Architecture Based Workload Analysis of UAS Multi-Aircraft Control: Implications of Implementation on MQ-1B Predator

An increased demand for use of Unmanned Aircraft Systems (UASs) without commensurate increases in pilot manpower has prompted proposals for simultaneous control of multiple aircraft by a single pilot or Multi-Aircraft Control (MAC). To understand the potential effects of MAC, an IMPRINT Pro, Multi-Resource Theory, pilot workload model was developed from pedigreed system architecture. Feedback from active UAS pilots was used to validate the model and establish a workload saturation threshold value of 60, above which pilots may experience performance degradation over extended periods of time. The model predicts that pilots experience low workload when operating one or two UASs during benign operations, and operate 91% of the time below a workload of 25 without saturation. However, conflict from multi-task overlap builds rapidly when the pilot is required to operate three or more aircraft. The percentage of time over the saturation threshold increases to 21% with four aircraft under benign operating conditions. When dynamic events are introduced the workload becomes unmanageable, with estimates regularly over 100 due to multi-task overlap and communication activities. The analysis indicates the need for techniques and technology to reduce task and communications demands on UAS pilots to effectively implement MAC

Use of laser speckle contrast imaging to assess digital microvascular function in primary Raynaud phenomenon and systemic sclerosis:a comparison using the Raynaud condition score diary

Objective.Evaluate objective assessment of digital microvascular function using laser speckle contrast imaging (LSCI) in a cross-sectional study of patients with primary Raynaud phenomenon (RP) and systemic sclerosis (SSc), comparing LSCI with both infrared thermography (IRT) and subjective assessment using the Raynaud Condition Score (RCS) diary.Methods.Patients with SSc (n = 25) and primary RP (n = 18) underwent simultaneous assessment of digital perfusion using LSCI and IRT with a cold challenge on 2 occasions, 2 weeks apart. The RCS diary was completed between assessments. The relationship between objective and subjective assessments of RP was evaluated. Reproducibility of LSCI/IRT was assessed, along with differences between primary RP and SSc, and the effect of sex.Results.There was moderate-to-good correlation between LSCI and IRT (Spearman rho 0.58–0.84, p &lt; 0.01), but poor correlation between objective assessments and the RCS diary (p &gt; 0.05 for all analyses). Reproducibility of IRT and LSCI was moderate at baseline (ICC 0.51–0.63) and immediately following cold challenge (ICC 0.56–0.86), but lower during reperfusion (ICC 0.3–0.7). Neither subjective nor objective assessments differentiated between primary RP and SSc. Men reported lower median daily frequency of RP attacks (0.82 vs 1.93, p = 0.03). Perfusion using LSCI/IRT was higher in men for the majority of assessments.Conclusion.Objective and subjective methods provide differing information on microvascular function in RP. There is good convergent validity of LSCI with IRT and acceptable reproducibility of both modalities. Neither subjective nor objective assessments could differentiate between primary RP and SSc. Influence of sex on subjective and objective assessment of RP warrants further evaluation.</jats:sec

Aneurysms and pseudoaneurysms in dialysis access

Aneurysms are a common and often difficult complication seen with arteriovenous vascular access for haemodialysis. The purpose of this narrative review is to define and describe the scale of the problem and suggested therapeutic strategies. A narrative review of the published literature illustrated by individual cases is presented with the aim of summarising the relevant literature. The definitions of aneurysm are inconsistent throughout the literature and therefore systematic review is impossible. They vary from qualitative descriptions to quantitative definitions using absolute size, relative size and also size plus characteristics. The incidence and aetiology are also ill defined but separation into true aneurysms and false, or pseudoaneurysms may be helpful in planning treatment, which may be conservative, surgical or radiological. The lack of useful definitions and classification along with the multitude of management strategies proposed make firm evidence based conclusions difficult to draw. Further robust well designed studies are required to define best practice for this common problem

The microaerophilic microbiota of de-novo paediatric inflammatory bowel disease: the BISCUIT study

&lt;p&gt;Introduction: Children presenting for the first time with inflammatory bowel disease (IBD) offer a unique opportunity to study aetiological agents before the confounders of treatment. Microaerophilic bacteria can exploit the ecological niche of the intestinal epithelium; Helicobacter and Campylobacter are previously implicated in IBD pathogenesis. We set out to study these and other microaerophilic bacteria in de-novo paediatric IBD.&lt;/p&gt; &lt;p&gt;Patients and Methods: 100 children undergoing colonoscopy were recruited including 44 treatment naïve de-novo IBD patients and 42 with normal colons. Colonic biopsies were subjected to microaerophilic culture with Gram-negative isolates then identified by sequencing. Biopsies were also PCR screened for the specific microaerophilic bacterial groups: Helicobacteraceae, Campylobacteraceae and Sutterella wadsworthensis.&lt;/p&gt; &lt;p&gt;Results: 129 Gram-negative microaerophilic bacterial isolates were identified from 10 genera. The most frequently cultured was S. wadsworthensis (32 distinct isolates). Unusual Campylobacter were isolated from 8 subjects (including 3 C. concisus, 1 C. curvus, 1 C. lari, 1 C. rectus, 3 C. showae). No Helicobacter were cultured. When comparing IBD vs. normal colon control by PCR the prevalence figures were not significantly different (Helicobacter 11% vs. 12%, p = 1.00; Campylobacter 75% vs. 76%, p = 1.00; S. wadsworthensis 82% vs. 71%, p = 0.312).&lt;/p&gt; &lt;p&gt;Conclusions: This study offers a comprehensive overview of the microaerophilic microbiota of the paediatric colon including at IBD onset. Campylobacter appear to be surprisingly common, are not more strongly associated with IBD and can be isolated from around 8% of paediatric colonic biopsies. S. wadsworthensis appears to be a common commensal. Helicobacter species are relatively rare in the paediatric colon.&lt;/p&gt

Quinpramine Ameliorates Rat Experimental Autoimmune Neuritis and Redistributes MHC Class II Molecules

Activation of inflammatory cells is central to the pathogenesis of autoimmune demyelinating diseases of the peripheral nervous system. The novel chimeric compound quinpramine—generated from imipramine and quinacrine—redistributes cholesterol rich membrane domains to intracellular compartments. We studied the immunological and clinical effects of quinpramine in myelin homogenate induced Lewis rat experimental autoimmune neuritis (EAN), a model system for acute human inflammatory neuropathies, such as the Guillain-Barré syndrome. EAN animals develop paresis of all limbs due to autoimmune inflammation of peripheral nerves. Quinpramine treatment ameliorated clinical disease severity of EAN and infiltration of macrophages into peripheral nerves. It reduced expression of MHC class II molecules on antigen presenting cells and antigen specific T cell proliferation both in vitro and in vivo. Quinpramine exerted its anti-proliferatory effect on antigen presenting cells, but not on responder T cells. Our data suggest that quinpramine represents a candidate pharmaceutical for inflammatory neuropathies

Tubulin binding cofactor C (TBCC) suppresses tumor growth and enhances chemosensitivity in human breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Microtubules are considered major therapeutic targets in patients with breast cancer. In spite of their essential role in biological functions including cell motility, cell division and intracellular transport, microtubules have not yet been considered as critical actors influencing tumor cell aggressivity. To evaluate the impact of microtubule mass and dynamics on the phenotype and sensitivity of breast cancer cells, we have targeted tubulin binding cofactor C (TBCC), a crucial protein for the proper folding of α and β tubulins into polymerization-competent tubulin heterodimers.</p> <p>Methods</p> <p>We developed variants of human breast cancer cells with increased content of TBCC. Analysis of proliferation, cell cycle distribution and mitotic durations were assayed to investigate the influence of TBCC on the cell phenotype. <it>In vivo </it>growth of tumors was monitored in mice xenografted with breast cancer cells. The microtubule dynamics and the different fractions of tubulins were studied by time-lapse microscopy and lysate fractionation, respectively. <it>In vitro </it>sensitivity to antimicrotubule agents was studied by flow cytometry. <it>In vivo </it>chemosensitivity was assayed by treatment of mice implanted with tumor cells.</p> <p>Results</p> <p>TBCC overexpression influenced tubulin fraction distribution, with higher content of nonpolymerizable tubulins and lower content of polymerizable dimers and microtubules. Microtubule dynamicity was reduced in cells overexpressing TBCC. Cell cycle distribution was altered in cells containing larger amounts of TBCC with higher percentage of cells in G2-M phase and lower percentage in S-phase, along with slower passage into mitosis. While increased content of TBCC had little effect on cell proliferation <it>in vitro</it>, we observed a significant delay in tumor growth with respect to controls when TBCC overexpressing cells were implanted as xenografts <it>in vivo</it>. TBCC overexpressing variants displayed enhanced sensitivity to antimicrotubule agents both <it>in vitro </it>and in xenografts.</p> <p>Conclusion</p> <p>These results underline the essential role of fine tuned regulation of tubulin content in tumor cells and the major impact of dysregulation of tubulin dimer content on tumor cell phenotype and response to chemotherapy. A better understanding of how the microtubule cytoskeleton is dysregulated in cancer cells would greatly contribute to a better understanding of tumor cell biology and characterisation of resistant phenotypes.</p

Prognostic value of metabolic response in breast cancer patients receiving neoadjuvant chemotherapy

<p>Abstract</p> <p>Background</p> <p>Today's clinical diagnostic tools are insufficient for giving accurate prognosis to breast cancer patients. The aim of our study was to examine the tumor metabolic changes in patients with locally advanced breast cancer caused by neoadjuvant chemotherapy (NAC), relating these changes to clinical treatment response and long-term survival.</p> <p>Methods</p> <p>Patients (n = 89) participating in a randomized open-label multicenter study were allocated to receive either NAC as epirubicin or paclitaxel monotherapy. Biopsies were excised pre- and post-treatment, and analyzed by high resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS). The metabolite profiles were examined by paired and unpaired multivariate methods and findings of important metabolites were confirmed by spectral integration of the metabolite peaks.</p> <p>Results</p> <p>All patients had a significant metabolic response to NAC, and pre- and post-treatment spectra could be discriminated with 87.9%/68.9% classification accuracy by paired/unpaired partial least squares discriminant analysis (PLS-DA) (<it>p </it>< 0.001). Similar metabolic responses were observed for the two chemotherapeutic agents. The metabolic responses were related to patient outcome. Non-survivors (< 5 years) had increased tumor levels of lactate (<it>p </it>= 0.004) after treatment, while survivors (≥ 5 years) experienced a decrease in the levels of glycine (<it>p </it>= 0.047) and choline-containing compounds (<it>p </it>≤ 0.013) and an increase in glucose (<it>p </it>= 0.002) levels. The metabolic responses were not related to clinical treatment response.</p> <p>Conclusions</p> <p>The differences in tumor metabolic response to NAC were associated with breast cancer survival, but not to clinical response. Monitoring metabolic responses to NAC by HR MAS MRS may provide information about tumor biology related to individual prognosis.</p

Bioinformatic analyses identifies novel protein-coding pharmacogenomic markers associated with paclitaxel sensitivity in NCI60 cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Paclitaxel is a microtubule-stabilizing drug that has been commonly used in treating cancer. Due to genetic heterogeneity within patient populations, therapeutic response rates often vary. Here we used the NCI60 panel to identify SNPs associated with paclitaxel sensitivity. Using the panel's GI50 response data available from Developmental Therapeutics Program, cell lines were categorized as either sensitive or resistant. PLINK software was used to perform a genome-wide association analysis of the cellular response to paclitaxel with the panel's SNP-genotype data on the Affymetrix 125 k SNP array. FastSNP software helped predict each SNP's potential impact on their gene product. mRNA expression differences between sensitive and resistant cell lines was examined using data from BioGPS. Using Haploview software, we investigated for haplotypes that were more strongly associated with the cellular response to paclitaxel. Ingenuity Pathway Analysis software helped us understand how our identified genes may alter the cellular response to paclitaxel.</p> <p>Results</p> <p>43 SNPs were found significantly associated (FDR < 0.005) with paclitaxel response, with 10 belonging to protein-coding genes (<it>CFTR</it>, <it>ROBO1</it>, <it>PTPRD</it>, <it>BTBD12</it>, <it>DCT</it>, <it>SNTG1</it>, <it>SGCD</it>, <it>LPHN2</it>, <it>GRIK1</it>, <it>ZNF607</it>). SNPs in <it>GRIK1</it>, <it>DCT</it>, <it>SGCD </it>and <it>CFTR </it>were predicted to be intronic enhancers, altering gene expression, while SNPs in <it>ZNF607 </it>and <it>BTBD12 </it>cause conservative missense mutations. mRNA expression analysis supported these findings as <it>GRIK1</it>, <it>DCT</it>, <it>SNTG1</it>, <it>SGCD </it>and <it>CFTR </it>showed significantly (p < 0.05) increased expression among sensitive cell lines. Haplotypes found in <it>GRIK1, SGCD, ROBO1, LPHN2</it>, and <it>PTPRD </it>were more strongly associated with response than their individual SNPs.</p> <p>Conclusions</p> <p>Our study has taken advantage of available genotypic data and its integration with drug response data obtained from the NCI60 panel. We identified 10 SNPs located within protein-coding genes that were not previously shown to be associated with paclitaxel response. As only five genes showed differential mRNA expression, the remainder would not have been detected solely based on expression data. The identified haplotypes highlight the role of utilizing SNP combinations within genomic loci of interest to improve the risk determination associated with drug response. These genetic variants represent promising biomarkers for predicting paclitaxel response and may play a significant role in the cellular response to paclitaxel.</p