219 research outputs found
Wetting and particle adsorption in nanoflows
Molecular dynamics simulations are used to study the behavior of
closely-fitting spherical and ellipsoidal particles moving through a
fluid-filled cylinder at nanometer scales. The particle, the cylinder wall and
the fluid solvent are all treated as atomic systems, and special attention is
given to the effects of varying the wetting properties of the fluid. Although
the modification of the solid-fluid interaction leads to significant changes in
the microstructure of the fluid, its transport properties are found to be the
same as in bulk. Independently of the shape and relative size of the particle,
we find two distinct regimes as a function of the degree of wetting, with a
sharp transition between them. In the case of a highly-wetting suspending
fluid, the particle moves through the cylinder with an average axial velocity
in agreement with that obtained from the solution of the continuum Stokes
equations. In contrast, in the case of less-wetting fluids, only the early-time
motion of the particle is consistent with continuum dynamics. At later times,
the particle is eventually adsorbed onto the wall and subsequently executes an
intermittent stick-slip motion.We show that van der Walls forces are the
dominant contribution to the particle adsorption phenomenon and that depletion
forces are weak enough to allow, in the highly-wetting situation, an initially
adsorbed particle to spontaneously desorb
Review of microdialysis in brain tumors, from concept to application: First Annual Carolyn Frye-Halloran Symposium
In individuals with brain tumors, pharmacodynamic and pharmacokinetic studies of therapeutic agents have historically used analyses of drug concentrations in serum or cerebrospinal fluid, which unfortunately do not necessarily reflect concentrations within the tumor and adjacent brain. This review article introduces to neurological and medical oncologists, as well as pharmacologists, the application of microdialysis in monitoring drug metabolism and delivery within the fluid of the interstitial space of brain tumor and its surroundings. Microdialysis samples soluble molecules from the extracellular fluid via a semipermeable membrane at the tip of a probe. In the past decade, it has been used predominantly in neurointensive care in the setting of brain trauma, vasospasm, epilepsy, and intracerebral hemorrhage. At the first Carolyn Frye-Halloran Symposium held at Massachusetts General Hospital in March 2002, the concept of microdialysis was extended to specifically address its possible use in treating brain tumor patients. In doing so we provide a rationale for the use of this technology by a National Cancer Institute consortium, New Approaches to Brain Tumor Therapy, to measure levels of drugs in brain tissue as part of phase 1 trials. Originally published Neuro-oncology, Vol. 6, No. 1, Jan 200
High temporal resolution delayed analysis of clinical microdialysate streams
We thank the Wellcome Trust DOH (HICF-0510-080), the
EPSRC (EP/H009744/1) (cycling experiments), and the Imperial
Confidence in Concept scheme, Ovarian Cancer Action UK
(ovarian tissue measurements), the National Science
Foundation (CHE-1608757), and the NIH (R01 MH104386) for
fundin
Surviving crack: a qualitative study of the strategies and tactics developed by Brazilian users to deal with the risks associated with the drug
<p>Abstract</p> <p>Background</p> <p>Due to marginalization, trafficking violence, conflicts with the police and organic and social psychological problems associated with the drug, crack is one of the most devastating drugs currently in use. However, there is evidence that some users manage to stay alive and active while using crack cocaine for many years, despite the numerous adversities and risks involved with this behavior. In this context, the aim of the present study was to identify the strategies and tactics developed by crack users to deal with the risks associated with the culture of use by examining the survival strategies employed by long-term users.</p> <p>Method</p> <p>A qualitative research method was used involving semi-structured, in-depth interviews. Twenty-eight crack users fulfilling a pre-defined enrollment criterion were interviewed. This criterion was defined as the long-term use of crack (i.e., at least four years). The sample was selected using information provided by key informants and distributed across eight different supply chains. The interviews were literally transcribed and analyzed via content analysis techniques using NVivo-8 software.</p> <p>Results</p> <p>There was diversity in the sample with regard to economic and education levels. The average duration of crack use was 11.5 years. Respondents believed that the greatest risks of crack dependence were related to the drug's psychological effects (e.g., cravings and transient paranoid symptoms) and those arising from its illegality (e.g., clashes with the police and trafficking). Protection strategies focused on the control of the psychological effects, primarily through the consumption of alcohol and marijuana. To address the illegality of the drug, strategies were developed to deal with dealers and the police; these strategies were considered crucial for survival.</p> <p>Conclusions</p> <p>The strategies developed by the respondents focused on trying to protect themselves. They proved generally effective, though they involved risks of triggering additional problems (e.g., other dependencies) in the long term.</p
PACT-UK (PAncreatic Cancer reporting Template-UK): A cross-specialty multi-institutional consensus panel development of a standardised radiological reporting proforma for pancreatic cancer
\ua9 Author(s) (or their employer(s)) 2023. Objective: Appropriate staging of pancreatic cancer is essential to ensure patients are offered all treatment options. This multispecialty national collaborative consensus project aimed to develop a succinct radiological reporting template, using the concept of structured reporting, to allow a more standardised means of reporting pancreatic cancer and ultimately optimise both patient care and research protocol design. Methods and analysis: In stage one, a core group of stakeholders (oncologists, radiologists and surgeons) identified the current landscape of radiological reporting, including a blinded radiological validation study and a national survey of consultant HPB surgeons. Stage two used consensus panel development methodology to generate a provisional template draft. Stage three involved trialling the template across all UK HPB units, with feedback assisting the development of a final version of the template. Results: Stage one results identified a core dataset to develop a provisional template. Every UK Hepatopancreatobiliary (HPB) unit trialled this in clinical practice, leading to further refinements via consensus meetings. Ideal factors regarding tumour staging, extent of vascular involvement and response to systemic anticancer therapy were identified. This resulted in the generation of the PACT-UK (PAncreatic Cancer reporting Template-UK) template that is presented within the manuscript, as well as a user guide. Conclusion: This project has successfully produced the first consensus-driven radiological reporting template for pancreatic cancer, with the aim of its use becoming standard practice in the UK, while upcoming workshops facilitated by Royal College of Radiologists/British Society of Gastrointestinal and Abdominal Radiology will establish buy-in from radiologists at all HPB units. Plans for the use of PACT-UK within national audit and clinical trials are underway
Intracellular Serotonin Modulates Insulin Secretion from Pancreatic β-Cells by Protein Serotonylation
Non-neuronal, peripheral serotonin deficiency causes diabetes mellitus and identifies an intracellular role for serotonin in the regulation of insulin secretion
Diagnostic accuracy for the extent and activity of newly diagnosed and relapsed Crohn’s disease: a multicentre prospective comparison of magnetic resonance enterography and small bowel ultrasound –The METRIC Trial
Background
Magnetic resonance enterography (MRE) and ultrasound (US) are used to image Crohn’s disease, but comparative accuracy for disease extent and activity is not known with certainty. We undertook a prospective multicentre cohort trial to address this
Methods
We recruited from 8 UK hospitals. Eligible patients were 16 years or older, newly diagnosed with Crohn’s disease, or had established disease with suspected relapse. Consecutive patients underwent MRE and US in addition to standard investigations. Discrepancy between MRE and US for small bowel (SB) disease presence triggered an additional investigation, if not already available. The primary outcome was difference in per patient sensitivity for SB disease extent (correct identification and segmental localisation) against a construct reference standard (panel diagnosis). Accuracy for SB and colonic disease presence and activity were secondary outcomes. The trial is completed (ISRCTN03982913).
Findings
284 patients completed the trial (133 new diagnosis, 151 relapse). MRE sensitivity (n=233) for SB disease extent (80% [95%CI 72 to 86]) and presence (97% [91 to 99]) were significantly greater than US (70% [62 to 78], 92% [84 to 96]); a 10% (1 to 18; p=0.027), and 5% (1 to 9), difference respectively. MRE specificity for SB disease extent (95% [85 to 98]) was significantly greater than US (81% [64 to 91]). Sensitivity for active SB disease was significantly greater for MRE than US (96% [92 to 99] vs. 90% [82 to 95]), difference 6% (2 to 11). Overall, there were no significant accuracy differences for colonic disease presence. Accuracy in newly diagnosed and relapse patients was similar, although US had significantly greater sensitivity for colonic disease than MRE in newly diagnosed patients (67% [49 to 81) vs. 47% [31 to 64]), difference 20% (1 to 39). There were no serious adverse events.
Interpretation
MRE has higher diagnostic accuracy for the extent and activity of SB Crohn’s disease than US when tested in a prospective multi centre cohort trial setting
Diagnostic accuracy of magnetic resonance enterography and small bowel ultrasound for the extent and activity of newly diagnosed and relapsed Crohn's disease (METRIC): a multicentre trial
Magnetic resonance enterography (MRE) and ultrasound are used to image Crohn's disease, but their comparative accuracy for assessing disease extent and activity is not known with certainty. Therefore, we did a multicentre trial to address this issue. We recruited patients from eight UK hospitals. Eligible patients were 16 years or older, with newly diagnosed Crohn's disease or with established disease and suspected relapse. Consecutive patients had MRE and ultrasound in addition to standard investigations. Discrepancy between MRE and ultrasound for the presence of small bowel disease triggered an additional investigation, if not already available. The primary outcome was difference in per-patient sensitivity for small bowel disease extent (correct identification and segmental localisation) against a construct reference standard (panel diagnosis). This trial is registered with the International Standard Randomised Controlled Trial, number ISRCTN03982913, and has been completed. 284 patients completed the trial (133 in the newly diagnosed group, 151 in the relapse group). Based on the reference standard, 233 (82%) patients had small bowel Crohn's disease. The sensitivity of MRE for small bowel disease extent (80% [95% CI 72-86]) and presence (97% [91-99]) were significantly greater than that of ultrasound (70% [62-78] for disease extent, 92% [84-96] for disease presence); a 10% (95% CI 1-18; p=0·027) difference for extent, and 5% (1-9; p=0·025) difference for presence. The specificity of MRE for small bowel disease extent (95% [85-98]) was significantly greater than that of ultrasound (81% [64-91]); a difference of 14% (1-27; p=0·039). The specificity for small bowel disease presence was 96% (95% CI 86-99) with MRE and 84% (65-94) with ultrasound (difference 12% [0-25]; p=0·054). There were no serious adverse events. Both MRE and ultrasound have high sensitivity for detecting small bowel disease presence and both are valid first-line investigations, and viable alternatives to ileocolonoscopy. However, in a national health service setting, MRE is generally the preferred radiological investigation when available because its sensitivity and specificity exceed ultrasound significantly. National Institute of Health and Research Health Technology Assessment. [Abstract copyright: Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.
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