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Each day in schools throughout the United States, students from diverse racial and ethnic backgrounds go into schools pursuing their right to a free and equitable public-school education. Due to the flourishing diversification of the United States, and the expanding immigrant refugee populations, the need for an educational system that provides all students with equal access to success in school is imperative. In urban areas, primarily those with minority and low-socioeconomic status students, continue to fall far behind their suburban white non-low socioeconomic status counterparts in terms of academic achievement. Students from low socioeconomic status backgrounds, primarily minority, within urban K12 school districts are struggling to meet the academic expectations in the United States. The authors seek to provide information that informs educators and policy makers on the history of the school system, educational policy and curriculum, and strategies and solutions that assist in closing the achievement gap for students of diverse backgrounds.

Several phenotypes of non-inflammatory palmar and plantar keratoderma (PPK) have been described in patients of Sub-Saharan African descent. They include keratosis punctata of the palmar creases, marginal keratoderma, also known as acrokeratoelastoidosis or focal acral hyperkeratosis, knuckle pads, other forms of diffuse hyperkeratosis, the very rare "mosaic acral keratosis", and ainhum. A previous survey has shown that these various forms of PPK are particularly frequent in patients of Sub-Saharan African descent and that they commonly occur concurrently, suggesting that they could form part of a single entity called "African" Acral Keratoderma (AAK).To assess the validity of the concept of AAK and clarify its main characteristics.A retrospective, descriptive, monocenter study was carried out on patients with AAK seen at our institution between 2009 and 2020.There were 42 patients (median age 38 years, range: 12-69 years), all of Sub-Saharan African descent. The male-female sex ratio was 0.3. Thirty-three (78%) had diffuse keratoderma, 25 (59%) had marginal keratoderma on their hands and/or feet, 20 (48%) had knuckle pads, 20 (48%) had keratosis punctata of the palmar creases, 3 had ainhum, and 2 had mosaic acral keratoderma. Mixed forms were seen in 76% of the patients (n = 32). Familial histories were reported by 17 patients (40%). Treatment was topical in over 90% of patients and systemic in 9 patients (21%). Ainhum was managed surgically.This retrospective study provides additional evidence for the concept of AAK. A genetic origin is suggested by the familial aggregation of cases.

Resume Introduction La survenue d’un melanome acral sur une keratodermie palmoplantaire (KPP) de type « mal de Meleda » a ete rarement decrite. Nous en rapportons un nouveau cas. Cette nouvelle observation fait discuter le caractere fortuit ou non de cette association. Observation Un homme de 64 ans, d’origine algerienne, etait suivi pour une maladie de Meleda familiale (MdM). Le diagnostic etait clinique sur une KPP non syndromique, diffuse, transgrediente et progrediente. Apres echec de l’acitretine, qui n’avait pas empeche une evolution retractile et mutilante de la KPP, plusieurs exereses avec greffes de peau avaient ete realisees. A l’âge de 59 ans un melanome acral lentigineux etait diagnostique histologiquement sur une tumeur bourgeonnante ulceree de la face dorsale de la premiere phalange du troisieme doigt de la main droite, s’etendant a la face palmaire sur une zone non greffee. Le bilan d’extension revelait une metastase ganglionnaire axillaire droite. Le traitement etait une amputation digitale du troisieme doigt avec curage ganglionnaire, suivis d’une chimiotherapie adjuvante par dacarbazine. Le suivi a cinq ans montrait une remission complete du melanome. Discussion La MdM est une KPP hereditaire diffuse non syndromique en rapport avec des mutations du gene SLURP1. Le diagnostic clinique est possible sur un phenotype evocateur a l’âge adulte. La survenue, chez un sujet de phototype type IV, d’une KPP rare et d’un melanome acral, forme rare de melanome (1 a 7 %), suggere une association non fortuite. Cette association pourrait etre expliquee par une dysregulation immunitaire locale plus que par l’inflammation chronique.

In much of the world, electricity grids are not instrumented at the customer level, limiting insights into the power quality experienced by utility customers. Moreover, to understand grid performance, regulators and investors must depend on utilities to self-report reliability data. To address these challenges, we introduce PowerWatch, an agile methodology to directly measure customer experience and aggregated grid performance without relying on the utility for deployment or management. PowerWatch employs a system of distributed sensors coupled with cloud-based analytics. We evaluate the PowerWatch methodology by deploying 462 sensors in homes and businesses in Accra, Ghana for over a year, yielding the largest open-source data set on electricity reliability at the customer-level in the region. We describe the architecture, design, and performance of PowerWatch, as well as the data that are collected, explaining how we determine the accuracy and coverage of our methodology without ground truth. Finally, we report on grid performance issues, finding nearly twice as many outages as the utility observed, suggesting a need for better grid performance monitoring.

BACKGROUND Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare subtype of hereditary epidermolysis bullosa, with a poorly understood pathogenesis and no satisfactory treatment. OBJECTIVES To assess the clinical and biological features, genetic basis and therapeutic management, to better characterize this rare genodermatosis. METHODS We have conducted a retrospective study, reviewing the clinical presentation, genetic diagnosis, immunohistopathological findings and biological characteristics and management of patients with dystrophic epidermolysis bullosa pruriginosa. This study was conducted in the Department of Dermatology at Saint-Louis Hospital and the Department of Genetics at Necker Hospital (Paris, France). All patients with a diagnosis of DEB-Pr seen between 2010 and 2020 were included. RESULTS Seven patients were included, the average age of 50.1 years [range 36-76]. Pruriginous-lichenified papules, plaques or nodules appeared at 27.6 years on average [range 7-66] on pretibial areas and forearms, associated with milia and toenails dystrophy. All patients received multiple treatments, but none could sustainably reduce pruritus. Immunohistopathological analysis of lesion skin revealed subepidermal blister with fibrosis, milia and mast cell infiltration. Serum TNFα, IL1β and IL6 levels were elevated in 2/6 patients. Total serum IgE levels were increased in 7/7 patients, with no history of atopy. Immunophenotyping of circulating T-cells revealed an increased Th2 subset in 4/4 patients, with reduced Th1 and Th17 subpopulations. Genetic analysis of COL7A1 identified 7 distinct causative mutations, six of which were new. Intra-familial clinical variability was documented in 5/7 patients and was associated with the co-inheritance of a recessive COL7A1 mutation or an FLG2 mutation in 2 families. CONCLUSION Our study confirms the stereotyped presentation of DEB-Pr with large intra-familial variability in disease expression. Mast cell infiltration, elevated IgE and increased Th2 subset without atopy strongly support a role of Th2-mediated immunity in DEB-Pr, and further argue for new targeted therapeutic options such as dupilumab.

In order to create an effective 21st century classroom that engages and meets the needs of students, teachers must be knowledgeable of what motivates students to learn and how technology plays a critical role in his/her instruction. Due to the limited exposure of computer science education in the mainstream P-16 curriculum, only a small portion of students from public schools go on to careers in technology. The purpose of this chapter was to examine how teacher preparation programs and districts can better prepare pre-service and inservice teachers with experiences and professional development opportunities to equip them with the tools to effectively and efficiently teach in P-16 classroom settings. As a result, not only school districts but colleges of education must begin to develop and plan for the uses of computer related technologies for its educators.

Wikipedia is the product of thousands of editors working collaboratively to provide free and up-to-date encyclopedic information to its users. This article asks to what degree Wikipedia articles in three languages --- Hindi, Urdu, and English --- achieve Wikipedia's mission of making neutrally-presented, reliable information on a polarizing, controversial topic available to people around the globe. We chose the topic of the recent revocation of Article 370 of the Constitution of India, which, along with other recent events in and concerning the region of Jammu and Kashmir, has drawn attention to related articles on Wikipedia. This work focuses on the English Wikipedia, being the preeminent language edition of the project, as well as the Hindi and Urdu editions. Hindi and Urdu are the two standardized varieties of Hindustani, a lingua franca of Jammu and Kashmir. We analyzed page view and revision data for three Wikipedia articles. Additionally, we interviewed editors from all three Wikipedias to learn differences in editing processes and motivations. While activity on South Asian language editions of Wikipedia is growing, at the time of writing, the Hindi and Urdu editions are still in their nascency. In Hindi and Urdu, as well as English, editors predominantly adhere to the principle of neutral point of view (NPOV), and these editors quash attempts by other editors to push political agendas.

Hypomorphic dominant-negative mutations in Caspase Recruitment Domain-containing Protein 11 (CARD11) is a rare cause of severe atopic dermatitis. CARD11 is a membrane protein involved in TCR signalling via the NF-kB pathway that has been identified as a predisposition locus for severe atopy. A loss of function activity of CARD11 due to a dominant-negative effect of CARD11 variant leads to severe atopic dermatitis associated with a defective T cell response that polarize toward a Th2 phenotype. We report the successful treatment of severe atopic dermatitis with dominant-negative CARD11 variant with Dupilumab.

This chapter focuses on the suggestions and strategies of technology being utilized in classroom settings. An emphasis is placed on digital technology and literacy integration. The authors explore the effectiveness of digital technology and literacy integration and identify external and internal factors limiting technology integration commonly found within a typical PreK-12th grade classroom setting. In addition to the authors discussing factors that limit school's integration, the authors provide solutions and recommendations suggesting resources throughout the chapter to improve and model digital technology and literacy integration in the classroom.

Space-filling curves have been used for decades to study the folding principles of globular proteins, compact polymers, and chromatin. Formally, space-filling curves trace a single circuit through a set of points (x,y,z); informally, they correspond to a polymer melt. Although not quite a melt, the folding principles of Human chromatin are likened to the Hilbert curve: a type of space-filling curve. Hilbert-like curves in general make biologically compelling models of chromatin; in particular, they lack knots which facilitates chromatin folding, unfolding, and easy access to genes. Knot complexity has been intensely studied with the aid of Alexander polynomials; however, the approach does not generalize well to cases of more than one chromosome. Crossing complexity is an understudied alternative better suited for quantifying entanglement between chromosomes. Do Hilbert-like configurations limit crossing complexity between chromosomes? How does crossing complexity for Hilbert-like configurations compare to equilibrium configurations? To address these questions, we extend the Mansfield algorithm to enable sampling of Hilbert-like space filling curves on a simple cubic lattice. We use the extended algorithm to generate equilibrium, intermediate, and Hilbert-like configurational ensembles and compute crossing complexity between curves (chromosomes) in each configurational snapshot. Our main results are twofold: (a) Hilbert-like configurations limit entanglement between chromosomes and (b) Hilbert-like configurations do not limit entanglement in a model of S-phase DNA. Our second result is particularly surprising yet easily rationalized with a geometric argument. We explore ergodicity of the extended algorithm and discuss our results in the context of more sophisticated models of chromatin.

An accurate DNA damage response pathway is critical for the repair of DNA double-strand breaks. Repair may occur by homologous recombination, of which many different sub-pathways have been identified. Some recombination pathways are conservative, meaning that the chromosome sequences are preserved, and others are non-conservative, leading to some alteration of the DNA sequence. We describe an in vivo genetic assay to study non-conservative intra-chromosomal deletions at regions of non-tandem direct repeats in Schizosaccharomyces pombe. This assay can be used to study both spontaneous breaks arising during DNA replication and induced double-strand breaks created with the S. cerevisiae homothallic endonuclease (HO). The preliminary genetic validation of this assay shows that spontaneous breaks require rad52+ but not rad51+, while induced breaks require both genes, in agreement with previous studies. This assay will be useful in the field of DNA damage repair for studying mechanisms of intra-chromosomal deletions.

Introduction La maladie de Hailey–Hailey (MHH) est une genodermatose rare qui se manifeste a l’âge adulte par un intertrigo erosif des grands plis evoluant par poussees dont la prise en charge est mal codifiee. L’efficacite de la naltrexone est suggeree dans quelques publications, mais la dose optimale reste sujette a discussion. Observations Une patiente de 52 ans presentant une MHH depuis 20 ans etait hospitalisee pour une poussee hyperalgique disseminee resistant a l’association propionate de clobetasol 1 % topique et cloxacilline. La patiente pesait 65 kg et la naltrexone etait introduite a 12,5 mg/j. On observait une amelioration franche des lesions apres 8 jours et une remission complete en 6 semaines avec une tolerance satisfaisante. Une seconde patiente de 36 ans etait hospitalisee pour une poussee severe de MHH malgre un traitement par propionate de clobetasol 1 % et 20 mg/semaine de methotrexate introduit 2 mois plus tot. La patiente pesait 112 kg ; les lesions atteignaient 15 % de la surface corporelle et etaient surinfectees. Apres 14 jours d’introduction de 12,5 mg/j de naltrexone, les plaques, qui ne s’etaient pas ameliorees sous Augmentin®, commencaient a cicatriser. Trois mois plus tard, elle etait toujours en remission complete sans aucun effet secondaire. Discussion Plusieurs equipes ont rapporte l’efficacite de petites doses (low dose LD) de naltrexone dans la MHH dans des « case reports » tres heterogenes en fonction des doses utilisees et de la qualite de la reponse. Les doses utilisees dans la MHH sont habituellement comprises entre 1,5 et 4,5 mg par jour (Antaxone® sirop disponible en ATU), tandis que la dose a visee anti-opioide est comprise entre 50 et 100 mg. Les LD sont connues pour avoir un effet antalgique et anti-inflammatoire. En effet, les LD ne saturent qu’une partie des recepteurs aux opioides entrainant paradoxalement la synthese de nouveaux recepteurs et la secretion d’endorphine. De plus, la naltrexone antagonise les Toll-like recepteurs 4 inhibant la production de cytokines pro-inflammatoires. Dans la plupart des cas rapportes, la dose standard de 50 mg ne permet pas une amelioration aussi importante que des LD. Cependant, des observations plus recentes suggerent qu’une dose plus elevee (12,5 mg voir 50 mg) pourrait, en relation avec la severite de l’atteinte cutanee, etre plus efficace. La dose intermediaire, contrairement a une dose standard anti-opioide, ne semble pas generer plus d’effets indesirables et permet une prescription plus facile, les comprimes de 50 mg etant secables. Il s’agit cependant d’un traitement suspensif et la rechute a l’arret reste generalement la regle, la reprise permettant le plus souvent une nouvelle reponse. Nos observations et celles de la litterature suggerent l’interet de la naltrexone dans la MHH, mais des essais controles avec des doses faibles, intermediaires et classiques sont indispensables pour en demontrer l’efficacite et la tolerance.

Development of acral malignant melanoma in Mal de Meleda is highly unusual. As far as we could ascertain, to date, only 10 previous cases have been published. Herein, we report a new case.A 64-year-old Algerian man was followed for familial Mal de Meleda. The diagnosis was based on clinical presentation as he had a non-syndromic hereditary foul-smelling and yellowish palmoplantar keratoderma transgrediens. After the failure of acitretin, which had not prevented retractile and mutilating progression of the palmoplantar keratoderma, he had undergone surgery with graft excision of both palms. At the age of 59 years, he presented a tumor on the dorsal aspect of the 1Mal de Meleda is a hereditary palmoplantar keratoderma due to mutation of the SLURP1 gene. Clinical diagnosis is based on the typical phenotype in adulthood. The occurrence of acral melanoma, which is a rare form of melanoma (1 to 7%), especially in the fingers, together with an unusual palmoplantar keratoderma in a subject of type IV phototype does not appear to be a chance event. This association seems to be the outcome of immune dysregulation rather than of chronic inflammation.

Introduction L’epidermolyse bulleuse prurigineuse (EBP) est une forme rare d’EB dystrophique (EBD). Le diagnostic est souvent tardif, cette genodermatose pauci bulleuse pouvant etre confondue avec une autre dermatose prurigineuse chronique. Materiel et methodes Cette etude retrospective monocentrique sur tous les cas d’EBP de notre service (2010–19) a recueilli les donnees demographiques, phenotypiques, therapeutiques et genotypiques. Resultats Cinq des 7 patients etaient des femmes, d’âge moyen 50,1 ans [36–76]. Tous les patients avaient une atteinte initiale congenitale ou precoce a type de fragilite cutanee sur les zones de traumatisme des membres. Le prurit apparaissait toujours secondairement, a un âge median de 27,6 ans [7–66] puis des lesions papuleuses inflammatoires, keratosiques, lineaires et reticulees, parfois des nodules, predominant a la face anterieure des membres inferieurs (7/7) et aux coudes (6/7). Des grains de milium etaient visibles sur ces lesions chez les 7 patients ainsi que quelques bulles occasionnelles. Il existait une hyponychie ou anonychie chez tous les patients (pieds: 7/7; mains 2/7). Les IgE totales plasmatiques etaient elevees chez 4/5 patients preleves, sans contexte d’atopie. L’histologie confirmait ou redressait le diagnostic dans 4 cas. Le prurit resistait a tous les traitements utilises: dermocorticoides, methotrexate, phototherapie UVB ou UVA, tacrolimus topique, thalidomide, acitretine, corticotherapie generale, aprepitant, emplâtres de lidocaine, pregabaline, gabapentine, doxepine, psychotherapie. Le delai moyen entre le debut des signes cliniques et le diagnostic etait de 35,8 ans [6–76]. Les diagnostics suspectes etaient prurigo (1/7), lichen verruqueux ou bulleux (2/7). Il existait une dissociation phenotypique familiale frequente: chez 4/7 patients les autres membres de la famille atteints d’EBD avaient des bulles et des cicatrices dystrophiques localisees sans prurit, par contre les patientes 2 et 3 etaient sœurs et avaient le meme tableau. Il n’y avait pas de correlation phenotype/genotype retrouvee et autant de mutations dominantes que recessives du gene du collagene 7. Discussion Notre etude confirme la presentation stereotypee de l’EBP: debut dans la petite enfance avec bulles et erosions puis apparition d’un prurigo lineaire des 4 membres. En l’absence d’antecedent connu d’EBD dans la famille, le diagnostic peut etre evoque sur la presence de grains de milium et parfois de rares bulles, la dystrophie ungueale et l’aspect histologique. Le traitement classique du prurigo ainsi que les traitements anti-inflammatoires locaux ou systemiques sont inefficaces. La presence d’IgE a des taux tres eleves chez tous les patients testes incite a s’orienter vers de nouvelles pistes therapeutiques. Conclusion L’EBP constitue une forme rare d’EBD, initialement peu severe, evoluant ensuite vers une atteinte prurigineuse invalidante resistant a tous les traitements classiques du prurigo.

Background Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare disease, currently considered a benign vascular proliferation of unknown etiology, and whose treatment is still unclear and challenging. Patients and methods Two women in their thirties consulted for itchy lesions of the right ear. Both presented with a reddish bleeding papulonodular infiltration of the auricle, with a nodule at the entrance to the external auditory canal in the first patient. Laboratory tests showed no abnormalities and in particular no hypereosinophilia or elevated serum immunoglobulin E. In both cases, histology of lesional skin showed vascular proliferation with thick-walled vessels lined by plump endothelial cells, protruding into the lumen, together with a mixed dermal inflammatory infiltrate consisting primarily of eosinophils and lymphocytes. A diagnosis of ALHE was made in both patients based on clinical and histological features. MRA revealed no underlying vascular malformation in both cases. Patients started treatment with 0.1% tacrolimus ointment twice daily. The pruritic sensation and bleeding had completely subsided within two weeks and the reddish infiltration and nodules had practically disappeared after two months of topical tacrolimus. Continuous application resulted in no recurrence at 6 months of follow-up. Discussion Treatment of ALHE is still poorly standardized due to doubts concerning the pathophysiology of this rare condition and the small number of available studies. Topical tacrolimus was originally developed for the treatment of moderate to severe atopic dermatitis because of its anti-inflammatory and immunomodulatory properties. Recent studies suggest that this drug may be effective in treating other forms of inflammatory dermatosis. Our two observations suggest that tacrolimus ointment also represents potentially valuable treatment in AHLE.

Introduction Les syndromes auto-inflammatoires (SAI) PAPASH, PsAPASH et PASS associent respectivement une spondylarthrite (Sp) peripherique, un rhumatisme psoriasique (RP) ou une Sp axiale a un pyoderma gangrenosum (PG), une acne, et une hidradenite suppuree (HS). Notre etude vise a preciser les phenotypes cutaneo-articulaires et les caracteristiques biologiques et therapeutiques de ces syndromes de description recente. Materiel et methodes Dans 2 centres experts, etude de cas sur les caracteristiques cliniques et biologiques incluant la recherche d’anticorps anti-saccharomyces cerevisiae (ASCA) ainsi que la reponse aux traitements. Une recherche de mutation des genes du complexe gamma-secretase (GS) APH1, NCSTN, PSENEN, PSTPIP1 et de NOD2 etait realisee. Resultats Neuf patients (4 hommes, 5 femmes) dont 2 PAPASH, 3 PASS, 1 PsAPASH et 3 patients avec une Sp mixte. L’âge moyen de debut de l’atteinte cutanee et/ou articulaire etait de 24,4 ans (14–40). L’HS etait constamment severe (Hurley III dans 8 cas), inaugurale (7), avec atteinte inguino-perineale et axillaire (9), ainsi qu’une acne cheloidienne de la nuque (3). La dermatose neutrophilique etait un PG (2), des pustules aseptiques disseminees (7), et/ou des abces aseptiques sous cutanes (2). L’asthenie constante etait parfois accompagnee de fievre (3). Le taux initial moyen de CRP etait de 82 mg/L, avec hypergammaglobulinemie (5/7) et SAA elevee (4/5). Les ASCA etaient positifs (7/8), sans signe endoscopique de maladie inflammatoire chronique intestinale (MICI) mais avec presence histologique d’abces ou d’infiltrat neutrophilique gastrique ou colique (3/5). Un patient presentait un RP, 3 une Sp axiale et peripherique, 3 une Sp axiale pure et 2 une atteinte peripherique seronegative. Aucune destruction articulaire n’etait observee. Aucune mutation n’etait trouvee. Les elements cutanes du syndrome dont l’HS resistaient a l’antibiotherapie, necessitant le recours aux immunomodulateurs (methotrexate, corticoides oraux, azathioprine, ciclosporine), tous en echec en monotherapie. Une reponse partielle a complete etait obtenue sous infliximab (jusqu’a 10 mg/kg/4 semaines) ou adalimumab (40 mg/semaine) combines a un autre immunomodulateur, avec des taux plasmatiques residuels d’anti-TNF souvent eleves. Discussion Les SAI PAPASH, PsAPASH et PASS sont severes par leur atteinte cutaneo-articulaire et systemique et partagent les ASCA comme biomarqueur commun, suggestif d’une dysbiose. Leur controle optimal est le plus souvent obtenu sous anti-TNF associe a un autre immunomodulateur, permettant parfois la chirurgie de l’HS. Conclusion Les SAI cutaneo-articulaires derives de l’HS, heterogenes sur le plan rhumatologique, sont particuliers par leur severite, par des marqueurs immunobiologiques communs et par la necessite d’un traitement immunosuppresseur intensif incluant un anti-TNF. Leur substratum genetique, inconnu, semble different de ceux de l’HS et d’autres SAI.

Significance Male and female pattern hair loss are common, chronic dermatologic disorders with limited therapeutic options. In recent years, a number of commercial devices using low-level laser therapy have been promoted, but there have been little peer-reviewed data on their efficacy. Objective To determine whether treatment with a low-level laser device, the US FDA-cleared HairMax Lasercomb®, increases terminal hair density in both men and women with pattern hair loss. Methods Randomized, sham device-controlled, double-blind clinical trials were conducted at multiple institutional and private practices. A total of 146 male and 188 female subjects with pattern hair loss were screened. A total of 128 male and 141 female subjects were randomized to receive either a lasercomb (one of three models) or a sham device in concealed sealed packets, and were treated on the whole scalp three times a week for 26 weeks. Terminal hair density of the target area was evaluated at baseline and at 16- and 26-week follow-ups, and analyzed to determine whether the hypothesis formulated prior to data collection, that lasercomb treatment would increase terminal hair density, was correct. The site investigators and the subjects remained blinded to the type of device they dispensed/received throughout the study. The evaluator of masked digital photographs was blinded to which trial arm the subject belonged. Results Seventy-eight, 63, 49, and 79 subjects were randomized in four trials of 9-beam lasercomb treatment in female subjects, 12-beam lasercomb treatment in female subjects, 7-beam lasercomb treatment in male subjects, and 9- and 12-beam lasercomb treatment in male subjects, compared with the sham device, respectively. Nineteen female and 25 male subjects were lost to follow-up. Among the remaining 122 female and 103 male subjects in the efficacy analysis, the mean terminal hair count at 26 weeks increased from baseline by 20.2, 20.6, 18.4, 20.9, and 25.7 per cm2 in 9-beam lasercomb-treated female subjects, 12-beam lasercomb-treated female subjects, 7-beam lasercomb-treated male subjects, and 9- and 12-beam lasercomb-treated male subjects, respectively, compared with 2.8 (p

Transmission spectroscopy has been successfully used from both the ground and in space to characterise the atmospheres of transiting exoplanets. This technique is challenging from the ground because ground-based spectrographs tend not to be designed to be photometrically stable, and effects such as variable slit losses cause significant systematic uncertainties. An alternative approach is to use simultaneous photometric observations in multiple wavebands to determine wavelength dependent transit depth differences. We report an application of this technique to one of the hottest known exoplanets, WASP-12b, using the triple-beam camera ULTRACAM. We obtained simultaneous light curves in Sloan u', and two narrow band filters centered on 4169 and 6010 angstroms, with FWHMs 52 and 118 angstroms respectively. We fit these light curves with a photometric model and determine the planetary radius in the three different bands. Our data show no evidence for a difference in planetary radius over the wavelength range we study, and are consistent with an atmosphere that is dominated by Rayleigh scattering from a high altitude haze, as well as more complicated atmosphere models which include the effects of molecules such as TiO. Our planetary radius measurements have an average precision of 2.6 per cent, compared to the ~1.4 - 2.4 per cent radius differences predicted by the models over this wavelength range. We also find a consistent time of ingress and egress across our three wavebands, in contrast to the early ingress which has been reported for this system at shorter wavelengths., Comment: MNRAS accepted. Some minor revisions to the text in response to the reviewer's comments. 10 pages with 2 tables and 4 figures

Resume Introduction Le syndrome hypereosinophilique (SHE) est defini par une eosinophilie superieure a 1,5 G/L persistant plus de six mois et associee a une atteinte viscerale specifique (cardiaque, neurologique, pulmonaire…), apres elimination des causes « classiques » d’hypereosinophilie. Une variante myeloproliferative de SHE est associee a la fusion des genes FIP1L1 et PGDFRα, entrainant l’activation constitutive d’un recepteur a activite tyrosine kinase. Nous en rapportons un cas, revele de facon inhabituelle par des ulcerations muqueuses. Observation Un homme de 50 ans consultait pour des ulcerations des muqueuses buccale et genitale. L’examen trouvait des erosions du gland et de la levre inferieure, ainsi qu’un discret dermographisme. Il existait une hypereosinophilie a 7,5 G/L ( n ® ) etait debute. L’evolution etait favorable en quelques mois, avec une remission complete apres un an de traitement. Discussion Les manifestations cutanees sont un mode de revelation frequent du SHE. Elles sont polymorphes, a type de prurit, macules, papules ou nodules erythemateux, urticaire etc. Les ulcerations muqueuses, rares, surviendraient plus frequemment au cours du SHE myeloproliferatif avec transcrit de fusion FIP1L1-PDGFRα. Un diagnostic precoce permet d’instituer un traitement cible par imatinib avant le developpement d’atteintes viscerales.

Introduction L’acitretine (Soriatane®) est le seul retinoide ayant l’EMA en Europe pour le traitement des ichthyoses hereditaires (IH). Sa teratogenicite (grossesse contre-indiquee 3 ans apres l’arret) justifie de disposer d’alternative therapeutique. Nous presentons ici les resultats d’une serie d’IH traitees par alitretinoine. Materiel et methodes Etude observationnelle retrospective multicentrique. Inclusion de toutes IH traites par alitretinoine. Etude approuvee par les instances reglementaires et ethiques (Loi Jarde) Resultats Treize patients etaient inclus (10 F/3 M), âge median 30 ans [12–38], formes : 10 ichtyoses autosomiques recessives (7 lamellaires et 3 erythrodermies ichtyosiformes), 1 syndrome de Netherton, 1 erythrokeratodermie et 1 syndrome KLICK. 7 formes moderees/4 severes/2 tres severes. Onze avaient eu au prealable de l’acitretine (dosage median de 0,4 mg/kg/j [0,2–0,5]). Le choix de l’alitretinoine etait base sur : souhait de grossesse (10 femmes), effets indesirables de l’acitretine ou efficacite insuffisante (3 hommes). L’alitretinoine etait debutee a 10 mg/j pour tous puis augmentee a 30 mg sauf pour 4 patients (cephalees pour 1, une efficacite suffisante pour 3). Duree mediane de traitement : 12 mois [1–36]. Traitement efficace chez 11/13, le plus souvent a 30 mg, variations selon le type d’ichtyose et les parametres etudies. Traitement particulierement efficace sur les phenotypes erythrodermiques avec squames fines et moins sur les phenotypes tres keratosiques et les keratodermies palmoplantaires epaisses. Concernant la tolerance clinique : cephalees chez 4 HI (a 30 mg pour 3, a 10 mg pour 1), qui n’ont pas conduit a l’arret du traitement. Hypertension intracrânienne benigne, decouverte sur des signes visuels (œdeme papillaire) justifiant l’arret du traitement avec regression complete des symptomes. Aucune anomalie biologique (lipidique, hepatique, thyroidienne). Discussion Nous rapportons la plus grande serie de patients atteints d’IH traitee par alitretinoine (Toctino®). Ce retinoide oral qui a l’AMM dans l’eczema des mains a une demi-vie plus courte que l’acitretine, contre-indiquant une grossesse jusqu’au premier mois suivant l’arret, au lieu de 3 annees pour l’acitretine. Six autres patients rapportes dans la litterature (2 KID, 1 ichtyose epidermolytique, 3 ichtyoses lamellaires) : efficacite sur l’erytheme et l’hyperkeratose, mais doses utilisees souvent plus etaient elevees, jusqu’a 60 mg/j. Deux cas d’hypothyroidie (dont 1 persistante : thyroidite auto-immune), ainsi que de cephalees. Le principal effet indesirable dans notre serie est la cephalee et le risque d’hypertension intracrânienne benigne, pas de dysthyroidie notee. Conclusion L’alitretinoine semble etre une bonne alternative a l’acitretine chez les patients presentant une forme erythrodermique a fines squames, notamment les femmes jeunes avec desir de grossesse a moyen terme.

We present high-speed, three-colour photometry of the eclipsing cataclysmic variables CTCV 1300, CTCV 2354 and SDSS 1152. All three systems are below the observed "period gap" for cataclysmic variables. For each system we determine the system parameters by fitting a parameterised model to the observed eclipse light curve by chi-squared minimisation. We also present an updated analysis of all other eclipsing systems previously analysed by our group. New donor masses are generally between 1 and 2 sigma of those originally published, with the exception of SDSS 1502 and DV UMa. We note that the donor mass of SDSS 1501 has been revised upwards by 0.024Msun. This system was previously identified as having evolved passed the minimum orbital period for cataclysmic variables, but the new mass determination suggests otherwise. Our new analysis confirms that SDSS 1035 and SDSS 1433 have evolved past the period minimum for cataclysmic variables, corroborating our earlier studies. We find that the radii of donor stars are oversized when compared to theoretical models, by approximately 10 percent. We show that this can be explained by invoking either enhanced angular momentum loss, or by taking into account the effects of star spots. We are unable to favour one cause over the other, as we lack enough precise mass determinations for systems with orbital periods between 100 and 130 minutes, where evolutionary tracks begin to diverge significantly. We also find a strong tendency towards high white dwarf masses within our sample, and no evidence for any He-core white dwarfs. The dominance of high mass white dwarfs implies that erosion of the white dwarf during the nova outburst must be negligible, or that not all of the mass accreted is ejected during nova cycles, resulting in the white dwarf growing in mass. (Abridged)

We present high-speed optical photometry of the soft gamma repeater SGR 0501+4516, obtained with ULTRACAM on two consecutive nights approximately 4 months after the source was discovered via its gamma-ray bursts. We detect SGR 0501+4516 at a magnitude of i' = 24.4+/-0.1. We present the first measurement of optical pulsations from an SGR, deriving a period of 5.7622+/-0.0003 s, in excellent agreement with the X-ray spin period of the neutron star. We compare the morphologies of the optical pulse profile with the X-ray and infrared pulse profiles; we find that the optical, infrared and harder X-rays share similar double-peaked morphologies, but the softer X-rays exhibit only a single-peaked morphology, indicative of a different origin. The optical pulsations appear to be in phase with the X-ray pulsations and exhibit a root-mean-square pulsed fraction of 52+/-7%, approximately a factor of two greater than in the X-rays. Our results find a natural explanation within the context of the magnetar model for SGRs.

The Rotating RAdio Transient (RRAT) J1819 1458 exhibits 3 ms bursts in the radio every 3 min, implying that it is visible for only 1 s per day. Assuming that the optical light behaves in a similar manner, long exposures of the eld would be relatively insensitive due to the accumulation of sky photons. A much better way of detecting optical emission from J1819 1458 would then be to observe with a high-speed optical camera simultaneously with radio observations, and co-add only those optical frames coincident with the dispersion-corrected radio bursts. We present the results of such a search, using simultaneous ULTRACAM and Lovell Telescope observations. We nd

Introduction La sclerose tubereuse de Bourneville (STB) est une genodermatose autosomique dominante caracterisee par la survenue d’hamartomes benins dans differents organes, peau, cerveau, rein, cœur, poumons, œil. Les localisations osseuses de la STB sont frequemment rapportees dans la litterature radiologique mais sont peu connues des dermatologues. Nous presentons le cas d’un patient presentant une atteinte osseuse de STB a type d’osteocondensations polyostiques. Observations Un homme de 28 ans etait pris en charge pour un premier bilan d’une STB certaine sur le plan dermatologique (multiples angiofibromes du visage, plaques peau de chagrin, macules hypochromiques, tumeurs de Koenen) et confirmee genetiquement (mutation heterozygote TSC2). L’IRM cerebrale mettait en evidence des tubers corticaux et un astrocytome periventriculaire. L’IRM renale revelait de nombreuses tumeurs et kystes renaux dont deux lesions atypiques, correspondant histologiquement a des angiomyolipomes epithelioides. Il existait un aspect typique de lymphangioleiomyomatose au scanner pulmonaire. Les radiologues nous alertaient sur la presence d’anomalies osseuses suspectes sur le scanner abdomino-pelvien a type d’osteocondensations des cotes, du bassin et du rachis. Apres discussion multidisciplinaire avec des radiologues specialises, ces condensations nodulaires eparses sur le squelette axial assez homogenes et a limites nettes etaient caracteristiques d’une atteinte osseuse sclerosante de la STB. Les osteoscleroses restaient stables et asymptomatiques apres 5 ans de suivi ( Fig. 1 ). Discussion Apres les angiomyolipomes renaux et les tubers corticaux, les lesions osseuses sclerotiques sont la troisieme anomalie par ordre de frequence diagnostiquee par l’imagerie chez les patients STB. Les osteoscleroses sont classiquement des foyers osseux denses, de petites tailles et multiples, localises dans l’os spongieux, principalement du rachis et du sacrum. Elles sont considerees comme des hamartomes dont la penetrance et l’expression augmentent avec l’âge. Des images kystiques cerclees, des lacunes phalangiennes, une association avec la dysplasie fibreuse des os, sont egalement decrites chez les patients STB. La prevalence et la signification clinique de ces differents types d’atteintes osseuses de la STB restent mal evaluees. Les diagnostics differentiels sont nombreux, principalement representes par les metastases dans ce contexte de predisposition genetique aux tumeurs. Ces atteintes sont classiquement non symptomatiques et non traitees mais doivent etre connues des cliniciens pour eviter des examens inutiles. Conclusion L’atteinte osseuse osteocondensante, particulierement axiale, est frequente au cours de la STB. Elle merite d’etre mieux connue des dermatologues car elle peut orienter a tort vers une autre pathologie lors du bilan d’extension ou du suivi de la maladie.

Introduction Le deficit en sous-unite M de la lactate deshydrogenase est une maladie genetique tres rare atteignant la peau et les muscles. L’histologie cutanee peut orienter le diagnostic. Nous decrivons un cas associe a une nouvelle mutation. Observations Une patiente caucasienne de 51 ans presentait depuis l’âge de 40 ans un tableau associant myalgies et rhabdomyolyse a l’effort, d’aggravation progressive. La biopsie musculaire etait normale. Elle rapportait egalement une dermatose psoriasiforme depuis la periode neonatale, evoluant par poussees erythrodermiques. Initialement decrites comme erythemato-squameuses, les lesions cutanees etaient devenues pustuleuses a l’âge adulte. La biopsie cutanee mettait en evidence un epiderme acanthosique avec disparition focale de la granuleuse ainsi qu’une clarification des cytoplasmes des deux tiers superieurs du corps muqueux, sans acantholyse ni dyskeratose. La couche cornee etait parakeratosique, seche, contenant des debris de polynucleaires neutrophiles. Devant l’association de myalgies a l’effort et de lesions psoriasiformes avec aspect clarifie des keratinocytes a l’histologie cutanee, le diagnostic de deficit en sous-unite M de la lactate deshydrogenase etait suspecte. La mise en evidence a l’etat homozygote d’une nouvelle mutation (predite pathogene) du gene LDHA (mutation non sens p.Trp188* ou c.563G > A) a permis de confirmer le diagnostic ( Fig. 1 et 2 ). Discussion Le deficit en sous-unite M de la lactate deshydrogenase (ou glycogenose de type XI, OMIM #612933) est une myopathie metabolique de transmission autosomique recessive. Une vingtaine de cas ont ete rapportes dans la litterature depuis sa description princeps en 1980, essentiellement au Japon. Le tableau clinique associe des myalgies et une faiblesse musculaire a l’effort, apparaissant a l’âge adulte, a des manifestations cutanees, debutant dans l’enfance. Celles-ci s’aggravent classiquement en ete. Il s’agit de plaques erythemato-squameuses, bien limitees, essentiellement acrales initialement puis d’extension progressive, avec une evolution pustuleuse a l’âge adulte. Des formes a type de pseudo-pellagre ont egalement ete rapportees. L’aspect histologique des lesions cutanees est tres particulier puisqu’il associe des remaniements psoriasiformes a des elements evocateurs de dermatose carentielle, avec un aspect clarifie des keratinocytes du corps muqueux. Le diagnostic de certitude repose sur la mise en evidence de mutations homozygotes ou heterozygotes composites de LDHA. Le traitement est symptomatique. Conclusion L’association d’une myopathie a l’effort, de lesions psoriasiformes avec une clarification des keratinocytes a l’histologie doit faire evoquer un deficit en sous-unite M de la lactate deshydrogenase.

We present high speed ULTRACAM photometry of the eclipsing post common envelope binaries DE CVn, GK Vir, NN Ser, QS Vir, RR Cae, RX J2130.6+4710, SDSS 0110+1326 and SDSS 0303+0054 and use these data to measure precise mid-eclipse times in order to detect any period variations. We detect a large (~ 250 sec) departure from linearity in the eclipse times of QS Vir which Applegate's mechanism fails to reproduce by an order of magnitude. The only mechanism able to drive this period change is a third body in a highly elliptical orbit. However, the planetary/sub-stellar companion previously suggested to exist in this system is ruled out by our data. Our eclipse times show that the period decrease detected in NN Ser is continuing, with magnetic braking or a third body the only mechanisms able to explain this change. The planetary/sub-stellar companion previously suggested to exist in NN Ser is also ruled out by our data. Our precise eclipse times also lead to improved ephemerides for DE CVn and GK Vir. The width of a primary eclipse is directly related to the size of the secondary star and variations in the size of this star could be an indication of Applegate's mechanism or Wilson (starspot) depressions which can cause jitter in the O-C curves. We measure the width of primary eclipses for the systems NN Ser and GK Vir over several years but find no definitive variations in the radii of the secondary stars. However, our data are precise enough (dRsec / Rsec < 10^-5) to show the effects of Applegate's mechanism in the future. We find no evidence of Wilson depressions in either system. We also find tentative indications that flaring rates of the secondary stars depend on their mass rather than rotation rates.

Resume Introduction Le voriconazole est un antifongique systemique qui peut engendrer un tableau de photosensibilite cutanee tres evocateur de porphyrie cutanee tardive (PCT), mais sans elevation des taux de porphyrines. A cet effet secondaire s’associe souvent une cheilite seche, attribuee a une interference avec le metabolisme des retinoides endogenes. Nous rapportons le cas d’un malade qui a developpe a la fois une cheilite et une authentique PCT peu apres l’introduction d’un traitement par voriconazole. Observation Un homme de 65 ans, ethylique sevre, presentait un tableau typique de PCT associe a une cheilite seche. Les symptomes etaient apparus 12 jours apres le debut du traitement d’une aspergillose pulmonaire par le voriconazole. Les examens biologiques confirmaient une authentique PCT dans sa forme sporadique. L’ensemble des lesions disparaissait en deux semaines apres remplacement du voriconazole par l’itraconazole, mais il persistait un certain degre de photosensibilite et de fragilite cutanee ; un traitement par saignees etait finalement suivi d’une remission clinique complete. Discussion Ce malade a presente a la fois une cheilite secondaire a la prise de voriconazole et une authentique PCT apparemment revelee par le meme medicament. Le mecanisme par lequel le voriconazole a pu precipiter la PCT reste hypothetique : baisse d’activite de l’uroporphyrinogene decarboxylase hepatique ou potentialisation de la phototoxicite cutanee des porphyrines par la toxicite cutanee du voriconazole ? Conclusion En pratique, la constatation d’un tableau clinique evocateur de pseudo-PCT chez un malade sous voriconazole rend indispensable la recherche d’une authentique PCT, meme en presence d’une cheilite.

BP9s exploration success in deepwater Block 31, offshore Angola, has been driven by conventional narrow-azimuth 3D seismic data coupled with the latest available imaging algorithms. However limitations in these data are now apparent and the data is deemed insufficient for the appraisal and development of the subsalt discoveries in the western part of the block. 3D acoustic finite-difference modelling was applied to Block 31 to evaluate the potential data quality uplift from a wide-azimuth towed streamer (WATS) survey. Results showed that a significant improvement in data quality is possible. The modelling also investigated key acquisition variables (acquisition direction, sail line separation, number of tiles, cable length) to arrive at a solution that optimized both data quality and cost. Acquisition of this survey began in December 2008 and it is expected to complete in August 2009. This is the first WATS seismic survey outside the Gulf of Mexico and the first in Angola.

The Marathon portion of the Ouachita thrust belt consists of a highly deformed allochthonous wedge of Cambrian-Pennsylvanian slope strata (Marathon facies) that was transported to the northwest and emplaced over Pennsylvanian foredeep sediments. The foredeep strata in turn overlie early-middle Paleozoic shelfal sediments which are deformed by late Paleozoic basement-involved reverse faults. The Dugout Creek thrust is the basal thrust of the allochthon. Shortening in this sheet and overlying sheets is w80%. Steep imbricate faults link the Dugout Creek thrust to upper level detachments forming complex duplex zones. Progressive thrusting and shortening within the allochthon folded the upper level detachments and associated thrust sheets. The Caballos Novaculite is the most competent unit within the Marathon facies and controlled development of prominent detachment folds. Deeper imbricate sheets composed of the Late Pennsylvanian foredeep strata, and possibly early-middle Paleozoic shelfal sediments developed concurrently with emplacement of the Marathon allochthon and folded the overlying allochthon. Following termination of thrusting in the earliest Permian, subsidence and deposition shifted northward to the Delaware, Midland and Val Verde foreland basins.

Various forms of containerised gas killing systems have been used to slaughter large numbers of poultry on farms during outbreaks of notifiable diseases. However, none of the systems have been fully evaluated to assess bird welfare, operators’ health and safety and biosecurity during operation. In addition, standard operating procedures associated with containerised gas killing systems are lacking in the literature. Therefore, a research and development project was initiated by the Department for Environment, Food and Rural Affairs (DEFRA) in the UK with the primary objective being to develop humane systems for culling poultry on farm and to produce operating procedures based on sound scientific principles. A series of studies have been conducted to achieve the objective and relevant observations and operating procedures are reviewed in this paper.

Successful mammalian reproduction requires that sperm migrate through a long and convoluted female reproductive tract before reaching oocytes. For many years, fertility studies have focused on biochemical and physiological requirements of sperm. Here we show that the biophysical environment of the female reproductive tract critically guides sperm migration, while at the same time preventing the invasion of sexually transmitted pathogens. Using a microfluidic model, we demonstrate that a gentle fluid flow and microgrooves, typically found in the female reproductive tract, synergistically facilitate bull sperm migration toward the site of fertilization. In contrast, a flagellated sexually transmitted bovine pathogen, Tritrichomonas foetus, is swept downstream under the same conditions. We attribute the differential ability of sperm and T. foetus to swim against flow to the distinct motility types of sperm and T. foetus; specifically, sperm swim using a posterior flagellum and are near-surface swimmers, whereas T. foetus swims primarily via three anterior flagella and demonstrates much lower attraction to surfaces. This work highlights the importance of biophysical cues within the female reproductive tract in the reproductive process and provides insight into coevolution of males and females to promote fertilization while suppressing infection. Furthermore, the results provide previously unidentified directions for the development of in vitro fertilization devices and contraceptives.

This paper specifies a macroeconometric model providing a simultaneous framework for estimating the natural rate of unemployment, the full-employment (FE) labor force and hours of work, the FE productivity growth rate, and the growth path of potential (FE) output during 1960–2000. The estimated output and unemployment gaps are consistent with Okun’s Law. Historical perspective is provided on the expansion of the nineties by comparing it with those of the three previous decades in terms of growth and utilization of potential output. Factors accounting for the growth of potential output, productivity and labor supply are identified and compared.

A review was undertaken of (a) the levels and prevalence of Salmonella spp., Campylobacter spp., Listeria monocytogenes, Escherichia coli 0157. Cryptosporidium parvum and Giardia intestinalis in livestock manure, and (b) factors which affect their survival during storage and following land application. Pathogens are commonly present in livestock manures and can survive in soil for several months or years after spreading or excretion onto land. Temperature was identified as being the most important factor influencing pathogen survival, although pH, UV light and drying were also important. Various practical measures to minimise the risk of pathogen transfer into the food chain were identified, including treatment, extended storage and no/harvest periods following land spreading. Guidelines are being developed on managing farm manures to minimise the risks of microbiological contamination of ready-to-eat crops.

Introduction Le syndrome de Birt-Hogg-Dube (BHD), de transmission autosomique dominante, associe hamartomes pilaires, kystes pulmonaires, pneumothorax spontane et carcinome renal. Les hamartomes pilaires sont classiquement decrits comme des papules ou acrochordons avec a l’histologie un aspect de fibrofolliculome (FF) ou de trichodiscome. Nous rapportons 4 cas inhabituels de forme kystique et comedonienne de BHD. Observation Les 4 patients etaient des hommes. L’âge moyen etait de 54 ans (35–72) au diagnostic et de 26 ans (20–30) lors des 1 ers signes cutanes (Tableau 1). Les lesions associees etaient : kyste pulmonaire et adenome colique en dysplasie de bas grade (cas 1,3,4), pneumothorax (cas 1), hematurie ou tumeur renale en cours d’exploration (cas 1,4). Le cas 2 (35 ans) n’avait pas d’atteinte viscerale identifiee mais un pneumothorax chez son pere. Tous avaient de multiples papules chair ou blanchâtres, de 1 a 5 mm de diametre, de la face, du cou et de la partie superieure du tronc. Ils avaient egalement des lesions nettement comedoniennes ou kystiques (Fig. 1) a la tete ou au tronc. L’histologie des lesions papuleuses etait celle de FF. L’analyse histologique des lesions comedoniennes/kystiques montrait un aspect de kyste folliculaire, contenant de la keratine, revetu d’un epithelium malpighien comportant une couche granuleuse. L’epithelium formait de fins prolongements peripheriques s’invaginant dans un stroma lâche, mucineux, pauci-cellulaire, parfois inflammatoire (lymphocytes et plasmocytes), permettant de diagnostiquer des FF dans une forme kystique. Discussion Cinq autres cas de forme comedonienne/kystique de BHD ont ete rapportes (Aivaz et al., 2015 ; Weintraub et Pinkus, 1977). La forme comedonienne/kystique du BHD est particuliere par sa presentation clinique faisant discuter les diagnostics differentiels de sebocystomatose et d’acne. Un facteur hormonal ou lie au sexe est possible car 8 des 9 cas sont des hommes (89 %) alors qu’il n’y a pas de predominance de genre dans le BHD. Il ne semble pas y avoir d’incidence de cette forme sur l’incidence des lesions viscerales associees. La mutation du gene FLCN , situe sur le chromosome 17p11.2 et codant pour la folliculine, est responsable du BHD. Cette mutation perte de fonction pourrait activer la voie mTOR. L’activation de la voie mTOR a ainsi ete montree dans des kystes pulmonaires de BHD (Furuya et al., 2012). Elle ouvre des perspectives therapeutiques. Une etude immunohistochimique de l’activation de la voie mTOR sur les FF kystiques est en cours. Conclusion Comedons et/ou kystes cutanes multiples doivent faire evoquer le BHD dans le diagnostic differentiel. Le role de l’anatomopathologiste est determinant dans le depistage. Cette forme kystique et comedonienne de BHD semble plus frequente chez l’homme, sans incidence pronostique. L’activation de la voie mTOR dans les lesions de BHD pourrait avoir une implication therapeutique.

Introduction Les ichtyoses hereditaires sont l’expression heterogene d’anomalies monogeniques de la cornification se traduisant par l’association sur l’ensemble du tegument d’une hyperkeratose et d’une desquamation anormale. L’inflammation (erytheme et prurit) et la fragilite de l’epiderme (bulles) peuvent se surajouter dans certains cas. Les ichtyoses congenitales autosomiques recessives (ARCI) sont un sous-groupe d’ichtyoses hereditaires, non syndromiques, non bulleuses et de transmission AR pour lequel 9 genes sont actuellement identifies. Le diagnostic moleculaire des ARCI n’est pas couramment accessible et la correlation phenotype/genotype est peu connue : nous rapportons les caracteristiques de la plus grande cohorte d’ARCI mutees ichthyin/NIPAL4 , second gene d’ ARCI en termes de frequence. Materiel et methodes Etude retrospective monocentrique, 31 patients (23 familles) ARCI mutes ichthyin/NIPAL4 . Resultats Donnees phenotypiques : cf tableau donnees genotypiques : large predominance de la mutation c.527C > Ap.Ala176Asp presente a l’etat homozygote chez 56,5 % des patients, a l’etat heterozygote chez 26 %, absente chez 17, 5 %. 10 nouvelles mutations. Discussion Cette etude montre que les ARCI/Ichthyin ont un phenotype intermediaire entre l’ichtyose lamellaire et l’erythrodermie ichtyosiforme congenitale seche (EICS) avec variabilite inter et intrafamiliale et egalement chez un meme individu sous l’effet du traitement. Le phenotype congenital est indifferemment celui de bebe collodion ou d’EICS. A l’âge adulte, les principales caracteristiques sont une disposition « reticulee » des squames particulierement evocatrices, une keratodermie palmoplantaire homogene plus ou moins epaisse mais jamais mutilante ni retractile, un ectropion inconstant et modere. Les retinoides systemiques a faible dose (acitretine surtout, allotretinoine et isotretinoine) sont souvent tres efficaces, leur tolerance au long cours est bonne, ils permettent d’alleger les soins locaux a base de keratolytiques, parfois suffisants mais plus contraignants. La microscopie optique (ichtyose par proliferation, parakeratose possible mais inconstante) et l’immunomarquage Ichtyin (positif car anomalie qualitative et non quantitative) ne sont pas contributifs au diagnostic et n’ont pas ete realises chez la majorite de nos patients de meme que la microscopie electronique qui montre par contre un aspect ARCI classe III tres specifique. Sur le plan moleculaire, la meme mutation est recurrente chez nos patients majoritairement d’origine europeenne comme dans les series scandinaves ou mediterraneennes, temoignant d’un hot spot mutationnel. Conclusion L’ARCI ichthyin/NIPAL4 est une ichtyose de gravite intermediaire repondant bien aux retinoides systemiques. Son diagnostic peut etre evoque cliniquement et en microscopie electronique meme si la confirmation moleculaire reste indispensable pour le conseil genetique.

Introduction Les anticorps Anti – Saccharomyces cerevisiae (ASCA), frequemment trouves dans la maladie de Crohn et la spondylarthrite ankylosante (SPA), sont un biomarqueur presume de deregulation de l’immunite innee en rapport avec une dysbiose digestive. Bien qu’un mecanisme physiopathologique similaire ait ete evoque dans la maladie de Verneuil ou hidrosadenite suppuree, la prevalence des ASCA n’a cependant jamais ete etudiee chez ces patients. Materiel et methodes Dans une etude prospective multicentrique, de 2012 a 2017, nous avons compare la frequence de la positivite des serologies et des isotypes (IgG et/ou IgA) des ASCA, par ELISA, entre 148 patients HS consecutifs, 159 avec psoriasis en plaque candidats a une therapie systemique et 162 donneurs de sang indemnes de ces pathologies (DS). La positivite etait definie par une concentration d’au moins 25 UA/ml en IgG ou IgA. Le logiciel R a ete utilise pour l’analyse des donnees (Test exact de Fischer et du Chi2). Resultats Les ASCA etaient positifs chez 24,3 % des HS contre 4,4 % et 4,3 % pour les groupes psoriasis et DS, respectivement (p Discussion Tandis que la prevalence des ASCA dans les populations psoriasis et DS sont proches des taux attribues dans la litterature a la population generale, la prevalence est significativement augmentee dans l’HS, preferentiellement dans les formes moderees a severes, avec syndrome inflammatoire biologique, et en cas de spondylarthropathie associee. Le tabagisme et l’IMC, potentiels facteurs de confusion, n’etaient pas associes a la positivite des ASCA. Conclusion Ces resultats identifient les ASCA (IgG et/ou IgA) comme un biomarqueur des formes severes d’HS, et renforcent l’hypothese d’une dysbiose dans l’HS, comme c’est le cas dans les modeles immunopathologiques de la maladie de Crohn et de la SPA, et ce a la difference du psoriasis.