BackgroundEvidence suggests that organizational models that provide care interventions including patient support programs may increase patient adherence to multiple sclerosis therapies by providing tailored symptom management, informational support, psychological and/or social support, lifestyle changes, emotional adjustment, health education, and tailored coaching, thus improving patients' overall quality of life across the disease course.ObjectiveThe main objective of this study was to describe MS patients' self-reported experience of a nurse-led, telephone-based PSP and to explore its potential role in improving disease and therapy management (...) skills.MethodsSurvey data were analyzed from a subset of patients relapsing–remitting MS using interferon beta-1a already registered in the adveva® PSP from three Italian multiple sclerosis centers with a consolidated experience in RRMS disease, treatment management, and PSP programs.ResultsIn total, 244 patient data at baseline were analyzed, of which 115 had a follow-up of at least 6 months. Results from this study provide an early view into the role of this PSP in improving the patients reported overall experience regarding disease management and injectable therapy, thus potentially ameliorating treatment adherence and decreasing health care cost. Moreover, study findings confirm the role of providing a patient-focused support by addressing non-medication-related topics in the PSP consultations. Indeed, patients involved in the adveva® PSP program reported a better psychological status in the follow up as demonstrated by an increased optimism regarding their future, tolerance of disease uncertainty, and their perceived ability to benefit from external help and social support.ConclusionsAs such, it is reasonable to conclude that the involvement in the adveva® PSP and the PSP's assistance in guiding patients on proper treatment self-management techniques is of great value to patients as it might contribute to improving engagement in their health care journey in terms of perceived self-care skills, emotional coping toward the future and the unpredictability of the disease course and their general attitudes toward the injection itself, involving pain tolerance. (shrink)

A possible explanation for policy implementation failure is that the views of the policy’s target groups are insufficiently taken into account during policy development. It has been argued that involving these groups in an interactive process of policy development could improve this. We analysed a project in which several target populations participated in workshops aimed to optimise the utilisation of an expensive novel drug (interferon beta) for patients with Multiple Sclerosis. All participants seemed to agree on the appropriateness (...) of establishing a central registry of Multiple Sclerosis patients and developing guidelines. Nevertheless, these policy measures were not implemented. Possible explanations include (1) the subject no longer had high priority when the costs appeared lower than expected, (2) the organisers had paid insufficient attention to the perceived problems of parties involved, and (3) changes within the socio-political context. The workshops in which representatives of the policy’s target populations participated did not provide enough interactivity to prevent policy implementation failure. (shrink)

Name der Zeitschrift: Byzantinische Zeitschrift Jahrgang: 107 Heft: 1 Seiten: 37-50.

Interferons (IFNs) are a diverse group of cytokines whose potent antitumor effects have piqued the interest of scientists for decades. Some of the most sustained clinical accomplishments have been in the field of myeloproliferative neoplasms (MPNs). Here, we discuss how both historical and novel breakthroughs in our understanding of IFN function may lead to more effective therapies for MPNs. The particular relevance and importance of modulating the novel IFN‐regulated ULK1 pathway to optimize IFN responses is highlighted.

Noradrenergic pathways are involved in mediating the central and peripheral effects of physiological arousal. The aim of the present study was to investigate the role of noradrenergic transmission in moral decision-making. We studied the effects in healthy volunteers of propranolol (a noradrenergic beta-adrenoceptor antagonist) on moral judgement in a set of moral dilemmas pitting utilitarian outcomes (e.g., saving five lives) against highly aversive harmful actions (e.g., killing an innocent person) in a double-blind, placebo-controlled, parallel group design. Propranolol (40 mg (...) orally) significantly reduced heart rate, but had no effect on self-reported mood. Importantly, propranolol made participants more likely to judge harmful actions as morally unacceptable, but only in dilemmas where harms were ‘up close and personal’. In addition, longer response times for such personal dilemmas were only found for the placebo group. Finally, judgments in personal dilemmas by the propranolol group were more decisive. These findings indicate that noradrenergic pathways play a role in responses to moral dilemmas, in line with recent work implicating emotion in moral decision-making. However, contrary to current theorising, these findings also suggest that aversion to harming is not driven by emotional arousal. Our findings are also of significant practical interest given that propranolol is a widely used drug in different settings, and is currently being considered as a potential treatment for post-traumatic stress disorder in military and rescue service personnel. (shrink)

The Protein Ontology (PRO) is designed as a formal and principled Open Biomedical Ontologies (OBO) Foundry ontology for proteins. The components of PRO extend from a classification of proteins on the basis of evolutionary relationships at the homeomorphic level to the representation of the multiple protein forms of a gene, including those resulting from alternative splicing, cleavage and/or posttranslational modifications. Focusing specifically on the TGF-beta signaling proteins, we describe the building, curation, usage and dissemination of PRO. PRO provides a (...) framework for the formal representation of protein classes and protein forms in the OBO Foundry. It is designed to enable data retrieval and integration and machine reasoning at the molecular level of proteins, thereby facilitating cross-species comparisons, pathway analysis, disease modeling and the generation of new hypotheses. (shrink)

This paper aims to enhance security in IoT device networks through a visual tool that utilizes three projection techniques, including Beta Hebbian Learning (BHL), t-distributed Stochastic Neighbor Embedding (t-SNE) and ISOMAP, in order to facilitate the identification of network attacks by human experts. This work research begins with the creation of a testing environment with IoT devices and web clients, simulating attacks over Message Queuing Telemetry Transport (MQTT) for recording all relevant traffic information. The unsupervised algorithms chosen provide a (...) set of projections that enable human experts to visually identify most attacks in real-time, making it a powerful tool that can be implemented in IoT environments easily. (shrink)

As it is well known, mobile phones have become a basic gadget for any individual that usually stores sensitive information. This mainly motivates the increase in the number of attacks aimed at jeopardizing smartphones, being an extreme concern above all on Android OS, which is the most popular platform in the market. Consequently, a strong effort has been devoted for mitigating mentioned incidents in recent years, even though few researchers have addressed the application of visualization techniques for the analysis of (...) malware. Within this field, the present work proposes the extension of a new technique called Hybrid Unsupervised Exploratory Plots to visualize Android malware datasets. More precisely, the novel Beta-Hebbian Learning (BHL) method is applied for the first time and validated under the frame of Hybrid Unsupervised Exploratory Plots, in conjunction with clustering methods. The informative visualization achieved provides a picture of the structure of the malware families, allowing subsequent analysis of their organization. To validate the Hybrid Unsupervised Exploratory Plot extension and its tuning, the popular Android Malware Genome dataset has been used in the experimental setting. Promising results have been obtained, suggesting that BHL applied in combination with clustering techniques in Hybrid Unsupervised Exploratory Plots are a viable resource for the visualization of malware families. (shrink)

Interferon (IFN) induced during a virus infection mediates antiviral effects both by direct inhibition of virus replication and by influencing the proliferation, differentiation, and chemotaxis of cyto‐toxic lymphocytes which control the infection. Cells from tissue taken from virus‐infected mice are conditioned by IFN to resist lysis by natural killer (NK) cells, while they become increasingly susceptible to lysis by cytotoxic Tlymphocytes (CTL). This is due to marked IFN‐induced biochemical changes, including an up‐regulation of major histocompatibility antigens, which are targets (...) for CTL. Cytopathic viruses, which inhibit cellular RNA and protein synthesis, render target cells refractory to IFN‐mediated protection against NK cells, thereby providing a mechanism for NK cells to mediate antiviral effect by preferentially lysing virus‐infected but not uninfected cells. (shrink)

The three main kinds of theory in normative ethics, namely, consequentialism, deontology, and virtue ethics, are often presented as the ‘palette’ from which we may choose, or use as a starting point for an investigation. However, this way of doing ethics and philosophy, by the palette, may be leading some of us astray. It has led some to believe that all that there is to ethics, and to ethics of AI, is given in terms of these already devised petrified categories (...) of theory. It has also led others to abandon normative ethics and philosophy altogether and to resort to descriptive methods that are then used to justify action. I wish to argue that (1) we should not abandon traditional philosophical approaches, but (2a) this does not entail that the petrified palette should constitute the beginning of our philosophical investigations. Further, (2b) I recommend a non-methodological approach in which it is instead radical questions that spur these investigations, which arise through consideration of the practical actions (potential or otherwise) of machines and their programmers. (shrink)

More than 15 million people have been affected by coronavirus disease 2019 (COVID‐19) and it has caused 640 016 deaths as of July 26, 2020. Currently, no effective treatment option is available for COVID‐19 patients. Though many drugs have been proposed, none of them has shown particular efficacy in clinical trials. In this article, the relationship between the Adrenergic system and the renin‐angiotensin‐aldosterone system (RAAS) is focused in COVID‐19 and a vicious circle consisting of the Adrenergic system‐RAAS‐Angiotensin converting enzyme 2 (...) (ACE2)‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) (which is referred to as the “ARAS loop”) is proposed. Hyperactivation of the ARAS loop may be the underlying pathophysiological mechanism in COVID‐19, and beta‐adrenergic blockers are proposed as a potential treatment option. Beta‐adrenergic blockers may decrease the SARS‐CoV‐2 cellular entry by decreasing ACE2 receptors expression and cluster of differentiation 147 (CD147) in various cells in the body. Beta‐adrenergic blockers may decrease the morbidity and mortality in COVID‐19 patients by preventing or reducing acute respiratory distress syndrome (ARDS) and other complications. Retrospective and prospective clinical trials should be conducted to check the validity of the hypothesis. Also see the video abstract here https://youtu.be/uLoy7do5ROo. (shrink)

Modal contingentists face a dilemma: there are two attractive principles of which they can only accept one. In this paper I show that the most natural way of resolving the dilemma leads to expressive limitations. I then develop an alternative resolution. In addition to overcoming the expressive limitations, the alternative picture allows for an attractive account of arithmetic and for a style of semantic theorizing that can be helpful to contingentists.

In order to survive, the developing conceptus must interrupt the normal ovarian cycle of the mother and extend the production of progesterone by the corpus luteum. An unusual Type 1 interferon (IFN), related structurally to the IFN–α molecule and produced in massive amounts for only a few days by the first epithelium (trophectoderm) of the preimplantation conceptus, has been implicated as the antiluteolytic agent in sheep and cattle. IFN‐a therapy during this critical period can also improve pregnancy success in (...) sheep. It remains unclear, however, whether the trophoblast IFN have specialized biological properties or whether they are unique merely in the timing, magnitude and site of their expression. (shrink)

The beta thymosins are a highly conserved family of strongly polar 5 kDa polypeptides that are widely distributed among vertebrate classes; most are now known to bind to monomeric actin and inhibit its polymerization. One beta thymosin, beta four, (Tβ4) is the predominant form in mammalian cells, present at up to 0.5 mM. Many species are known to produce at least two beta thymosin isoforms, in some cases in the same cell. Their expression can be separately (...) regulated. When present outside the cell, the N‐terminal tetrapeptide of beta four appears to affect cell cycle regulation; beta thymosins or smaller fragments derived from them may have additional regulatory functions. We suggest that many developmental changes in beta thymosin levels within cells and tissues may be related to changes in G‐actin pool size. (shrink)

Stroke remains one of the leading causes of various disabilities, including debilitating motor and language impairments. Though various treatments exist, post-stroke impairments frequently become chronic, dramatically reducing daily life quality, and requiring specific rehabilitation. A critical goal of chronic stroke rehabilitation is to induce, usually through behavioral training, experience-dependent plasticity processes in order to promote functional recovery. However, the efficiency of such interventions is typically modest, and very little is known regarding the neural dynamics underpinning recovery processes and possible biomarkers (...) of their efficiency. Some studies have emphasized specific alterations of excitatory–inhibitory balance within distributed neural networks as an important recovery correlate. Neural processes sensitive to these alterations, such as task-dependent oscillatory activity in beta as well as alpha bands, may be candidate biomarkers of chronic stroke functional recovery. In this review, we discuss the results of studies on motor and language recovery with a focus on oscillatory processes centered around the beta band and their modulations during functional recovery in chronic stroke. The discussion is based on a framework where task-dependent modulations of beta and alpha oscillatory activity, generated by the deep cortical excitatory–inhibitory microcircuits, serve as a neural mechanism of domain-general top-down control processes. We discuss the findings, their limitations, and possible directions for future research. (shrink)

In three recent articles it was shown that β‐catenin is crucial for the establishment and the maintenance of the overall polarity and especially for the character ‘posterior’ in planarians. If the transcription of the β‐catenin gene was silenced by RNA interference, the overall polarity is lost, and in regenerating fragments a posterior blastema displays anterior characters by forming eyes and anterior ganglia. An attempt is made to integrate these new data, well‐known older observations, and observations from other regenerating systems into (...) an outline of a model that will clarify our current understanding as well as highlight areas still to be developed. (shrink)

Neurosteroid 17 beta-estradiol (E2) is a steroid synthesized de novo in the nervous system that might influence neuronal activity and behavior. Nevertheless, the impact of E2 on the functioning of those neural systems in which it is slightly synthesized is less questioned. The vestibulo-ocular reflex (VOR) adaptation, may provide an ideal arena for investigating this issue. Indeed, E2 modulates cerebellar parallel fiber-Purkinje cell synaptic plasticity that underlies encoding of VOR adaptation. Moreover, aromatase expression in the cerebellum of adult rodents (...) is maintained at very low levels and localized to Purkinje cells. The significance of age-related maintenance of low levels of aromatase expression in the cerebellum on behavior, however, has yet to be explored. Our aim in this study was to determine whether E2 synthesis exerts an effective and persistent modulation of VOR adaptation in adult male rats. To answer this question, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in VOR adaptation using an oral dose (2.5 mg/kg) of the aromatase inhibitor Letrozole in peri-pubertal and post-pubertal male rats. We found that Letrozole acutely impaired gain increases and decreases in VOR adaptation without altering basal ocular-motor performance and that these effects were similar in peri-pubertal and post-pubertal rats. Thus, in adult male rats neurosteroid E2 effectively modulates VOR adaptation in both of the periods studied. These findings imply that the adult cerebellum uses E2 synthesis for modulating motor memory formation and suggest that low and extremely localized E2 production may play a role in adaptive phenomena. (shrink)

Logicians have strongly preferred first-order natural deductive systems over Peirce's Beta Graphs even though both are equivalent to each other. One of the main reasons for this preference, I claim, is that inference rules for Beta Graphs are hard to understand, and, therefore, hard to apply for deductions. This paper reformulates the Beta rules to show more fine-grained symmetries built around visual features of the Beta system, which makes the rules more natural and easier to use (...) and understand. Noting that the rules of a natural deductive system are natural in a different sense, this case study shows that the naturalness and the intuitiveness of rules depends on the type of representation system to which they belong. In a diagrammatic system, when visual features are discovered and fully used, we have a more efficacious deductive system. I will also show that this project not only helps us to apply these rules more easily but to understand the validity of the system at a more intuitive level. (shrink)

Phi Beta Kappa Romanell Lectures, given at Michigan State University, February 2008.

Alpha-beta pruning is a technique for pruning trees in artificial intelligence game-playing. This note draws an analogy between the technique, which is, in essence, an application of many-valued logic to the cut-off of the evaluation of conditionals in computer programs (for efficiency).

Let ${\beta(\mathbb{N})}$ denote the Stone–Čech compactification of the set ${\mathbb{N}}$ of natural numbers (with the discrete topology), and let ${\mathbb{N}^\ast}$ denote the remainder ${\beta(\mathbb{N})-\mathbb{N}}$ . We show that, interpreting modal diamond as the closure in a topological space, the modal logic of ${\mathbb{N}^\ast}$ is S4 and that the modal logic of ${\beta(\mathbb{N})}$ is S4.1.2.

The theory of existential graphs, which Peirce ultimately divided into four quadrants , is a rich method of analysis in the philosophy of logic. Its $$\upbeta $$ β -part boasts a diagrammatic theory of quantification, which by 1902 Peirce had used in the logical analysis of natural-language expressions such as complex donkey-type anaphora, quantificational patterns describing new mathematical concepts, and cognitive information processing. In the $$\upbeta $$ β -quadrant, he came close to inventing independence-friendly logic, the idea of which he (...) found indispensable in fulfilling the tasks –. (shrink)

Nine leading scholars of ancient philosophy from Europe, the UK, and North America offer a systematic study of Book Beta of Aristotle's Metaphysics. The work takes the form of a series of aporiai or 'difficulties' which Aristotle presents as necessary points of engagement for those who wish to attain wisdom. The topics include causation, substance, constitution, properties, predicates, and generally the ontology of both the perishable and the imperishable world. Each contributor discusses one or two of these aporiai in (...) sequence: the result is a discursive commentary on this seminal text of Western philosophy. (shrink)

The argument is that Davies is irresponsible to take a religious approach to interferon treatment.

Beta integrals for several non-integer values of the exponents were calculated by Leonhard Euler in 1730, when he was trying to find the general term for the factorial function by means of an algebraic expression. Nevertheless, 70 years before, Pietro Mengoli (1626–1686) had computed such integrals for natural and half-integer exponents in his Geometriae Speciosae Elementa (1659) and Circolo(1672) and displayed the results in triangular tables. In particular, his new arithmetic–algebraic method allowed him to compute the quadrature of the (...) circle. The aim of this article is to show how Mengoli calculated the values of these integrals as well as how he analysed the relation between these values and the exponents inside the integrals. This analysis provides new insights into Mengoli’s view of his algorithmic computation of quadratures. (shrink)

The well‐known “Consequence Argument” for the incompatibility of freedom and determinism relies on a certain rule of inference; “Principle Beta”. Thomas Crisp and Ted Warfield have recently argued that all hitherto suggested counterexamples to Beta can be easily circumvented by proponents of the Consequence Argument. I present a new counterexample which, I argue, is free from the flaws Crisp and Warfield detect in earlier examples.

Although the type‐I interferon (IFN‐I) response is considered vertebrate‐specific, recent findings about the Intracellular Pathogen Response (IPR) in nematode Caenorhabditis elegans indicate that there are similarities between these two transcriptional immunological programs. The IPR is induced during infection with natural intracellular fungal and viral pathogens of the intestine and promotes resistance against these pathogens. Similarly, the IFN‐I response is induced by viruses and other intracellular pathogens and promotes resistance against infection. Whether the IPR and the IFN‐I response evolved in (...) a divergent or convergent manner is an unanswered and exciting question, which could be addressed by further studies of immunity against intracellular pathogens in C. elegans and other simple host organisms. Here we highlight similar roles played by RIG‐I‐like receptors, purine metabolism enzymes, proteotoxic stressors, and transcription factors to induce the IPR and IFN‐I response, as well as the similar consequences of these defense programs on organismal development. (shrink)