Unusual orbital, scleral and choroidal findings in Erdheim-Chester disease: a case report.

This case report highlights a unique presentation of Erdheim-Chester Disease (ECD) with bilateral scleral lesions, choroidal infiltration, and extensive sinus involvement. It is the first case report where the diagnosis was confirmed through a scleral biopsy after an initial presentation of a unilateral nodular scleritis. There was a gradual disease progression and ocular examination later revealed bilateral subconjunctival hyperemic lesions and mild exophthalmos, ophthalmoplegia, and extensive choroidal infiltration. Infiltration of the frontal and maxillary sinus was present and extended into the nasal cavity and both orbits. The diagnostic work-up is described in detail. Current treatment options are analyzed. It is emphasized that the ophthalmologist can play a crucial role in the diagnosis of ECD, given the substantial prevalence of orbital and ocular symptoms. The overall prognosis for ECD remains unfavorable, particularly in cases with orbital involvement. This case underscores the complexity and importance of a multidisciplinary approach in managing ECD.

Scaling of bird wings and feathers for efficient flight.

Aves are an incredibly diverse class of animals, ranging greatly in size and thriving in a wide variety of environments. Here, we explore the scaling trends of bird wings in connection with their flight performance. The tensile strength of avian bone is hypothesized to be a limiting factor in scaling the humerus with mass, which is corroborated by its experimentally determined allometric scaling trend. We provide a mechanics analysis that explains the scaling allometry of the wing humerus length, L H, with body weight W, L H ∝ W 0.44. Lastly, wing feathers are demonstrated to generally scale isometrically with bird mass, with the exception of the spacing between barbules, which falls within the same range for birds of all masses. Our findings provide insight into the "design" of birds and may be translatable to more efficient bird-inspired aircraft structures.

A Novel Piperazine-Based Drug Lead for Cryptosporidiosis from the Medicines for Malaria Venture Open-Access Malaria Box.

Cryptosporidiosis causes life-threatening diarrhea in children under the age of 5 years and prolonged diarrhea in immunodeficient people, especially AIDS patients. The standard of care, nitazoxanide, is modestly effective in children and ineffective in immunocompromised individuals. In addition to the need for new drugs, better knowledge of drug properties that drive in vivo efficacy is needed to facilitate drug development. We report the identification of a piperazine-based lead compound for Cryptosporidium drug development, MMV665917, and a new pharmacodynamic method used for its characterization. The identification of MMV665917 from the Medicines for Malaria Venture Malaria Box was followed by dose-response studies, in vitro toxicity studies, and structure-activity relationship studies using commercial analogues. The potency of this compound against Cryptosporidium parvum Iowa and field isolates was comparable to that against Cryptosporidium hominis Furthermore, unlike nitazoxanide, clofazimine, and paromomycin, MMV665917 appeared to be curative in a NOD SCID gamma mouse model of chronic cryptosporidiosis. MMV665917 was also efficacious in a gamma interferon knockout mouse model of acute cryptosporidiosis. To determine if efficacy in this mouse model of chronic infection might relate to whether compounds are parasiticidal or parasitistatic for C. parvum, we developed a novel in vitro parasite persistence assay. This assay suggested that MMV665917 was parasiticidal, unlike nitazoxanide, clofazimine, and paromomycin. The assay also enabled determination of the concentration of the compound required to maximize the rate of parasite elimination. This time-kill assay can be used to prioritize early-stage Cryptosporidium drug leads and may aid in planning in vivo efficacy experiments. Collectively, these results identify MMV665917 as a promising lead and establish a new method for characterizing potential anticryptosporidial agents.

Reinforcements in avian wing bones: Experiments, analysis, and modeling.

Almost all species of modern birds are capable of flight; the mechanical competency of their wings and the rigidity of their skeletal system evolved to enable this outstanding feat. One of the most interesting examples of structural adaptation in birds is the internal structure of their wing bones. In flying birds, bones need to be sufficiently strong and stiff to withstand forces during takeoff, flight, and landing, with a minimum of weight. The cross-sectional morphology and presence of reinforcing structures (struts and ridges) found within bird wing bones vary from species to species, depending on how the wings are utilized. It is shown that both morphology and internal features increases the resistance to flexure and torsion with a minimum weight penalty. Prototypes of reinforcing struts fabricated by 3D printing were tested in diametral compression and torsion to validate the concept. In compression, the ovalization decreased through the insertion of struts, while they had no effect on torsional resistance. An elastic model of a circular ring reinforced by horizontal and vertical struts is developed to explain the compressive stiffening response of the ring caused by differently oriented struts.

High-velocity deformation of Al0.3CoCrFeNi high-entropy alloy: Remarkable resistance to shear failure.

The mechanical behavior of a single phase (fcc) Al0.3CoCrFeNi high-entropy alloy (HEA) was studied in the low and high strain-rate regimes. The combination of multiple strengthening mechanisms such as solid solution hardening, forest dislocation hardening, as well as mechanical twinning leads to a high work hardening rate, which is significantly larger than that for Al and is retained in the dynamic regime. The resistance to shear localization was studied by dynamically-loading hat-shaped specimens to induce forced shear localization. However, no adiabatic shear band could be observed. It is therefore proposed that the excellent strain hardening ability gives rise to remarkable resistance to shear localization, which makes this material an excellent candidate for penetration protection applications such as armors.

[Stigma of mental illness among students]. / Stigmatisierung psychischer Erkrankung unter Schülern.

BACKGROUND: Social stigma connected to mental illness is a societal problem for which we lack data, especially among children and teenagers. OBJECTIVES: The purpose of this study was to assess how adolescents stigmatize mental illness in peers and to investigate if stigmatizing attitudes differed as a function of other variables (e. g. age, gender, level of education). MATERIALS AND METHODS: A German translation of the Revised Attribution Questionnaire (r-AQ), a nine-item survey, was administered to 246 pupils between 14 and 16 years of age, who were recruited from seven German schools. RESULTS: The pupils investigated in the study scored in the non-stigmatizing range of the questionnaire. Demographic factors did not have a significant effect on their stigmatizing attitude. CONCLUSIONS: The low stigmatizing tendencies can be explained by existing contact with the mentally ill or by possible effects of recruitment. Future research should take knowledge about mental illness as a possible factor influencing stigmatizing attitudes into account.

Multiple births by a captive swellshark Cephaloscyllium ventriosum via facultative parthenogenesis.

Using a novel set of 12 microsatellites, a captive, adult female swellshark Cephaloscyllium ventriosum that produced five pups via parthenogenesis is described; naturally occurring parthenogenesis has been observed in every vertebrate class with the exception of mammals. As demonstrated in this study, a captive environment is ideal for long-term monitoring of animals under controlled conditions, and easily allows the detection of particular facets of their biology.

Inter-rater reliability of the APD, SFU and UTD grading systems in fetal sonography and MRI.

INTRODUCTION: Antenatal hydronephrosis (ANH) is frequently detected on screening obstetric ultrasonography. Common ANH grading systems include the anterior-posterior diameter (APD) and the Society for Fetal Urology (SFU) grading system. Recent developments in the management of ANH include the use of fetal magnetic resonance imaging (MRI), and a new grading system - Urinary Tract Dilation (UTD). This study reviewed patients who underwent fetal MRI and ultrasound, and compared the grading systems across these imaging modalities. MATERIALS AND METHODS: Patients who underwent paired fetal MRI and ultrasound studies between January 2012 and January 2014 were included. Two pediatric urologists and a pediatric radiologist reviewed the studies. Data collected included APD, SFU grade, and UTD grade. Fleiss' kappa statistic determined the inter-rater reliability (IRR) of the SFU and UTD grading within each imaging modality. Intra-class correlation assessed the consistency of the APD measurements. RESULTS: Forty-seven patients and 88 renal units were evaluated. Median gestational age was 22 weeks. Kappa values of the SFU grading system indicated fair IRR for ultrasound imaging and moderate IRR for MRI imaging, while the UTD grading system reached moderate IRR for both. The IRR of the SFU grading system was improved with the use of MRI, while the UTD grading system was no different. The APD intraclass correlation coefficient improved significantly when measured by MRI. As the ultrasound SFU grade increased, the odds of the MRI SFU grade being scored higher increased by a factor of 3.7. There was no difference between ultrasound and MRI when using the UTD grading system. DISCUSSION: This study was the first to assess the UTD system in a cohort of patients who underwent paired ultrasound and MRI studies. The results suggested that the UTD system might improve IRR, compared with the SFU system. The use of fetal MRI may improve the IRR of the SFU grading system. It also found that the proportion of SFU grades was affected by the imaging modality, raising the possibility that MRI 'overcalls' the SFU grade, compared with ultrasound. This difference was not observed using the UTD grading system. The most important limitation was the selection bias favoring complex pathology with severe ANH diagnosed at an early gestational age. CONCLUSIONS: In this unique cohort, the UTD system improved IRR when compared to the SFU grading system. Fetal MRI improved the IRR of the SFU grading system, and improved the APD intraclass correlation. The SFU grading was likely to be higher when assessed by MRI vs ultrasound, but the UTD grade was not affected by the imaging modality.

Supersonic Dislocation Bursts in Silicon.

Dislocations are the primary agents of permanent deformation in crystalline solids. Since the theoretical prediction of supersonic dislocations over half a century ago, there is a dearth of experimental evidence supporting their existence. Here we use non-equilibrium molecular dynamics simulations of shocked silicon to reveal transient supersonic partial dislocation motion at approximately 15 km/s, faster than any previous in-silico observation. Homogeneous dislocation nucleation occurs near the shock front and supersonic dislocation motion lasts just fractions of picoseconds before the dislocations catch the shock front and decelerate back to the elastic wave speed. Applying a modified analytical equation for dislocation evolution we successfully predict a dislocation density of 1.5 × 10(12) cm(-2) within the shocked volume, in agreement with the present simulations and realistic in regards to prior and on-going recovery experiments in silicon.

Head and neck adenoid cystic carcinoma: A prospective multicenter REFCOR study of 95 cases.

OBJECTIVES: To describe the clinical, histological and therapeutic characteristics of a prospective multicenter series of 95 head and neck adenoid cystic carcinoma patients, and to determine any prognostic factors for disease-free survival. PATIENTS AND METHODS: Ninety-five patients with adenoid cystic carcinoma were included in the Réseau d'Expertise Français Des Cancers ORL Rares (REFCOR, French Rare Head and Neck Cancer Expert Network) database between 2009 and 2012. The primary site was the salivary glands in 39 cases, sinus cavities (including hard palate) in 36 cases, pharynx-larynx-trachea in 14 cases, and lips and oral cavity in 4 cases. The tumor was stage I in 15% of cases, stage II in 23%, stage III in 26% and stage IV in 36%. Nine patients had cervical lymph node involvement and 5 had metastases at diagnosis. Fifty-six percent of patients were managed by surgery with postoperative radiation therapy. During follow-up, 3 patients died, 9 developed metastases and 12 showed recurrence or local progression. RESULTS: Mean follow-up was 18 months. On univariate analysis, disease-free survival correlated with T stage (P=0.05), N stage (P=0.003), resection margins (P=0.04), lymph node involvement on histology (P=0.01), and absence of chemotherapy (P=0.03). On multivariate analysis, disease-free survival correlated with T stage (P=0.01), N stage (P=0.09) and surgery (P=0.005). CONCLUSION: The essential issue in adenoid cystic carcinoma is long-term control. The present results confirm that the reference attitude is radical surgical resection for optimal local control. Adjuvant radiation therapy did not emerge as a prognostic factor. This study also provides a starting-point for translational studies in pathology and genetics.

Probing the character of ultra-fast dislocations.

Plasticity is often controlled by dislocation motion, which was first measured for low pressure, low strain rate conditions decades ago. However, many applications require knowledge of dislocation motion at high stress conditions where the data are sparse, and come from indirect measurements dominated by the effect of dislocation density rather than velocity. Here we make predictions based on atomistic simulations that form the basis for a new approach to measure dislocation velocities directly at extreme conditions using three steps: create prismatic dislocation loops in a near-surface region using nanoindentation, drive the dislocations with a shockwave, and use electron microscopy to determine how far the dislocations moved and thus their velocity at extreme stress and strain rate conditions. We report on atomistic simulations of tantalum that make detailed predictions of dislocation flow, and find that the approach is feasible and can uncover an exciting range of phenomena, such as transonic dislocations and a novel form of loop stretching. The simulated configuration enables a new class of experiments to probe average dislocation velocity at very high applied shear stress.

Phase Transformation in Tantalum under Extreme Laser Deformation.

The structural and mechanical response of metals is intimately connected to phase transformations. For instance, the product of a phase transformation (martensite) is responsible for the extraordinary range of strength and toughness of steel, making it a versatile and important structural material. Although abundant in metals and alloys, the discovery of new phase transformations is not currently a common event and often requires a mix of experimentation, predictive computations, and luck. High-energy pulsed lasers enable the exploration of extreme pressures and temperatures, where such discoveries may lie. The formation of a hexagonal (omega) phase was observed in recovered monocrystalline body-centered cubic tantalum of four crystallographic orientations subjected to an extreme regime of pressure, temperature, and strain-rate. This was accomplished using high-energy pulsed lasers. The omega phase and twinning were identified by transmission electron microscopy at 70 GPa (determined by a corresponding VISAR experiment). It is proposed that the shear stresses generated by the uniaxial strain state of shock compression play an essential role in the transformation. Molecular dynamics simulations show the transformation of small nodules from body-centered cubic to a hexagonal close-packed structure under the same stress state (pressure and shear).

Variable nutrient stoichiometry (carbon:nitrogen:phosphorus) across trophic levels determines community and ecosystem properties in an oligotrophic mangrove system.

Our study investigated the carbon:nitrogen:phosphorus (C:N:P) stoichiometry of mangrove island of the Mesoamerican Barrier Reef (Twin Cays, Belize). The C:N:P of abiotic and biotic components of this oligotrophic ecosystem was measured and served to build networks of nutrient flows for three distinct mangrove forest zones (tall seaward fringing forest, inland dwarf forests and a transitional zone). Between forest zones, the stoichiometry of primary producers, heterotrophs and abiotic components did not change significantly, but there was a significant difference in C:N:P, and C, N, and P biomass, between the functional groups mangrove trees, other primary producers, heterotrophs, and abiotic components. C:N:P decreased with increasing trophic level. Nutrient recycling in the food webs was highest for P, and high transfer efficiencies between trophic levels of P and N also indicated an overall shortage of these nutrients when compared to C. Heterotrophs were sometimes, but not always, limited by the same nutrient as the primary producers. Mangrove trees and the primary tree consumers were P limited, whereas the invertebrates consuming leaf litter and detritus were N limited. Most compartments were limited by P or N (not by C), and the relative depletion rate of food sources was fastest for P. P transfers thus constituted a bottleneck of nutrient transfer on Twin Cays. This is the first comprehensive ecosystem study of nutrient transfers in a mangrove ecosystem, illustrating some mechanisms (e.g. recycling rates, transfer efficiencies) which oligotrophic systems use in order to build up biomass and food webs spanning various trophic levels.

Structure and mechanical properties of naturally occurring lightweight foam-filled cylinder--the peacock's tail coverts shaft and its components.

Feather shaft, which is primarily featured by a cylinder filled with foam, possesses a unique combination of mechanical robustness and flexibility with a low density through natural evolution and selection. Here the hierarchical structures of peacock's tail coverts shaft and its components are systematically characterized from millimeter to nanometer length scales. The variations in constituent and geometry along the length are examined. The mechanical properties under both dry and wet conditions are investigated. The deformation and failure behaviors and involved strengthening, stiffening and toughening mechanisms are analyzed qualitatively and quantitatively and correlated to the structures. It is revealed that the properties of feather shaft and its components have been optimized through various structural adaptations. Synergetic strengthening and stiffening effects can be achieved in overall rachis owing to increased failure resistance. This study is expected to aid in deeper understandings on the ingenious structure-property design strategies developed by nature, and accordingly, provide useful inspiration for the development of high-performance synthetic foams and foam-filled materials.

The use of blood lactate concentration as an indicator of temperament and its impact on growth rate and tenderness of steaks from Simmental × Angus steers.

The objective of this study was to evaluate the use of blood lactate concentration as an objective measure of beef cattle temperament and determine if the temperament of steers affected growth rate and tenderness of beef steaks. Angus×Simmental steers (n=154) were evaluated for blood lactate (BL), exit velocity (EV) and chute score (CS), and humanely harvested. Carcass characteristics were assessed and loin samples were obtained for tenderness evaluation. All measures of the temperament were significantly correlated to each other (r=0.14-0.47; P≤0.04). Steaks from steers in the medium BL classification were significantly more tender than steaks from steers from the high BL classification. The steers with faster EV tended to result in steaks with higher shear force values (P=0.07). The steers classified as fast growing resulted in steaks with lower shear force values (P=0.02) compared to steaks from steers classified as slow growing. Results suggest that the temperament contributes to variations in growth rate, blood lactate, and tenderness.

Oestrogens improve human pancreatic islet transplantation in a mouse model of insulin deficient diabetes.

AIMS/HYPOTHESIS: Pancreatic islet transplantation (PIT) offers a physiological treatment for type 1 diabetes, but the failure of islet engraftment hinders its application. The female hormone 17ß-oestradiol (E2) favours islet survival and stimulates angiogenesis, raising the possibility that E2 may enhance islet engraftment following PIT. METHODS: To explore this hypothesis, we used an insulin-deficient model with xenotransplantation of a marginal dose of human islets in nude mice rendered diabetic with streptozotocin. This was followed by 4 weeks of treatment with vehicle, E2, the non-feminising oestrogen 17α-oestradiol (17α-E2), the oestrogen receptor (ER) α agonist propyl-pyrazole-triol (PPT), the ERß agonist diarylpropionitrile (DPN) or the G protein-coupled oestrogen receptor (GPER) agonist G1. RESULTS: Treatment with E2, 17α-E2, PPT, DPN or G1 acutely improved blood glucose and eventually promoted islet engraftment, thus reversing diabetes. The effects of E2 were retained in the presence of immunosuppression and persisted after discontinuation of E2 treatment. E2 produced an acute decrease in graft hypoxic damage and suppressed beta cell apoptosis. E2 also acutely suppressed hyperglucagonaemia without altering insulin secretion, leading to normalisation of blood glucose. CONCLUSIONS/INTERPRETATION: During PIT, E2 synergistic actions contribute to enhancing human islet-graft survival, revascularisation and functional mass. This study identifies E2 as a short-term treatment to improve PIT.

Evaluating systemic lupus erythematosus patients for lung involvement.

INTRODUCTION: We set out to determine the frequency of respiratory symptoms, abnormal lung function, and shrinking lung syndrome (SLS) among patients with systemic lupus erythematosus (SLE) and to determine correlates of SLS. METHODS: Consecutive adult patients who fulfilled the American College of Rheumatology classification criteria for SLE were enrolled. Demographics, clinical, and serologic characteristics were recorded; all patients underwent pulmonary function tests (PFT) and had either a chest X-ray or computed tomography scan. SLS was defined as dyspnea with restrictive lung physiology (defined as a forced vital capacity (FVC) <80% predicted in the absence of obstruction) who did not have any evidence of interstitial lung disease on chest imaging; controls were symptomatic patients with no restrictive physiology and the absence of interstitial changes on chest imaging. RESULTS: Sixty-nine out of 110 (63%) patients had respiratory symptoms, 73 (66%) patients had abnormal lung function, and 11 (10%) patients met the definition for SLS. In a multivariate model controlling for disease duration, a history of pleuritis, modified American College of Rheumatology total score, seropositivity for dsDNA and RNP antibodies, increased disease duration (odds ratio (OR) = 1.2; 95% confidence interval (CI) of 1.0-1.3, p = 0.04), seropositivity for anti-RNP (OR = 24.4; 95% CI of 1.6-384.0, p = 0.02), and a history of serositis were significantly associated with SLS when compared with symptomatic controls. CONCLUSION: Respiratory symptoms, abnormal lung function, and SLS are common in SLE. Clinicians should consider evaluation for SLS among symptomatic patients with long-standing disease and a history of pleuritis.

A review of zoonotic disease surveillance supported by the Armed Forces Health Surveillance Center.

The Armed Forces Health Surveillance Center (AFHSC), Division of Global Emerging Infections Surveillance and Response System conducts disease surveillance through a global network of US Department of Defense research laboratories and partnerships with foreign ministries of agriculture, health and livestock development in over 90 countries worldwide. In 2010, AFHSC supported zoonosis survey efforts were organized into four main categories: (i) development of field assays for animal disease surveillance during deployments and in resource limited environments, (ii) determining zoonotic disease prevalence in high-contact species which may serve as important reservoirs of diseases and sources of transmission, (iii) surveillance in high-risk human populations which are more likely to become exposed and subsequently infected with zoonotic pathogens and (iv) surveillance at the human-animal interface examining zoonotic disease prevalence and transmission within and between human and animal populations. These efforts have aided in the detection, identification and quantification of the burden of zoonotic diseases such as anthrax, brucellosis, Crimean Congo haemorrhagic fever, dengue fever, Hantaan virus, influenza, Lassa fever, leptospirosis, melioidosis, Q fever, Rift Valley fever, sandfly fever Sicilian virus, sandfly fever Naples virus, tuberculosis and West Nile virus, which are of military and public health importance. Future zoonotic surveillance efforts will seek to develop local capacity for zoonotic surveillance focusing on high risk populations at the human-animal interface.

Structure and mechanical properties of Saxidomus purpuratus biological shells.

The strength and fracture behavior of Saxidomus purpuratus shells were investigated and correlated with the structure. The shells show a crossed lamellar structure in the inner and middle layers and a fibrous/blocky and porous structure composed of nanoscaled particulates (~100 nm diameter) in the outer layer. It was found that the flexure strength and fracture mode are a function of lamellar organization and orientation. The crossed lamellar structure of this shell is composed of domains of parallel lamellae with approximate thickness of 200-600 nm. These domains have approximate lateral dimensions of 10-70 µm with a minimum of two orientations of lamellae in the inner and middle layers. Neighboring domains are oriented at specific angles and thus the structure forms a crossed lamellar pattern. The microhardness across the thickness was lower in the outer layer because of the porosity and the absence of lamellae. The tensile (from flexure tests) and compressive strengths were analyzed by means of Weibull statistics. The mean tensile (flexure) strength at probability of 50%, 80-105 MPa, is on the same order as the compressive strength (~50-150 MPa) and the Weibull moduli vary from 3.0 to 7.6. These values are significantly lower than abalone nacre, in spite of having the same aragonite structure. The lower strength can be attributed to a smaller fraction of the organic interlayer. The fracture path in the specimens is dominated by the orientation of the domains and proceeds preferentially along lamella boundaries. It also correlates with the color changes in the cross section of the shell. The cracks tend to undergo a considerable change in orientation when the color changes abruptly. The distributions of strengths, cracking paths, and fracture surfaces indicate that the mechanical properties of the shell are anisotropic with a hierarchical nature.