, or educational level.Self-collection of specimens for SARS-CoV-2 testing, and preparing and shipping specimens for analysis, were acceptable in a diverse group of US adults. Further refinement of materials and instructions to support self-collection of saliva, OPS and DBS specimens for COVID-related testing is needed. The global SARS-CoV-2 pandemic has resulted in explosive patterns of transmission in most countries ,2. ContrThere are a number of barriers to expanding testing . Since tThe iCollect study recruited 159 US adults for a study of the acceptability and sufficiency of at-home self-collected samples for SARS-CoV-2 PCR and immune response testing. We have previously documented the study protocol .After paThe methods for the iCollect study have been previously described . BrieflyFollowing specimen collection, the clinicians asked participants for suggestions about how to improve the collection instructions or process. Participants were also administered an online survey that collected data on the acceptability of the collection of the three specimen types, the process of packing and shipping the specimens, and how confident the participants were that they had collected the specimens adequately to be accurate as diagnostic specimens. Participants were also asked three open-ended questions in the online survey to gather qualitative data on suggestions for improvement of the specimen collection instructions. Specifically, they were asked to document suggestions to improve the clarity of instructions to collect or pack each specimen type. We analyzed the data by describing Likert scale scores  proportions for acceptability of specimen collection and packing/shipping and medians and interquartile ranges for each acceptability item. We used Kruskal-Wallis tests  to descrTelehealth observers recorded verbal participant feedback on the process, including participant suggestions of how to improve collection and shipping materials and instructions. Two coders independently read through all participant comments and created themes; they then worked together to develop a codebook that was used to independently code the data. A thematic analysis was conducted  seeking Of 159 participants who consented to be in the study, 153 participants provided at least one self-collected specimen, and 148 (97%) completed the post-collection survey for at least one specimen type and provided data on the acceptability of the specimen collection methods and packing/shipping. Six participants returned no specimen. Most participants were female (59%), non-Hispanic white (70%), and had at least some education beyond high school (97%); median age was 38 years (IQR: 27–49). Most surveys were completed within two days of the specimen collection , with 23 completed on the same day (16%), 46 on the first (31%), and 31 on the second (21%) day after the collection. A total of 82 participants provided 135 responses (some containing more than one code or theme) to open-ended survey items with suggestions for improving the specimen collection process. Fifty comments were provided for the DBS collection (34% of those submitting DBS specimens), 53 for saliva collection , and 32 for throat swab collection (21% of those submitting a throat swab specimen).Acceptability of the collection of all three specimen types was high >84%, .Over 90%Most participants (87%) reported feeling confident or very confident in the submission of their self-collected specimens for laboratory testing . There wspecimen collection instructions were most common (n = 98 comments) and were so coded if they described a lack of clarity in the wording or structure of the instruction guide. This included concerns about imprecise or overly technical wording of instructions, inconsistent terminology, lack of sequential ordering of steps, lack of appropriate detail, and inaccessible font type and size. If specifically describing difficulties or suggestions related to the images in the instruction guide, comments were categorized as specimen collection diagrams. Thirty comments related to kit packaging detailed difficulties finding the instructions, devices, or supplies inside the kit due to how materials were packaged or organized. Common suggestions within this category were to color code all materials to match the instruction guide, clearly separate and label the three specimen types, and place the instruction guide on top of all other kit materials. Comments in this category were less common and were typically about needing more diagrams, more detail with the diagrams and inconsistencies between the images and written text. Twenty comments about device complexity detailed difficulties with the collection process due to physical characteristics of the specimen collection devices and offered suggestions to improve clarity of instructions to help participants identify kit components. The saliva device and the DBS collection lancets were described most frequently as being unfamiliar or complex. Comments about specimen contamination potential were uncommon (n = 9) and related to perceived contamination of the samples during testing due to either the design of the devices or the instructions. In particular, a few participants were concerned with contaminating the OP swab by touching or dropping it before collection. They were also concerned with contaminating the DBS card by touching the paper directly. Four comments related to missing kit materials described one or more of the components of the kit missing during testing due to packing error. The participants in this category described missing shipping materials, lancets, or biohazard bags. The final category of kit shipping included only two responses related to opportunities to clarify the procedure for packaging and return shipping the kit. More comments were made about saliva specimen collection  among participants in a different, large online sample of US persons. In that study, like the present study, willingness did not vary by race/ethnicity or sex. Younger For HIV self-specimen collection systems, hypothetical interest in use was reported to be high before tests became commercially available, but uptake was quite low after they reached the market. ,20 In thhttps://vimeo.com/138977095) to illustrate the key steps of the process and to draw attention to potential errors in self-collection that were observed in the pilot phase. In this case, we will use the data from participant suggestions to clarify instructions, redesign the user experience in terms of the assembly and order of kit components, take steps to minimize touching of the DBS card before specimen collection, and include more explicit instructions for packaging and returning the kit. With these modifications in place, we will re-pilot the usability of the modified kit to test the impact of the modifications.Overall, about half of participants did not provide suggestions to improve the specimen collection process. Of those who did, nearly two-thirds of recommendations were for improvements to the written instructions or diagrams, which can be implemented with minimal redesign of kit components. Our observations of the participants using these kits was the first step in a multi-phased process of developing kits for broader use. We have used this staged process in the past to develop home-use kits for collection of DBS specimens and for home testing devices.,23 The dThe feedback of the participants is interpreted in light of the evaluation of the specimen quality by clinicians and laboratorians. The specOur study has important limitations. Our participants represent a convenience sample, and it is likely that they are a biased sample and may over-represent people interested in COVID-19-related testing generally, or people concerned about their own SARS-CoV-2 infection status. It is unclear how these biases might impact the results of our self-evaluation of acceptability of specimen collection. Further, the lay opinions of participants about their confidence in the sufficiency of specimens they collected may be naive since they were not selected for healthcare or laboratory expertise. However, the results of clinician observation and laboratorian assessment supported their views of the sufficiency of their samples; the triangulation of these three assessments lends credence to the potential sufficiency of self-collected specimens for COVID testing. We did nThe United States is in dire need of options to increase screening for SARS-CoV-2 infection and immune experience, and survey data suggest that people might be more willing to collect specimens at home for research and clinical purposes than to travel into labs or clinics to provide specimens.,18 At-ho


While adoption of the Ponseti method has continued gradually, its use to manage patients with congenital talipes equinovarus (CTEV) has been limited in low- and middle-income countries (LMICs) for a number of reasons including a lack of clinical training on technique and lack of appropriate clinical equipment. There are a frequent number of emerging studies that report on the role of clubfoot training programmes; however, little is known in regard to cumulative benefits.P < 0.05). Skill retention was examined by multiple choice (MCQ) examination style questions before and after the training programme in two studies; both showed an improvement (MCQ answers improved from 59% to 73%). All studies showed an improvement in participants' self-reported understanding of the Ponseti method and confidence in its use in future practice (P < 0.05). There were improved benefits of knowledge and clinical application of the Ponseti method by participants in the programmes in all studies examined. However, there was a significant lack of follow-up and exploration of long-term effects of these programmes. Implementing training programmes based on perceived benefits rather than actual long-term benefits may have a negative impact on healthcare delivery and patient management in LMICs.A systematic review was undertaken through Medline, the Cochrane Library and Web of Science for studies analysing clubfoot training programmes. There were no limitations on time, up until the review was commenced on January 2020. The systematic review was registered with PROSPERO as 165657. Ten articles complied with the inclusion criteria and were deemed fit for analysis. Training programmes lasted an average of 2–3 days. There was a reported increase in knowledge of applying the Ponseti method in managing clubfoot by participants (four studies  As such, the importance of an evidence-based approach is vital to consider. Costs of running the programmes and long-term retention/application of skills are factors that should be monitored closely with such programmes.The aim of the present article is to systematically review the literature to determine the role and long-term effectiveness of clubfoot training programmes in LMICs and categorise these reported benefits. In the event that statistical reported benefits differ, we shall use a narrative analysis to identify common themes and discuss in depth the reported benefits and significance of them.A systematic review was undertaken through Medline, the Cochrane Library and Web of Science. There were no limitations on time, up until the review was commenced in January 2020. The systematic review was registered with PROSPERO as 165657.A literature search was conducted electronically with no time constraints using ‘’ AND ‘(Programme)’, including MeSH terms  with no language restrictions. Included were the introduction of training programmes specific to management of clubfoot in LMICs; excluded were training programmes not related to clubfoot and where no clear description of training programme implemented was given.Following the recommended PRISMA guidance, three authors  examined the selected studies against an inclusion criterion . InclusiKey data including author names, date of publication, study design, location, number of participants, duration of follow-up and results were extracted and formulated. We included a quality analysis for quantitative studies for further evaluation, including risk of bias assessment.Where possible, a data analytical analysis was performed for improvement in skills, confidence after training and retention of skills gained. If different statistical methods were used, a narrative analysis on common themes was opted for.17The Cochrane tool for assessing risk of bias was used to assess the quality of included studies, adapted from Higgins and Altman.Ten articles complied with the inclusion criteria and were deemed fit for analysis. All papers reviewed were published in 2007–2018.P < 0.05).There was a reported increase in the knowledge of the Ponseti method in managing clubfoot in participants in all studies. Two studies opted for multiple choice (MCQ) examination style questions before and after the training programme; both showed an improvement (MCQ answers improved from 59% to 73%). All other studies opted for the use of questionnaires that were given after the training programmes were completed (range = 1–5 days), focusing on confidence and perceived improvement in understanding of the Ponseti method after the training session. All studies showed an improvement in participants' self-reported understanding of the Ponseti method and confidence in its use in future practice . Of them, 94% attributed this to the training programme.Nogueira et al.Training programmes lasted an average of 2–3 days in the studies examined. The content of the training programmes varied between hands-on casting, lectures/workshops and directly observing qualified Ponseti clinicians manage patients.To analyse gained benefits, the majority of studies utilised questionnaires before and after the programme. The rate of completion for the questionnaires was in the range of 50%–70%. The duration for completion was in the range of 1–5 days after the programme. Few studies examined the benefits of programmes in relation to skill retention after seven days.The majority of participants in the programmes were orthopaedic surgeons, physiotherapists and nurse practitioners. No study examined the differences between skills retained and practised between non-physicians and physicians.There were no randomised control trials/comparative studies found.Most studies reviewed were observational. Overall, the majority of studies were reported as fair, with lack of reporting on withdrawals/drop-outs reducing a large proportion of the quality of the studies. Further, only few studies reported yearly assessments. Most studies scored 2–3 for methods of data collection, reflecting on the frequent use of self-reported questionnaires and rarely any objective assessment of retained skill.21 However, there was some disparity on the contents of each clubfoot training programme.On review of the available literature on CTEV training programmes in LMICs, we have identified common themes of improvement in knowledge of management of CTEV and a subsequent increase in the proportion of clinical cases managed by attendees in their own practice  and 2. M1 non-invasive methods of managing the condition are a significant cost-efficient technique in comparison to invasive intervention. Thus, short training programmes to teach LMIC participants the Ponseti method as well as other non-invasive methods to implement in their own practice are well warranted.Given the prevalence of CTEV, particularly in LMICs,22 Other studies have reported similar findings.23 Considering the low costs of training programmes in relation to DALY, it would make financial sense for LMICs to continue invest in training methods of non-invasive techniques for its healthcare delivery personnel.Furthermore, on quantifying the economic burden of clubfoot in LMICs, we note a reported average of 7.42 disability-adjusted life years (DALY) averted with a cost-effectiveness ratio of US $22.46 per DALY averted in sub-Saharan African countries as a result of contribution to society due to CTEV.24 The authors' suspicions are that although training programmes may be beneficial in the short term, it would be wise to reassess gained skills to cement the notion that clubfoot training programmes benefit LMICs, as well as ensure the correct level of quality of care provided by the trained participants.However, training programmes reported in the literature do not provide a reliable measure of long-term impact given the short duration of follow-up. Previous studies have alluded to loss of knowledge gained unless continually used or reassessed in a given capacity.25 Programmes that did record follow-ups demonstrated some coherent structure to evaluate the benefits of implemented programmes over a recorded timescale .A well-managed training programme must take into consideration the materials that are sourced in LMICs, the number of cases of clubfoot seen by each practitioner, and follow-up on the effectiveness of the programme to monitor the following:29 Implementing training programmes based on perceived benefits rather than actual benefits may have a negative impact on healthcare delivery and management of patients in LMICs. It is thus incredibly important that alongside clear rationale, which the majority of CTEV training programme studies provide, there must be a structured, robust follow-up scheme in place to employ good sustainability of reported benefits. Neglecting the long-term effects of training programmes can cause under-reporting of complications and overestimation of perceived benefits.30 Further, important factors that must be objectively explored include the level of skill retention over a longer duration and continuous assessment of participants current/future practice. The bias in self-reported questionnaires may not report the full extent of the impact of training. Rather, we suggest objective assessments such as MCQs or Objective Clinical Situation Evaluations (OSCEs) as a formal assessment of retained skills. These should ideally take place over a yearly time span.The importance of the evidence base for medical/surgical training has been well explored.The present study highlights the effects of CTEV training programmes in LMICs. There are improved benefits of knowledge and application in all studies examined. However, there is a significant lack of follow-up and long-term effects of said programmes. As a result, it is difficult to ascertain the long-term benefits of implementing these programmes. The authors agree that this can be ameliorated with objective follow-up measures in place to examine application of knowledge and skill. Given the number of studies that highlight reasons for relapse of CTEV, training programmes would do well to address highlighted reasons such as lack of parental understanding of the condition, as well as foster long-term collaboration and partnership between institutions to ensure long-term follow-up from training programmes. Future studies should focus on the long-term effects of CTEV training programmes on the impact on practice in LMICs.This is the first systematic review in the literature assessing the impact of CTEV training programmes in LMICs. A robust analysis of the literature revealed a significant lack of important follow-up data on CTEV training programmes.The limitations of this study include the small sample size and lack of current CTEV training programme studies. This could be due to the recent implementation of such programmes in LMICs.


Dear Readers,The Journal of Innovations in Cardiac Rhythm Management is my most favorite issue of the year. It often contains articles reflecting on the major discoveries in the field of cardiac electrophysiology that occurred in the last year. In addition, this December’s issue contains an important original research article by Doshi et al. titled “Predictors of Elevated Defibrillation Threshold with the Subcutaneous Implantable Cardioverter-defibrillator.” The authors analyzed the defibrillation threshold (DFT) in 50 patients who underwent subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation and found that increased body mass index, body surface area, and septal or posterior wall thickness were associated with high DFT.The December issue of The introduction of the S-ICD represented a major step forward in the field of cardiac defibrillation. This technology provides many advantages in comparison with conventional devices, mostly due to the associated elimination of intravascular leads. While all features of conventional ICDs have been studied extensively, data regarding some aspects of S-ICD use, including DFT, remain scarce. The study mentioned above included a small number of patients; however, it has important clinical implications and it highlights the need to develop advanced screening tools to identify patients who may have high DFT.The Journal of Innovations in Cardiac Rhythm Management this past year. Our authors and peer reviewers are integral to the success of the journal’s efforts to ensure that only manuscripts of the highest quality that discuss relevant topics within the electrophysiology industry are published. I would also like to thank the editorial team whose dedication, skill, and professionalism have been critical for the delivery of the high level of educational content of this publication.I would like to end this letter by thanking both the authors who submitted manuscripts and the peer reviewers who provided their thoughts on these manuscripts for inclusion in Best wishes for happy holidays and a healthy New Year.Sincerely,MD, FHRS, FACCMoussa Mansour, Editor-in-ChiefThe Journal of Innovations in Cardiac Rhythm ManagementMMansour@InnovationsInCRM.comDirector, Atrial Fibrillation ProgramJeremy Ruskin and Dan Starks Endowed Chair in CardiologyMassachusetts General HospitalBoston, MA 02114


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible virus, making hospitals potential loci for outbreaks and placing health care workers (HCWs) at risk of acquiring the infection. The high demand for hospital care and the associated morbidity and mortality in the early phases of the coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need to protect the safety and health of HCWs. With over 15.7 million cases . In JuneIn managing patients with COVID-19 infection, proper use of personal protective equipment is crucial for the protection of HCWs . HoweverMalaysia reported its first case of COVID-19 on January 24, 2020 . SubsequOne of the main pillars of the Malaysian pandemic preparedness programme is the public health approach of contact tracing complemented with targeted testing of close contacts. From the outset of the pandemic, the Ministry of Health (MoH) Malaysia through its district health offices has been implementing intensive contact tracing for every confirmed COVID-19 case nationwide, and testing of all identified contacts. Within the confines of the hospital population, UMMC took over the responsibility for contact tracing and testing activities among its HCWs. In general, these activities follow the criteria and guidelines issued by the MoH but are adapted to allow for the nature of clinical work performed by HCWs.The HCW surveillance team is notified when any patient or HCW tests positive. Listings of close contacts are obtained through interviews with the index case and supplemented with information obtained from the hospital’s electronic medical records (EMR). The EMR enables tracking of patients’ movements throughout their care processes within the hospital and the identification of HCWs who may have interacted with them during their periods of infectivity. Subsequently, all identified close contacts will have their risk of exposure evaluated and stratified into high, medium or low risk. It includes a list of standardised questions such as the duration of exposure, clinical symptoms of the COVID-19 case and whether the case was wearing a face mask and whether an aerosol-generating procedure was performed as well as the type of personal protective equipment that was used by the HCW. Risk assessment is being carried out for every new exposure to a COVID-19 case. These HCWs are tested with real-time PCR for SARS CoV-2. A 14-day and 7-day quarantine notice is issued to HCWs with high and medium risk of exposure, respectively. Meanwhile, a two-day sick leave is provided for HCWs with low risk of exposure while awaiting PCR results, which are available within 24 hours. The management algorithm for HCWs with work-related exposure  for UMMCAll HCWs, with identifiable risk, are then placed under daily symptom surveillance for 14 days from the last exposure to a COVID-19 case. HCWs were initially contacted via social messaging systems and direct calls to ensure compliance to this daily surveillance. An online risk assessment and symptom surveillance system, linked to the EMRs and human resource records, was subsequently developed and deployed to automate the process. HCWs now receive an automated reminder through mass texting service as a prompt for self-assessment and self-reporting of symptoms through the UMMC staff portal. To ensure ethical compliance, all the records of the risk assessment and symptom surveillance are treated as medical records and included in the EMR.The outbreak management team continuously monitors all activities to detect any secondary propagation of disease transmission within the hospital community. An epidemiologist leads a multidisciplinary outbreak investigation into all potential hospital clusters to provide remedial plans for infection control and prevention activities. In addition to these core components of disease surveillance, UMMC has also instituted a daily COVID-19 symptom roll call for all HCWs, which is incorporated into their daily attendance records. HCWs with symptoms will be provided with appropriate advice and care, and if appropriate, referred to a staff health clinic for assessment.Between February and July 2020, a total of 2401 risk assessments were carried out among 1408 HCWs who were either exposed to a COVID-19 case in the hospital or the community. Of these assessments, 16.5% were stratified as moderate or high-risk exposure. In extension, 1292 HCWs underwent at least 14 days of symptom surveillance. Cumulative incidence of COVID-19 amongst health care workers was 0.3%. The number of HCWs who underwent risk assessment and were placed under active daily symptom surveillance is subject to changes due to the dynamic situation of COVID-19 pandemic in the country.The rapid spread of the COVID-19 pandemic necessitates that every hospital takes extraordinary measures to protect its health workforce. We believe that the HCW surveillance programme implemented in UMMC limits intrahospital transmission of COVID-19 and ensures better patient and staff safety during these difficult times.


To evaluate ways to improve the generalizability of a deep learning algorithm for identifying glaucomatous optic neuropathy (GON) using a limited number of fundus photographs, as well as the key features being used for classification.A total of 944 fundus images from Taipei Veterans General Hospital (TVGH) were retrospectively collected. Clinical and demographic characteristics, including structural and functional measurements of the images with GON, were recorded. Transfer learning based on VGGNet was used to construct a convolutional neural network (CNN) to identify GON. To avoid missing cases with advanced GON, an ensemble model was adopted in which a support vector machine classifier would make final classification based on cup-to-disc ratio if the CNN classifier had low-confidence score. The CNN classifier was first established using TVGH dataset, and then fine-tuned by combining the training images of TVGH and Drishti-GS datasets. Class activation map (CAM) was used to identify key features used for CNN classification. Performance of each classifier was determined through area under receiver operating characteristic curve (AUC) and compared with the ensemble model by diagnostic accuracy.In 187 TVGH test images, the accuracy, sensitivity, and specificity of the CNN classifier were 95.0%, 95.7%, and 94.2%, respectively, and the AUC was 0.992 compared to the 92.8% accuracy rate of the ensemble model. For the Drishti-GS test images, the accuracy of the CNN, the fine-tuned CNN and ensemble model was 33.3%, 80.3%, and 80.3%, respectively. The CNN classifier did not misclassify images with moderate to severe diseases. Class-discriminative regions revealed by CAM co-localized with known characteristics of GON.The ensemble model or a fine-tuned CNN classifier may be potential designs to build a generalizable deep learning model for glaucoma detection when large image databases are not available. Glaucoma is one of the leading causes of irreversible blindness . Early dOptic disc photography remains the fundamental approach in glaucoma screening ,9. Disc In the pre-deep learning era, automated glaucoma detection using fundus images was based primarily on the cup-to-disc ratio (CDR), and in some cases, defects of the retinal nerve fiber layer (RNFL) or the presence of parapapillary atrophy ; howeverThis study aimed to evaluate the performance of a CNN algorithm constructed with limited training images to discern glaucomatous change in images from different resources, benefits of including CDR estimation as an ensemble model, and the key features extracted for the classification in the CNN algorithm.This study included fundus photographs in JPEG format of 465 non-glaucomatous eyes and 479 eyes with primary open angle glaucoma (POAG), which were collected retrospectively from the image database of the Department of Ophthalmology, Taipei Veterans General Hospital (TVGH). The fundus images were obtained from subjects with POAG at regular follow-up, and subjects who visited our department for ocular screening or disorders not affecting the optic disc and retina. This study followed the tenets of the Declaration of Helsinki, and was approved by the Institutional Review Board of TVGH. The written informed consent was waived because of the retrospective nature of the study and the analysis was performed using anonymized clinical data and images.Eyes with POAG were diagnosed in the presence of glaucomatous disc changes with corresponding RNFL loss and reproducible visual field (VF) defects, and a normal open angle on gonioscopy. In all subjects with POAG, VF analysis using the 24–2 Swedish interactive threshold algorithm standard of the Humphrey Field Analyzer 750i  and RNFL scanning using Cirrus HD-OCT  were performed. The normal eyes had an intraocular pressure (IOP) of < 21 mmHg, and a disc with normal appearance without RNFL defect. The fundus images were acquired using three fundus cameras, Canon CR-DGi NM fundus camera, Canon CX-1 hybrid mydriatic/non-mydriatic digital retinal camera, and Canon CR-2 PLUS AF non-mydriatic retinal camera  at 45° centered at the macula. All images included had a clear view of the disc. The images were reviewed by two glaucoma specialists (YK and CL) to confirm the diagnosis and define the vertical CDR. Standard anonymization was performed for all images before further analysis.http://cvit.iiit.ac.in/projects/mip/drishti-gs/mip-dataset2/Home.php), an open-access datasets containing training and test datasets of 50 and 51 images, respectively were used to evaluate the diagnostic ability of our model.The fundus images were 3888 x 2552 pixels in size, with resolution of 120 dpi and bit depth of 24. The images were divided into a training set and test set for model training and evaluation based on stratified sampling with 763 images and 181 images at the training and test sets, respectively. The clinical information of the images is listed in The workflow of our detection system is illustrated in https://keras.io/).Fundus images were first preprocessed to compensate for the levels of brightness and clarity of each image. Unsharp masking by Gaussian blur method was used to enhance the optic disc structure and blood vessels. ROI detection centered at the disc was implemented to remove redundant features using the concept of guided backpropagation . FollowiIn our CNN model, preprocessed and qualified images were submitted for processing through a series of convolutional, nonlinear functions (ReLU), pooling, fully connected (FC) layers, and finally softmax loss layer, which incorporated the concept of cross entropy and softmax layer to provide a probability value for the final classification of each image. Moreover, Stochastic Gradient Descent was performed for optimization to minimize the loss of function. Instead of training a model from scratch, transfer learning was performed using VGGNet  , a pre-tWe performed 5-fold cross validation to evaluate the performance and to avoid overfitting of the CNN model. Within each fold, the combined images were partitioned into independent training and validation sets using an 80–20 percentage split. The performance of each fold was evaluated not only on the validation sets, but also the test images. The parameters of the fold with best performance were selected as the final model, unless there were significant variation on the performance of each fold.CAM was applied to identify features recognized by the proposed CNN model to differentiate between the glaucomatous and normal discs . ThroughThe characteristic changes of the glaucomatous disc, including an increased value of CDR, and thinning of the superior or inferior neuroretinal rim were selected as the features for SVM classifier. Preprocessed images were first processed with the green and red channel. The disc margin was determined by the red channel, and the cup area by green channel. The vertical disc diameter was decided according to the superior and inferior junctional points of the disc boundary along the vertical meridian. K-means clustering was used to determine the cup area after removing the redundant information by subtracting the mean and standard deviation from the green channels, and the K value was set to 2 as dividing the preprocessing image into two regions  28]. Th. Th28]. The performance of our model was evaluated by the indices of sensitivity, specificity, and accuracy defined as the sum of correct classification of both the healthy and glaucomatous images divided by the total number of test images. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were plotted using the python scikit-learn library according to the definition, wherein, the true positive rate is the Y-axis, and the false positive rate is the X-axis. Nonparametric tests were used to compare the clinical characteristics between images with correct and incorrect prediction because most measurements of the test images were not normally distributed. Mann-Whitney U test was used for continuous variables, and chi-square test for categorical variables. The analyses were conducted using SPSS .In a total of 187 test images from the Taipei Veterans General Hospital (TVGH) dataset, the diagnostic accuracy of the TVGH-CNN model was 95.0%, sensitivity was 95.7%, and specificity was 94.2% in differentiating the glaucomatous eyes from the normal eyes; the AUC of the TVGH-CNN model for identifying glaucomatous eyes was 0.992 . HoweverFifty training images of the Drishti-GS dataset were added to the TVGH training dataset to establish a fine-tuned CNN model (T&D-CNN model), which improved the classification accuracy of the CNN model applied to the Drishti-GS test images. The diagnostic accuracy of the T&D-CNN model for Drishti-GS test images was improved to 80.3%, with a sensitivity of 73.6%, specificity of 100%, and an AUC of 0.937 . To deteAn ensemble model for classification was also established with the aim to avoid missing subjects with moderate to advanced disease, which used a SVM classifier based on CDR for final classification when the probability value of the CNN classifier was lower than the threshold of 0.85. The probability value refers to the binary classification confidence of the CNN classifier for the predicted classification. The threshold value was selected by calculating the sensitivity and specificity of the ensemble model with different threshold values starting from 0.5 with an increment of 0.05 till 1.0. The ensemble model had highest sensitivity and specificity on test images including TVGH and Drishti-GS datasets at a threshold value of 0.85. The SVM classifier, which was established based on the TVGH dataset, had a diagnostic accuracy of 76.7% and 72.5% for the TVGH and Drishti-GS test images, respectively. The ensemble model had better diagnostic accuracy for the Drishti-GS test images than that of the TVGH-CNN model, but similar diagnostic accuracy as that of the fine-tuned T&D-CNN model; moreover, there was no increase in the overall diagnostic accuracy for the TVGH test images than that of the TVGH-CNN model .To understand the potential factors leading to misclassification through our model, we compared the clinical characteristics for the images with correct and incorrect prediction . For glaCAM was used to reveal features recognized by our CNN model for classification. Areas critical for the classification were marked as red, while areas with low impact as blue. The CAM was different between the glaucomatous and healthy eyes. The hot spots were located most commonly at the cup area and region of parapapillary atrophy in the images of the glaucomatous eyes, but at the neuroretinal rim or along the retinal nerve bundles in the images of the healthy eyes. The superimposed images revealed the difference between the two groups .This study found that CNN-based automated glaucoma detection using color fundus images acquired by a desktop fundus camera achieved high accuracy on test images whose quality is similar to that of the training dataset. However, the generalizability of the classification model depended on the diversity of the training data. Addition of a limited number of images from the target test population to the training dataset significantly increased the accuracy of the CNN detection model. With this modification, CNN achieved similar or better diagnostic performance than the ensemble model that considered CDR. CAM revealed that our CNN model captured characteristics areas of the optic disc as that through human perception to identify glaucomatous changes.The key to achieving accurate classification of retinal images using deep learning is the number and quality of the training images ,20. UnliThe generalizability of our deep learning model trained with limited fundus images was inadequate. Lack of diversity of our database may explain the poor generalizability of our model; however, it is unclear if the generalizability of a deep learning model would be improved by using a larger number of images of various origins because verification of the CNN model on other database has not been thoroughly evaluated ,16. PhenWe proposed two approaches to improve the generalizability of our model: The first was to fine-tune the CNN model with limited number of images from the target test dataset which could dramatically improve the diagnostic performance of this mixed model for images of different origin. This approach is not novel but practical, with an aim to build clinic-based glaucoma screening algorithm using limited images from each clinic when neither a universal deep learning algorithm for glaucoma detection nor the access to large-scale glaucoma image datasets is available. Similar finding was noted in Diaz-Pinto et al’s study . They usThe CAM revealed that the class-discriminative regions of the CNN model co-localized with the known characteristics of GON. The hot spots of the CAM were located at the cup area in most images that were correctly classified as glaucoma, but at the neuroretinal rim and nerve bundles in the images of healthy eyes. This finding agreed with the report of Christopher et al that the inferior and superior regions of the neuroretinal rim are the most important parts for distinguishing between the eyes with GON and healthy eyes through deep learning algorithm . These fOur study has some limitations. The major limitation is that the training dataset was collected at one medical center with limited number of images, which may lead to questionable generalizability of our model. As expected, our model showed poor performance on test images of other origin, which could be overcome by using the fine-tuned model. Further evaluation to verify the generalizability of deep learning algorithm for glaucoma detection is needed since the fundus images taken for glaucoma diagnosis may vary in layout, clarity, and visibility of the RNFL, especially for population-based glaucoma screening. The second limitation of our study is that ROI centered at the ONH was used to construct the model to reduce the image size and complexity, which may result in loss of information and complicated preprocessing at clinical application. However, ROI extraction increased both the sensitivity and specificity of the model as compared with those of the whole images . Third, The proposed deep learning model trained with limited fundus images achieved high accuracy in identifying GON on images of similar quality, and did not misclassify any cases with moderate to advanced disease. The model could be successfully fine-tuned to increase its diagnostic accuracy for images of different origins, which might be a feasible approach to build CNN classifier for clinic-based glaucoma screening. The CAM revealed that the model captured similar characteristics in identifying GON as those through human perception. Based on these findings, deep learning assisted detection of GON may be a viable option to assist glaucoma screening, but the generalizability of a deep learning model must be verified first before being applied to the targeted test population.


This special Research Topic of Frontiers in Physiology and Frontiers in Cell and Developmental Biology collates a series of review and research articles on the dynamic properties of endothelial cells, the key inner lining cells of blood and lymphatic vessels. Over the past decade, we have learnt that the vasculature is not a static tissue, but instead relies on the dynamic interactions of endothelial cells with each other, with the vascular microenvironment and with other cell types. For instance, new vessel formation occurs through collective migration and critically relies on rearrangements of interactions between endothelial cells. As such, endothelial cells are equipped with a variety of dynamic molecular systems that allow these cells to adapt to physiological and pathophysiological changes. Studying the systems that underlie endothelial dynamics brings fundamental insights into how vessels form and respond to their microenvironment. This knowledge is crucial to understand the development of cardiovascular disease, and it provides potential leads to guide the opening and closing of the vasculature for therapeutic applications in chronic inflammation and cancer.Duong and Vestweber now overview the complementary mechanisms that take place at endothelial cell-cell junctions beyond the VE-cadherin receptor in intact blood and lymphatic vessels. The importance of other adhesion receptors such as ESAM, Claudins and their anchoring to the dynamic actomyosin cytoskeleton is discussed as important contributors to endothelial integrity. In an original research paper by Werner et al., a new member of VE-cadherin-based endothelial junctions is identified: the actin-binding protein Coronin 1B. The authors investigated the molecular mechanism behind actomyosin relaxation and subsequent protrusive cytoskeletal activity evoked by Coronin 1B to seal the junctions.Endothelial tissue integrity depends on adherens junctions that are based on the actin-anchored VE-cadherin receptor . The impLi et al. have investigated the importance of VEGF-A-mediated VEGFR2 activation and downstream VE-cadherin phosphorylation in experimental myocardial infarction models. Intriguingly, VEGFR2 Y949F knock-in mice are protected from cardiac edema, and these findings indicate that vascular leakage may be therapeutically targeted to improve heart tissue perfusion after infarction. The Neuropilins act as coreceptors for the VEGFRs and are well-known to support angiogenic signaling  and the contractile actomyosin cytoskeleton. Tight crosstalk occurs between endothelial adhesion structures during mechanotransduction: integrins translate forces from the ECM to actomyosin-based contractility, which in turn controls pulling forces on endothelial cell-cell contacts  in combination with specific loss- or gain-of-function of molecular players.Genetic interference and fluorescence-based endothelial monitoring has led to impressive insights of endothelial cell dynamics during angiogenesis and vascular repair  and has a research agreement with Merck & Co. Inc  and with Venthera . The remaining 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.


Air exchange through a porous medium depends partly on a pressure gradient induced in it, i.e., air-flow conditions of the outer air. Consequently, response of diffusion-type detectors to radon and thoron may vary with air-flow conditions surrounding the detectors. This effect may be significant for thoron measurement because thoron has a shorter half-life than radon. The present study examined response of diffusion-type detectors (RADUETs and one AlphaGUARD) to thoron with respect to wind speed using a thoron calibration chamber. Response of RADUETs to thoron increased with wind speed. Response of the AlphaGUARD increased with wind speed, but it became constant at a high wind speed. Different response trends to thoron between the RADUETs and the AlphaGUARD could be qualitatively explained by flow states induced by the pressure gradient in the filter or the sponge of these detectors. For RADUETs, laminar (Darcy) flow was induced in the sponge in the examined wind speed range, which meant that thoron entry into the detector increased with wind speed. For the AlphaGUARD, laminar flow was induced in the filter in the low wind speed range, whereas flow was changed to turbulent (non-Darcy) flow at a high wind speed for which thoron entry into the detector did not depend on wind speed. The response of RADUETs to thoron increased with wind speed, which implied that advection in the state of laminar (Darcy) flow caused thoron entry into the detector. In contrast, the response of the AlphaGUARD increased with wind speed, but it became constant at high wind speed. This different trend implied that flow regimes for thoron entry into the detector changed from laminar flow to turbulent (non-Darcy) flow. The finding that the responses of the detectors to thoron varied depending on wind field should provide insights into improving measurement of thoron and processes of quality assurance and quality control for diffusion-type thoron detectors.