scholarly journals 760Multi-stage models of cancer and disease

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Anthony Webster
Keyword(s):  
Genetic Markers ◽  
Epidemiological Studies ◽  
Stage Model ◽  
Stage Models ◽  
Multi Stage ◽  
Cancer Models ◽  
Stage Process ◽  
Models Of Disease ◽  
Insight Into ◽  
Lateral Sclerosis

Abstract Background Since Armitage and Doll's publication of “a multi-stage theory of carcinogenesis” in 1954, the multi-stage model has underpinned our conceptual understanding of cancer. In the last few years the model has been applied to other diseases, such as Amyotrophic Lateral Sclerosis (Motor Neurone Disease), providing new insight into how the disease can arise and progress. Methods The multi-stage model is simplified and generalised. The result is a simple mathematical toolkit to describe carcinogenesis or other multi-stage models of disease, with simple formulae corresponding to pictorial diagrams of the multi-stage process. Important practical issues are described regarding the fitting of data and the use of multi-stage models to interpret results. Results Relationships between established cancer models are clarified, and derivations are simplified. We provide examples and highlight pitfalls of fitting multistage models to data. It is explained how genetic markers and the multi-stage paradigm can provide new insights into mechanisms of disease. Limitations of the model are discussed in the context of recent cancer research. Conclusions A simple mathematical recipe can convert biologically-motivated models for each step in a disease’s progression, into a mathematical model. The framework provides a mathematical toolkit to study the failure of complex systems, biological or otherwise, simplifying the formulation and interpretation of multi-stage models. Key messages Multi-stage models are increasingly easy to use and understand. When combined with big data and genetic markers for stratification, they offer a new tool for epidemiological studies.

A Bayesian approach for multi-stage models with linear time-dependent hazard rate

2019 ◽  
Vol 25 (4) ◽  
pp. 307-316
Author(s):  
Hoa Pham ◽  
Huong T. T. Pham
Keyword(s):  
Hazard Rate ◽  
Linear Time ◽  
Simulated Data ◽  
Time Dependent ◽  
Stage Model ◽  
Stage Duration ◽  
Stage Models ◽  
Multi Stage ◽  
Mh Algorithm ◽  
Number Of Individuals

Abstract Multi-stage models have been used to describe progression of individuals which develop through a sequence of discrete stages. We focus on the multi-stage model in which the number of individuals in each stage is assessed through destructive samples for a sequence of sampling time. Moreover, the stage duration distributions of the model are effected by a time-dependent hazard rate. The multi-stage models become complex with a stage having time-dependent hazard rate. The main aim of this paper is to derive analytically the approximation of the likelihood of the model. We apply the approximation to the Metropolis–Hastings (MH) algorithm to estimate parameters for the model. The method is demonstrated by applying to simulated data which combine non-hazard rate, stage-wise constant hazard rate and time-dependent hazard rates in stage duration distributions.

Deep Multi-stage Model for Automated Landmarking of Craniomaxillofacial CT Scans

2021 ◽  
Author(s):  
S. Palazzo ◽  
G. Bellitto ◽  
L. Prezzavento ◽  
F. Rundo ◽  
U. Bagci ◽  
...  
Keyword(s):  
Ct Scans ◽  
Stage Model ◽  
Multi Stage

scholarly journals Cryo-EM structure of amyloid fibrils formed by the entire low complexity domain of TDP-43

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qiuye Li ◽  
W. Michael Babinchak ◽  
Witold K. Surewicz
Keyword(s):  
Amyloid Fibrils ◽  
Low Complexity ◽  
Structural Features ◽  
Protein Fragments ◽  
Hydrophobic Residues ◽  
Backbone Conformation ◽  
Hydrophobic Amino Acids ◽  
Insight Into ◽  
Lateral Sclerosis

AbstractAmyotrophic lateral sclerosis and several other neurodegenerative diseases are associated with brain deposits of amyloid-like aggregates formed by the C-terminal fragments of TDP-43 that contain the low complexity domain of the protein. Here, we report the cryo-EM structure of amyloid formed from the entire TDP-43 low complexity domain in vitro at pH 4. This structure reveals single protofilament fibrils containing a large (139-residue), tightly packed core. While the C-terminal part of this core region is largely planar and characterized by a small proportion of hydrophobic amino acids, the N-terminal region contains numerous hydrophobic residues and has a non-planar backbone conformation, resulting in rugged surfaces of fibril ends. The structural features found in these fibrils differ from those previously found for fibrils generated from short protein fragments. The present atomic model for TDP-43 LCD fibrils provides insight into potential structural perturbations caused by phosphorylation and disease-related mutations.

scholarly journals Correlation between Detection of a Plasmid and High-Level Virulence of Vibrio nigripulchritudo, a Pathogen of the Shrimp Litopenaeus stylirostris

2008 ◽  
Vol 74 (10) ◽  
pp. 3038-3047 ◽  
Author(s):  
Yann Reynaud ◽  
Denis Saulnier ◽  
Didier Mazel ◽  
Cyrille Goarant ◽  
Frédérique Le Roux
Keyword(s):  
Genetic Markers ◽  
New Caledonia ◽  
Subtractive Hybridization ◽  
Epidemiological Studies ◽  
Etiological Agent ◽  
Subtraction Library ◽  
High Virulence ◽  
High Level ◽  
Mass Mortalities ◽  
Coral Pathogen

ABSTRACT Vibrio nigripulchritudo, the etiological agent of Litopenaeus stylirostris summer syndrome, is responsible for mass mortalities of shrimp in New Caledonia. Epidemiological studies led to the suggestion that this disease is caused by an emergent group of pathogenic strains. Genomic subtractive hybridization was carried out between two isolates exhibiting low and high virulence. Our subtraction library was constituted of 521 specific fragments; 55 of these were detected in all virulent isolates from our collection (n = 32), and 13 were detected only in the isolates demonstrating the highest pathogenicity (n = 19), suggesting that they could be used as genetic markers for high virulence capacity. Interestingly, 10 of these markers are carried by a replicon of 11.2 kbp that contains sequences highly similar to those of a plasmid detected in Vibrio shilonii, a coral pathogen. The detection of this plasmid was correlated with the highest pathogenicity status of the isolates from our collection. The origin and consequence of this plasmid acquisition are discussed.

scholarly journals Safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis: a multi-stage, randomised, double-blind, placebo-controlled trial

2014 ◽  
Vol 13 (11) ◽  
pp. 1083-1091 ◽  
Author(s):  
Merit E Cudkowicz ◽  
Sarah Titus ◽  
Marianne Kearney ◽  
Hong Yu ◽  
Alexander Sherman ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Controlled Trial ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Double Blind Placebo ◽  
Multi Stage ◽  
Lateral Sclerosis

HuR-targeted agents: an insight into medicinal chemistry, biophysical, computational studies and pharmacological effects on cancer models

2021 ◽  
pp. 114088
Author(s):  
Giulia Assoni ◽  
Valeria La Pietra ◽  
Rosangela Digilio ◽  
Caterina Ciani ◽  
Nausicaa Valentina Licata ◽  
...  
Keyword(s):  
Medicinal Chemistry ◽  
Computational Studies ◽  
Pharmacological Effects ◽  
Targeted Agents ◽  
Cancer Models ◽  
Insight Into

A Bayesian approach for parameter estimation in multi-stage models

2018 ◽  
Vol 48 (10) ◽  
pp. 2459-2482 ◽  
Author(s):  
Hoa Pham ◽  
Darfiana Nur ◽  
Huong T. T. Pham ◽  
Alan Branford
Keyword(s):  
Parameter Estimation ◽  
Bayesian Approach ◽  
Stage Models ◽  
Multi Stage

Rotation and Radial Motion Thresholds Support a Two-Stage Model of Differential-Motion Analysis

Perception ◽  
1996 ◽  
Vol 25 (1) ◽  
pp. 5-26 ◽  
Author(s):  
Kevin Gurney ◽  
Michael J Wright
Keyword(s):  
Receptive Field ◽  
Optic Flow ◽  
Radial Flow ◽  
Relative Orientation ◽  
Stage Model ◽  
Two Stage ◽  
Differential Motion ◽  
Component Orientation ◽  
Stage Process ◽  
Temporal And Spatial

Lower motion thresholds for rotational and radial flow have been measured for stimuli consisting of four closely packed circular apertures, each containing patches of drifting grating or plaid. Detection and direction thresholds were measured for gratings and plaids as a function of the relative orientation of the pattern components. There was a similarity between both types of threshold, supporting the existence of specialised rotation and radial-flow detectors. Further, thresholds increased with the relative component orientation for both gratings and plaids. This suggests that component information from a first stage, tuned spatiotemporally and to orientation, is being used directly to compute the optic flow in a two-stage process. A model based on this architecture is described by means of simple template receptive-field arrays with separable temporal and spatial tuning at the first stage.

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