50 research outputs found
Decision-making and the role of feedback in complex tasks
This thesis investigates the process of decision-making in relation to complex tasks and considers the important role which dynamic information and real-time feedback play in shaping response behaviour and adaptation within such environments. Through empirical studies, the thesis explores the extent to which decision-makers can be said to act rationally when challenged by complex decision-making environments. Evidence relating to demand for information and the impact of feedback on behaviour is provided with two studies: The first uses a simulated auction platform to examine behaviour within overlapping auctions of short duration with close-to-identical items and minimal participation costs. Mouse tracking is used to capture data on relevant interactions of participants with the simulated online platform, including switching behaviour independent of bidding. The resulting data suggests that participants did behave in a manner consistent with utility maximisation, seeking to acquire the item at the lowest possible price and showing no bias in terms of auction preference. The impact of fixed-price offers in the form of a “Buy it Now” option is also examined with some evidence that participants again seek, and respond to, current information when deciding on their bidding strategy.
The second study is a test of the impact of real-time feedback and demand for information within the context of financial markets. The study again uses a novel simulated environment which provides access to considerable amounts of relevant data which participants can choose to access. In addition, participants are exposed to regular feedback with regard to their own performance. Overall, demand for information is found to be dependent upon the type of feedback received and its context. Decision-makers then appear to behave objectively, apparently seeking the latest available information to support current decisions, although investor style is found to be important in determining overall trading propensity.
The thesis starts by considering a number of the foundations and pathways which run through the judgment and decision-making literature. It is not a complete description, review or analysis of all of the prevailing lines of enquiry. Nevertheless, it seeks to achieve coherence in terms of bringing together some of the key themes dealing with risky choice under conditions of uncertainty and ambiguity. The field of judgment and decision-making is inevitably vast; its scope owing much to the fact that it transcends individual disciplines. The emergent behavioural sciences thus draw together important strands from various sources, notably Economics and Finance. In many areas, psychological traits can be applied to explain inconsistencies which are found in classical theory of rational behaviour. The recognition of behavioural traits has thus contributed greatly to the evolution of decisionmaking theories under conditions of uncertainty and ambiguity which are, in many cases, substantially more adaptable and robust than early normative theories of rational behaviour.
The classical approach to rational decision making within Economics, together with some theoretical and empirical challenges to it, are considered in Chapter 1. It is here that we are introduced to the Rational Man. Like the mythical creatures found in Classical Antiquity, the Rational Man does not actually exist in the real world; he is nevertheless central to the concept of utility maximising rational choice which provided much of the foundation of Economics. Developments of expected utility theory (EUT) are considered, including its replacement of expected value, and the formalisation of rational behaviour within the context of axioms. When those logical axioms apply, decision-makers can be said to behave 'as if' they are utility maximises. The chapter ends with some empirical evidence, showing the types of approaches often used to explore rational decision-making. Some violations of EUT are explored, both in relation to notional gambles and consistency with regard to revealed preferences. Chapter 2 extends the narrative by considering rational decision-making in cases where there is no objective information about possible outcomes. Subjective utility theory (SEU) is then introduced, describing objective functions based upon preferences derived from combined utility and probability functions. The implications of the Allais’ and Ellsberg paradoxes are discussed, along with some possible solutions. It is here that we explore the concepts of uncertainty and ambiguity in more details and consider some theoretical formulations for addressing them.
Chapter 3 covers the significant contribution to decision-making under conditions of uncertainty provided by Prospect Theory and, later, Cumulative Prospect Theory (CPT). Their evolution from the pioneering work of Markowitz is discussed within the context of reference points relative to which outcomes can be evaluated. The significance of stochastic dominance and rank dependence are explored. By this stage, we have examined numerous theories which have fundamentally transformed standard EUT into much more flexible and adaptable frameworks of rational choice. The core concepts of utility maximisation remain yet the initial, strictly concave utility function describing diminishing marginal utility is now substantially replaced by more complex weighted preference functions.
From this theoretical base, the process of choice reduction and the application of heuristics in decision-making are considered. We again describe axiomatic behaviour compatible with rational choice. Therefore, decision-makers faced with multiple choices about which there may be little or no objective information about likely outcomes can nevertheless develop rational beliefs and expectations which can then be applied to reduce complex tasks to more manageable proportions. As well as considering these aspects from the point of view of actual choices, we also consider the processes by which decisions are taken. Thus, process tracing methods are introduced into the discussion. The chapter also explicitly considers the role of feedback in decision making. This includes a consideration of Bayesian inference as a process for updating probabilistic expectations subject to new information.
From considering theoretical formulations form which we can judge rational behaviour, Chapter 5 looks at evidence for sub-optimal decision-making and bias. Bias with regard to probability assessments are considered along with empirical evidence of bias in relation to intertemporal discounting. Sunk cost bias is also considered as a clear example of irrational behaviour, leading in to a specific discussion about a number of persistent behavioural biases identified within financial markets. As an introduction to later chapters, this also covers the basic theoretical principles of market efficiency and evidence that real markets fail to adhere to those principles in important ways.
Chapters 6 and 8 describe the empirical studies with Chapter 7 providing a more detailed introduction to the financial markets experiment, considering aspects of market efficiency, models of behaviour and other empirical evidence
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas
This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing
molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin
Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context
Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images
Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images
of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL
maps are derived through computational staining using a convolutional neural network trained to
classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and
correlation with overall survival. TIL map structural patterns were grouped using standard
histopathological parameters. These patterns are enriched in particular T cell subpopulations
derived from molecular measures. TIL densities and spatial structure were differentially enriched
among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial
infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic
patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for
the TCGA image archives with insights into the tumor-immune microenvironment
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. Fütterer
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 users’ 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 D’Onofrio
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 Garrè, Andrea Rossi
O32 Structured reporting and beyond
Hebert Alberto Vargas
O33 Massachusetts General Hospital experience with structured reporting
Theresa C. McLoud
O34 The oncologist’s 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. Fütterer
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 D’Hoore, 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 – are management studies sufficient as surrogate for patient outcome?
C. Pfannenberg, B. Gückel, SC Schüle, AC Müller, 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 imaging—can 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
D’Onofrio 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 Alarcón, E Eyheremnedy
P8 Image guided biopsy of thoracic masses and reduction of pneumothorax risk: 25 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 – 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 González Zapico, E Gainza Jauregui, R Álvarez Francisco, S Ibáñez Alonso, I Tavera Bahillo, L Múgica Álvarez
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 Richter’s 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 can’t 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 – 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 Alarcón, 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
Prevalence and architecture of de novo mutations in developmental disorders.
The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year
Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types
Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead