Taming Model Uncertainty in Self-adaptive Systems Using Bayesian Model Averaging

Research on uncertainty quantification and mitigation of software-intensive systems and (self-)adaptive systems, is increasingly gaining momentum, especially with the availability of statistical inference techniques (such as Bayesian reasoning) that make it possible to mitigate uncertain (quality) attributes of the system under scrutiny often encoded in the system model in terms of model parameters. However, to the best of our knowledge, the uncertainty about the choice of a specific system model did not receive the deserved attention.This paper focuses on self-adaptive systems and investigates how to mitigate the uncertainty related to the model selection process, that is, whenever one model is chosen over plausible alternative and competing models to represent the understanding of a system and make predictions about future observations. In particular, we propose to enhance the classical feedback loop of a self-adaptive system with the ability to tame the model uncertainty using Bayesian Model Averaging. This method improves the predictions made by the analyze component as well as the plan that adopts metaheuristic optimizing search to guide the adaptation decisions. Our empirical evaluation demonstrates the cost-effectiveness of our approach using an exemplar case study in the robotics domain

Human herpesvirus 6: An emerging pathogen.

Infections with human herpesvirus 6 (HHV-6), a beta-herpesvirus of which two variant groups (A and B) are recognized, is very common, approaching 100% in seroprevalence. Primary infection with HHV-6B causes roseola infantum or exanthem subitum, a common childhood disease that resolves spontaneously. After primary infection, the virus replicates in the salivary glands and is shed in saliva, the recognized route of transmission for variant B strains; it remains latent in lymphocytes and monocytes and persists at low levels in cells and tissues. Not usually associated with disease in the immunocompetent, HHV-6 infection is a major cause of opportunistic viral infections in the immunosuppressed, typically AIDS patients and transplant recipients, in whom HHV-6 infection/reactivation may culminate in rejection of transplanted organs and death. Other opportunistic viruses, human cytomegalovirus and HHV-7, also infect or reactivate in persons at risk. Another disease whose pathogenesis may be correlated with HHV-6 is multiple sclerosis. Data in favor of and against the correlation are discussed

SKIN, INFLAMMATION AND SULFUROUS WATERS: WHAT IS KNOWN, WHAT IS BELIEVED

One could argue that balneotherapy and mud therapy would have not lasted 2,000 years or so If they were not effective. No doubt a long history cannot be taken per se as scientific proof of efficacy. Some empiricism is still present in the field: the concept of spa itself is quite confounding, whereas spring waters are used for leisure purposes but also for non-acute patient therapy and late phases of clinical recovery. These confounding elements ultimately feed the opinion of those who aprioristically reject any potential beneficial effect of balneotherapy: instead, it should at least generate questions that deserve scientific answers. Clinical practices sequentially integrating pharmacological therapy with those natural principles for which a sufficient scientific demonstration is available, would probably cut the costs of public health, generating widespread advantages for the community. Recently, it has become evident that mineral waters may have intrinsic pharmacological properties. Of the numerous salts dissolved in thermal waters that might show pharmacological properties, for certain hydrogen sulfide (H2S) contained in sulfurous waters is the one that has obtained greater scientific attention, to which should be added the extensive scientific effort recently dedicated to H2S as a cellular gasotransmitter, independently from its natural sources. Dermatology and cosmetics are among the most studied applications of sulfurous waters, around which, however, some empiricism still confounds opinions: we therefore considered that a state-of-the-art focus on this topic might be timely and useful for future studies

The Geography of Sexual Orientation: Structural Stigma and Sexual Attraction, Behavior, and Identity Among Men Who Have Sex with Men Across 38 European Countries.

: While the prevalence of sexual identities and behaviors of men who have sex with men (MSM) varies across countries, no study has examined country-level structural stigma toward sexual minorities as a correlate of this variation. Drawing on emerging support for the context-dependent nature of MSM's open sexual self-identification cross-nationally, we examined country-level structural stigma as a key correlate of the geographic variation in MSM's sexual attraction, behavior, and identity, and concordance across these factors. Data come from the European MSM Internet Survey, a multi-national dataset containing a multi-component assessment of sexual orientation administered across 38 European countries (N = 174,209). Country-level stigma was assessed using a combination of national laws and policies affecting sexual minorities and a measure of attitudes toward sexual minorities held by the citizens of each country. Results demonstrate that in more stigmatizing countries, MSM were significantly more likely to report bisexual/heterosexual attractions, behaviors, and identities, and significantly less likely to report concordance across these factors, than in less stigmatizing countries. Settlement size moderated associations between country-level structural stigma and odds of bisexual/heterosexual attraction and behavior, such that MSM living in sparsely populated locales within high-structural stigma countries were the most likely to report bisexual or heterosexual behaviors and attractions. While previous research has demonstrated associations between structural stigma and adverse physical and mental health outcomes among sexual minorities, this study was the first to show that structural stigma was also a key correlate not only of sexual orientation identification, but also of MSM's sexual behavior and even attraction. Findings have implications for understanding the ontology of MSM's sexuality and suggest that a comprehensive picture of MSM's sexuality will come from attending to the local contexts surrounding this important segment of the global population.<br/

Tracking fibrosis in myeloproliferative neoplasms by CCR2 expression on CD34+ cells

In myeloproliferative neoplasm (MPNs), bone marrow fibrosis - mainly driven by the neoplastic megakaryocytic clone - dictates a more severe disease stage with dismal prognosis and higher risk of leukemic evolution. Therefore, accurate patient allocation into different disease categories and timely identification of fibrotic transformation are mandatory for adequate treatment planning. Diagnostic strategy still mainly relies on clinical/laboratory assessment and bone marrow histopathology, which, however, requires an invasive procedure and frequently poses challenges also to expert hemopathologists. Here we tested the diagnostic accuracy of the detection, by flow cytometry, of CCR2+CD34+ cells to discriminate among MPN subtypes with different degrees of bone marrow fibrosis. We found that the detection of CCR2 on MPN CD34+ cells has a very good diagnostic accuracy for the differential diagnosis between “true” ET and prePMF (AUC 0.892, P&lt;0.0001), and a good diagnostic accuracy for the differential diagnosis between prePMF and overtPMF (AUC 0.817, P=0.0089). Remarkably, in MPN population, the percentage of CCR2-expressing cells parallels the degree of bone marrow fibrosis. In ET/PV patients with a clinical picture suggestive for transition into spent phase, we demonstrated that only patients with confirmed secondary MF showed significantly higher levels of CCR2+CD34+ cells. Overall, flow cytometric CCR2+CD34+ cell detection can be envisioned in support of conventional bone marrow histopathology in compelling clinical scenarios, with the great advantage of being extremely rapid. For patients in follow-up, its role can be conceived as an initial patient screening for subsequent bone marrow biopsy when disease evolution is suspected

ROS in platelet biology: Functional aspects and methodological insights

© 2020 by the authors. Reactive oxygen species (ROS) and mitochondria play a pivotal role in regulating platelet functions. Platelet activation determines a drastic change in redox balance and in platelet metabolism. Indeed, several signaling pathways have been demonstrated to induce ROS production by NAPDH oxidase (NOX) and mitochondria, upon platelet activation. Platelet-derived ROS, in turn, boost further ROS production and consequent platelet activation, adhesion and recruitment in an auto-amplifying loop. This vicious circle results in a platelet procoagulant phenotype and apoptosis, both accounting for the high thrombotic risk in oxidative stress-related diseases. This review sought to elucidate molecular mechanisms underlying ROS production upon platelet activation and the effects of an altered redox balance on platelet function, focusing on the main advances that have been made in platelet redox biology. Furthermore, given the increasing interest in this field, we also describe the up-to-date methods for detecting platelets, ROS and the platelet bioenergetic profile, which have been proposed as potential disease biomarkers

Buffering Adaptive Immunity by Hydrogen Sulfide

Abstract: T cell-mediated adaptive immunity is designed to respond to non-self antigens and pathogens through the activation and proliferation of various T cell populations. T helper 1 (Th1), Th2, Th17 and Treg cells finely orchestrate cellular responses through a plethora of paracrine and autocrine stimuli that include cytokines, autacoids, and hormones. Hydrogen sulfide (H2S) is one of these mediators able to induce/inhibit immunological responses, playing a role in inflammatory and autoimmune diseases, neurological disorders, asthma, acute pancreatitis, and sepsis. Both endogenous and exogenous H2S modulate numerous important cell signaling pathways. In monocytes, polymorphonuclear, and T cells H2S impacts on activation, survival, proliferation, polarization, adhesion pathways, and modulates cytokine production and sensitivity to chemokines. Here, we offer a comprehensive review on the role of H2S as a natural buffer able to maintain over time a functional balance between Th1, Th2, Th17 and Treg immunological responses

Different waters for different performances: Can we imagine sport-related natural mineral spring waters?

Preserving the hydration status means to balance daily fluids and salt losses with gains, where the losses depend on several physiological and environmental factors. Especially for athletes, these losses could be relevant and negatively influence the performance: therefore, their hydro-saline status must be preserved with personalized pre-and rehydration plans all along the performance period. Scientific literature in this field is mainly dedicated to artificial sport drinks. Different territories in most world areas are rich in drinking natural mineral spring waters with saline compositions that reflect their geological origin and that are used for human health (often under medical prescription). However, scarce scientific attention has been dedicated to the use of these waters for athletes. We therefore reviewed the existing literature from the innovative viewpoint of matching spring water mineral compositions with different athletic performances and their hydro-saline requirements