891 research outputs found

    Economics in International Relations

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    The general topic for this morning is Economics in International Relations. This is another one of those impossible academic titles which includes a body of material deserving at least a lifetime of study

    Leukopenia Associated with Long-Term Colchicine Adminsitration

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    Purpose A case of leukopenia in a patient receiving colchicine for calcium pyrophosphate dihydrate deposition disease, or pseudogout, is reported. Summary An 85-year-old man experienced leukopenia likely due to colchicine. His medical history included chronic lymphocytic leukemia (CLL), pseudogout, osteoarthritis, and hypertension. In February 2011, his white blood cell (WBC) count was 2700 cells/μL, and his absolute neutrophil count (ANC) was 2200 cells/μL. Colchicine 0.6 mg orally daily was initiated in March for the prophylaxis of pseudogout. His WBC count decreased, and his colchicine dosage was reduced to 0.6 mg every other day. Despite this decreased dosage, his WBC count and ANC were 600 and 100 cells/μL, respectively, in September. In October, the patient received chemotherapy for presumed worsening of his CLL. One month later, his WBC count and ANC were 400 and 200 cells/μL, respectively. Subcutaneous filgrastim was administered, and colchicine was discontinued. At the end of November, he received another cycle of chemotherapy followed by pegfilgrastim. On the day of pegfilgrastim administration, the patient\u27s WBC count and ANC were 2000 and 1300 cells/μL, respectively. Two weeks later, his WBC count was 8800 cells/μL, and his ANC was 8300 cells/μL. Daily colchicine was restarted at the end of December. Two months later, his WBC count and ANC were 800 and 500 cells/μL, respectively. Given the symptomatic relief with colchicine, therapy was continued with close monitoring. Conclusion A patient with CLL developed leukopenia in association with colchicine administration for pseudogout

    Microwave-assisted synthesis and electrochemical evaluation of VO2 (B) nanostructures

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    Understanding how intercalation materials change during electrochemical operation is paramount to optimizing their behaviour and function and in situ characterization methods allow us to observe these changes without sample destruction. Here we first report the improved intercalation properties of bronze phase vanadium dioxide VO2 (B) prepared by a microwave-assisted route which exhibits a larger electrochemical capacity (232 mAh g-1) compared with VO2 (B) prepared by a solvothermal route (197 mAh g-1). These electrochemical differences have also been followed using in situ X-ray absorption spectroscopy allowing us to follow oxidation state changes as they occur during battery operation

    Raman Spectroscopy with 2D Perturbation Correlation Moving Windows for the Characterization of Heparin–Amyloid Interactions

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    It has been shown extensively that glycosaminoglycan (GAG)–protein interactions can induce, accelerate, and impede the clearance of amyloid fibrils associated with systemic and localized amyloidosis. Obtaining molecular details of these interactions is fundamental to our understanding of amyloid disease. Consequently, there is a need for analytical approaches that can identify protein conformational transitions and simultaneously characterize heparin interactions. By combining Raman spectroscopy with two-dimensional (2D) perturbation correlation moving window (2DPCMW) analysis, we have successfully identified changes in protein secondary structure during pH- and heparin-induced fibril formation of apolipoprotein A-I (apoA-I) associated with atherosclerosis. Furthermore, from the 2DPCMW, we have identified peak shifts and intensity variations in Raman peaks arising from different heparan sulfate moieties, indicating that protein–heparin interactions vary at different heparin concentrations. Raman spectroscopy thus reveals new mechanistic insights into the role of GAGs during amyloid fibril formation

    The Effect of Tropical Temperatures on the Quality of RNA Extracted from Stabilized Whole-Blood Samples

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    Whole-blood-derived transcriptional profiling is widely used in biomarker discovery, immunological research, and therapeutic development. Traditional molecular and high-throughput transcriptomic platforms, including molecular assays with quantitative PCR (qPCR) and RNAsequencing (RNA-seq), are dependent upon high-quality and intact RNA. However, collecting high-quality RNA from field studies in remote tropical locations can be challenging due to resource restrictions and logistics of post-collection processing. The current study tested the relative performance of the two most widely used whole-blood RNA collection systems, PAXgene® and Tempus™, in optimal laboratory conditions as well as suboptimal conditions in tropical field sites, including the effects of extended storage times and high storage temperatures. We found that Tempus™ tubes maintained a slightly higher RNA quantity and integrity relative to PAXgene® tubes at suboptimal tropical conditions. Both PAXgene® and Tempus™ tubes gave similar RNA purity (A260/A280). Additionally, Tempus™ tubes preferentially maintained the stability of mRNA transcripts for two reference genes tested, Succinate dehydrogenase complex, subunit A (SDHA) and TATA-box-binding protein (TBP), even when RNA quality decreased with storage length and temperature. Both tube types preserved the rRNA transcript 18S ribosomal RNA (18S) equally. Our results suggest that Tempus™ blood RNA collection tubes are preferable to PAXgene® for whole-blood collection in suboptimal tropical conditions for RNA-based studies in resource-limited settings

    Rapid Quantification of Molecular Diversity for Selective Database Acquisition

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    There is an increasing need to expand the structural diversity of the molecules investigated in lead-discovery programs. One way in which this can be achieved is by acquiring external datasets that will enhance an existing database. This paper describes a rapid procedure for the selection of external datasets using a measure of structural diversity that is calculated from sums of pairwise intermolecular structural similarities

    Соматоформная вегетативная дисфункция у лиц молодого возраста в свете современньїх представлений об этиопатогенезе, диагностике и методах восстановительного лечения

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    Guiding the self-assembly of materials by controlling the shape of the individual particle constituents is a powerful approach to material design. We show that colloidal silica superballs crystallize into canted phases in the presence of depletants. Some of these phases are consistent with the so-called "Λ1" lattice that was recently predicted as the densest packing of superdisks. As the size of the depletant is reduced, however, we observe a transition to a square phase. The differences in these entropically stabilized phases result from an interplay between the size of the depletants and the fine structure of the superball shape. We find qualitative agreement of our experimental results both with a phase diagram computed on the basis of the volume accessible to the depletants and with simulations. By using a mixture of depletants, one of which is thermosensitive, we induce solid-to-solid phase transitions between square and canted structures. The use of depletant size to leverage fine features of the shape of particles in driving their self-assembly demonstrates a general and powerful mechanism for engineering novel materials

    Applying phylogenomics to understand the emergence of Shiga Toxin producing Escherichia coli O157:H7 strains causing severe human disease in the United Kingdom

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    Shiga Toxin producing Escherichia coli (STEC) O157:H7 is a recently emerged zoonotic pathogen with considerable morbidity. Since the serotype emerged in the 1980s, research has focussed on unravelling the evolutionary events from the E. coli O55:H7 ancestor to the contemporaneous globally dispersed strains. In this study the genomes of over 1000 isolates from human clinical cases and cattle, spanning the history of STEC O157:H7 in the United Kingdom were sequenced. Phylogenetic analysis reveals the ancestry, key acquisition events and global context of the strains. Dated phylogenies estimate the time to the most recent common ancestor of the current circulating global clone to 175 years ago, followed by rapid diversification. We show the acquisition of specific virulence determinates occurred relatively recently and coincides with its recent detection in the human population. Using clinical outcome data from 493 cases of STEC O157:H7 we assess the relative risk of severe disease including HUS from each of the defined clades in the population and show the dramatic effect Shiga toxin complement has on virulence. We describe two strain replacement events that have occurred in the cattle population in the UK over the last 30 years; one resulting in a highly virulent strain that has accounted for the majority of clinical cases in the UK over the last decade. This work highlights the need to understand the selection pressures maintaining Shiga-toxin encoding bacteriophages in the ruminant reservoir and the study affirms the requirement for close surveillance of this pathogen in both ruminant and human populations

    Combining random forest and 2D correlation analysis to identify serum spectral signatures for neuro-oncology

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    Fourier transform infrared (FTIR) spectroscopy has long been established as an analytical tech- nique for the measurement of vibrational modes of molecular systems. More recently, FTIR has been used for the analysis of biofluids with the aim of becoming a tool to aid diagnosis. For the clinician, this represents a convenient, fast, non-subjective option for the study of biofluids and the diagnosis of disease states. The patient also benefits from this method, as the procedure for the collection of serum is much less invasive and stressful than traditional biopsy. This is especially true of patients in whom brain cancer is suspected. A brain biopsy carries a degree of morbidity and mortality and on occasion may even be inconclusive. We therefore present a method for the diagnosis of brain cancer from serum samples using FTIR and machine learning techniques. The scope of the study involved 433 patients from whom were collected 9 spectra each in the range 600-4000 cm−1. To begin development of the novel method, various pre-processing steps were investigated and ranked in terms of final accuracy of the diagnosis. Random Forest machine learning was utilised as a classifier to separate patients into cancer or non-cancer categories based upon the intensities of wavenumbers present in their spectra. Generalised 2D correlational analysis was then employed to further augment the machine learning, and also to establish spec- tral features important for the distinction between cancer and non-cancer serum samples. Using these methods, sensitivities of up to 92.8% and specificities of up to 91.5% were possible. Fur- thermore, ratiometrics were also investigated in order to establish any correlations present in the dataset. We show a rapid, computationally light, accurate, statistically robust methodology for the identification of spectral features present in differing disease states. With current advances in IR technology, such as the development of rapid discrete frequency collection, this approach is import to allow future clinical translation and enables IR to achieve its potential
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