358 research outputs found
The nuclear membrane in multidrug resistance: microinjection of epirubicin into bladder cancer cell lines
No full textObjevtive: to assess whether microinjecting epirubicin into cells showing multidrug resistance (MDR, common to many cancers, including bladder cancer, with resistance to, e.g. anthracyclines and mitomycin C) spares the nucleus, as when these drugs accumulate, distribution in MDR cells characteristically spares the nucleus, suggesting that the nuclear membrane is responsible for excluding cytotoxic drugs from MDR nuclei.Materials and methods: nuclear exclusion of drugs is an important feature of resistance in MDR cells, as many MDR-susceptible drugs have cytotoxic actions within the nucleus. Drug accumulation in 'classical' P-glycoprotein-mediated MDR cells is greatly reduced by efflux. Microinjection of epirubicin into the cytoplasm of MDR cells bypasses the P-glycoprotein efflux pump on the plasma membrane. Nuclear sparing would directly implicate the nuclear membrane in this phenomenon. Because of their fluorescence properties, which allow study by confocal microscopy and flow cytometry, anthracyclines have also been used extensively to investigate MDR. Thus sensitive (MGH-U1 and RT112) and MDR (MGH-U1R and MGH-U1-MMC) bladder cancer cell lines were used. Adherent cells from each cell line were individually microinjected with epirubicin (0.5 mg/mL) and a 77 kDa fluorescein isothiocyanate (FITC)-dextran (0.5 mg/mL). The pattern of nuclear epirubicin uptake in injected cells was then evaluated by confocal microscopy. The 77 kDa FITC-dextran allowed easier identification of injected cells and was also excluded from their nuclei.Results: sensitive bladder cancer cell lines all showed a nuclear accumulation pattern of epirubicin, consistent with their normal uptake after exposure to epirubicin. The MDR cell lines showed the characteristic nuclear-sparing pattern of epirubicin uptake, similar to the normal uptake pattern after epirubicin exposure. The 77 kDa FITC-dextran showed clearly which cells had been microinjected, and was excluded from the nuclei of all injected cells. Cell viability was confirmed by acridine-orange staining after initial visualization of injected cells.Conclusion: the nuclear membrane is responsible for the nuclear exclusion of epirubicin in MDR cells. Further work is necessary to determine the mechanisms involved
THE AI REVOLUTION: TRANSFORMING INDUSTRIES AND SOCIETY
No full text<p>Author: Vinit Parmar </p><p>Designation: Founder and CEO of The Flyhyer </p><p>Affiliation: The Flyhyer </p><p>Contact Number: 9099972157 </p><p>Email Address: [email protected] </p><p>Address: At Post Bhalod, New Vashahat Parmar Faliya, House No. 1171 District: Bharuch Taluka: Jhaghadia</p>
A statistical framework for quantifying clinical equipoise for individual cases during randomized controlled surgical trials
No full textBackground
Randomised controlled trials are being increasingly used to evaluate new surgical interventions. There are a number of problematic methodological issues specific to surgical trials, the most important being identifying whether patients are eligible for recruitment into the trial. This is in part due to the diversity in practice patterns across institutions and the enormous range of available interventions that often leads to a low level of agreement between clinicians about both the value and the appropriate choice of intervention. We argue that a clinician should offer patients the option of recruitment into a trial, even if the clinician is not individually in a position of equipoise, if there is collective (clinical) equipoise amongst the wider clinical community about the effectiveness of a proposed intervention (the clinical equipoise principle). We show how this process can work using data collected from an ongoing trial of a surgical intervention.
Results
We describe a statistical framework for the assessment of uncertainty prior to patient recruitment to a clinical trial using a panel of expert clinical assessors and techniques for eliciting, pooling and modelling of expert opinions. The methodology is illustrated using example data from the UK Heel Fracture Trial. The statistical modelling provided results that were clear and simple to present to clinicians and showed how decisions regarding recruitment were influenced by both the collective opinion of the expert panel and the type of decision rule selected.
Conclusions
The statistical framework presented has potential to identify eligible patients and assist in the simplification of eligibility criteria which might encourage greater participation in clinical trials evaluating surgical interventions
Design issues and extensions of multi-arm multi-stage clinical trials
No full textThe increasing cost of randomised controlled trials is hindering the rate at which new, effective therapies reach patients. To accelerate drug development, more efficient clinical trial designs are needed. One such design which has had success in speeding up the evaluation of therapies in cancer is the multi-arm multi-stage (MAMS) design. This particular design compares multiple new treatments against a control in a single trial, obviating the need for multiple two-arm studies, and ceases recruitment to poorly performing arms during the study. To further increase efficiency, interim assessments can be based on an intermediate outcome which is on the causal pathway to the primary outcome of the trial, thus allowing phases 2 and 3 of evaluation to be incorporated into a single, seamless design. The MAMS design was initially developed for trials in cancer where time to event outcomes are commonly used. To make it more widely applicable to other disease areas, we first extend the design to other types of outcome measure such as binary. The new designs are then applied to trials in tuberculosis --- a disease area with many new treatments currently in the clinical pipeline and which may therefore benefit from using more efficient trial designs. We then consider more general design issues such as familywise error rate and expected sample size and present calculations of both measures using simulation. Methods are developed for finding designs which have the desired overall operating characteristics and which are the most efficient under particular optimality criteria, known as admissible designs. Guidance is provided for choosing the number of stages and allocation ratio for a particular number of arms and we apply the methods developed in the thesis to existing and hypothetical MAMS trials. Throughout, Stata programs are created and updated to accommodate the use of the methods in practice
Contact lens-based expansion and transplantation of autologous epithelial progenitors for ocular surface reconstruction: Crossover control
No full text[No abstract available]Di Girolamo N, 2009, TRANSPLANTATION, V87, P1571, DOI 10.1097-TP.0b013e3181a4bbf2; Ozbek Z, 2006, CORNEA, V25, P245, DOI 10.1097-01.ico.0000176602.49258.ea; Parmar DN, 2006, AM J OPHTHALMOL, V141, P299, DOI 10.1016-j.ajo.2005.09.0080
Workflow Driven Decision Support Systems: A case of an intra-operative visualization system for surgeons
No full textInadequate visualization during Minimally Invasive Surgeries (MIS) has led several technology research labs to develop decision support systems such as Intra-operative Visualization Systems (IVS). IVS focuses on providing surgeons with real-time imaging support to improve task visualization and navigation. Though exciting, this emerging field also presents challenges in terms of design, development, implementation and integration of various technologies in the surgical workplace. While developing a technically robust IVS which integrates various imaging sources may help visualizing the patient data, it may not serve its true purpose: to adequately support surgeons in making the right decisions. Development of IVS should therefore be not just “technology intensive”; but “Knowledge Intensive Visualization System (KIVS)”. This means that these systems should aim to provide the knowledge to make informed decisions by providing the surgeon with the necessary patient information. This thesis is an example of the role design as a discipline can play in guiding the user-centered technological innovation in the area of medical informatics, especially in the case where the development depends on creating collaborative design between different scientific disciplines: surgical, technological (medical informatics) and design. Visualization of the patient information which supports surgical decision making in KIVS is dependent on knowledge of surgical workflow- which means knowledge of how surgeons solve problems and make decisions while performing the procedure. Surgical workflow depends on a dynamic information flow between the system, the surgeon, the patient, and the surgical team. Surgical workflow is also linked in time over the three surgical phases: pre-operative (before surgery), intra-operative (during surgery), and post-operative (post surgery). This thesis focuses on answering the following research questions: (a) What are the constituents or task boundaries of the surgical workspace that influence the surgical workflow or the surgical problem-solving process? (b) How can the knowledge of the surgical workflow be incorporated into the design of KIVS so as to improve decision-making and thus the performance of the surgeons?(c) In a multidisciplinary development team of surgeons, technology engineers and designers, what steps are required in the KIVS development process to facilitate collaborative design? Based on empirical studies with surgeons, this thesis proposed a design framework called “Workflow-centered design framework”. This framework assists in analyzing the surgical workflow which eventually leads to the development of the knowledge repository of surgical procedure, information and design requirements for the KIVS. This framework has been applied to support workflow driven development of two KIVS prototypes taking a case of upcoming MIS to treat cancer in liver called Radio frequency Ablation (RFA). These prototypes have been developed involving real-time image fusion between imaging modalities such as intra-operative Ultrasound (US) and pre-operative Computerized Tomography (CT) scan. The results from the evaluative study showed significant improvements in the performance of expert intervention radiologists and medical students while performing RFA using KIVS compared to US. In particular, intra-operative planning time and task accuracy of hitting the right tumor in the center showed significant improvement. The findings demonstrated the importance of workflow driven patient data visualization in improving surgical decision making. The framework proposed in this thesis serves as a means to generate the scientific knowledge required to drive user-centered development of KIVS. The contribution of this thesis is at three levels: - The framework proposed in this thesis contributes to design and ergonomics literature as a practical example of application of user centered design to drive innovative technological development of KIVS for complex workspaces such as the surgical theatre. - It contributes to the medical informatics by integrating cognitive theories as a foundation which guides the development of KIVS. - The KIVS prototype serves as a development aid to guide future technological innovation in the area of intra-operative visualization system for RFA and for MIS in general.Product Innovation ManagementIndustrial Design Engineerin
Highlights of Library Automation related documents in the INSPEC
No full textThe paper has attempted to analyse the Library Automation related records in the INSPEC (1969 to July 2004). The growth of Library Automation related literature, country of input, scattering of literature in different publication types, core journals publishing Library Automation related publications, language-wise proportion of the literature, content analysis through keywords/descriptors, availability of URLs (Universal Resource Locator) for full text articles as alternative locations were the main focus of the study. After the year 1984, the literature grows approximately linearly with a growth rate of about 600 items per year. The USA is the predominant publishing country of Library Automation related literature. Journals are the most preferred publication media, followed by Conference/Proceedings-Papers, Book-Chapters, and Reports publications. Most productive journals are: Library Hi Tech, followed by Computers in Libraries, VINE, Information Technology and Libraries, and Program. English articles constitute 91.83% of the total literature. That means the non-English articles constitute only 8.17%. The keyword analysis indicates that the key areas of Library Automation were cataloguing; academic-libraries; information-retrieval; Internet; and information-services. The most occurred URL was http://www.dlib.org/ as alternative locations in the availability notes of Library Automation related records
A simulation study comparing the power of nine tests of the treatment effect in randomized controlled trials with a time-to-event outcome
No full textBackground: The logrank test is routinely applied to design and analyse randomized controlled trials (RCTs) with time-to-event outcomes. Sample size and power calculations assume the treatment effect follows proportional hazards (PH). If the PH assumption is false, power is reduced and interpretation of the hazard ratio (HR) as the estimated treatment effect is compromised. Using statistical simulation, we investigated the type 1 error and power of the logrank (LR)test and eight alternatives. We aimed to identify test(s) that improve power with three types of non-proportional hazards (non-PH): early, late or near-PH treatment effects. /
Methods: We investigated weighted logrank tests (early, LRE; late, LRL), the supremum logrank test (SupLR) and composite tests (joint, J; combined, C; weighted combined, WC; versatile and modified versatile weighted logrank, VWLR, VWLR2) with two or more components. Weighted logrank tests are intended to be sensitive to particular non-PH patterns. Composite tests attempt to improve power across a wider range of non-PH patterns. Using extensive simulations based on real trials, we studied test size and power under PH and under simple departures from PH comprising pointwise constant HRs with a single change point at various follow-up times. We systematically investigated the influence of high or low control-arm event rates on power. /
Results: With no preconceived type of treatment effect, the preferred test is VWLR2. Expecting an early effect, tests with acceptable power are SupLR, C, VWLR2, J, LRE and WC. Expecting a late effect, acceptable tests are LRL, VWLR, VWLR2, WC and J. Under near-PH, acceptable tests are LR, LRE, VWLR, C, VWLR2 and SupLR. Type 1 error was well controlled for all tests, showing only minor deviations from the nominal 5%. The location of the HR change point relative to the cumulative proportion of control-arm events considerably affected power. /
Conclusions: Assuming ignorance of the likely treatment effect, the best choice is VWLR2. Several non-standard tests performed well when the correct type of treatment effect was assumed. A low control-arm event rate reduced the power of weighted logrank tests targeting early effects. Test size was generally well controlled. Further investigation of test characteristics with different types of non-proportional hazards of the treatment effect is warranted
Fitness-AQA Dataset
No full textLargest Fine-grained Exercise Action Quality Assessment Dataset.
Dataset available from the following webpage: https://github.com/ParitoshParmar/Fitness-AQA.
If you find our work useful, please consider citing our ECCV 2022 conference paper that can be found at:
https://link.springer.com/chapter/10.1007/978-3-031-19839-7_7
or
https://arxiv.org/abs/2202.14019
Bibtex file:
@article{parmar2022domain,
title={Domain Knowledge-Informed Self-Supervised Representations for Workout Form Assessment},
author={Parmar, Paritosh and Gharat, Amol and Rhodin, Helge},
journal={arXiv preprint arXiv:2202.14019},
year={2022}
}Only available for non-commercial purposes. Users agree to terms and conditions of usage
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