Calibration of the modified Bartlett-Lewis model using global optimization techniques and alternative objective functions

The calibration of stochastic point process rainfall models, such as of the Bartlett-Lewis type, suffers from the presence of multiple local minima which local search algorithms usually fail to avoid. To meet this shortcoming, four relatively new global optimization methods are presented and tested for their ability to calibrate the Modified Bartlett-Lewis Model. The list of tested methods consists of: the Downhill Simplex Method, Simplex-Simulated Annealing, Particle Swarm Optimization and Shuffled Complex Evolution. The parameters of these algorithms are first optimized to ensure optimal performance, after which they are used for calibration of the Modified Bartlett-Lewis model. Furthermore, this paper addresses the choice of weights in the objective function. Three alternative weighing methods are compared to determine whether or not simulation results (obtained after calibration with the best optimization method) are influenced by the choice of weights

Automated motion analysis of bony joint structures from dynamic computer tomography images: A multi-atlas approach

Dynamic computer tomography (CT) is an emerging modality to analyze in-vivo joint kinematics at the bone level, but it requires manual bone segmentation and, in some instances, landmark identification. The objective of this study is to present an automated workflow for the assessment of three-dimensional in vivo joint kinematics from dynamic musculoskeletal CT images. The proposed method relies on a multi-atlas, multi-label segmentation and landmark propagation framework to extract bony structures and detect anatomical landmarks on the CT dataset. The segmented structures serve as regions of interest for the subsequent motion estimation across the dynamic sequence. The landmarks are propagated across the dynamic sequence for the construction of bone embedded reference frames from which kinematic parameters are estimated. We applied our workflow on dynamic CT images obtained from 15 healthy subjects on two different joints: thumb base (n = 5) and knee (n = 10). The proposed method resulted in segmentation accuracies of 0.90 ± 0.01 for the thumb dataset and 0.94 ± 0.02 for the knee as measured by the Dice score coefficient. In terms of motion estimation, mean differences in cardan angles between the automated algorithm and manual segmentation, and landmark identification performed by an expert were below 1◦. Intraclass correlation (ICC) between cardan angles from the algorithm and results from expert manual landmarks ranged from 0.72 to 0.99 for all joints across all axes. The proposed automated method resulted in reproducible and reliable measurements, enabling the assessment of joint kinematics using 4DCT in clinical routine

Lung adenocarcinoma originates from retrovirus infection of proliferating type 2 pneumocytes during pulmonary post-natal development or tissue repair

Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer

A Bayesian view of murine seminal cytokine networks

It has long been established that active agents in seminal fluid are key to initiating and coordinating mating-induced immunomodulation. This is in part governed by the actions of a network of cytokine interactions which, to date, remain largely undefined, and whose interspecific evolutionary conservation is unknown. This study applied Bayesian methods to illustrate the interrelationships between seminal profiles of interleukin (IL)-1alpha, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12 (p70), IL-13, IL-17, eotaxin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon (IFN)-gamma, keratinocyte-derived chemokine (KC), monocyte chemoattractant protein (MCP-1), macrophage inflammatory protein (MIP-1) alpha, MIP-1beta, regulated on activation normal T cell expressed and secreted (RANTES), tumour necrosis factor (TNF)-alpha, leptin, inducible protein (IP)-10 and vascular endothelial growth factor (VEGF) in a rat model. IL-2, IL-9, IL-12 (p70), IL-13, IL-18, eotaxin, IFN-gamma, IP-10, KC, leptin, MCP-1, MIP-1alpha and TNF-alpha were significantly higher in serum, whilst IL-1beta, IL-5, IL-6, IL-10, IL-17, G-CSF and GM-CSF were significantly higher in seminal fluid. When compared to mouse profiles, only G-CSF was present at significantly higher levels in the seminal fluid in both species. Bayesian modelling highlighted key shared features across mouse and rat networks, namely TNF-alpha as the terminal node in both serum and seminal plasma, and MCP-1 as a central coordinator of seminal cytokine networks through the intermediary of KC and RANTES. These findings reveal a marked interspecific conservation of seminal cytokine networks

Self-adjuvanting polymer-peptide conjugates as therapeutic vaccine candidates against cervical cancer

Dendrimers are structurally well-defined, synthetic polymers with sizes and physicochemical properties often resembling those of biomacromolecules (e.g. proteins). As a result they are promising candidates for peptide-based vaccine delivery platforms. Herein, we established a synthetic pathway to conjugate a human papillomavirus (HPV) E7 protein-derived peptide antigen to a star-polymer to create a macromolecular vaccine candidate to treat HPV-related cancers. These conjugates were able to reduce tumor growth and eradicate E7-expressing TC-1 tumors in mice after a single immunization, without the help of any external adjuvant

Fixation of the Cemented Stem: Clinical Relevance of the Porosity and Thickness of the Cement Mantle

The aim of this review paper is to define the fixation of the cemented stem. Polymethyl methacrylate, otherwise known as “bone cement”, has been used in the fixation of hip implants since the early 1960s. Sir John Charnley, the pioneer of modern hip replacement, incorporated the use of cement in the development of low frictional torque hip arthroplasty. In this paper, the concepts of femoral stem design and fixation, clinical results, and advances in understanding of the optimal use of cement are reviewed. The purpose of this paper is to help understanding and discussions on the thickness and the porosity of the cement mantle in total hip arthroplasty. Cement does not act as an adhesive, as sometimes thought, but relies on an interlocking fit to provide mechanical stability at the cement–bone interface, while at the prosthesis– cement interface it achieves stability by optimizing the fit of the implant in the cement mantle, such as in a tapered femoral stem