86 research outputs found
Anterior prostatic tumours are difficult to diagnose without MRI
It is often uncertain whether a repeat biopsy is necessary in patients with at least one previous negative prostate biopsy but persistent suspicion of prostate cancer. Here we present the use of multi-parametric magnetic resonance imaging (mp-MRI) to successfully detect and localize a prostate cancer and we suggest that MRI can be useful in optimising repeat biopsy procedures of the prostate in patients with clinically significant carcinoma
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The Green's function model intercomparison project (GFMIP) protocol
The atmospheric Green's function method is a technique for modeling the response of the atmosphere to changes in the spatial field of surface temperature. While early studies applied this method to changes in atmospheric circulation, it has also become an important tool to understand changes in radiative feedbacks due to evolving patterns of warming, a phenomenon called the âpattern effect.â To better study this method, this paper presents a protocol for creating atmospheric Green's functions to serve as the basis for a model intercomparison project, GFMIP. The protocol has been developed using a series of sensitivity tests performed with the HadAM3 atmosphereâonly general circulation model, along with existing and new simulations from other models. Our preliminary results have uncovered nonlinearities in the response of the atmosphere to surface temperature changes, including an asymmetrical response to warming versus cooling patch perturbations, and a change in the dependence of the response on the magnitude and size of the patches. These nonlinearities suggest that the pattern effect may depend on the heterogeneity of warming as well as its location. These experiments have also revealed tradeoffs in experimental design between patch size, perturbation strength, and the length of control and patch simulations. The protocol chosen on the basis of these experiments balances scientific utility with the simulation time and setup required by the Green's function approach. Running these simulations will further our understanding of many aspects of atmospheric response, from the pattern effect and radiative feedbacks to changes in circulation, cloudiness, and precipitation
The significance of accumulated oropharyngeal secretions and swallowing frequency in predicting aspiration
This study retrospectively investigated the value of both endoscopically visible oropharyngeal secretions in the hypopharynx and swallowing frequency in the prediction of aspiration of food and liquid. Fiberoptic endoscopic evaluation of swallowing (FEES) was performed on a total of 69 individuals that included hospitalized elderly, nonhospitalized elderly, and young normal subjects. A four-level rating scale for determining the severity of accumulated orpharyngeal secretions was developed and employed to rate subjects prior to the presentation of food or liquid during the FEES. Spontaneous dry swallows were also counted during the observation period of the FEES. It was found that the accumulation of endoscopically visible oropharyngeal secretions located within the laryngeal vestibule was highly predictive of aspiration of food or liquid. There were significantly fewer spontaneous swallows in hospitalized subjects when compared with nonhospitalized subjects. There was also a significant decrease in the frequency of spontaneous swallows in aspirating hospitalized subjects when compared with nonaspirating hospitalized subjects. Results are discussed in terms of integrating this information with clinical bedside examination techniques.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41360/1/455_2004_Article_BF00417898.pd
Insulin and IGF1 signalling pathways in human astrocytes <i>in vitro</i> and <i>in vivo</i>; characterisation, subcellular localisation and modulation of the receptors.
Background
The insulin/IGF1 signalling (IIS) pathways are involved in longevity regulation and are dysregulated in neurons in Alzheimerâs disease (AD). We previously showed downregulation in IIS gene expression in astrocytes with AD-neuropathology progression, but IIS in astrocytes remains poorly understood. We therefore examined the IIS pathway in human astrocytes and developed models to reduce IIS at the level of the insulin or the IGF1 receptor (IGF1R).
Results
We determined IIS was present and functional in human astrocytes by immunoblotting and showed astrocytes express the insulin receptor (IR)-B isoform of Ir. Immunocytochemistry and cell fractionation followed by western blotting revealed the phosphorylation status of insulin receptor substrate (IRS1) affects its subcellular localisation. To validate IRS1 expression patterns observed in culture, expression of key pathway components was assessed on post-mortem AD and control tissue using immunohistochemistry. Insulin signalling was impaired in cultured astrocytes by treatment with insulinâ+âfructose and resulted in decreased IR and Akt phosphorylation (pAkt S473). A monoclonal antibody against IGF1R (MAB391) induced degradation of IGF1R receptor with an associated decrease in downstream pAkt S473. Neither treatment affected cell growth or viability as measured by MTT and CyquantÂź assays or GFAP immunoreactivity.
Discussion
IIS is functional in astrocytes. IR-B is expressed in astrocytes which differs from the pattern in neurons, and may be important in differential susceptibility of astrocytes and neurons to insulin resistance. The variable presence of IRS1 in the nucleus, dependent on phosphorylation pattern, suggests the function of signalling molecules is not confined to cytoplasmic cascades. Down-regulation of IR and IGF1R, achieved by insulinâ+âfructose and monoclonal antibody treatments, results in decreased downstream signalling, though the lack of effect on viability suggests that astrocytes can compensate for changes in single pathways. Changes in signalling in astrocytes, as well as in neurons, may be important in ageing and neurodegeneration
Expanded repertoire of RASGRP2 variants responsible for platelet dysfunction and severe bleeding.
Heritable platelet function disorders (PFDs) are genetically heterogeneous and poorly characterized. Pathogenic variants in RASGRP2, which encodes calcium and diacylglycerol-regulated guanine exchange factor I (CalDAG-GEFI), have been reported previously in 3 pedigrees with bleeding and reduced platelet aggregation responses. To better define the phenotype associated with pathogenic RASGRP2 variants, we compared high-throughput sequencing and phenotype data from 2042 cases in pedigrees with unexplained bleeding or platelet disorders to data from 5422 controls. Eleven cases harbored 11 different, previously unreported RASGRP2 variants that were biallelic and likely pathogenic. The variants included 5 high-impact variants predicted to prevent CalDAG-GEFI expression and 6 missense variants affecting the CalDAG-GEFI CDC25 domain, which mediates Rap1 activation during platelet inside-out αIIbÎČ3 signaling. Cases with biallelic RASGRP2 variants had abnormal mucocutaneous, surgical, and dental bleeding from childhood, requiring â„1 blood or platelet transfusion in 78% of cases. Platelets displayed reduced aggregation in response to adenosine 5'-diphosphate and epinephrine, but variable aggregation defects with other agonists. There were no other consistent clinical or laboratory features. These data enable definition of human CalDAG-GEFI deficiency as a nonsyndromic, recessive PFD associated with a moderate or severe bleeding phenotype and complex defects in platelet aggregation
A plasmid DNA-launched SARS-CoV-2 reverse genetics system and coronavirus toolkit for COVID-19 research
The recent emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the underlying cause of Coronavirus Disease 2019 (COVID-19), has led to a worldwide pandemic causing substantial morbidity, mortality, and economic devastation. In response, many laboratories have redirected attention to SARS-CoV-2, meaning there is an urgent need for tools that can be used in laboratories unaccustomed to working with coronaviruses. Here we report a range of tools for SARS-CoV-2 research. First, we describe a facile single plasmid SARS-CoV-2 reverse genetics system that is simple to genetically manipulate and can be used to rescue infectious virus through transient transfection (without in vitro transcription or additional expression plasmids). The rescue system is accompanied by our panel of SARS-CoV-2 antibodies (against nearly every viral protein), SARS-CoV-2 clinical isolates, and SARS-CoV-2 permissive cell lines, which are all openly available to the scientific community. Using these tools, we demonstrate here that the controversial ORF10 protein is expressed in infected cells. Furthermore, we show that the promising repurposed antiviral activity of apilimod is dependent on TMPRSS2 expression. Altogether, our SARS-CoV-2 toolkit, which can be directly accessed via our website at https://mrcppu-covid.bio/, constitutes a resource with considerable potential to advance COVID-19 vaccine design, drug testing, and discovery science
Nitazoxanide Stimulates Autophagy and Inhibits mTORC1 Signaling and Intracellular Proliferation of Mycobacterium tuberculosis
Tuberculosis, caused by Mycobacterium tuberculosis infection, is a major cause of morbidity and mortality in the world today. M. tuberculosis hijacks the phagosome-lysosome trafficking pathway to escape clearance from infected macrophages. There is increasing evidence that manipulation of autophagy, a regulated catabolic trafficking pathway, can enhance killing of M. tuberculosis. Therefore, pharmacological agents that induce autophagy could be important in combating tuberculosis. We report that the antiprotozoal drug nitazoxanide and its active metabolite tizoxanide strongly stimulate autophagy and inhibit signaling by mTORC1, a major negative regulator of autophagy. Analysis of 16 nitazoxanide analogues reveals similar strict structural requirements for activity in autophagosome induction, EGFP-LC3 processing and mTORC1 inhibition. Nitazoxanide can inhibit M. tuberculosis proliferation in vitro. Here we show that it inhibits M. tuberculosis proliferation more potently in infected human THP-1 cells and peripheral monocytes. We identify the human quinone oxidoreductase NQO1 as a nitazoxanide target and propose, based on experiments with cells expressing NQO1 or not, that NQO1 inhibition is partly responsible for mTORC1 inhibition and enhanced autophagy. The dual action of nitazoxanide on both the bacterium and the host cell response to infection may lead to improved tuberculosis treatment
Proceedings of the International Cancer Imaging Society (ICIS) 16th Annual Teaching Course
Table of contents
O1 Tumour heterogeneity: what does it mean?
Dow-Mu Koh
O2 Skeletal sequelae in adult survivors of childhood cancer
Sue Creviston Kaste
O3 Locoregional effects of breast cancer treatment
Sarah J Vinnicombe
O4 Imaging of cancer therapy-induced CNS toxicity
Giovanni Morana, Andrea Rossi
O5 Screening for lung cancer
Christian J. Herold
O6Risk stratification of lung nodules
Theresa C. McLoud
O7 PET imaging of pulmonary nodules
Kirk A Frey
O8 Transarterial tumour therapy
Bernhard Gebauer
O9 Interventional radiology in paediatric oncology
Derek Roebuck
O10 Image guided prostate interventions
Jurgen J. FĂŒtterer
O11 Imaging cancer predisposition syndromes
Alexander J. Towbin
O12Chest and chest wall masses
Thierry AG Huisman
O13 Abdominal masses: good or bad?
Anne MJB Smets
O14 Hepatobiliary MR contrast: enhanced liver MRI for HCC diagnosis and management
Giovanni Morana
O15 Role of US elastography and multimodality fusion for managing patients with chronic liver disease and HCC
Jeong Min Lee
O16 Opportunities and challenges in imaging metastatic disease
Hersh Chandarana
O17 Diagnosis, treatment monitoring, and follow-up of lymphoma
Marius E. Mayerhoefer, Markus Raderer, Alexander Haug
O18 Managing high-risk and advanced prostate cancer
Matthias Eiber
O19 Immunotherapy: imaging challenges
Bernhard Gebauer
O20 RECIST and RECIST 1.1
Andrea Rockall
O21 Challenges of RECIST in oncology imaging basics for the trainee and novice
Aslam Sohaib
O22 Lymphoma: PET for interim and end of treatment response assessment: a usersâ guide to the Deauville Score
Victoria S Warbey
O23 Available resources
Hebert Alberto Vargas
O24 ICIS e-portal and the online learning community
Dow-Mu Koh
O25 Benign lesions that mimic pancreatic cancer
Jay P Heiken
O26 Staging and reporting pancreatic malignancies
Isaac R Francis, Mahmoud, M Al-Hawary, Ravi K Kaza
O27 Intraductal papillary mucinous neoplasm
Giovanni Morana
O28 Cystic pancreatic tumours
Mirko DâOnofrio
O29 Diffusion-weighted imaging of head and neck tumours
Harriet C. Thoeny
O30 Radiation injury in the head and neck
Ann D King
O31 PET/MR of paediatric brain tumours
Giovanni Morana, Arnoldo Piccardo, Maria Luisa GarrĂš, Andrea Rossi
O32 Structured reporting and beyond
Hebert Alberto Vargas
O33 Massachusetts General Hospital experience with structured reporting
Theresa C. McLoud
O34 The oncologistâs perspective: what the oncologist needs to know
Nick Reed
O35 Towards the cure of all children with cancer: global initiatives in pediatric oncology
Carlos Rodriguez-Galindo
O36 Multiparametric imaging of renal cancers
Hersh Chandarana
O37 Linking imaging features of renal disease and their impact on management strategies
Hebert Alberto Vargas
O38 Adrenals, retroperitoneum and peritoneum
Isaac R Francis, Ashish P Wasnik
O39 Lung and pleura
Stefan Diederich
O40 Advances in MRI
Jurgen J. FĂŒtterer
O41 Advances in molecular imaging
Wim J.G. Oyen
O42 Incorporating advanced imaging, impact on treatment selection and patient outcome
Cheng Lee Chaw, Nicholas van As
S1 Combining ADC-histogram features improves performance of MR diffusion-weighted imaging for Lymph node characterisation in cervical cancer
Igor Vieira, Frederik De Keyzer, Elleke Dresen, Sileny Han, Ignace Vergote, Philippe Moerman, Frederic Amant, Michel Koole, Vincent Vandecaveye
S2 Whole-body diffusion-weighted MRI for surgical planning in patients with colorectal cancer and peritoneal metastases
R Dresen, S De Vuysere, F De Keyzer, E Van Cutsem, A DâHoore, A Wolthuis, V Vandecaveye
S3 Role of apparent diffusion coefficient (ADC) diffusion-weighted MRI for predicting extra capsular extension of prostate cancer.
P. Pricolo ([email protected]), S. Alessi, P. Summers, E. Tagliabue, G. Petralia
S4 Generating evidence for clinical benefit of PET/CT â are management studies sufficient as surrogate for patient outcome?
C. Pfannenberg, B. GĂŒckel, SC SchĂŒle, AC MĂŒller, S. Kaufmann, N. Schwenzer, M. Reimold,C. la Fougere, K. Nikolaou, P. Martus
S5 Heterogeneity of treatment response in skeletal metastases from breast cancer with 18F-fluoride and 18F-FDG PET
GJ Cook, GK Azad, BP Taylor, M Siddique, J John, J Mansi, M Harries, V Goh
S6 Accuracy of suspicious breast imagingâcan we tell the patient?
S Seth, R Burgul, A Seth
S7 Measurement method of tumour volume changes during neoadjuvant chemotherapy affects ability to predict pathological response
S Waugh, N Muhammad Gowdh, C Purdie, A Evans, E Crowe, A Thompson, S Vinnicombe
S8 Diagnostic yield of CT IVU in haematuria screening
F. Arfeen, T. Campion, E. Goldstraw
S9 Percutaneous radiofrequency ablation of unresectable locally advanced pancreatic cancer: preliminary results
DâOnofrio M, Ciaravino V, Crosara S, De Robertis R, Pozzi Mucelli R
S10 Iodine maps from dual energy CT improve detection of metastases in staging examinations of melanoma patients
M. Uhrig, D. Simons, H. Schlemmer
S11Can contrast enhanced CT predict pelvic nodal status in malignant melanoma of the lower limb?
Kate Downey
S12 Current practice in the investigation for suspected Paraneoplastic Neurological Syndromes (PNS) and positive malignancy yield.
S Murdoch, AS Al-adhami, S Viswanathan
P1 Technical success and efficacy of Pulmonary Radiofrequency ablation: an analysis of 207 ablations
S Smith, P Jennings, D Bowers, R Soomal
P2 Lesion control and patient outcome: prospective analysis of radiofrequency abaltion in pulmonary colorectal cancer metastatic disease
S Smith, P Jennings, D Bowers, R Soomal
P3 Hepatocellular carcinoma in a post-TB patient: case of tropical infections and oncologic imaging challenges
TM Mutala, AO Odhiambo, N Harish
P4 Role of apparent diffusion coefficient (ADC) diffusion-weighted MRI for predicting extracapsular extension of prostate cancer
P. Pricolo, S. Alessi, P. Summers, E. Tagliabue, G. Petralia
P5 What a difference a decade makes; comparison of lung biopsies in Glasgow 2005 and 2015
M. Hall, M. Sproule, S. Sheridan
P6 Solid pseudopapillary tumour of pancreas: imaging features of a rare neoplasm
KY Thein, CH Tan, YL Thian, CM Ho
P7 MDCT - pathological correlation in colon adenocarcinoma staging: preliminary experience
S De Luca, C Carrera, V Blanchet, L AlarcĂłn, E Eyheremnedy
P8 Image guided biopsy of thoracic masses and reduction of pneumothorax risk: 25Â years experience
B K Choudhury, K Bujarbarua, G Barman
P9 Tumour heterogeneity analysis of 18F-FDG-PET for characterisation of malignant peripheral nerve sheath tumours in neurofibromatosis-1
GJ Cook, E Lovat, M Siddique, V Goh, R Ferner, VS Warbey
P10 Impact of introduction of vacuum assisted excision (VAE) on screen detected high risk breast lesions
L Potti, B Kaye, A Beattie, K Dutton
P11 Can we reduce prevalent recall rate in breast screening?
AA Seth, F Constantinidis, H Dobson
P12 How to reduce prevalent recall rate? Identifying mammographic lesions with low Positive Predictive Value (PPV)
AA Seth ([email protected]), F Constantinidis, H Dobson
P13 Behaviour of untreated pulmonary thrombus in oncology patients diagnosed with incidental pulmonary embolism on CT
R. Bradley, G. Bozas, G. Avery, A. Stephens, A. Maraveyas
P14 A one-stop lymphoma biopsy service â is it possible?
S Bhuva, CA Johnson, M Subesinghe, N Taylor
P15 Changes in the new TNM classification for lung cancer (8th edition, effective January 2017)
LE Quint, RM Reddy, GP Kalemkerian
P16 Cancer immunotherapy: a review of adequate imaging assessment
G GonzĂĄlez Zapico, E Gainza Jauregui, R Ălvarez Francisco, S Ibåñez Alonso, I Tavera Bahillo, L MĂșgica Ălvarez
P17 Succinate dehydrogenase mutations and their associated tumours
O Francies, R Wheeler, L Childs, A Adams, A Sahdev
P18 Initial experience in the usefulness of dual energy technique in the abdomen
SE De Luca, ME Casalini Vañek, MD Pascuzzi, T Gillanders, PM Ramos, EP Eyheremendy
P19 Recognising the serious complication of Richterâs transformation in CLL patients
C Stove, M Digby
P20 Body diffusion-weighted MRI in oncologic practice: truths, tricks and tips
M. Nazar, M. Wirtz, MD. Pascuzzi, F. Troncoso, F. Saguier, EP. Eyheremendy
P21 Methotrexate-induced leukoencephalopathy in paediatric ALL Patients
D.J. Quint, L. Dang, M. Carlson, S. Leber, F. Silverstein
P22 Pitfalls in oncology CT reporting. A pictorial review
R Rueben, S Viswanathan
P23 Imaging of perineural extension in head and neck tumours
B Nazir, TH Teo, JB Khoo
P24 MRI findings of molecular subtypes of breast cancer: a pictorial primer
K Sharma, N Gupta, B Mathew, T Jeyakumar, K Harkins
P25 When cancer canât wait! A pictorial review of oncological emergencies
K Sharma, B Mathew, N Gupta, T Jeyakumar, S Joshua
P26 MRI of pancreatic neuroendocrine tumours: an approach to interpretation
D Christodoulou, S Gourtsoyianni, A Jacques, N Griffin, V Goh
P27 Gynaecological cancers in pregnancy: a review of imaging
CA Johnson, J Lee
P28 Suspected paraneoplastic neurological syndromes - review of published recommendations to date, with proposed guideline/flowchart
JA Goodfellow, AS Al-adhami, S Viswanathan
P29 Multi-parametric MRI of the pelvis for suspected local recurrence of prostate cancer after radical prostatectomy
R Bradley
P30 Utilisation of PI-RADS version 2 in multi-parametric MRI of the prostate; 12-months experience
R Bradley
P31 Radiological assessment of the post-chemotherapy liver
A Yong, S Jenkins, G Joseph
P32 Skeletal staging with MRI in breast cancer â what the radiologist needs to know
S Bhuva, K Partington
P33 Perineural spread of lympoma: an educational review of an unusual distribution of disease
CA Johnson, S Bhuva, M Subesinghe, N Taylor
P34 Visually isoattenuating pancreatic adenocarcinoma. Diagnostic imaging tools.
C Carrera, A Zanfardini, S De Luca, L AlarcĂłn, V Blanchet, EP Eyheremendy
P35 Imaging of larynx cancer: when is CT, MRI or FDG PET/CT the best test?
K Cavanagh, E Lauhttp://deepblue.lib.umich.edu/bitstream/2027.42/134651/1/40644_2016_Article_79.pd
A high-throughput sequencing test for diagnosing inherited bleeding, thrombotic, and platelet disorders.
Inherited bleeding, thrombotic, and platelet disorders (BPDs) are diseases that affect âŒ300 individuals per million births. With the exception of hemophilia and von Willebrand disease patients, a molecular analysis for patients with a BPD is often unavailable. Many specialized tests are usually required to reach a putative diagnosis and they are typically performed in a step-wise manner to control costs. This approach causes delays and a conclusive molecular diagnosis is often never reached, which can compromise treatment and impede rapid identification of affected relatives. To address this unmet diagnostic need, we designed a high-throughput sequencing platform targeting 63 genes relevant for BPDs. The platform can call single nucleotide variants, short insertions/deletions, and large copy number variants (though not inversions) which are subjected to automated filtering for diagnostic prioritization, resulting in an average of 5.34 candidate variants per individual. We sequenced 159 and 137 samples, respectively, from cases with and without previously known causal variants. Among the latter group, 61 cases had clinical and laboratory phenotypes indicative of a particular molecular etiology, whereas the remainder had an a priori highly uncertain etiology. All previously detected variants were recapitulated and, when the etiology was suspected but unknown or uncertain, a molecular diagnosis was reached in 56 of 61 and only 8 of 76 cases, respectively. The latter category highlights the need for further research into novel causes of BPDs. The ThromboGenomics platform thus provides an affordable DNA-based test to diagnose patients suspected of having a known inherited BPD.This study, including the enrollment of cases, sequencing, and analysis received support from the National Institute for Health Research (NIHR) BioResourceâRare Diseases. The NIHR BioResource is funded by the NIHR (http://www.nihr.ac.uk). Research in the Ouwehand Laboratory is also supported by grants from Bristol-Myers Squibb, the British Heart Foundation, the British Society of Haematology, the European Commission, the MRC, the NIHR, and the Wellcome Trust; the laboratory also receives funding from National Health Service Blood and Transplant (NHSBT). The clinical fellows received funding from the MRC (C.L. and S.K.W.); the NIHRâRare Diseases Translational Research Collaboration (S. Sivapalaratnam); and the British Society for Haematology and National Health Service Blood and Transplant (T.K.B.).This is the author accepted manuscript. The final version is available from American Society of Hematology via http://dx.doi.org/10.1182/blood-2015-12-688267
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