Beyond persons: extending the personal / subpersonal distinction to non-rational animals and artificial agents

The distinction between personal level explanations and subpersonal ones has been subject to much debate in philosophy. We understand it as one between explanations that focus on an agent’s interaction with its environment, and explanations that focus on the physical or computational enabling conditions of such an interaction. The distinction, understood this way, is necessary for a complete account of any agent, rational or not, biological or artificial. In particular, we review some recent research in Artificial Life that pretends to do completely without the distinction, while using agent-centered concepts all the way. It is argued that the rejection of agent level explanations in favour of mechanistic ones is due to an unmotivated need to choose among representationalism and eliminativism. The dilemma is a false one if the possibility of a radical form of externalism is considered

Adaptable image quality assessment using meta-reinforcement learning of task amenability

The performance of many medical image analysis tasks are strongly associated with image data quality. When developing modern deep learning algorithms, rather than relying on subjective (human-based) image quality assessment (IQA), task amenability potentially provides an objective measure of task-specific image quality. To predict task amenability, an IQA agent is trained using reinforcement learning (RL) with a simultaneously optimised task predictor, such as a classification or segmentation neural network. In this work, we develop transfer learning or adaptation strategies to increase the adaptability of both the IQA agent and the task predictor so that they are less dependent on high-quality, expert-labelled training data. The proposed transfer learning strategy re-formulates the original RL problem for task amenability in a meta-reinforcement learning (meta-RL) framework. The resulting algorithm facilitates efficient adaptation of the agent to different definitions of image quality, each with its own Markov decision process environment including different images, labels and an adaptable task predictor. Our work demonstrates that the IQA agents pre-trained on non-expert task labels can be adapted to predict task amenability as defined by expert task labels, using only a small set of expert labels. Using 6644 clinical ultrasound images from 249 prostate cancer patients, our results for image classification and segmentation tasks show that the proposed IQA method can be adapted using data with as few as respective 19.7 % % and 29.6 % % expert-reviewed consensus labels and still achieve comparable IQA and task performance, which would otherwise require a training dataset with 100 % % expert labels

The Virtual Physiological Human: Ten Years After

Biomedical research and clinical practice are struggling to cope with the growing complexity that the progress of health care involves. The most challenging diseases, those with the largest socioeconomic impact (cardiovascular conditions; musculoskeletal conditions; cancer; metabolic, immunity, and neurodegenerative conditions), are all characterized by a complex genotype–phenotype interaction and by a “systemic” nature that poses a challenge to the traditional reductionist approach. In 2005 a small group of researchers discussed how the vision of computational physiology promoted by the Physiome Project could be translated into clinical practice and formally proposed the term Virtual Physiological Human. Our knowledge about these diseases is fragmentary, as it is associated with molecular and cellular processes on the one hand and with tissue and organ phenotype changes (related to clinical symptoms of disease conditions) on the other. The problem could be solved if we could capture all these fragments of knowledge into predictive models and then compose them into hypermodels that help us tame the complexity that such systemic behavior involves. In 2005 this was simply not possible—the necessary methods and technologies were not available. Now, 10 years later, it seems the right time to reflect on the original vision, the results achieved so far, and what remains to be done

Dupuytren's disease in bosnia and herzegovina. An epidemiological study

BACKGROUND: It is generally held that Dupuytren's disease is more common in northern than in southern Europe, but there are very few studies from southern European countries. METHODS: We examined the hands of 1207 men and women over the age of 50 years in Bosnia and Herzegovina. RESULTS: The prevalence of Dupuytren's disease was highly age-dependent, ranging from 17% for men between 50–59 years to 60% in the oldest men. The prevalence among women was lower. The great majority only had palmar changes without contracture of the digit. The prevalence was significantly lower among Bosnian Muslim men than among Bosnian Croat and Serbian men and significantly increased among diabetics. No association could be detected between Dupuytren's disease and smoking, alcohol consumption or living in rural or urban areas. CONCLUSION: We conclude that, contrary to previous opinion, Dupuytren's disease is common in Bosnia and Herzegovina

Prototypical few-shot segmentation for cross-institution male pelvic structures with spatial registration

The prowess that makes few-shot learning desirable in medical image analysis is the efficient use of the support image data, which are labelled to classify or segment new classes, a task that otherwise requires substantially more training images and expert annotations. This work describes a fully 3D prototypical few-shot segmentation algorithm, such that the trained networks can be effectively adapted to clinically interesting structures that are absent in training, using only a few labelled images from a different institute. First, to compensate for the widely recognised spatial variability between institutions in episodic adaptation of novel classes, a novel spatial registration mechanism is integrated into prototypical learning, consisting of a segmentation head and an spatial alignment module. Second, to assist the training with observed imperfect alignment, support mask conditioning module is proposed to further utilise the annotation available from the support images. Extensive experiments are presented in an application of segmenting eight anatomical structures important for interventional planning, using a data set of 589 pelvic T2-weighted MR images, acquired at seven institutes. The results demonstrate the efficacy in each of the 3D formulation, the spatial registration, and the support mask conditioning, all of which made positive contributions independently or collectively. Compared with the previously proposed 2D alternatives, the few-shot segmentation performance was improved with statistical significance, regardless whether the support data come from the same or different institutes

Variability in EIT Images of Lung Ventilation as a Function of Electrode Planes and Body Positions

This study is aimed at investigating the variability in resistivity changes in the lung region as a function of air volume, electrode plane and body position. Six normal subjects (33.8 ± 4.7 years, range from 26 to 37 years) were studied using the Sheffield Electrical Impedance Tomography (EIT) portable system. Three transverse planes at the level of second intercostal space, the level of the xiphisternal joint, and midway between upper and lower locations were chosen for measurements. For each plane, sixteen electrodes were uniformly positioned around the thorax. Data were collected with the breath held at end expiration and after inspiring 0.5, 1.0, or 1.5 liters of air from end expiration, with the subject in both the supine and sitting position. The average resistivity change in five regions, two 8x8 pixel local regions in the right lung, entire right, entire left and total lung regions, were calculated. The results show the resistivity change averaged over electrode positions and subject positions was 7-9% per liter of air, with a slightly larger resistivity change of 10 % per liter air in the lower electrode plane. There was no significant difference (p\u3e0.05) between supine and sitting. The two 8x8 regions show a larger inter individual variability (coefficient of variation, CV, is from 30% to 382%) compared to the entire left, entire right and total lung (CV is from 11% to 51%). The results for the global regions are more consistent. The large inter individual variability appears to be a problem for clinical applications of EIT, such as regional ventilation. The variability may be mitigated by choosing appropriate electrode plane, body position and region of interest for the analysis

Characterization of highly stable liposomal and immunoliposomal formulations of vincristine and vinblastine

Liposome and immunoliposome formulations of two vinca alkaloids, vincristine and vinblastine, were prepared using intraliposomal triethylammonium sucroseoctasulfate and examined for their ability to stabilize the drug for targeted drug delivery in vivo. The pharmacokinetics of both the encapsulated drug (vincristine or vinblastine) and liposomal carrier were examined in Sprague Dawley rats, and the in vivo drug release rates determined. Anti-HER2 immunoliposomal vincristine was prepared from a human anti-HER2/neu scFv and studied for targeted cytotoxic activity in cell culture, and antitumor efficacy in vivo. Nanoliposome formulations of vincristine and vinblastine demonstrated similar pharmacokinetic profiles for the liposomal carrier, but increased clearance for liposome encapsulated vinblastine (t 1/2 = 9.7 h) relative to vincristine (t 1/2 = 18.5 h). Immunoliposome formulations of vincristine targeted to HER2 using an anti-HER2 scFv antibody fragment displayed a marked enhancement in cytotoxicity when compared to non-targeted liposomal vincristine control; 63- or 253-fold for BT474 and SKBR3 breast cancer cells, respectively. Target-specific activity was also demonstrated in HER2-overexpressing human tumor xenografts, where the HER2-targeted formulation was significantly more efficacious than either free vincristine or non-targeted liposomal vincristine. These results demonstrate that active targeting of solid tumors with liposomal formulations of vincristine is possible when the resulting immunoliposomes are sufficiently stabilized

Matching Models Across Abstraction Levels with Gaussian Processes

Biological systems are often modelled at different levels of abstraction depending on the particular aims/resources of a study. Such different models often provide qualitatively concordant predictions over specific parametrisations, but it is generally unclear whether model predictions are quantitatively in agreement, and whether such agreement holds for different parametrisations. Here we present a generally applicable statistical machine learning methodology to automatically reconcile the predictions of different models across abstraction levels. Our approach is based on defining a correction map, a random function which modifies the output of a model in order to match the statistics of the output of a different model of the same system. We use two biological examples to give a proof-of-principle demonstration of the methodology, and discuss its advantages and potential further applications.Comment: LNCS forma

A direct physical interaction between Nanog and Sox2 regulates embryonic stem cell self-renewal

Embryonic stem (ES) cell self-renewal efficiency is determined by the Nanog protein level. However, the protein partners of Nanog that function to direct self-renewal are unclear. Here, we identify a Nanog interactome of over 130 proteins including transcription factors, chromatin modifying complexes, phosphorylation and ubiquitination enzymes, basal transcriptional machinery members, and RNA processing factors. Sox2 was identified as a robust interacting partner of Nanog. The purified Nanog–Sox2 complex identified a DNA recognition sequence present in multiple overlapping Nanog/Sox2 ChIP-Seq data sets. The Nanog tryptophan repeat region is necessary and sufficient for interaction with Sox2, with tryptophan residues required. In Sox2, tyrosine to alanine mutations within a triple-repeat motif (S X T/S Y) abrogates the Nanog–Sox2 interaction, alters expression of genes associated with the Nanog-Sox2 cognate sequence, and reduces the ability of Sox2 to rescue ES cell differentiation induced by endogenous Sox2 deletion. Substitution of the tyrosines with phenylalanine rescues both the Sox2–Nanog interaction and efficient self-renewal. These results suggest that aromatic stacking of Nanog tryptophans and Sox2 tyrosines mediates an interaction central to ES cell self-renewal