Raman spectroscopy: elucidation of biochemical changes in carcinogenesis of oesophagus

Several techniques are under development to diagnose oesophageal adenocarcinoma at an earlier stage. We have demonstrated the potential of Raman spectroscopy, an optical diagnostic technique, for the identification and classification of malignant changes. However, there is no clear recognition of the biochemical changes that distinguish between the different stages of disease. Our aim is to understand these changes through Raman mapping studies. Raman spectral mapping was used to analyse 20-μm sections of tissue from 29 snap-frozen oesophageal biopsies. Contiguous haematoxylin and eosin sections were reviewed by a consultant pathologist. Principal component analysis was used to identify the major differences between the spectra across each map. Pseudocolour score maps were generated and the peaks of corresponding loads identified enabling visualisation of the biochemical changes associated with malignancy. Changes were noted in the distribution of DNA, glycogen, lipids and proteins. The mean spectra obtained from selected regions demonstrate increased levels of glycogen in the squamous area compared with increased DNA levels in the abnormal region. Raman spectroscopy is a highly sensitive and specific technique for demonstration of biochemical changes in the carcinogenesis of Barrett's oesophagus. There is potential for in vivo application for real-time endoscopic optical diagnosis

24-h sheltering behaviour of individually kept horses during Swedish summer weather

Provision of shelter for horses kept on summer pasture is rarely considered in welfare guidelines, perhaps because the benefits of shelter in warm conditions are poorly documented scientifically. For cattle, shade is a valued resource during summer and can mitigate the adverse effects of warm weather on well-being and performance. We found in a previous study that horses utilized shelters frequently in summer. A shelter with a roof and closed on three sides (shelter A) was preferred and can reduce insect pressure whereas a shelter with roof and open on three sides was not utilized. However, shelter A restricts the all-round view of a horse, which may be important for horses as flight animals. Therefore, we studied whether a shelter with roof, where only the upper half of the rear wall was closed (shelter B), would be utilized while maintaining insect protection properties and satisfying the horses’ sense for security. A third shelter was offered with walls but no roof (shelter C) to evaluate whether the roof itself is an important feature from the horse’s perspective. Eight Warmblood horses were tested each for 2 days, kept individually for 24 h in two paddocks with access to shelters A and B, or shelters A and C, respectively. Shelter use was recorded continuously during the night (1800–2400 h, 0200–0600 h) and the following day (0900–1600 h), and insect defensive behaviour (e.g., tail swish) in instantaneous scan samples at 5-min intervals during daytime

A Minimal Model for Multiple Epidemics and Immunity Spreading

Pathogens and parasites are ubiquitous in the living world, being limited only by availability of suitable hosts. The ability to transmit a particular disease depends on competing infections as well as on the status of host immunity. Multiple diseases compete for the same resource and their fate is coupled to each other. Such couplings have many facets, for example cross-immunization between related influenza strains, mutual inhibition by killing the host, or possible even a mutual catalytic effect if host immunity is impaired. We here introduce a minimal model for an unlimited number of unrelated pathogens whose interaction is simplified to simple mutual exclusion. The model incorporates an ongoing development of host immunity to past diseases, while leaving the system open for emergence of new diseases. The model exhibits a rich dynamical behavior with interacting infection waves, leaving broad trails of immunization in the host population. This obtained immunization pattern depends only on the system size and on the mutation rate that initiates new diseases

Local Difference Measures between Complex Networks for Dynamical System Model Evaluation

Acknowledgments We thank Reik V. Donner for inspiring suggestions that initialized the work presented herein. Jan H. Feldhoff is credited for providing us with the STARS simulation data and for his contributions to fruitful discussions. Comments by the anonymous reviewers are gratefully acknowledged as they led to substantial improvements of the manuscript.Peer reviewedPublisher PD

Design of a decision support system for multiobjective activity planning and programming using global bacteria optimization

The success of any project lies in a great manner on keeping costs in the estimated values, as well as meeting customer required due date. Therefore, there is a current need of developing an information system that facilitates the creation and managing of projects and their processes, including costing schemes, as well as monitoring an optimizing project’s makespan. In order to address this situation a user-friendly information system (IS) was developed. This IS includes an optimization module that reduces the project’s execution time, thus, minimizing costs and ultimately providing the manager with the right tools for the correct development of the project. Therefore, a better planning of activities in a reduced time is accomplished. In this way, the project manager is equipped with a decision support system (DSS) that allows a better decision making and, thanks to this performance optimization, a cost-effective solution can be delivered to the company. The optimization module is the main innovative component in this IS, considering that addresses the problem as a multiobjective one, considering at the same time makespan and cost. This module is based on global bacteria optimization (GBO). This becomes the most relevant improvement when compared to other ISs in the market

Recommender Systems

The ongoing rapid expansion of the Internet greatly increases the necessity of effective recommender systems for filtering the abundant information. Extensive research for recommender systems is conducted by a broad range of communities including social and computer scientists, physicists, and interdisciplinary researchers. Despite substantial theoretical and practical achievements, unification and comparison of different approaches are lacking, which impedes further advances. In this article, we review recent developments in recommender systems and discuss the major challenges. We compare and evaluate available algorithms and examine their roles in the future developments. In addition to algorithms, physical aspects are described to illustrate macroscopic behavior of recommender systems. Potential impacts and future directions are discussed. We emphasize that recommendation has a great scientific depth and combines diverse research fields which makes it of interests for physicists as well as interdisciplinary researchers.Comment: 97 pages, 20 figures (To appear in Physics Reports

Relationship between the expansion of drylands and the intensification of Hadley circulation during the late twentieth century

The changes in coverage by arid climate and intensity of the Hadley circulation during the second half of the twentieth century were examined using observations and the multi-model ensemble (MME) mean of Twentieth-Century Coupled Climate Model (20C3M) simulations. It was found that the area of dry climate, which comprises steppe and desert climates following the Köppen climate classification, expanded to an appreciable extent in observation and, to a lesser degree, in MME simulation. The areal extent of steppe climate (the outer boundary of arid climate) tends to encroach on the surrounding climate groups, which, in turn, feeds desert climate (the inner part of arid climate) and causes it to grow. This result indicates the importance of accurate prediction for climate regimes that border steppe climate. Concomitant with the expansion of drylands, the observed intensity of the Hadley cell is persistently enhanced, particularly during boreal winter, suggesting the validity of a self-induction of deserts through a positive biogeophysical feedback (also known as Charney’s cycle). In comparison, the simulated Hadley circulation in the MME mean remains invariant in time. The current climate models, therefore, disagree with the observation in the long-term linkage between desertification and Hadley cell. Finally, the implication of such discrepancy is discussed as a possible guidance to improve models

A Small Peptide Modeled after the NRAGE Repeat Domain Inhibits XIAP-TAB1-TAK1 Signaling for NF-κB Activation and Apoptosis in P19 Cells

In normal growth and development, apoptosis is necessary to shape the central nervous system and to eliminate excess neurons which are not required for innervation. In some diseases, however, apoptosis can be either overactive as in some neurodegenerative disorders or severely attenuated as in the spread of certain cancers. Bone morphogenetic proteins (BMPs) transmit signals for regulating cell growth, differentiation, and apoptosis. Responding to BMP receptors stimulated from BMP ligands, neurotrophin receptor-mediated MAGE homolog (NRAGE) binds and functions with the XIAP-TAK1-TAB1 complex to activate p38MAPK and induces apoptosis in cortical neural progenitors. NRAGE contains a unique repeat domain that is only found in human, mouse, and rat homologs that we theorize is pivotal in its BMP MAPK role. Previously, we showed that deletion of the repeat domain inhibits apoptosis, p38MAPK phosphorylation, and caspase-3 cleavage in P19 neural progenitor cells. We also showed that the XIAP-TAB1-TAK1 complex is dependent on NRAGE for IKK-α/β phosphorylation and NF-κB activation. XIAP is a major inhibitor of caspases, the main executioners of apoptosis. Although it has been shown previously that NRAGE binds to the RING domain of XIAP, it has not been determined which NRAGE domain binds to XIAP. Here, we used fluorescence resonance energy transfer (FRET) to determine that there is a strong likelihood of a direct interaction between NRAGE and XIAP occurring at NRAGE's unique repeat domain which we also attribute to be the domain responsible for downstream signaling of NF-κB and activating IKK subunits. From these results, we designed a small peptide modeled after the NRAGE repeat domain which we have determined inhibits NF-κB activation and apoptosis in P19 cells. These intriguing results illustrate that the paradigm of the NRAGE repeat domain may hold promising therapeutic strategies in developing pharmaceutical solutions for combating harmful diseases involving excessive downstream BMP signaling, including apoptosis

How does our motor system determine its learning rate?

Motor learning is driven by movement errors. The speed of learning can be quantified by the learning rate, which is the proportion of an error that is corrected for in the planning of the next movement. Previous studies have shown that the learning rate depends on the reliability of the error signal and on the uncertainty of the motor system’s own state. These dependences are in agreement with the predictions of the Kalman filter, which is a state estimator that can be used to determine the optimal learning rate for each movement such that the expected movement error is minimized. Here we test whether not only the average behaviour is optimal, as the previous studies showed, but if the learning rate is chosen optimally in every individual movement. Subjects made repeated movements to visual targets with their unseen hand. They received visual feedback about their endpoint error immediately after each movement. The reliability of these error-signals was varied across three conditions. The results are inconsistent with the predictions of the Kalman filter because correction for large errors in the beginning of a series of movements to a fixed target was not as fast as predicted and the learning rates for the extent and the direction of the movements did not differ in the way predicted by the Kalman filter. Instead, a simpler model that uses the same learning rate for all movements with the same error-signal reliability can explain the data. We conclude that our brain does not apply state estimation to determine the optimal planning correction for every individual movement, but it employs a simpler strategy of using a fixed learning rate for all movements with the same level of error-signal reliability

The impact of financial incentives on the implementation of asthma or diabetes self-management: A systematic review

Introduction: Financial incentives are utilised in healthcare systems in a number of countries to improve quality of care delivered to patients by rewarding practices or practitioners for achieving set targets. Objectives: To systematically review the evidence investigating the impact of financial incentives for implementation of supported self-management on quality of care including: organisational process outcomes, individual behavioural outcomes, and health outcomes for individuals with asthma or diabetes; both conditions with an extensive evidence base for self-management. Methods: We followed Cochrane methodology, using a PICOS search strategy to search eight databases in November 2015 (updated May 2017) including a broad range of implementation methodologies. Studies were weighted by robustness of methodology, number of participants and the quality score. We used narrative synthesis due to heterogeneity of studies. Results: We identified 2,541 articles; 12 met our inclusion criteria. The articles were from the US (n = 7), UK (n = 4) and Canada (n = 1). Measured outcomes were HbA1c tests undertaken and/or the level achieved (n = 10), written action plans for asthma (n = 1) and hospital/emergency department visits (n = 1). Three of the studies were part of a larger incentive scheme including many conditions; one focused on asthma; eight focussed on diabetes. In asthma, the proportion receiving ‘perfect care’ (including providing a written action plan) increased from 4% to 88% in one study, and there were fewer hospitalisations/emergency department visits in another study. Across the diabetes studies, quality-of-care/GP performance scores improved in three, were unchanged in six and deteriorated in one. Conclusions: Results for the impact of financial incentives for the implementation of self-management were mixed. The evidence in diabetes suggests no consistent impact on diabetic control. There was evidence from a single study of improved process and health outcomes in asthma. Further research is needed to confirm these findings and understand the process by which financial incentives may impact (or not) on care