We present a theoretical model to describe the response of a one dimensional mechanical system under cyclic loading. Specifically, the model addresses the non-linear response on loading, hysteretic ...behaviour on unloading and reloading, and the phenomenon of ratcheting under very many cycles. The methods developed are formulated within the hyperplasticity framework. The model can be expressed in the form of general incremental relationships, can therefore be applied without modification directly to any loading history, and can be readily implemented within a time-stepping numerical code. A rigorous procedure is described to accelerate the ratcheting process, so that the effects of very large numbers of cycles can be analysed through a reduced number of cycles. A generalisation from unidirectional to multidirectional loading is described, together with a tensorial form for application to material modelling. The original motivation was for the application to design of piles under lateral loading, and an example of this application is provided. However, the model is equally applicable to many other problems involving unidirectional or bi-directional cyclic loading in which the system exhibits a similar character of hysteretic behaviour, with ratcheting under large numbers of cycles.
Summary
Background
Data on dermatological manifestations of cardiofaciocutaneous syndrome (CFCS) remain heterogeneous and almost without expert dermatological classification.
Objectives
To describe ...the dermatological manifestations of CFCS; to compare them with the literature findings; to assess those discriminating CFCS from other RASopathies, including Noonan syndrome (NS) and Costello syndrome (CS); and to test for dermatological phenotype–genotype correlations.
Methods
We performed a 4‐year, large, prospective, multicentric, collaborative dermatological and genetic study.
Results
Forty‐five patients were enrolled. Hair abnormalities were ubiquitous, including scarcity or absence of eyebrows and wavy or curly hair in 73% and 69% of patients, respectively. Keratosis pilaris (KP), ulerythema ophryogenes (UO), palmoplantar hyperkeratosis (PPHK) and multiple melanocytic naevi (MMN; over 50 naevi) were noted in 82%, 44%, 27% and 29% of patients, respectively. Scarcity or absence of eyebrows, association of UO and PPHK, diffuse KP and MMN best differentiated CFCS from NS and CS. Oral acitretin may be highly beneficial for therapeutic management of PPHK, whereas treatment of UO by topical sirolimus 1% failed. No significant dermatological phenotype–genotype correlation was determined.
Conclusions
A thorough knowledge of CFCS skin manifestations would help in making a positive diagnosis and differentiating CFCS from CS and NS.
What's already known about this topic?
Data on dermatological manifestations of cardiofaciocutaneous syndrome (CFCS) remain heterogeneous and almost without expert dermatological input.
Dermatological findings remain essential to diagnose CFCS and to differentiate it from other RASopathies that it resembles phenotypically, specifically Noonan syndrome (NS) and Costello syndrome (CS).
What does this study add?
Scarcity or absence of eyebrows, association of ulerythema ophryogenes and palmoplantar keratoderma, diffuse keratosis pilaris and multiple melanocytic naevi appeared pertinent manifestations in assisting the positive diagnosis of CFCS and differentiating it from CS and NS.
Oral acitretin could be highly beneficial for therapeutic management of PPHK.
No significant dermatological phenotype–genotype correlation in the presence or absence of BRAF mutation could be determined.
Linked Comment: Moss. Br J Dermatol 2019; 180:21.
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Reconstructing and characterizing introduction routes is a key step towards understanding the ecological and evolutionary factors underlying successful invasions and disease emergence. Here, we aimed ...to decipher scenarios of introduction and stochastic demographic events associated with the global spread of an emerging disease of bananas caused by the destructive fungal pathogen Mycosphaerella fijiensis. We analysed the worldwide population structure of this fungus using 21 microsatellites and 8 sequence‐based markers on 735 individuals from 37 countries. Our analyses designated South‐East Asia as the source of the global invasion and supported the location of the centre of origin of M. fijiensis within this area. We confirmed the occurrence of bottlenecks upon introduction into other continents followed by widespread founder events within continents. Furthermore, this study suggested contrasting introduction scenarios of the pathogen between the African and American continents. While potential signatures of admixture resulting from multiple introductions were detected in America, all the African samples examined seem to descend from a single successful founder event. In combination with historical information, our study reveals an original and unprecedented global scenario of invasion for this recently emerging disease caused by a wind‐dispersed pathogen.
The reconstruction of geographic and demographic scenarios of dissemination for invasive pathogens of crops is a key step toward improving the management of emerging infectious diseases. Nowadays, ...the reconstruction of biological invasions typically uses the information of both genetic and historical information to test for different hypotheses of colonization. The Approximate Bayesian Computation framework and its recent Random Forest development (ABC‐RF) have been successfully used in evolutionary biology to decipher multiple histories of biological invasions. Yet, for some organisms, typically plant pathogens, historical data may not be reliable notably because of the difficulty to identify the organism and the delay between the introduction and the first mention. We investigated the history of the invasion of Africa by the fungal pathogen of banana Pseudocercospora fijiensis, by testing the historical hypothesis against other plausible hypotheses. We analyzed the genetic structure of eight populations from six eastern and western African countries, using 20 microsatellite markers and tested competing scenarios of population foundation using the ABC‐RF methodology. We do find evidence for an invasion front consistent with the historical hypothesis, but also for the existence of another front never mentioned in historical records. We question the historical introduction point of the disease on the continent. Crucially, our results illustrate that even if ABC‐RF inferences may sometimes fail to infer a single, well‐supported scenario of invasion, they can be helpful in rejecting unlikely scenarios, which can prove much useful to shed light on disease dissemination routes.
In this study, we illustrate that, in some cases, accepting not to use available historical data can be a fruitful way of reconsidering invasion processes using the model of the worldwide emergence of the fungal banana pathogen Pseudocercospora finjiensis. Using an ABC‐RF approach, we investigated the history of the invasion of Africa by P. fijiensis by testing the historical hypothesis against other plausible hypotheses. We do find evidence for an invasion front consistent with the historical hypothesis, but also for the existence of another front never mentioned in historical records and question the historical introduction point of the disease on the continent.
Summary
Background
Data on dermatological manifestations of Noonan syndrome (NS) remain heterogeneous and are based on limited dermatological expertise.
Objectives
To describe the dermatological ...manifestations of NS, compare them with the literature findings, and test for dermatological phenotype–genotype correlations with or without the presence of PTPN11 mutations.
Methods
We performed a large 4‐year, prospective, multicentric, collaborative dermatological and genetic study.
Results
Overall, 129 patients with NS were enrolled, including 65 patients with PTPN11‐NS, 34 patients with PTPN11‐NS with multiple lentigines (NSML), and 30 patients with NS who had a mutation other than PTPN11. Easy bruising was the most frequent dermatological finding in PTPN11‐NS, present in 53·8% of patients. Multiple lentigines and café‐au‐lait macules (n ≥ 3) were present in 94% and 80% of cases of NSML linked to specific mutations of PTPN11, respectively. Atypical forms of NSML could be associated with NS with RAF1 or NRAS mutations. In univariate analysis, patients without a PTPN11 mutation showed (i) a significantly higher frequency of keratinization disorders (P = 0·001), including keratosis pilaris (P = 0·005), ulerythema ophryogenes (P = 0·0001) and palmar and/or plantar hyperkeratosis (P = 0·06, trend association), and (ii) a significantly higher frequency of scarce scalp hair (P = 0·035) and scarce or absent eyelashes (P = 0·06, trend association) than those with PTPN11 mutations.
Conclusions
The cutaneous phenotype of NS with a PTPN11 mutation is generally mild and nonspecific, whereas the absence of a PTPN11 mutation is associated with a high frequency of keratinization disorders and hair abnormalities.
What's already known about this topic?
Data on dermatological manifestations of Noonan syndrome (NS) remain heterogeneous and almost entirely without expert dermatological input.
A broad spectrum of dermatological findings is present in NS and better knowledge might help to define phenotype–genotype correlations and differentiate forms of NS from other RASopathies, specifically cardiofaciocutaneous syndrome.
What does this study add?
NS with PTPN11 mutations is usually associated with a mild and nonspecific cutaneous phenotype.
NS with multiple lentigines is typically associated with specific mutations of PTPN11 but atypical forms can be linked to RAF1 or NRAS mutations.
Absence of PTPN11 mutation in NS is associated with a higher frequency of keratinization disorders and hair abnormalities, the latter being commonly observed in cardiofaciocutaneous syndrome.
What is the translational message?
Abnormalities of the genes of the Ras–MAPK signalling pathway that are involved in NS underlie a spectrum of cutaneous manifestations including hair abnormalities, keratinization, pigmentary and connective tissue disorders and multiple melanocytic naevi.
This study adds new information to improve the definition of the cutaneous phenotype of NS and differentiate it phenotypically from RASopathies, specifically cardiofaciocutaneous syndrome and Costello syndrome.
Linked Comment: Carcavilla. Br J Dermatol 2019; 180:1293.
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This paper presents an analytical methodology for calibration of the Hyperplastic Accelerated Ratcheting Model (HARM, Houlsby et al., 2017 3), based on a closed-form expression for the accumulation ...of ratcheting strain with cyclic history. The proposed method requires the fit of one test response and of a few continuous cyclic tests. The initial motivation for this work is the calibration of models for the design of piles subjected to long-term cyclic lateral loading, and the test results from Abadie et al. (2018, 2015) 1,2 are used for calibration and proofing of the model. Nevertheless, the method is applicable to other problems of similar behaviour.
Résumé Objectif : Comparer les prises en charge observées en 1999 et en 2004, établir un bilan de la situation épidémiologique du cancer du sein en Aquitaine en 2004. Méthodes : Enquête descriptive ...transversale par sondage aléatoire incluant les patientes admises en affection de longue durée pour un cancer du sein en 2004. Résultats : L’incidence brute annuelle a progressé de 126 à 159 cas pour 100 000 femmes. Le taux des tumeurs in situ était de 10,6 % ± 2,1, celui des tumeurs infiltrantes de 89,4 % ± 2,1. Le taux des tumeurs invasives de taille inférieure ou égale à 10 mm était de 23,1 % (9,6 % en 1999). Les comptes-rendus anatomopathologiques étaient mieux renseignés, notamment pour les facteurs prédictifs de récidive. Certains écarts persistaient : nombre de ganglions examinés lors d’un curage axillaire inférieur à 10 pour 28,7 %, prescription trop fréquente des marqueurs tumoraux plasmatiques (40,1 %). La technique du ganglion sentinelle s’était développée (24,8 % des traitements chirurgicaux). Exceptés 15 prélèvements ganglionnaires non justifiés, les pratiques concernant les cancers in situ étaient conformes aux référentiels. Conclusion : L’incidence médico-administrative du cancer du sein a augmenté depuis cinq ans en Aquitaine. Une amélioration de la prise en charge des patientes a été constatée mais certains écarts aux référentiels persistaient. Ces constats soulignent l’intérêt de ces évaluations régionales menées en partenariat avec un groupe d’experts. En dressant un état des lieux des prises en charge, elles permettent aux professionnels de poursuivre la réflexion sur les pratiques. Prat Organ Soins 2010;41(1):11-21
Abadie C, Blanchet C, Baux D, Larrieu L, Besnard T, Ravel P, Biboulet R, Hamel C, Malcolm S, Mondain M, Claustres M, Roux A‐F. Audiological findings in 100 USH2 patients.
Bilateral sensorineural ...hearing loss (HL), classically described as mild to severe with a typically down‐sloping audiometric configuration, is the earliest symptom occurring in Usher syndrome type II (USH2).
Audiological findings were analyzed in a total of 100 USH2 patients (92 families) divided into three groups according to the gene involved: 88 USH2A, 10 GPR98 and 2 DFNB31 patients. A fine analysis of audiograms was performed (pure tone average, degree of severity, configuration).
The median age of HL diagnosis was 5 years (range 8 months–31 years) although the median age at USH2 diagnosis was 34.5 (range 8–76). Moderate HL was predominant (76%) and a gently down‐sloping configuration characterized most audiograms (66%). No statistically significant difference was found between USH2A and GPR98 patients but a tendency was clearly noted for more GPR98 patients to present with severe hearing loss. It is not possible to predict the mutated gene from audiograms.
Dermatological manifestations in Noonan syndrome Bessis, D.; Miquel, J.; Bourrat, E. ...
British journal of dermatology (1951),
June 2019, 2019-06-00, 20190601, Letnik:
180, Številka:
6
Journal Article
Recenzirano
Summary
Noonan syndrome (NS) is a genetic disorder affecting up to 1 in 1000 people. It is recognised by an unusual facial appearance, heart defects and small stature. Some people with features of NS ...also have lots of small dark brown flecks on their skin (lentigines), a condition formerly known as LEOPARD syndrome but now called NS with multiple lentigines (NSML). There are also some atypical (unusual) “Noonan‐like” syndromes: this overlapping group of “Rasopathies” also includes Costello syndrome and cardio‐facio‐cutaneous syndrome. About 10 genes responsible for these conditions are now known, but the dermatological (skin) features of the different genetic types have never been clearly defined. Therefore, these French doctors, based at 10 different hospitals, systematically recorded the skin abnormalities seen in patients with any kind of NS attending their clinics over a 4‐year period, and correlated them with NS subtype and gene. Of 129 patients, aged from 9 months to 77 years, three quarters had mutations (changes) in the PTPN11 gene and of these 65 were diagnosed as NS and 34 as NSML. Dermatological features in the NS patients were mild and non‐specific such as easy bruising, raised hair follicles (keratosis pilaris), lax skin or wavy hair. NSML patients additionally had dozens of lentigines, larger brown patches and usually had particular PTPN11 mutations. NS patients with mutations in a different gene were more likely to have striking skin features including unusually curly hair, sparse eyebrows, marked keratosis pilaris or multiple moles. This research highlights the value of careful dermatological documentation in patients with genetic syndromes.
Linked Article: Bessis et al. Br J Dermatol 2019; 180:1438–1448
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