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In situ investigations of cracks propagating at up to 2.5 km s-1 along an (001) plane of a silicon single crystal are reported, using X-ray diffraction megahertz imaging with intense and time-structured synchrotron radiation. The studied system is based on the Smart Cut process, where a buried layer in a material (typically Si) is weakened by microcracks and then used to drive a macroscopic crack (10-1 m) in a plane parallel to the surface with minimal deviation (10-9 m). A direct confirmation that the shape of the crack front is not affected by the distribution of the microcracks is provided. Instantaneous crack velocities over the centimetre-wide field of view were measured and showed an effect of local heating by the X-ray beam. The post-crack movements of the separated wafer parts could also be observed and explained using pneumatics and elasticity. A comprehensive view of controlled fracture propagation in a crystalline material is provided, paving the way for the in situ measurement of ultra-fast strain field propagation. [ABSTRACT FROM AUTHOR]

Recent works on three-planet mean motion resonances (MMRs) have highlighted their importance for understanding the details of the dynamics of planet formation and evolution. While the dynamics of two-planet MMRs are well understood and approximately described by a one-degree-of-freedom Hamiltonian, little is known of the exact dynamics of three-body resonances besides the cases of zeroth-order MMRs or when one of the bodies is a test particle. In this work, I propose the first general integrable model for first-order three-planet mean motion resonances. I show that one can generalize the strategy proposed in the two-planet case to obtain a one-degree-of-freedom Hamiltonian. The dynamics of these resonances are governed by the second fundamental model of resonance. The model is valid for any mass ratio between the planets and for every first-order resonance. I show the agreement of the analytical model with numerical simulations. As examples of application, I show how this model could improve our understanding of the capture into MMRs as well as their role in the stability of planetary systems. [ABSTRACT FROM AUTHOR]

Introduction: Intraoperative navigation during liver resection remains difficult and requires high radiologic skills because liver anatomy is complex and patient-specific. Augmented reality (AR) during open liver surgery could be helpful to guide hepatectomies and optimize resection margins but faces many challenges when large parenchymal deformations take place. We aimed to experiment a new vision-based AR to assess its clinical feasibility and anatomical accuracy. Patients and Methods: Based on preoperative CT scan 3-D segmentations, we applied a non-rigid registration method, integrating a physics-based elastic model of the liver, computed in real time using an efficient finite element method. To fit the actual deformations, the model was driven by data provided by a single RGB-D camera. Five livers were considered in this experiment. In vivo AR was performed during hepatectomy (n = 4), with manual handling of the livers resulting in large realistic deformations. Ex vivo experiment (n = 1) consisted in repeated CT scans of explanted whole organ carrying internal metallic landmarks, in fixed deformations, and allowed us to analyze our estimated deformations and quantify spatial errors. Results: In vivo AR tests were successfully achieved in all patients with a fast and agile setup installation (< 10 min) and real-time overlay of the virtual anatomy onto the surgical field displayed on an external screen. In addition, an ex vivo quantification demonstrated a 7.9 mm root mean square error for the registration of internal landmarks. Conclusion: These first experiments of a markerless AR provided promising results, requiring very little equipment and setup time, yet providing real-time AR with satisfactory 3D accuracy. These results must be confirmed in a larger prospective study to definitively assess the impact of such minimally invasive technology on pathological margins and oncological outcomes. [ABSTRACT FROM AUTHOR]

K2-19 hosts a planetary system composed of two outer planets, b and c, with size of 7.0 ± 0.2 R⊕ and 4.1 ± 0.2 R⊕, and an inner planet, d, with a radius of 1.11 ± 0.05 R⊕. A recent analysis of Transit-Timing Variations (TTVs) suggested b and c are close to but not in 3:2 mean motion resonance (MMR) because the classical resonant angles circulate. Such an architecture challenges our understanding of planet formation. Indeed, planet migration through the protoplanetary disc should lead to a capture into the MMR. Here, we show that the planets are in fact, locked into the 3:2 resonance despite circulation of the conventional resonant angles and aligned periapses. However, we show that such an orbital configuration cannot be maintained for more than a few hundred million years due to the tidal dissipation experienced by planet d. The tidal dissipation remains efficient because of a secular forcing of the innermost planet eccentricity by planets b and c. While the observations strongly rule out an orbital solution where the three planets are on close to circular orbits, it remains possible that a fourth planet is affecting the TTVs such that the four planet system is consistent with the tidal constraints. [ABSTRACT FROM AUTHOR]

Permits are one of the most effective and common tools for state agencies to regulate the operation of overweight and oversize trucks to ensure the safety of passenger and freight traffic and to minimize damage to pavements and bridges. Although the State of Illinois uses a relatively comprehensive permit system, many of its parts have not been revised for more than 30 years. Therefore, the objective of this study was to evaluate up-to-date impacts of overweight (OW) trucks and develop an equitable permit system. In this study, impacts of OW trucks on bridges, pavements, and traffic safety were evaluated; and individual fees were developed for each. The most recent databases on infrastructure condition and state-of-the-art prediction algorithms were employed to produce realistic and up-to-date assessment of OW trucks' impact. Finally, two approaches were recommended to combine individual fees. The first approach requires developed frameworks for calculating individual fees to be integrated with existing geographic information system-based online permit tools that are currently used by many departments of transportations (DOTs). These tools compute the fee for each vehicle by reporting a route based on user-input origin/destination. The information specific to each OW vehicle (e.g., mile, axle spacing, weight, bridge inventory rating) can be extracted from the reported routes and injected into the developed frameworks. Thereby, the fee can be computed in an equitable and more accurate way. The second approach is converting the frameworks into a formula to conform to the conventional permit fee calculation schemes (e.g., table format). The highlights of this paper include but not limited to: ● First time in the literature, field performance data for bridges and pavement were used for developing the policy to penalize overweight vehicles. ● First time in the literature, the safety cost related to overweight vehicles is incorporated into overweight vehicle fee. ● First time in the literature, a geographical information system based online implementation was suggested for implementing developed policy. [ABSTRACT FROM AUTHOR]

• Bus substitution strategy with pooled standby fleet to control schedule deviations in multiline systems. • Stochastic dynamic program based on bus operation dynamics and substitution decisions • Approximate dynamic programming algorithm with offline simulations and estimation • Multi-period dynamic program to address fleet management in time-varying systems • Numerical examples demonstrate the performance and applicability of the proposed strategy Traditional bus bunching control methods (e.g., adding slack to schedules, adapting cruising speed), in one way or another, trade commercial speed for better system stability and, as a result, may impose the burden of additional travel time on passengers. Recently, a dynamic bus substitution strategy, where standby buses are dispatched to take over service from late/early buses, was proposed as an attempt to enhance system reliability without sacrificing too much passenger experience. This paper further studies this substitution strategy in the context of multiple bus lines under either time-independent or time-varying settings. In the latter scenario, the fleet of standby buses can be dynamically utilized to save on opportunity costs. We model the agency's substitution decisions and retired bus repositioning decisions as a stochastic dynamic program so as to obtain the optimal policy that minimizes the system-wide costs. Numerical results show that the dynamic substitution strategy can benefit from the "economies of scale" by pooling the standby fleet across lines, and there are also benefits from dynamic fleet management when transit demand varies over time. Numerical examples are presented to illustrate the applicability and advantage of the proposed strategy. The substitution strategy not only holds the promise to outperform traditional holding methods in terms of reducing passenger costs, they also can be used to complement other methods to better control very unstable systems. [ABSTRACT FROM AUTHOR]

Bus headways are typically susceptible to external disturbances (e.g., due to traffic congestion, clustered passenger arrivals, and special passenger needs), which create gaps in the system that grow eventually into bunching. Although many control strategies, such as static and dynamic holding strategies, have been implemented to mitigate the effects of unreliable bus schedules, most of them would impose longer dwell times on the passengers. In this paper, we investigate the potential of an alternative bus substitution strategy that is currently implemented by some transit agencies in an ad-hoc manner. In this strategy, the agency deploys a fleet of standby buses to take over service from any early or late buses so as to contain deviations from schedule, and the intention is to impose minimum penalties on the onboard passengers. We develop a discrete-time infinite-horizon approximate dynamic programming approach to find the optimal policy to minimize the overall agency and passenger costs. It is shown through numerical examples that schedule deviations can be controlled by regularly inserting standby buses as substitutions. In some implementation scenarios, the proposed strategy holds the potential to achieve comparable performance with some of the most advanced strategies, and to outperform the conventional slack-based schedule control scheme. In light of the emerging opportunities associated with autonomous driving, the performance of the proposed strategy can become even stronger due to the reduction in costs for keeping the fleet of standby buses. [ABSTRACT FROM AUTHOR]

In a two-planet system, a topological boundary that is created by Sundman (1912, Acta Math., 36, 105) inequality can forbid close encounters between the two planets for an infinite time. A system is said to be Hill stable if it verifies this topological condition. Hill stability is widely used in the study of extrasolar planet dynamics. However, the coplanar and circular orbit approximation is often used. In this paper, we explain how the Hill stability can be understood in the framework of angular momentum deficit (AMD). In the secular approximation, AMD allows us to discriminate between a priori stable systems and systems for which a more in-depth dynamical analysis is required. We show that the general Hill stability criterion can be expressed as a function of only semimajor axes, masses, and total AMD of the system. The proposed criterion is only expanded in the planets-to-star mass ratio ε and not in the semimajor axis ratio, eccentricities, nor the mutual inclination. Moreover, the expansion in ε remains excellent up to values of about 10−3 even for two planets with very different mass values. We performed numerical simulations in order to highlight the sharp change of behavior between Hill stable and Hill unstable systems. We show that Hill stable systems tend to be very regular, whereas Hill unstable systems often lead to rapid planet collisions. We also note that Hill stability does not provide protection from the ejection of the outer planet. [ABSTRACT FROM AUTHOR]

The article discusses a rare genetic condition called acrogeria, which is characterized by the resorption of bones in the distal phalanges. It is caused by a mutation in the LMNA gene and shares similarities with other laminopathies. The article describes a case of acrogeria in a 35-year-old woman from South Korea and highlights the clinical features and diagnostic methods used. Acrogeria is distinguished by its unique distribution of progeroid traits and the absence of widespread osteoporosis. The article emphasizes the importance of considering cardiovascular complications in patients with acrogeria. [Extracted from the article]

This paper presents a method for tracking a 3D textureless object which undergoes elastic deformations, using the point cloud data provided by an RGB-D sensor and in real-time. This solution is expected to be useful for enhanced manipulation of humanoid robotic systems, especially in the case of pizza dough to be ideally manipulated by a pizza chef robot. Our tracking framework relies on a prior visual segmentation of the object in the image. The segmented point cloud is registered first in a rigid manner and then by non-rigidly fitting the mesh, based on the Finite Element Method to model elasticity, and on geometrical point-to-point correspondences to compute external forces exerted on the mesh. The system has been evaluated on synthetic and real data, and by integrating it into manipulation experiments on the RoDyMan 1 1 http://www.rodyman.eu/ . The research leading to these results has been supported by the RoDyMan project, which has received funding from the European Research Council (FP7 IDEAS) under Advanced Grant agreement number 320992 . The authors are solely responsible for its content. It does not represent the opinion of the European Community and the Community is not responsible for any use that might be made of the information contained therein. humanoid robotic platform. [ABSTRACT FROM AUTHOR]

This paper presents design methods for a flexible-route transit system, in which vehicles travel within predetermined areas to provide door-to-door service. The main advantage of this system is that passengers no longer have to access transit stations in order to gain service. This system is suitable for low and heterogeneous passenger demand distribution as it features a hybrid system layout that includes both a hub-and-spoke network in the peripheral region and a grid network in the central region, along with heterogeneous local routes that address local demand variations. Continuum approximation (C.A.) is used to reduce the computation burden by formulating the design problem with respect to a few decision variables. We compare the performance of the proposed transit system with (i) the typical fixed-route system, (ii) the homogeneous flexible-route grid system, and (iii) the flexible-route grid system with local routes, in hypothetical settings. It is found through our numerical examples that the integration of the three proposed features (i.e. flexible transit, local tubes, and hybrid structure), as compared to counterparts with only two or fewer features, yields lower combined agency and user costs under the assumed low heterogeneous demand distribution. We then apply the design framework to a more realistic case for the City of Changzhi, China. An implementable design for Changzhi is developed, and its performance verified with simulations, demonstrating accuracy and applicability of the proposed continuum approximation model. • Flexible-route transit system for low and spatially heterogeneous demand. • Continuum approximation model to design hybrid network structure and local routes. • Schematic design translated into implementable design that conform with street networks. • Significant agency and user cost reduction as compared to traditional transit networks. • Simulations validate performance predictions for a real-world case study. [ABSTRACT FROM AUTHOR]

Metal production in galaxies traces star formation, and is highly concentrated towards the centres of galactic discs. This suggests that galaxies should have inhomogeneous metal distributions with strong radial gradients, but observations of present-day galaxies show only shallow gradients with little azimuthal variation, implying the existence of a redistribution mechanism. We study the role of gravitational instability-driven turbulence as a mixing mechanism by simulating an isolated galactic disc at high resolution, including metal fields treated as passive scalars. Since any cylindrical field can be decomposed into a sum of Fourier-Bessel basis functions, we set up initial metal fields characterized by these functions and study how different modes mix. We find both shear and turbulence contribute to mixing, but the mixing strongly depends on the symmetries of the mode. Non-axisymmetric modes have decay times smaller than the galactic orbital period because shear winds them up to small spatial scales, where they are erased by turbulence. The decay time-scales for axisymmetric modes are much greater, though for all but the largest scale inhomogeneities the mixing time-scale is still short enough to erase chemical inhomogeneities over cosmological times. These different time-scales provide an explanation for why galaxies retain metallicity gradients while there is almost no variation at a fixed radius. Moreover, the comparatively long time-scales required for mixing axisymmetric modes may explain the greater diversity of metallicity gradients observed in high redshift galaxies as compared to local ones: these systems have not yet reached equilibrium between metal production and diffusion. [ABSTRACT FROM AUTHOR]

Algebra offers an elegant and powerful approach to understand regular languages and finite automata. Such framework has been notoriously lacking for timed languages and timed automata. We introduce the notion of monoid recognizability for data languages, which includes timed languages as special case, in a way that respects the spirit of the classical situation. We study closure properties and hierarchies in this model and prove that emptiness is decidable under natural hypotheses. Our class of recognizable languages properly includes many families of deterministic timed languages that have been proposed until now, and the same holds for non-deterministic versions. [Copyright &y& Elsevier]

• Designing a spatially heterogeneous bus route network with time-dependent service headways. • Representing both the transit and the car network in efficient and realistic settings. • Incorporating elastic demand scenarios with mode choice into the transit design problem. This paper proposes an integrated methodological framework to design a spatially heterogeneous bus route network and time-dependent service headways to serve travel demand that varies over time and space. Travelers choose to use either the transit mode or the driving mode (as well as travel paths in the corresponding modal network) that minimizes their equilibrium travel cost. In addition, transit routes involve dedicated bus lanes that occupy part of the city streets and affect the capacity reserved for private cars. Hence, roadway congestion depends on the transit route design, and its dynamic evolution is described by regional macroscopic fundamental diagrams. The proposed modeling framework consists of two parts: a bus network optimization module based on continuum approximation that produces optimal headways and local route spacing, and a dynamic aggregated network model that determines route choice, mode split, and user equilibrium conditions. An iterative solution algorithm is developed to solve the integrated model. Numerical experiments are used to demonstrate the applicability of the proposed modeling framework, and to conduct a careful analysis on the influence of the demand pattern on the transit network design, roadway congestion, and the overall system performance. [ABSTRACT FROM AUTHOR]

Kimura disease (KD) is a rare, chronic angiolymphoproliferative inflammatory disease appearing to be mostly restricted to the skin and soft tissue. Cutaneous involvement of KD includes head and/or neck nodules showing suggestive histological features, frequently associated with an atopic dermatitis-like or prurigo-like presentation. KD is challenging to treat, with high rate of recurrence using current therapeutic strategies. Evidence for involvement of a T-helper type 2 (Th2) immune response in KD pathogenesis has been found in previous studies. Consequently, this study aimed to determine the efficacy and safety of dupilumab, a human monoclonal antibody that inhibits signalling of key Th2 cytokines, interleukin (IL)-4 and IL-13, within a single-centre cohort of patients with cutaneous KD. Two adults with a diagnosis of refractory (failure of at least one treatment line) cutaneous-restricted KD based on clinical, biological, histological, molecular and imaging findings received dupilumab for KD, and showed dramatic response with a good safety profile. [ABSTRACT FROM AUTHOR]

Introduction: Software to predict the impact of aging on physical appearance is increasingly popular. But it does not consider the complex interplay of factors that contribute to skin aging. Objectives: To predict the +15‐year progression of clinical signs of skin aging by developing Causal Bayesian Belief Networks (CBBNs) using expert knowledge from dermatologists. Material and methods: Structures and conditional probability distributions were elicited worldwide from dermatologists with experience of at least 15 years in aesthetics. CBBN models were built for all phototypes and for ages ranging from 18 to 65 years, focusing on wrinkles, pigmentary heterogeneity and facial ptosis. Models were also evaluated by a group of independent dermatologists ensuring the quality of prediction of the cumulative effects of extrinsic and intrinsic skin aging factors, especially the distribution of scores for clinical signs 15 years after the initial assessment. Results: For easiness, only models on African skins are presented in this paper. The forehead wrinkle evolution model has been detailed. Specific atlas and extrinsic factors of facial aging were used for this skin type. But the prediction method has been validated for all phototypes, and for all clinical signs of facial aging. Conclusion: This method proposes a skin aging model that predicts the aging process for each clinical sign, considering endogenous and exogenous factors. It simulates aging curves according to lifestyle. It can be used as a preventive tool and could be coupled with a generative AI algorithm to visualize aging and, potentially, other skin conditions, using appropriate images. [ABSTRACT FROM AUTHOR]

Introduction: Leprosy reactions (LRs) are inflammatory responses observed in 30%-50% of people with leprosy. First-line treatment is glucocorticoids (GCs), often administered at high doses with prolonged courses, resulting in high morbi-mortality. Methotrexate (MTX) is an immunomodulating agent used to treat inflammatory diseases and has an excellent safety profile and worldwide availability. In this study, we describe the efficacy, GCs-sparing effect and safety of MTX in LRs. Methods: We conducted a retrospective multicentric study in France consisting of leprosy patients receiving MTX for a reversal reaction (RR) and/or erythema nodosum leprosum (ENL) since 2016. The primary endpoint was the rate of good response (GR) defined as the complete disappearance of inflammatory cutaneous or neurological symptoms without recurrence during MTX treatment. The secondary endpoint was the GCs-sparing effect, safety and clinical relapse after MTX discontinuation. Results: Our study included 13 patients with LRs (8 men, 5 women): 6 had ENL and 7 had RR. All patients had had at least one previous course of GCs and 2 previous treatment lines before starting MTX. Overall, 8/13 (61.5%) patients had GR, allowing for GCs-sparing and even GCs withdrawal in 6/11 (54.5%). No severe adverse effects were observed. Relapse after MTX discontinuation was substantial (42%): the median relapse time was 5.5 months (range 3–14) after stopping treatment. Conclusion: MTX seems to be an effective alternative treatment in LRs, allowing for GCs-sparing with a good safety profile. Furthermore, early introduction during LRs may lead to a better therapeutic response. However, its efficacy seems to suggest prolonged therapy to prevent recurrence. Author summary: Leprosy reactions (LRs) are acute inflammatory episodes that complicate 30% to 50% of Mycobacterium leprae infections. Type 1 is known as reversal reaction (RR), and type 2 is known as erythema nodosum leprosum (ENL). The two types have relatively distinct pathogenesis and clinical features; furthermore, they can advance to become severe and progress to irreversible nerve damage and deformities. Beyond leprosy infection, LR can bring about neurological burden, poor quality of life, and risk of further descent into poverty for often young patients. Despite effective standardized treatment of leprosy infection with multidrug therapy (MDT) since 1981, treating LRs prove to be challenging. First-line treatment of LR is based on prolonged systemic glucocorticoids (GCs) therapy. The current challenge in leprosy is now to develop and evaluate new therapeutic alternatives to reduce not only the sequelae and morbidity of LR but also the lasting side effects of GCs. Thalidomide is an effective alternative in moderate to severe ENL, but its use is limited given its numerous adverse effects. Methotrexate (MTX) is an immunomodulating agent used to treat inflammatory diseases and has an excellent safety profile and worldwide availability. Here, we describe the efficacy, GCs-sparing effect, and safety of MTX in LR. [ABSTRACT FROM AUTHOR]

Simple Summary: Gliomas remain the most common primary brain tumor in adults. Although they are classified based on the IDH mutation status very little is known considering this alteration in the elderly glioma population. Because IDH-mutated gliomas are associated with better prognosis in the young population, it is essential to characterize its role in elderly and more frail patients to help physicians' therapeutic decisions. In this study, we demonstrated that elderly IDH-mutated gliomas had very similar characteristics to those found in the younger population but were significantly different from elderly IDH wild-type gliomas. However, patient management in this population appeared to be suboptimal, with less frequent gross total resection and irradiation. We showed that an optimal therapeutic combination of radio-chemotherapy could be safe and feasible for these elderly patients to aid in their management. Finally, we identified specific geriatric prognostic factors such as mobility, neuropsychological disorders, body mass index, and autonomy that can help physicians make future therapeutic decisions for this specific elderly population with a better prognosis. Background: Describe the characteristics, patterns of care, and predictive geriatric factors of elderly patients with IDHm high-grade glioma (HGG) included in the French POLA network. Material and Methods: The characteristics of elderly (≥70 years) patients IDHm HGG were compared to those of younger patients IDHm HGG (<70 years) and of elderly patients IDHwt HGG. Geriatric features were collected. Results: Out of 1433 HGG patients included, 119 (8.3%) were ≥70 years. Among them, 39 presented with IDHm HGG. The main characteristics of elderly IDHm HGG were different from those of elderly IDHwt HGG but similar to those of younger IDHm HGG. In contrast, their therapeutic management was different from those of younger IDHm HGG with less frequent gross total resection and radiotherapy. The median progression-free survival (PFS) and overall survival (OS) were longer for elderly patients IDHm HGG (29.3 months and 62.1 months) than elderly patients IDHwt HGG (8.3 months and 13.3 months) but shorter than those of younger patients IDHm HGG (69.1 months and not reached). Geriatric factors associated with PFS and OS were mobility, neuropsychological disorders, body mass index, and autonomy. Geriatric factors associated with PFS and OS were mobility, neuropsychological disorders, and body mass index, and autonomy. Conclusion: the outcome of IDHm HGG in elderly patients is better than that of IDHwt HGG. Geriatric assessment may be particularly important to optimally manage these patients. [ABSTRACT FROM AUTHOR]

Background: Livedoid vasculopathy (LV) is a chronic dermatosis associated with micro-thrombosis of the vessels of the dermis, leading to ischemic lesions and painful skin ulcerations of the lower limbs. This thrombosing occlusive vasculopathy, clearly distinct from 'classical vasculitis' (not related to alteration of vessel walls), may lead to peripheral neuropathy. Objective: To clarify the main clinical, electrophysiological and pathological characteristics of peripheral neuropathy linked to LV. Method: We presented a series of personal cases of peripheral neuropathy due to LV. We also conducted a review of the literature (since the first description of LV in 1974) using multiple combinations of keywords from 'PubMed', 'Google Scholar' and 'ScienceDirect' databases according to the 'Preferred Reporting Items for Systematic reviews and Meta-Analyses' guidelines. Results: We identified 16 patients (6 personal cases and 10 cases from the medical literature). Our personal cases were five females and one male, with a median age (at the onset of cutaneous signs of LV) of 38 (range 25–62). Several types of skin lesions of the lower limbs were observed. Median age at the onset of peripheral neuropathy symptoms was 48 years (range 29–66), with a main clinical and electrophysiological pattern of mononeuropathy multiplex. Discussion: We observed a typical pattern of peripheral neuropathy, mostly mononeuropathy multiplex, whose pathophysiology might be related to occlusions of the small vessels of the nerves, as seen in the dermis. Moreover, LV may also be associated with other types of peripheral neuropathies (sometimes of autoimmune etiology) not directly related to the skin lesions. Conclusion: The 'ischemic form' of peripheral neuropathy linked to LV is mainly responsible for sensory disturbances (with multifocal distribution), sometimes for motor disturbances. This type of peripheral neuropathy has to be distinguished from 'classical vasculitic neuropathies' which are usually treated with antithrombotic therapies. [ABSTRACT FROM AUTHOR]

Background: At present there is no standard nomenclature for describing the diversity of human constitutive skin colour. Objectives: To develop a standard nomenclature to describe human constitutive skin colour. Methods: Monthly focus group discussions were carried out among a multidisciplinary group of specialists over a 7‐month period. Topics covered were (i) limitations and unmet needs of current nomenclature(s) pertaining to human cutaneous diversity, (ii) practical considerations about the function and role of any proposed nomenclature pertaining to human cutaneous diversity, (iii) review of the cellular basis and current molecular genetic understanding of variation in human skin pigmentation and (iv) in vivo methods to evaluate human skin pigmentation. In addition, a preliminary review of the published literature was undertaken to collate data on published skin reflectance measurements, notably melanin index values for well‐referenced human populations. Results: We developed a five‐point scale to describe the full spectrum of human constitutive skin colour, termed the Eumelanin Human Skin Colour Scale. The nomenclature of the scale uses eumelanin, the dominant chromophore of human skin, as a central descriptive word. The categories of the scale (nomenclature and melanin index values) are eumelanin low (EML), < 25; eumelanin intermediate low (EMIL), 25 to < 50; eumelanin intermediate (EMI), 50 to < 75; eumelanin intermediate high (EMIH), 75 to < 100; and eumelanin high (EH), ≥ 100. Conclusions: The Eumelanin Human Skin Colour Scale enables the complete range of human constitutive skin colour to be described in an objective, equitable and understandable manner. In future, this scale can be used as the basis for developing other scales that address the specific functional aspects of human skin, such as response to ultraviolet radiation. [ABSTRACT FROM AUTHOR]

Intra-arterial therapy is an effective way of performing chemotherapy or radiation therapy in patients with primary liver cancer (i.e. hepatocellular carcinoma). Although this minimally invasive approach is now an established treatment option, support tools for pre-operative planning and intra-operative assistance might be helpful. We developed an approach for semi-automatic segmentation of computed tomography angiography images of the main arterial branches (required for access path to the treatment site), automatic segmentation of the liver, arterial and venous tree, and interactive segmentation of the tumors (required for procedure-specific planning). This approach was then integrated into a liver-specific workflow within EndoSize® solution, a planning software for endovascular procedures. The main branches extraction approach was qualitatively evaluated inside the software, while the automatic segmentation methods were quantitatively assessed. Main branches extraction provides a success rate of 85% (i.e. all arteries correctly extracted) in a dataset of 172 patients. On public databases, a mean DICE of 0.91, 0.47 and 0.92 was obtained for liver, venous and arterial trees segmentation, respectively. This pipeline is suitable for directly accessing the treatment site, giving anatomic measurements, and visualizing the hepatic trees, liver, and surrounding arteries during the pre-operative planning. HCC: hepatocellular carcinoma; TACE: transarterial chemoembolization; SIRT: selective internal radiation therapy; CT: computed tomography; CTA: computed tomography angiography; AMS: superior mesenteric artery; LGA: left gastric artery; RHA: right hepatic artery; LHA: left hepatic artery; rbHA: right branch of the hepatic artery; lbHA: left branch of the hepatic artery; GDA: gastroduodenal artery; VOI: volume of interest; SD: standard deviation; MICCAI: medical image computing and computer assisted interventions; MR: magnetic resonance [ABSTRACT FROM AUTHOR]

Background: In addition to general measures, pharmacological treatment is the basis of the management of scabies. No recent data in real‐life are available on the efficacy and safety of 10% benzyl benzoate emulsion for skin application administered as monotherapy. Method: This prospective, multicenter, French observational study comprised a registry and a prospective cohort with a follow‐up at 28 days and a telephone call at week 12. To participate in the registry, patients had to be over 1 month old, ambulatory, presenting common, nonhyperkeratotic, untreated scabies. To be included in the cohort, patients had to be included in the registry and treated with two applications of 10% benzyl benzoate emulsion 8 days apart. The primary endpoint was cure at day 28. Results: Of the 186 patients included in the registry, 116 were included in the cohort. Fourteen patients were included in the cohort without being included in the registry, which led to a total of 130 patients in the cohort. At day 28, 119/130 (91.5%; 95% CI 85.4–95.6%) were clinically cured. The cure was confirmed by dermoscopy in 44/47 patients (93%). Among the 130 patients, the cure rate was 82% at week 12. Of the 119 patients cured at day 28, the rate of cure at week 12 was 89.9%. Conclusion: In real life, two applications of 10% benzyl benzoate emulsion 8 days apart provides high cure rates in patients with common scabies. [ABSTRACT FROM AUTHOR]

The article titled "Back Cover" is based on the original article "Predicting the evolution of clinical skin aging in a multi-ethnic population: Developing causal Bayesian networks using dermatological expertise" by Hussein Jouni et al. The study focuses on predicting the progression of skin aging in a diverse population using Bayesian networks. The authors include a wide range of experts in the field of dermatology and explore the impact of various factors on skin aging. This research provides valuable insights into understanding and addressing skin aging in different ethnic groups. [Extracted from the article]

We describe 7 cases of extensive tinea corporis since 2018 in a hospital in Paris, France, after failure to cure with terbinafine. Molecular analysis indicated Trichophyton mentagrophytes internal transcribed spacer type VIII (T. indotineae). This strain, which has mutations in the squalene epoxidase gene, is spreading on the Indian subcontinent. [ABSTRACT FROM AUTHOR]

Background: Some keloids show cystic cavities that give rise to acute inflammatory flares and oozing. These suppurative keloids (SK) have rarely been systematically studied. We conducted a retrospective cohort study to evaluate SK frequency and its risk factors. We also reviewed microbiological analyses as well as the histological features of removed SKs. Methods: Between July 1, 2015, and September 30, 2016, all adult patients attending a specialized keloid clinic were asked to participate. Clinical information and microbiological results were extracted from each patient's file. Histological features were observed and interpreted. Results: In this study, we observed an SK rate of 26% for a mean keloid history of 17.2 years. Male gender, African ancestry, and a family history of keloids were significantly associated with suppuration. Microbiological examination revealed commensal skin flora 7/9 (77.8%), Staphylococcus aureus 1/9 (11.1%), and Enterococcus faecalis 1/9 (11.1%). Conclusion: Suppuration is a common complication of keloids occurring in patients with severe keloid disease and may arise from pilosebaceous occlusion and aseptic inflammation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Effective postoperative analgesia is essential for early rehabilitation after surgery. Continuous wound infiltration (CWI) of local anesthetics has been proposed as an alternative to epidural analgesia (EA) during colorectal surgery. This prospective, double-blind trial compared CWI and EA in patients undergoing elective open colorectal surgery. METHODS: Fifty consecutive patients were randomized to receive EA or CWI for 48 h. In both groups, patients were managed according to Enhanced Recovery After Surgery recommendations. The primary outcome was the dynamic pain score measured during mobilization 24 h after surgery (H24) using a 100-mm verbal numerical scale. Secondary outcomes were time to functional recovery, analgesic technique-related side effects, and length of hospital stay. RESULTS: Median postoperative dynamic pain score was lower in the EA than in the CWI group (10 [interquartile range: 1.6-20] vs. 37 [interquartile range: 30-49], P < 0.001) and remained lower until hospital discharge. The median times to return of gut function and tolerance of a normal, complete diet were shorter in the EA than in the CWI group (P < 0.01 each). Sleep quality was also better in the EA group, but there was no difference in urinary retention rate (P = 0.57). The median length of stay was lower in the EA than in the CWI group (4 [interquartile range: 3.4-5.3] days vs. 5.5 [interquartile range: 4.5-7] days; P = 0.006). CONCLUSION: Within an Enhanced Recovery After Surgery program, EA provided quicker functional recovery than CWI and reduced length of hospital stay after open colorectal surgery. [ABSTRACT FROM AUTHOR]

Background: Leishmaniases are regularly seen in non-endemic areas due to the increase of international travels. They include cutaneous leishmaniases (CL) and mucocutaneous (MC) caused by different Leishmania species, and visceral leishmaniases (VL) which present with non-specific symptoms.Methods: We reviewed all consecutive leishmaniasis cases seen between September 2012 and May 2020. The diagnostic strategy included microscopy after May-Grünwald-Giemsa staining, a diagnostic quantitative PCR (qPCR) assay, and species identification based on sequencing of the cytochrome b gene.Results: Eighty-nine patients had a definitive leishmaniasis diagnosis. Nine patients had VL with Leishmania infantum. Eighty patients had CL. Twelve patients acquired CL after trips in Latin America (7 Leishmania guyanensis, 2 Leishmania braziliensis, 2 Leishmania mexicana, and 1 Leishmania panamensis). Species could be identified in 63 of the 68 CLs mainly after travel in North Africa (59%) with Leishmania major (65%), Leishmania tropica/killicki (24%), and L. infantum (11%), or in West Sub-Saharan Africa (32%), all due to L. major. The median day between appearance of the lesions and diagnosis was 90 [range 60-127].Conclusions: Our diagnostic strategy allows both positive diagnoses and species identifications. Travelers in West Sub-Saharan Africa and North Africa should be better aware of the risk of contracting leishmananiasis. [ABSTRACT FROM AUTHOR]

Abstract: We describe an atypical primary HSV 1 genital infection with bilateral palmar involvement. Two routes of dissemination of HSV are discussed, self-inoculation and blood dissemination. This case highlights the role of HSV 1 in extragenital pustules in the context of sexually transmitted diseases. [Copyright &y& Elsevier]

Folliculitis decalvans (FD) is a chronic inflammatory disease of unknown aetiology. Although Staphylococcus aureus, frequently found on lesional skin, is thought to play a causal role, the importance of its involvement remains controversial. To examine the role of S aureus, we compared superficial and subepidermal microbiota in 20 FD patients who had S aureus on lesional skin and in 20 healthy controls using culture techniques and genomic identification, before and after an anti‐staphylococcal treatment; we also screened for S aureus virulence factors. When present on lesional skin, S aureus colonized non‐lesional and subepidermal skin in 80% of cases. These data imply a break in the epidermal barrier integrity and that an abnormal non‐lesional skin microbiota persists in FD. S aureus had no superantigenic toxin in 31% of cases and no toxin specificity. Clinical improvement obtained in most cases upon treatment was associated with the disappearance of S aureus in all studied areas, with an incomplete restoration of normal microbiota and a significant increase in negative bacterial samples. This persistent unbalanced, subepidermal microbiota may act as a reservoir of abnormal flora and explain the chronicity of FD, suggesting new avenues of research to restore normal microbiota. [ABSTRACT FROM AUTHOR]

Background Context: Balloon kyphoplasty (BKP) is a commonly performed vertebral augmentation procedure for painful osteoporotic vertebral compression fractures (OVCFs).Objective: This study aimed to support a non-inferiority finding for the use of a titanium implantable vertebral augmentation device (TIVAD) compared to BKP.Study Design: Prospective, parallel group, controlled comparative randomized study.Patient Sample: Patients who presented with one or two painful OVCFs located between T7 and L4 aged <3 months, failed conservative treatment, and had an Oswestry Disability Index (ODI) score ≥30/100 were eligible for the study.Outcome Measures: The primary composite endpoint was defined as: reduction in VCF fracture-related pain at 12 months from baseline and maintenance or functional improvement (ODI) at 12 months from baseline, and absence of device-related adverse event or surgical reintervention. If the primary composite endpoint was successful, a fourth component (absence of adjacent level fracture) was added for analysis. If the analysis of this additional composite endpoint was successful, then midline target height restoration at 6 and 12 months was assessed. Secondary clinical outcomes included back pain intensity, ODI score, EQ-5D index score (range 0=death to 1=full health) and EQ-VAS score (range 0-100).Methods: Patients were recruited in 13 hospitals across 5 countries and were randomly assigned (1:1) to either TIVAD or BKP with electronic randomization as described in the protocol. A total of 152 patients with OVCFs were initially randomized. Eleven patients were excluded (six met exclusion criteria, one with evidence of tumor, and four patients had T score out of requested range). Anterior vertebral body height ratio, midline vertebral body height ratio, and Cobb angle were measured preoperatively and postoperatively by an independent imaging core lab. Adjacent and subsequent fractures and safety parameters were recorded throughout the study. Cement extravasation was evaluated on X-rays. All patients were followed at screening at 5 days, 1 month, 6 months, and 12 months postoperatively. This study was supported by Vexim SA. Seven authors received study-specific support less than $10,000 per year and seven authors received no study-specific support.Results: Among the 141 patients (78.7% female, mean age 73.3±9.5 years) who underwent surgery (TIVAD=68; BKP=73), 126 patients (89.4%) completed the 12-month follow-up period (TIVAD=61; BKP=65). The analysis of primary endpoint on the ITT population demonstrated non-inferiority of the TIVAD to BKP. The analysis of the additional composite endpoint demonstrated the superiority of TIVAD over BKP (p<0.0001) at 6 months (88.1% vs. 60.9%) and at 12 months (79.7% vs. 59.3%). Midline VB height restoration was more improved for TIVAD than for BKP at 6 months (1.14±2.61 mm vs. 0.31±2.22 mm); p=0.0246) and 12 months after surgery (1.31±2.58 mm vs. 0.10±2.34 mm; p=0.0035). No statistically significant differences were shown between procedures for improvement in functional capacity and quality of life. Pain relief was significantly more marked in the TIVAD group compared to the BKP group at 1 month (p=0.029) and at 6 months (p=0.021) after surgery. No patient required surgical reintervention or retreatment at the treated level. No symptomatic cement leakage was reported. Adverse events were similar for both groups (41.2% in the TIVAD group and 45.2% in the BKP group). The incidence of adjacent fractures was significantly lower after the TIVAD procedure than after BKP (12.9% vs. 27.3%; p=0.043).Conclusions: Study results demonstrated non-inferiority of the TIVAD to the predicate BKP with an excellent risk/benefit profile for results up to 12 months. [ABSTRACT FROM AUTHOR]

Nous rapportons le cas d'une patiente atteinte de polyarthrite rhumatoïde. Alors que la maladie articulaire était en rémission sous adalimumab et méthotrexate, sont apparus des nodules rhumatoïdes sous-cutanés ayant conduit à des modifications thérapeutiques successives. À l'introduction du tofacitinib et malgré la poursuite du méthotrexate, une rapide et spectaculaire disparition des nodules rhumatoïdes était constatée. Nous discutons des mécanismes possibles qui pourraient impliquer les interférons. Comme le rituximab, le tofacitinib pourrait représenter un traitement préférentiel des polyarthrites avec nodules rhumatoïdes. [ABSTRACT FROM AUTHOR]

The article presents a case study of an 87-year-old woman with acquired bullous dermatosis associated with immunoglobulin A (IgA) multiple myeloma. The woman manifested a pruriginous bullous eruption on the body with subepodermal blisters, cutaneous vasculitis, and bullous dermatosis. It reveals that IgA multiple myeloma and the recurrence of the skin lesions predicted the relapse of the myeloma and its association with leukocytoclastic vasculitis.

Background To assess the influence of the time interval between surgical resection and standard combined chemoradiotherapy on survival in newly diagnosed and homogeneously treated (surgical resection plus standard combined chemoradiotherapy) glioblastoma patients; while controlling confounding factors (extent of resection, carmustine wafer implantation, functional status, neurological deficit, and postoperative complications). Methods From 2005 to 2011, 692 adult patients (434 men; mean of 57.5 ± 10.8 years) with a newly diagnosed glioblastoma were enrolled in this retrospective multicentric study. All patients were treated by surgical resection (65.5% total/subtotal resection, 34.5% partial resection; 36.7% carmustine wafer implantation) followed by standard combined chemoradiotherapy (radiotherapy at a median dose of 60 Gy, with daily concomitant and adjuvant temozolomide). Time interval to standard combined chemoradiotherapy was analyzed as a continuous variable and as a dichotomized variable using median and quartiles thresholds. Multivariate analyses using Cox modeling were conducted. Results The median progression-free survival was 10.3 months (95% CI, 10.0–11.0). The median overall survival was 19.7 months (95% CI, 18.5–21.0). The median time to initiation of combined chemoradiotherapy was 1.5 months (25% quartile, 1.0; 75% quartile, 2.2; range, 0.1–9.0). On univariate and multivariate analyses, OS and PFS were not significantly influenced by time intervals to adjuvant treatments. On multivariate analysis, female gender, total/subtotal resection and RTOG-RPA classes 3 and 4 were significant independent predictors of improved OS. Conclusions Delaying standard combined chemoradiotherapy following surgical resection of newly diagnosed glioblastoma in adult patients does not impact survival. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Temozolomide and concomitant radiotherapy followed by temozolomide has been used as a standard therapy for the treatment of newly diagnosed glioblastoma multiform since 2005. A search for prognostic factors was conducted in patients with glioblastoma routinely treated by this strategy in our institution. METHODS: This retrospective study included all patients with histologically proven glioblastoma diagnosed between June 1, 2005, and January 1, 2012, in the Franche-Comté region and treated by radiotherapy (daily fractions of 2 Gy for a total of 60 Gy) combined with temozolomide at a dose of 75 mg/m² per day, followed by six cycles of maintenance temozolomide (150-200 mg/m², five consecutive days per month). The primary aim was to identify prognostic factors associated with overall survival (OS) in this cohort of patients. RESULTS: One hundred three patients were included in this study. The median age was 64 years. The median OS was 13.7 months (95% confidence interval, 12.5-15.9 months). In multivariate analysis, age over 65 years (hazard ratio [HR] = 1.88; P = 0.01), Medical Research Council (MRC) scale 3-4 (HR = 1.62; P = 0.038), and occurrence of postoperative complications (HR = 2.15; P = 0.028) were associated with unfavorable OS. CONCLUSIONS: This study identified three prognostic factors in patients with glioblastoma eligible to the standard chemotherapy and radiotherapy treatment. Age over 65 years, MRC scale 3-4, and occurrence of postoperative complications were associated with unfavorable OS. A simple clinical evaluation including these three factors enables to estimate the patient prognosis. MRC neurological scale could be a useful, quick, and simple measure to assess neurological status in glioblastoma patients. [ABSTRACT FROM AUTHOR]

The article discusses a study which addressed the influence of bleomycin-lidocaine-epinephrine (BLE) ingredients and temperature storage on bleomycin efficacy in the refrigerator and room temperature. Topics discussed include the study's aim of determining the optimal conditions and duration of storage that provide stable BLE magistral preparation to patients and a stability study of BLE preparation conducted in comparison to bleomycin reconstituted separately in normal saline.

Background Livedoid vasculopathy ( LV) is a thrombotic vasculopathy of the skin of unknown origin. No treatment has been validated in this indication, but case reports suggest the successful use of intravenous immunoglobulins (IVIG) in LV. Methods Outcomes in five patients treated with IVIG for treatment-resistant ulcerated LV were retrospectively analyzed. Results Treatment with IVIG induced complete remission (based on clinical evaluation and a pain-related visual analog scale) in four patients but was ineffective in one patient. Three patients relapsed; the median time to relapse was 10.7 months. Re-treatment with IVIG in these three patients was successful. Conclusions These cases confirm previous reports that IVIG seems to be a rapid, effective, and safe treatment for patients with idiopathic refractory ulcerated LV. However, a placebo-controlled study is mandatory to confirm these results. [ABSTRACT FROM AUTHOR]

Epidermolysis bullosa acquisita (EBA) is a rare autoimmune bullous disease (AIBD). However, higher EBA incidence and predisposing genetic factor(s) involving an HLA haplotype have been suspected in some populations. This retrospective study assessed the overrepresentation of black patients with EBA, its link with HLA-DRB1*15:03, and their clinical and immunological characteristics. Between 2005 and 2009, 7/13 (54%) EBA and 6/183 (3%) other-AIBD patients seen consecutively in our department were black (P=10−6); moreover 7/13 (54%) black patients and 6/183 (3%) white patients had EBA (P=10−6). In addition, between 1983 and 2005, 12 black patients had EBA. Finally, among the 19 black EBA patients, most of them had very atypical clinical presentations, 9 were natives of sub-Saharan Africa, 1 from Reunion Island, 7 from the West Indies, and 2 were of mixed ancestry. HLA-DRB1*15:03 allelic frequencies were 50% for African patients, significantly higher than the control population (P<10−3), and 21% for the West Indians (nonsignificant). High EBA frequencies have already been reported in American blacks significantly associated with the HLA-DR2. In conclusion, black-skinned patients developing EBA seem to have a genetic predisposition, and EBA should be suspected systematically for every AIBD seen in this population. [ABSTRACT FROM AUTHOR]

The article examines whether the soluble form of the receptor for advanced glycation end products (sRAGE) is a marker of acute lung injury and acute respiratory distress syndrome in the intensive care unit. It is known that the levels of sRAGE are elevated during acute lung injury, but it is unknown if the elevation is linked to alveolar epithelium injury or in systemic inflammation. The results of the study revealed that sRAGE levels are elevated regardless of the presence or absence of severe sepsis.

Prurigo nodularis is a pruritic dermatosis of unknown origin. Human T-cell lymphotropic virus type I (HTLV- 1) causes adult T-cell leukaemia/lymphoma. HTLV-1 is not considered to be a cause of prurigo nodularis. A 52-year-old black man, from the French West Indies, who had had prurigo nodularis for 12 years, presented with a distinct micropapular eruption with the typical pathological picture of epidermotropic T-cell lymphoma. Based on HTLV-1-positive serology and monoclonal integration of HTLV-1 we diagnosed smouldering adult T-cell leukaemia/lymphoma. Re-examinination of previous skin biopsies revealed that the disease had been evolving for 12 years. Treatment with n-interferon, 3 × 106 units three times a week, associated with zidovudine, I g daily, resulted in complete remission within 4 months. When investigating a prurigo nodularis, we therefore recommend: (1) performing HTLV-1 serology if the patient comes' from an endemic area; (ii) if positive, performing CD25 staining and looking for a HTLV-1 clonal integration; and (iii) if positive, using a treatment targeting HTLV-1. [ABSTRACT FROM AUTHOR]

• Multicentric reticulohistiocytosis is a rare non-Langerhans histiocytosis characterized by red papulonodular skin lesions and destructive polyarthritis. • Multicentric reticulohistiocytosis can be associated with malignancies, including lung cancers, or with autoimmune diseases. • Pulmonary involvement in multicentric reticulohistiocytosis is rare, and may include lung nodules, pleuritic, usual interstitial pneumonia or organizing pneumonia. [ABSTRACT FROM AUTHOR]

We investigate extensions of Alur and Dill''s timed automata, based on the possibility to update the clocks in a more elaborate way than simply reset them to zero. We call these automata updatable timed automata. They form an undecidable class of models, in the sense that emptiness checking is not decidable. However, using an extension of the region graph construction, we exhibit interesting decidable subclasses. In a surprising way, decidability depends on the nature of the clock constraints which are used, diagonal-free or not, whereas these constraints play identical roles in timed automata. We thus describe in a quite precise way the thin frontier between decidable and undecidable classes of updatable timed automata.We also study the expressive power of updatable timed automata. It turns out that any updatable automaton belonging to some decidable subclass can be effectively transformed into an equivalent timed automaton without updates but with silent transitions. The transformation suffers from an enormous combinatorics blow-up which seems unavoidable. Therefore, updatable timed automata appear to be a concise model for representing and analyzing large classes of timed systems. [Copyright &y& Elsevier]

The article presents a case study of a 67-year-old man with feeling of malaise and was diagnosed with erythematous papules on the abdomen and limbs. He was given topical steroids and developed asthenia, fever, inflammatory bilateral edema and arthralgia. The patient has a physical examination which shows lesions and vasculitis. The patient receives antihistamines and topical steroids with home decontamination for bed bug.