Visual parameter optimisation for biomedical image processing

Background: Biomedical image processing methods require users to optimise input parameters to ensure high quality output. This presents two challenges. First, it is difficult to optimise multiple input parameters for multiple input images. Second, it is difficult to achieve an understanding of underlying algorithms, in particular, relationships between input and output. Results: We present a visualisation method that transforms users’ ability to understand algorithm behaviour by integrating input and output, and by supporting exploration of their relationships. We discuss its application to a colour deconvolution technique for stained histology images and show how it enabled a domain expert to identify suitable parameter values for the deconvolution of two types of images, and metrics to quantify deconvolution performance. It also enabled a breakthrough in understanding by invalidating an underlying assumption about the algorithm. Conclusions: The visualisation method presented here provides analysis capability for multiple inputs and outputs in biomedical image processing that is not supported by previous analysis software. The analysis supported by our method is not feasible with conventional trial-and-error approaches

Measuring Dissociation Rate Constants of Protein Complexes through Subunit Exchange: Experimental Design and Theoretical Modeling

Protein complexes are dynamic macromolecules that constantly dissociate into, and simultaneously are assembled from, free subunits. Dissociation rate constants, koff, provide structural and functional information on protein complexes. However, because all existing methods for measuring koff require high-quality purification and specific modifications of protein complexes, dissociation kinetics has only been studied for a small set of model complexes. Here, we propose a new method, called Metabolically-labeled Affinity-tagged Subunit Exchange (MASE), to measure koff using metabolic stable isotope labeling, affinity purification and mass spectrometry. MASE is based on a subunit exchange process between an unlabeled affinity-tagged variant and a metabolically-labeled untagged variant of a complex. The subunit exchange process was modeled theoretically for a heterodimeric complex. The results showed that koff determines, and hence can be estimated from, the observed rate of subunit exchange. This study provided the theoretical foundation for future experiments that can validate and apply the MASE method

Binary Mixtures of SH- and CH3-Terminated Self-Assembled Monolayers to Control the Average Spacing Between Aligned Gold Nanoparticles

This paper presents a method to control the average spacing between organometallic chemical vapor deposition (OMCVD) grown gold nanoparticles (Au NPs) in a line. Focused ion beam patterned CH3-terminated self-assembled monolayers are refilled systematically with different mixtures of SH- and CH3-terminated silanes. The average spacing between OMCVD Au NPs is demonstrated systematically to decrease by increasing the v/v% ratio of the thiols in the binary silane mixtures with SH- and CH3-terminated groups

Effects of deletion of the Streptococcus pneumoniae lipoprotein diacylglyceryl transferase gene lgt on ABC transporter function and on growth in vivo

Lipoproteins are an important class of surface associated proteins that have diverse roles and frequently are involved in the virulence of bacterial pathogens. As prolipoproteins are attached to the cell membrane by a single enzyme, prolipoprotein diacylglyceryl transferase (Lgt), deletion of the corresponding gene potentially allows the characterisation of the overall importance of lipoproteins for specific bacterial functions. We have used a Δlgt mutant strain of Streptococcus pneumoniae to investigate the effects of loss of lipoprotein attachment on cation acquisition, growth in media containing specific carbon sources, and virulence in different infection models. Immunoblots of triton X-114 extracts, flow cytometry and immuno-fluorescence microscopy confirmed the Δlgt mutant had markedly reduced lipoprotein expression on the cell surface. The Δlgt mutant had reduced growth in cation depleted medium, increased sensitivity to oxidative stress, reduced zinc uptake, and reduced intracellular levels of several cations. Doubling time of the Δlgt mutant was also increased slightly when grown in medium with glucose, raffinose and maltotriose as sole carbon sources. These multiple defects in cation and sugar ABC transporter function for the Δlgt mutant were associated with only slightly delayed growth in complete medium. However the Δlgt mutant had significantly reduced growth in blood or bronchoalveolar lavage fluid and a marked impairment in virulence in mouse models of nasopharyngeal colonisation, sepsis and pneumonia. These data suggest that for S. pneumoniae loss of surface localisation of lipoproteins has widespread effects on ABC transporter functions that collectively prevent the Δlgt mutant from establishing invasive infection

Collective Animal Behavior from Bayesian Estimation and Probability Matching

Animals living in groups make movement decisions that depend, among other factors, on social interactions with other group members. Our present understanding of social rules in animal collectives is based on empirical fits to observations and we lack first-principles approaches that allow their derivation. Here we show that patterns of collective decisions can be derived from the basic ability of animals to make probabilistic estimations in the presence of uncertainty. We build a decision-making model with two stages: Bayesian estimation and probabilistic matching.
In the first stage, each animal makes a Bayesian estimation of which behavior is best to perform taking into account personal information about the environment and social information collected by observing the behaviors of other animals. In the probability matching stage, each animal chooses a behavior with a probability given by the Bayesian estimation that this behavior is the most appropriate one. This model derives very simple rules of interaction in animal collectives that depend only on two types of reliability parameters, one that each animal assigns to the other animals and another given by the quality of the non-social information. We test our model by obtaining theoretically a rich set of observed collective patterns of decisions in three-spined sticklebacks, Gasterosteus aculeatus, a shoaling fish species. The quantitative link shown between probabilistic estimation and collective rules of behavior allows a better contact with other fields such as foraging, mate selection, neurobiology and psychology, and gives predictions for experiments directly testing the relationship between estimation and collective behavior

The Founder’s Lecture 2009: advances in imaging of osteoporosis and osteoarthritis

The objective of this review article is to provide an update on new developments in imaging of osteoporosis and osteoarthritis over the past three decades. A literature review is presented that summarizes the highlights in the development of bone mineral density measurements, bone structure imaging, and vertebral fracture assessment in osteoporosis as well as MR-based semiquantitative assessment of osteoarthritis and quantitative cartilage matrix imaging. This review focuses on techniques that have impacted patient management and therapeutic decision making or that potentially will affect patient care in the near future. Results of pertinent studies are presented and used for illustration. In summary, novel developments have significantly impacted imaging of osteoporosis and osteoarthritis over the past three decades

Evaluating the impact of Relative Total Dose Intensity (RTDI) on patients' short and long-term outcome in taxane- and anthracycline-based chemotherapy of metastatic breast cancer- a pooled analysis

Background: Chemotherapy dose delay and/or reduction lower relative total dose intensity (RTDI) and may affect short- and long-term outcome of metastatic breast cancer (MBC) patients. Methods: Based on 933 individual patients' data of from 3 randomized MBC trials using an anthracycline and taxane we examined the impact of RTDI on efficacy and determined the lowest optimal RTDI for MBC patients. Results: Median time to disease progression (TTDP) and overall survival (OS) of all patients were 39 and 98 weeks. Overall higher RTDI was correlated with a shorter TTDP (log-rank p = 0.0525 for 85% RTDI cut-off). Proportional hazards assumption was violated, there was an early drop in the TTDP-curve for the high RTDI group. It was explained by the fact that patients with primary disease progression (PDP) do have a high RTDI per definition. Excluding those 114 patients with PDP the negative correlation between RTDI and TTDP vanished. However, non-PDP patients with RTDI-cut-off levels <85% showed a shorter OS than patients with higher RTDI levels (p = 0.0086). Conclusions: Optimizing RTDI above 85% appears to improve long-term outcome of MBC patients receiving first-line chemotherapy. Lowering RTDI had no negative influence on short term outcome like OR and TTDP

The associations between body and knee height measurements and knee joint structure in an asymptomatic cohort

<p>Abstract</p> <p>Background</p> <p>It has been suggested that knee height is a determinant of knee joint load. Nonetheless, no study has directly examined the relationship between anthropometric measures of height and knee joint structures, such as cartilage.</p> <p>Methods</p> <p>89 asymptomatic community-based adults aged 25-62 with no diagnosed history of knee arthropathy were recruited. Anthropometric data (knee height and body height) were obtained by standard protocol, while tibial cartilage volume and defects, as well as bone area were determined from magnetic resonance imaging. Static knee alignment was measured from the joint radiograph.</p> <p>Results</p> <p>All anthropometric height measures were associated with increasing compartmental tibial bone area (<it>p </it>≤ 0.05). Although knee height was associated with tibial cartilage volume (e.g. β = 27 mm³95% CI 7- 48; <it>p </it>= 0.009 for the medial compartment), these relationship no longer remained significant when knee height as a percentage of body height was analysed. Knee height as a percentage of body height was associated with a reduced risk of medial tibial cartilage defects (odds ratio 0.6; 95% confidence interval 0.4 - 1.0; <it>p </it>= 0.05).</p> <p>Conclusion</p> <p>The association between increased anthropometric height measures and increased tibial bone area may reflect inherently larger bony structures. However the beneficial associations demonstrated with cartilage morphology suggest that an increased knee height may confer a beneficial biomechanical environment to the chondrocyte of asymptomatic adults.</p

PET imaging of the autonomic myocardial function: methods and interpretation.

Cardiac positron emission tomography (PET) is mainly applied in myocardial perfusion and viability detection. Noninvasive imaging of myocardial innervation using PET is a valuable additional methodology in cardiac imaging. Novel methods and different PET ligands have been developed to measure presynaptic and postsynaptic function of the cardiac neuronal system. Obtained PET data can be analysed quantitatively or interpreted qualitatively. Thus far, PET is not a widely used clinical application in autonomic heart imaging; however, due to its technical advantages, the excellent properties of the imaging agents, and the availability of tools for quantification, it deserves a better position in the clinic. From a historical point of view, the focus of PET software packages for image analysis was mainly oncology and neurology driven. Actually, commercially available software for cardiac PET image analysis is still only available for the quantification of myocardial blood flow. Thus far, no commercial software package is available for the interpretation and quantification of PET innervation scans. However, image data quantification and analysis of kinetic data can be performed using adjusted generic tools. This paper gives an overview of different neuronal PET ligands, interpretation and quantification of acquired PET data

Pathways to health: a framework for health-focused research and practice

Public health research and practice is faced with three problems: 1) a focus on disease instead of health, 2) consideration of risk factor/disease relationships one at a time, and 3) attention to individuals with limited regard for the communities in which they live. We propose a framework for health-focused research and practice. This framework encompasses individual and community pathways to health while incorporating the dynamics of context and overall population vulnerability and resilience. Individual pathways to health may differ, but commonalities will exist. By understanding these commonalities, communities can work to support health-promoting pathways in addition to removing barriers. The perspective afforded by viewing health as a dynamic process instead of as a collection of risk factors and diseases expands the number of approaches to improving health globally. Using this approach, multidisciplinary research teams working with active community participants have the potential to reshape health and intervention sciences