Band-Resolved Imaging of Photocurrent in a Topological Insulator.

We study the microscopic origins of photocurrent generation in the topological insulator Bi_{2}Se_{3} via time- and angle-resolved photoemission spectroscopy. We image the unoccupied band structure as it evolves following a circularly polarized optical excitation and observe an asymmetric electron population in momentum space, which is the spectroscopic signature of a photocurrent. By analyzing the rise times of the population we identify which occupied and unoccupied electronic states are coupled by the optical excitation. We conclude that photocurrents can only be excited via resonant optical transitions coupling to spin-orbital textured states. Our work provides a microscopic understanding of how to control photocurrents in systems with spin-orbit coupling and broken inversion symmetry.

Automatic depletion with Spectra Optia allows a safe 16% reduction of red blood cell pack consumption in exchanged sickle cell anemia patients.

BACKGROUND: Chronic red blood cell exchanges (RBCXs) are frequently used to prevent complications in patients with sickle cell anemia, but the scarcity of matched red blood cell packs (RBCPs) is a serious concern. The main goal of this study was to compare the number of RBCPs used during RBCXs between the Spectra Optia (SO) device (with the automatic depletion step) and the former Cobe Spectra (CSP) device. STUDY DESIGN AND METHODS: The performances and safety of 300 SO sessions using the automatic depletion step (SO/DE) in 50 patients with sickle cell anemia under a chronic transfusion program over a 1-year period were prospectively analyzed. The numbers of RBCPs saved using this protocol compared to the SO device without depletion and to the CSP device were determined. RESULTS: The SO/DE protocol appeared to be safe, as only 5% and 17% of the sessions were characterized by a significant decrease in blood pressure and increase in heart rate (grade 2 adverse events), respectively. Postapheresis hematocrit and fraction of cells remaining reached expected values. The SO/DE protocol required 16% fewer RBCPs compared to SO without depletion, allowing a mean saving of 12 RBCPs per patient and per year and 13% fewer compared to CSP device. Interestingly, the saving was more important for patients with high total blood volume and/or high preapheresis hematocrit. CONCLUSION: The SO/DE protocol is an efficient, safe and cost-effective procedure for patients with sickle cell anemia under a chronic transfusion program.

Morphological comparison of the ampullae of Lorenzini of three sympatric benthic rays.

This study investigated and compared the morphology of the electrosensory system of three species of benthic rays. Neotrygon trigonoides, Hemitrygon fluviorum and Maculabatis toshi inhabit similar habitats within Moreton Bay, Queensland, Australia. Like all elasmobranchs, they possess the ability to detect weak electrical fields using their ampullae of Lorenzini. Macroscopically, the ampullary organs of all three species are aggregated in three bilaterally paired clusters: the mandibular, hyoid and superficial ophthalmic clusters. The hyoid and superficial ophthalmic clusters of ampullae arise from both dorsal and ventral ampullary pores. The dorsal pores are typically larger than the ventral pores in all three species, except for the posterior ventral pores of the hyoid grouping. Ampullary canals arising from the hyoid cluster possessed a quasi-sinusoidal shape, but otherwise appeared similar to the canals described for other elasmobranchs. Ultrastructure of the ampullae of Lorenzini of the three species was studied using a combination of light, confocal and electron microscopy. All possess ampullae of the alveolar type. In N. trigonoides and M. toshi, each ampullary canal terminates in three to five sensory chambers, each comprising several alveoli lined with receptor and supportive cells and eight to 11 sensory chambers in H. fluviorum. Receptor cells of all three species possess a similar organization to those of other elasmobranchs and were enveloped by large, apically nucleated supportive cells protruding well into the alveolar sacs. The luminally extended chassis of supportive cells protruding dramatically into the ampullary lumen had not previously been documented for any elasmobranch species.

Emergency Department care of childhood epistaxis.

OBJECTIVE: The aim of this review is to determine an efficient and safe primary strategy care for paediatric epistaxis. DATA SOURCES: We searched PubMed and Cochrane databases for studies referenced with key words 'epistaxis AND childhood'. This search yielded 32 research articles about primary care in childhood epistaxis (from 1989 to 2015). Bibliographic references found in these articles were also examined to identify pertinent literature. We compared our results to the specific management of adult epistaxis classically described in the literature. RESULTS: Epistaxis is one of the most common reasons for referral of children to a hospital ENT outpatient department. The bleeding usually originates from the anterior septum, as opposed to adults. Crusting, digital trauma, foreign bodies and nasal colonisation with Staphylococcus aureus have been suggested as specific nosebleed factors in children. Rare aetiologies as juvenile nasopharyngeal angiofibroma appear later during adolescence. There are different modes of management of mild epistaxis, which begin with clearing out blood clots and bidigital compression. An intranasal topical local anaesthetic and decongestant can be used over 6 years of age. In case of active bleeding, chemical cauterisation is preferred to anterior packing and electric cauterisation but is only feasible if the bleeding site is clearly visible. In case of non-active bleeding in children, and in those with recurrent idiopathic epistaxis, antiseptic cream is easy to apply and can avoid 'acrobatic' cauterisation liable to cause further nasal cavity trauma. CONCLUSIONS: Aetiologies and treatment vary with patient age and the existence or not of active bleeding at the time of the examination. Local treatments are usually easy to perform, but physicians have to ponder their indications depending on the possible complications in order to inform parents and to know paediatric epistaxis specificities.

Mutations in proteins of the Conserved Oligomeric Golgi Complex affect polarity, cell wall structure, and glycosylation in the filamentous fungus Aspergillus nidulans.

We have described two Aspergillus nidulans gene mutations, designated podB1 (polarity defective) and swoP1 (swollen cell), which cause temperature-sensitive defects during polarization. Mutant strains also displayed unevenness and abnormal thickness of cell walls. Un-polarized or poorly-polarized mutant cells were capable of establishing normal polarity after a shift to a permissive temperature, and mutant hyphae shifted from permissive to restrictive temperature show wall and polarity abnormalities in subsequent growth. The mutated genes (podB=AN8226.3; swoP=AN7462.3) were identified as homologues of COG2 and COG4, respectively, each predicted to encode a subunit of the multi-protein COG (Conserved Oligomeric Golgi) Complex involved in retrograde vesicle trafficking in the Golgi apparatus. Down-regulation of COG2 or COG4 resulted in abnormal polarization and cell wall staining. The GFP-tagged COG2 and COG4 homologues displayed punctate, Golgi-like localization. Lectin-blotting indicated that protein glycosylation was altered in the mutant strains compared to the wild type. A multicopy expression experiment showed evidence for functional interactions between the homologues COG2 and COG4 as well as between COG2 and COG3. To date, this work is the first regarding a functional role of the COG proteins in the development of a filamentous fungus.

Epidemiological burden of postmenopausal osteoporosis in Italy from 2010 to 2020: estimations from a disease model.

The article describes the adaptation of a model to estimate the burden of postmenopausal osteoporosis in women aged 50 years and over in Italy between 2010 and 2020. For this purpose, a validated postmenopausal osteoporosis disease model developed for Sweden was adapted to Italy. For each year of the study, the 'incident cohort' (women experiencing a first osteoporotic fracture) was identified and run through a Markov model using 1-year cycles until 2020. Health states were based on the number of fractures and deaths. Fracture by site (hip, clinical vertebral, non-hip non-vertebral) was tracked for each health state. Transition probabilities reflected fracture site-specific risk of death and subsequent fractures. Model inputs specific to Italy included population size and life tables from 1970 to 2020, incidence of hip fracture and BMD by age in the general population (mean and standard deviation). The model estimated that the number of postmenopausal osteoporotic women would increase from 3.3 million to 3.7 million between 2010 and 2020 (+14.3%). Assuming unchanged incidence rates by age group over time, the model predicted the overall number of osteoporotic fractures to increase from 285.0 to 335.8 thousand fractures between 2010 and 2020 (+17.8%). The estimated expected increases in hip, vertebral and non-hip non-vertebral fractures were 22.3, 17.2 and 16.3%, respectively. Due to demographic changes, the burden of fractures is expected to increase markedly by 2020.

Chronic in vivo load alteration induces degenerative changes in the rat tibiofemoral joint.

OBJECTIVE: We investigated the relationship between the magnitude and duration of sustained compressive load alteration and the development of degenerative changes in the rat tibiofemoral joint. METHODS: A varus loading device was attached to the left hind limb of mature rats to apply increased compression to the medial compartment and decreased compression to the lateral compartment of the tibiofemoral joint of either 0% or 100% body weight for 0, 6 or 20 weeks. Compartment-specific assessment of the tibial plateaus included biomechanical measures (articular cartilage aggregate modulus, permeability and Poisson's ratio, and subchondral bone modulus) and histological assessments (articular cartilage, calcified cartilage, and subchondral bone thicknesses, degenerative scoring parameters, and articular cartilage cellularity). RESULTS: Increased compression in the medial compartment produced significant degenerative changes consistent with the development of osteoarthritis (OA) including a progressive decrease in cartilage aggregate modulus (43% and 77% at 6 and 20 weeks), diminished cellularity (38% and 51% at 6 and 20 weeks), and increased histological degeneration. At 20 weeks, medial compartment articular cartilage thickness decreased 30% while subchondral bone thickness increased 32% and subchondral bone modulus increased 99%. Decreased compression in the lateral compartment increased calcified cartilage thickness, diminished region-specific subchondral bone thickness and revealed trends for reduced cellularity and decreased articular cartilage thickness at 20 weeks. CONCLUSIONS: Altered chronic joint loading produced degenerative changes consistent with those observed clinically with the development of OA and may replicate the slow development of non-traumatic OA in which mechanical loads play a primary etiological role.

Identification of Plasmopara viticola genes potentially involved in pathogenesis on grapevine suggests new similarities between oomycetes and true fungi.

Plant diseases caused by fungi and oomycetes result in significant economic losses every year. Although phylogenetically distant, these organisms share many common features during infection. We identified genes in the oomycete Plasmopara viticola that are potentially involved in pathogenesis in grapevine by using fungal databases and degenerate primers. Fragments of P. viticola genes encoding NADH-ubiquinone oxidoreductase (PvNuo), laccase (PvLac), and invertase (PvInv) were obtained. PvNuo was overexpressed at 2 days postinoculation (dpi), during the development of the first hyphal structures and haustoria. PvLac was overexpressed at 5 dpi when genes related to pterostilbene biosynthesis were induced in grapevine. Transcript level for PvInv increased between 1 and 4 dpi before reaching a plateau. These results might suggest a finely tuned strategy of infection depending on nutrition and plant response. Phylogenetic analyses of PvNuo showed that P. viticola clustered with other oomycetes and was associated with brown algae and diatoms, forming a typical Straminipila clade. Based on the comparison of available sequences for laccases and invertases, the group formed by P. viticola and other oomycetes tended to be more closely related to Opisthokonta than to Straminipila. Convergent evolution or horizontal gene transfer could explain the presence of fungus-like genes in P. viticola.

Developmental factors associated with inappropriate coping strategies among sexual aggressors of children.

BACKGROUND: Many studies in the field of sexual offending focus on the presence of inadequate coping strategies prior to sexual offending, and the role these strategies play in the sequence of the offense. However, little is known about the development of strategies-such as substance abuse and, especially, deviant sexual fantasies-to manage daily difficulties. OBJECTIVE: To better understand the antecedents of the development of inadequate coping strategies, we conducted a series of structural equation modeling (SEM) analyses. PARTICIPANTS AND SETTINGS: Based on 274 sexual aggressors of children, these analyses were based on components of Maniglio (2011a) theoretical model, in which victimization before the age of 18 leads to the development of psychological problems and, ultimately, the reliance on deviant sexual fantasies as a coping strategy. METHODS: Two models were created through exploratory factorial analysis: the first model comprised 19 manifest variables, while the second model consisted of 15 manifest variables. All the retained variables were related to Maniglio's (2011a) hypothesis. RESULTS: The analyses not only confirm Maniglio's hypothesis but also produced two statistically significant models (RMSEA = 0.069, CFI = 0.93 and TLI = 0.92 for Model 1 & RMSEA = 0.074, CFI = 0.93 and TLI = 0.91 for Model 2) composed of three indirect trajectories and one direct trajectory on the one hand, and four indirect trajectories and one direct trajectory on the other hand. CONCLUSIONS: These results are consistent with those of studies that have highlighted the heterogeneity of sexual aggressors of children.

A comparison of three methods for detecting KRAS mutations in formalin-fixed colorectal cancer specimens.

BACKGROUND: KRAS mutation testing is required to select patients with metastatic colorectal cancer (CRC) to receive anti-epidermal growth factor receptor antibodies, but the optimal KRAS mutation test method is uncertain. METHODS: We conducted a two-site comparison of two commercial KRAS mutation kits - the cobas KRAS Mutation Test and the Qiagen therascreen KRAS Kit - and Sanger sequencing. A panel of 120 CRC specimens was tested with all three methods. The agreement between the cobas test and each of the other methods was assessed. Specimens with discordant results were subjected to quantitative massively parallel pyrosequencing (MPP). DNA blends were tested to determine detection rates at 5% mutant alleles. RESULTS: Reproducibility of the cobas test between sites was 98%. Six mutations were detected by cobas that were not detected by Sanger, and five were confirmed by MPP. The cobas test detected eight mutations which were not detected by the therascreen test, and seven were confirmed by MPP. Detection rates with 5% mutant DNA blends were 100% for the cobas and therascreen tests and 19% for Sanger. CONCLUSION: The cobas test was reproducible between sites, and detected several mutations that were not detected by the therascreen test or Sanger. Sanger sequencing had poor sensitivity for low levels of mutation.

Physicochemical and microbiological stability of insulin eye drops in an artificial tear vehicle used in the treatment of refractory neurotrophic keratopathy.

Neurotrophic keratopathy (NK) is a degenerative corneal disease with a loss of corneal sensitivity and impairment of corneal healing. Low dose insulin eyedrops have been shown to be a simple and effective treatment for refractory NK when the response to the usual treatment is incomplete. At present, there are no commercially available forms, and there is no data regarding the stability of these products as prepared by compounding pharmacies. In this work, we studied the physicochemical and microbiological stability of an insulin ophthalmic formulation obtained by mixing insulin lispro in artificial tears with a polyethylene and propylene glycol base. The stability of this 1IU/mL insulin ophthalmic formulation was analysed for 12 months in low-density polyethylene (LDPE) multidose eye droppers at 4°C. The studied parameters of physicochemical stability were: visual inspection, turbidity, UV spectral absorption, osmolality and pH. In addition, insulin and m-cresol concentrations and quantification of impurities (insulin covalent aggregates and insulin fragments) were studied thanks to the development of a new Size Exclusion Chromatographic method. For unopened eye droppers, all tested physicochemical parameters remained stable for 12 months at 4°C, and excellent microbiological stability was obtained. In conditions of simulated use, these parameters also remained stable for one month at 4°C, and no impact of potential temperature rises on the insulin and m-cresol concentrations in the insulin eyedropper was observed.

Composite anatomical-clinical-molecular prognostic model in non-small cell lung cancer.

The objective of the present study was to elaborate a survival model that integrates anatomic factors, according to the 2010 seventh edition of the tumour, node and metastasis (TNM) staging system, with clinical and molecular factors. Pathologic TNM descriptors (group A), clinical variables (group B), laboratory parameters (group C) and molecular markers (tissue microarrays; group D) were collected from 512 early-stage nonsmall cell lung cancer (NSCLC) patients with complete resection. A multivariate analysis stepped supervised learning classification algorithm was used. The prognostic performance by groups was: areas under the receiver operating characteristic curve (C-index): 0.67 (group A), 0.65 (Group B), 0.57 (group C) and 0.65 (group D). Considering all variables together selected for each of the four groups (integrated group) the C-index was 0.74 (95% CI 0.70-0.79), with statistically significant differences compared with each isolated group (from p = 0.006 to p < 0.001). Variables with the greatest prognostic discrimination were the presence of another ipsilobar nodule and tumour size > 3 cm, followed by other anatomical and clinical factors, and molecular expressions of phosphorylated mammalian target of rapamycin (phospho-mTOR), Ki67cell proliferation index and phosphorylated acetyl-coenzyme A carboxylase. This study on early-stage NSCLC shows the benefit from integrating pathological TNM, clinical and molecular factors into a composite prognostic model. The model of the integrated group classified patients with significantly higher accuracy compared to the TNM 2010 staging.

Development and validation of a disease model for postmenopausal osteoporosis.

UNLABELLED: This article describes the development of a model for postmenopausal osteoporosis (PMO) based on Swedish data that is easily adaptable to other countries. INTRODUCTION: The aims of the study were to develop and validate a model to describe the current/future burden of PMO in different national settings. METHODS: For validation purposes, the model was developed using Swedish data and provides estimates from 1990. For each year of the study, the "incident cohort" (women experiencing a first osteoporotic fracture) was identified and run through a Markov model using 1-year cycles until 2020. Health states were based on the number of fractures and death. Fracture by site (hip, vertebral, and non-hip non-vertebral) was tracked for each health state. Transition probabilities reflected site-specific risk of death and subsequent fractures. Bone mineral density (BMD) was included as a model output; model inputs included population size and life tables from 1970 to 2020, incidence of fracture, relative risk of subsequent fractures based on prior fracture, relative risk of death following a fracture by site, and BMD by age (mean and standard deviation). RESULTS: Model predictions averaged across age groups estimated the incidence of hip, vertebral, and other osteoporotic fractures within a 5% margin of error versus published data. In Sweden, the number of osteoporotic fractures is expected to rise by 11.5% between 2009 and 2020, with a shift towards more vertebral fractures and multiple fractures. CONCLUSION: The current PMO disease model is easily adaptable to other countries, providing a consistent measure of present and future burden of PMO in different settings.

Diurnal evolution of cycling biomechanical parameters during a 60-s Wingate test.

The purpose of this study was to assess the evolution of pedaling kinetics and kinematics during a short-term fatigue cycling exercise at two times of day. Twenty active male subjects were asked to perform a 60-s Wingate test against a constant braking resistance during two experimental sessions at 06:00 and 18:00 hours, i.e., very close to the hours of core temperature values, which are, respectively, the lowest and the highest. The results showed that the fatigue index was higher (P<0.05) at 18:00 hours (71.4%) than at 06:00 hours (69.2%) and power output was higher (P<0.05) in the evening than in the morning during the first 20 s of the test, after which no difference was observed. Taken together, these results showed a greater progression of fatigue in the evening than in the morning. The diurnal variations in performance and fatigue were associated (P<0.001) with diurnal changes in cycling kinematic parameters, characterized by a reduction in the range of motion of the ankle angle in the evening. These findings show that a time-of-day effect on movement patterns occurs during an anaerobic cycling exercise and that this phenomenon has a direct influence on performance and fatigue.

[Corneal perforation with tyrosine kinase inhibitor chemotherapy: REGORAFENIB]. / Perforation cornéenne sous chimiothérapie inhibiteur des tyrosines kinases : REGORAFENIB.

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) are active in a variety of metastatic cancers. They have a good general tolerance with mainly hepatic and dermatological side effects. Rarely, ophthalmologic side effects may occur: eyelash abnormalities, eyelids abnormalities, disorders of the ocular surface with ocular dryness or even corneal erosions that can even lead to perforation. Regorafenib is a new oral multi-targeted tyrosine kinase inhibitor that inhibits multiple protein kinases, including those involved in tumor angiogenesis, oncogenesis and tumor microenvironment. CASE DESCRIPTION: We describe, to the best of our knowledge, the first case of complicated bilateral ulcers of corneal perforation in a patient under REGORAFENIB. OBSERVATION: 20-year-old patient with metastatic chondrosarcomas of the pelvis, mandible and thorax received chemotherapy with REGORAFENIB. A few weeks after initiation of treatment, he experienced an increased dry eye syndrome associated with bilateral corneal ulcers complicated by perforation. Despite discontinuation of chemotherapy and maximal medical and surgical treatment (iterative amniotic membrane grafts and corneal transplantation), the progression was unfavorable. DISCUSSION: This is the first known case of corneal perforation under REGORAFENIB. The pathophysiology is multifactorial. On the one hand, this chemotherapy targets angiogenesis (VEGFR), oncogenesis (KIT, RET, RAF1, BRAF) and the tumor microenvironment (PDGFR, FGFR). On the other hand, other triggers are added, namely mixed dry eye syndrome, hypovitaminosis A (anorexia), the neurotrophic component, as well as the toxicity of chemotherapy via tears. CONCLUSION: First described case of corneal perforation under REGORAFENIB, non-regressive at the end of chemotherapy, and despite medical and surgical treatments. Ophthalmologic surveillance is therefore necessary for patients under chemotherapy with tyrosine kinase inhibitors, as serious ocular complications, especially corneal ones, may occur.

[Interstitial keratitis diagnosis and treatment (French translation of the article)]. / Kératites interstitielles : prise en charge diagnostique et thérapeutiques.

Interstitial keratitis is a non-ulcerative, non-suppurative, more or less vascularized inflammation of the corneal stroma. The corneal lesions result from the host response to bacterial, viral (40% of cases) or parasitic antigens, or from an autoimmune response (1% of cases) without active corneal infection. The natural history of the disease is divided into two phases : acute and cicatricial. This type of keratitis is less common than ulcerative bacterial keratitis, but it is a non-negligible cause of visual loss. It is associated with systemic or infectious disease and requires early diagnosis and appropriate treatment to optimize visual prognosis and avoid other complications.