Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study

Chronic Fatigue Syndrome (CFS) is a multisystem illness, which may be associated with imbalances in gut microbiota. This study builds on recent evidence that sleep may be influenced by gut microbiota, by assessing whether changes to microbiota in a clinical population known to have both poor sleep and high rates of colonization with gram-positive faecal Streptococcus, can improve sleep. Twenty-one CFS participants completed a 22- day open label trial. Faecal microbiota analysis was performed at baseline and at the end of the trial. Participants were administered erythromycin 400 mg b.d. for 6 days. Actigraphy and questionnaires were used to monitor sleep, symptoms and mood. Changes in patients who showed a clinically significant change in faecal Streptococcus after treatment (responders; defined as post-therapy distribution<6%) were compared to participants who did not respond to treatment. In the seven responders, there was a significant increase in actigraphic total sleep time (p=0.028) from baseline to follow up, compared with non-responders. Improved vigour scores were associated with a lower Streptococcus count (ρ=-0.90, p=0.037). For both the responders and the whole group, poorer mood was associated with higher Lactobacillus. Short term antibiotic treatment appears to be insufficient to effect sustainable changes in the gut ecosystem in most CFS participants. Some improvement in objective sleep parameters and mood were found in participants with reduced levels of gram-positive gut microbiota after antibiotic treatment, which is encouraging. Further study of possible links between gut microorganisms and sleep and mood disturbances is warranted

Online optimal and adaptive integral tracking control for varying discrete‐time systems using reinforcement learning

Conventional closed‐form solution to the optimal control problem using optimal control theory is only available under the assumption that there are known system dynamics/models described as differential equations. Without such models, reinforcement learning (RL) as a candidate technique has been successfully applied to iteratively solve the optimal control problem for unknown or varying systems. For the optimal tracking control problem, existing RL techniques in the literature assume either the use of a predetermined feedforward input for the tracking control, restrictive assumptions on the reference model dynamics, or discounted tracking costs. Furthermore, by using discounted tracking costs, zero steady‐state error cannot be guaranteed by the existing RL methods. This article therefore presents an optimal online RL tracking control framework for discrete‐time (DT) systems, which does not impose any restrictive assumptions of the existing methods and equally guarantees zero steady‐state tracking error. This is achieved by augmenting the original system dynamics with the integral of the error between the reference inputs and the tracked outputs for use in the online RL framework. It is further shown that the resulting value function for the DT linear quadratic tracker using the augmented formulation with integral control is also quadratic. This enables the development of Bellman equations, which use only the system measurements to solve the corresponding DT algebraic Riccati equation and obtain the optimal tracking control inputs online. Two RL strategies are thereafter proposed based on both the value function approximation and the Q‐learning along with bounds on excitation for the convergence of the parameter estimates. Simulation case studies show the effectiveness of the proposed approach

Providing Self-Aware Systems with Reflexivity

We propose a new type of self-aware systems inspired by ideas from higher-order theories of consciousness. First, we discussed the crucial distinction between introspection and reflexion. Then, we focus on computational reflexion as a mechanism by which a computer program can inspect its own code at every stage of the computation. Finally, we provide a formal definition and a proof-of-concept implementation of computational reflexion, viewed as an enriched form of program interpretation and a way to dynamically "augment" a computational process.Comment: 12 pages plus bibliography, appendices with code description, code of the proof-of-concept implementation, and examples of executio

On Component Forces in Physics: A Pragmatic View

Do component forces exist? I argue that the answer lies in the affirmative, on historical and operational grounds

Within You / Without You: Biotechnology, Ontology, and Ethics

As Implantable Cardioverter Defibrillators (ICDs) have become more common, ethical issues have arisen regarding the deactivation of these devices. Goldstein et al., have shown that both patients and cardiologists consider ICD deactivation to be different from the discontinuation of other life-sustaining treatments. It cannot be argued ethically that ICDs raise new questions about the distinction between withholding and withdrawing treatment, and neither the fact that they are used intermittently, nor the duration of therapy, nor the mere fact that they are located inside the body can be considered unique to these devices and morally decisive. However, frequent allusions to the fact that they are located inside the body might provide a clue about what bothers patients and physicians. As technology progresses, some interventions seem to become a part of the patient as a unified whole person, completely replacing body parts and lost physiological functions rather than merely substituting for impaired structure and function. If a life-sustaining intervention can be considered a “replacement”—a part of the patient as a unified whole person—then it seems that deactivation is better classified as a case of killing rather than a case of forgoing a life-sustaining treatment. ICDs are not a “replacement” therapy in this sense. The deactivation of an ICD is best classified, under the proper conditions, as the forgoing of an extraordinary means of care. As technology becomes more sophisticated, however, and new interventions come to be best classified as “replacements” (a heart transplant would be a good example), “discontinuing” these interventions should be much more morally troubling for those clinicians who oppose euthanasia and assisted suicide

Association networks and social temporal dynamics in ewes and lambs

This is the final version. Available on open access from Elsevier via the DOI in this recordSheep are highly social domesticated animals that evolved to live in large and structured groups. As in other group-living species, individuals differ in the level of association they have with others, and these associations often result in lasting and stable social bonds. However, there are substantial gaps in our knowledge of the temporal social dynamics in sheep, and how their social bonds vary in relation to environmental changes. Here, we aimed to assess the social relationships between ewes and lambs, collecting dyadic associations data of 41 ewes and 55 lambs through the use of proximity loggers on a commercial farm. We computed association indices between each pair of animals to estimate the proportion of time any two individuals associated. We first generated an aggregated network of the whole 13-day observation period, and we compared the values of association indices between different types of dyads (i.e., lamb-mother, lamb-ewe non-mother, lambs littermates, lambs non-littermates, ewe-ewe). We generated aggregated contact networks on a daily scale to compare the ego-networks of individuals obtained in successive time windows to determine how stable social associations were over time. As would be expected, the highest values of association indices were found in dyads formed by dams and lambs (0.17±0.11) and by lambs of the same litter (0.32±0.09). Both single-born and twin-born lambs showed high association values with their dams (single-born: 0.24±0.11; twin-born: 0.1±0.05), although twin-born lambs had stronger associations with their littermates compared with those with their mothers (p-value < 0.001). At a temporal level, the flock exhibited periods of high network stability at the beginning and at the end of the study period. However, periods of social instability occurred one-two days after management interventions, such as changes in field size. These transitory periods of social instability were driven by changes in the association patterns of ewes and single born lambs. In contrast, the ego-networks of twin-born lambs remained relatively stable, supported by strong association levels between twins. Thus, the social instability of the social network was not a global one, but some parts of the network remained stable while others underwent important changes. Our study represents a first step to track social associations within an ewe-lamb group using proximity tags and advances our understanding of the social organisation of sheep. We highlight the importance of detecting social network instability as a consequence of different types of perturbations in order to identify the presence of social rearrangements.Biotechnology & Biological Sciences Research Council (BBSRC)CRT Foundatio

Validation of methods for converting the original Disease Activity Score (DAS) to the DAS28

© The Author(s) 2018.The Disease Activity Score (DAS) is integral in tailoring the clinical management of rheumatoid arthritis (RA) patients and is an important measure in clinical research. Different versions have been developed over the years to improve reliability and ease of use. Combining the original DAS and the newer DAS28 data in both contemporary and historical studies is important for both primary and secondary data analyses. As such, a methodologically robust means of converting the old DAS to the new DAS28 measure would be invaluable. Using data from The Early RA Study (ERAS), a sub-sample of patients with both DAS and DAS28 data were used to develop new regression imputation formulas using the total DAS score (univariate), and using the separate components of the DAS score (multivariate). DAS were transformed to DAS28 using an existing formula quoted in the literature, and the newly developed formulas. Bland and Altman plots were used to compare the transformed DAS with the recorded DAS28 to ascertain levels of agreement. The current transformation formula tended to overestimate the true DAS28 score, particularly at the higher end of the scale. A formula which uses all separate components of the DAS was found to estimate the scores with a higher level of precision. A new formula is proposed that can be used by other early RA cohorts to convert the original DAS to DAS28.Peer reviewedFinal Published versio

Laser treatment in diabetic retinopathy

Diabetic retinopathy is a leading cause of visual impairment and blindness in developed countries due to macular edema and proliferative diabetic retinopathy (PDR). For both complications laser treatment may offer proven therapy: the Diabetic Retinopathy Study demonstrated that panretinal scatter photocoagulation reduces the risk of severe visual loss by >= 50% in eyes with high-risk characteristics. Pan-retinal scatter coagulation may also be beneficial in other PDR and severe nonproliferative diabetic retinopathy (NPDR) under certain conditions. For clinically significant macular edema the Early Treatment of Diabetic Retinopathy Study could show that immediate focal laser photocoagulation reduces the risk of moderate visual loss by at least 50%. When and how to perform laser treatment is described in detail, offering a proven treatment for many problems associated with diabetic retinopathy based on a high evidence level. Copyright (c) 2007 S. Karger AG, Basel