4,884 research outputs found

    Incidence of Benign Paroxysmal Positional Vertigo and Course of Treatment Following Mild Head Trauma-Is It Worth Looking For?

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    BACKGROUND: This study aimed to identify the incidence of benign paroxysmal positional vertigo following head trauma. METHODS: This study is a prospective cross-sectional study. Initially, a targeted search for the identification of patients with the international ­classification of diseases (ICD-10) diagnosis of cerebral commotio at relevant emergency units in the Northern Region of Denmark was done. This was followed by a clinical examination to determine the incidence of benign paroxysmal positional vertigo (BPPV) within this population. Of the 295 patients diagnosed with commotio cerebri during a 4-and-a-half month period, 85 patients were included. All patients underwent clinical examination in a mechanical repositional chair wearing Video Frenzel Goggles. Additional examinations included a complete video head impulse test. RESULTS: A total of six patients were identified with benign paroxysmal positional vertigo (BPPV) following minor head trauma. Bilateral BPPV, multicanal BPPV, and BPPV of a single semicircular canal were identified. All patients experienced relief of benign paroxysmal positional vertigo-related symptoms within 3 treatment sessions. Five patients were identified with a pathological video head impulse test, 54 with an inconclusive examination, and 15 with a normal video head impulse test. CONCLUSION: The incidence of benign paroxysmal positional vertigo following minor head trauma was 7%. A relatively high number of atypical subtypes of benign paroxysmal positional vertigo was found. When applying strict criteria for the interpretation of video head impulse test examination, the number of patients with inconclusive video head impulse test examination was higher than expected and 6.7% of patients had a pathological video head impulse test examination. No relationship between benign paroxysmal positional vertigo and pathological video head impulse test was observed

    Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis

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    Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer necessitates knowledge of the degree of genomic concordance between different steps of malignant progression as primary tumors often are used as surrogates of systemic disease. Based on exome sequencing we performed copy number profiling and point mutation detection on successive steps of breast cancer progression from one breast cancer patient, including two different regions of Ductal Carcinoma In Situ (DCIS), primary tumor and an asynchronous metastasis. We identify a remarkable landscape of somatic mutations, retained throughout breast cancer progression and with new mutational events emerging at each step. Our data, contrary to the proposed model of early dissemination of metastatic cells and parallel progression of primary tumors and metastases, provide evidence of linear progression of breast cancer with relatively late dissemination from the primary tumor. The genomic discordance between the different stages of tumor evolution in this patient emphasizes the importance of molecular profiling of metastatic tissue directing molecularly targeted therapy at recurrence

    A 1D microphysical cloud model for Earth, and Earth-like exoplanets. Liquid water and water ice clouds in the convective troposphere

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    One significant difference between the atmospheres of stars and exoplanets is the presence of condensed particles (clouds or hazes) in the atmosphere of the latter. The main goal of this paper is to develop a self-consistent microphysical cloud model for 1D atmospheric codes, which can reproduce some observed properties of Earth, such as the average albedo, surface temperature, and global energy budget. The cloud model is designed to be computationally efficient, simple to implement, and applicable for a wide range of atmospheric parameters for planets in the habitable zone. We use a 1D, cloud-free, radiative-convective, and photochemical equilibrium code originally developed by Kasting, Pavlov, Segura, and collaborators as basis for our cloudy atmosphere model. The cloud model is based on models used by the meteorology community for Earth's clouds. The free parameters of the model are the relative humidity and number density of condensation nuclei, and the precipitation efficiency. In a 1D model, the cloud coverage cannot be self-consistently determined, thus we treat it as a free parameter. We apply this model to Earth (aerosol number density 100 cm^-3, relative humidity 77 %, liquid cloud fraction 40 %, and ice cloud fraction 25 %) and find that a precipitation efficiency of 0.8 is needed to reproduce the albedo, average surface temperature and global energy budget of Earth. We perform simulations to determine how the albedo and the climate of a planet is influenced by the free parameters of the cloud model. We find that the planetary climate is most sensitive to changes in the liquid water cloud fraction and precipitation efficiency. The advantage of our cloud model is that the cloud height and the droplet sizes are self-consistently calculated, both of which influence the climate and albedo of exoplanets.Comment: To appear in Icaru

    Genomic Analyses of Breast Cancer Progression Reveal Distinct Routes of Metastasis Emergence

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    A main controversy in cancer research is whether metastatic abilities are present in the most advanced clone of the primary tumor or result from independently acquired aberrations in early disseminated cancer cells as suggested by the linear and the parallel progression models, respectively. The genetic concordance between different steps of malignant progression is mostly unexplored as very few studies have included cancer samples separated by both space and time. We applied whole exome sequencing and targeted deep sequencing to 26 successive samples from six patients with metastatic estrogen receptor (ER)-positive breast cancer. Our data provide support for both linear and parallel progression towards metastasis. We report for the first time evidence of metastasis-to-metastasis seeding in breast cancer. Our results point to three distinct routes of metastasis emergence. This may have profound clinical implications and provides substantial novel molecular insights into the timing and mutational evolution of breast cancer metastasis

    The NAME trial:a direct comparison of classical oral Navelbine versus metronomic Navelbine in metastatic breast cancer

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    Chemotherapy for metastatic breast cancer (MBC) is in general given in cycles of maximum tolerated doses to potentially maximize the therapeutic outcome. However, when compared with targeted therapies for MBC, conventional and dose intensified chemotherapy has caused only modest survival benefits during the recent decades, often compromising the quality of life considerably. Navelbine is an antineoplastic agent that has shown efficacy in the treatment of a variety of cancer types, including breast cancer. Early clinical trials involving both breast cancer and lung cancer patients suggest that metronomic dosing of Navelbine might be at least as effective as classical administration (once weekly, etc.). The NAME trial compares these two strategies of Navelbine administration in MBC patients

    The schizophrenia associated BRD1 gene regulates behavior, neurotransmission, and expression of schizophrenia risk enriched gene sets in mice

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    BackgroundThe schizophrenia-associated BRD1 gene encodes a transcriptional regulator whose comprehensive chromatin interactome is enriched with schizophrenia risk genes. However, the biology underlying the disease association of BRD1 remains speculative.MethodsThis study assessed the transcriptional drive of a schizophrenia-associated BRD1 risk variant in vitro. Accordingly, to examine the effects of reduced Brd1 expression, we generated a genetically modified Brd1+/- mouse and subjected it to behavioral, electrophysiological, molecular, and integrative genomic analyses with focus on schizophrenia-relevant parameters.ResultsBrd1+/- mice displayed cerebral histone H3K14 hypo-acetylation and a broad range of behavioral changes with translational relevance to schizophrenia. These behaviors were accompanied by striatal dopamine/serotonin abnormalities and cortical excitation-inhibition imbalances involving loss of parvalbumin immunoreactive interneurons. RNAseq analyses of cortical and striatal micropunches from Brd1+/- and wild-type mice revealed differential expression of genes enriched for schizophrenia risk including several schizophrenia GWAS risk genes (e.g. calcium channel subunits (Cacna1c and Cacnb2), cholinergic muscarinic receptor 4 (Chrm4), dopamine receptor D2 (Drd2), and transcription factor 4 (Tcf4)). Integrative analyses further found differentially expressed genes to cluster in functional networks and canonical pathways associated with mental illness and molecular signaling processes (e.g. glutamatergic, monaminergic, calcium, cAMP, DARPP-32, and CREB signaling).ConclusionsOur study bridges the gap between genetic association and pathogenic effects and yields novel insights into the unfolding molecular changes in the brain of a new schizophrenia model that incorporates genetic risk at three levels: allelic, chromatin interactomic, and brain transcriptomic

    Investigation of Ni/SiO2 catalysts prepared at different conditions for hydrogen production from ethanol steam reforming

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    Ni/SiO2 catalysts prepared by a sol–gel method have been investigated for hydrogen production via steam reforming of ethanol using a continuous flow, fixed bed reactor system. Chemical equilibrium calculations were also performed to determine the effects of temperature and molar steam to carbon ratio on hydrogen production. The acidity of the preparation solution (modified by nitric acid and ammonia) and calcination atmosphere (air and N2) were investigated in the preparation of the catalysts. BET surface area and porosity, temperature-programmed oxidation (TPO), X-ray diffraction (XRD), transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used to characterise the prepared catalysts. The BET surface area was reduced when the solution acidity was lowered during the sol–gel preparation process. A pH value less than 2.0 was necessary to achieve high metal dispersion in the catalyst. Smaller NiO particles were obtained when the catalyst was calcined in N2. Material balances on ethanol steam reforming at 600 °C using the prepared Ni/SiO2 catalysts were determined, and higher hydrogen production with lower coke deposition on the reacted catalysts were also obtained from the catalysts calcined in N2 atmosphere
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