A Bayesian Reanalysis of the Phase III Aducanumab (ADU) Trial

In this article we have conducted a reanalysis of the phase III aducanumab (ADU) summary statistics announced by Biogen, in particular the result of the Clinical Dementia Rating-Sum of Boxes (CDR-SB). The results showed that the evidence on the efficacy of the drug is very low and a more clearer view of the results of clinical trials are presented in the Bayesian framework that can be useful for future development and research in the field

Basic emotions: Differences in time sequence and functional imaging with low resolution brain electrical tomography (LORETA)

The aim of the present study is to investigate the relationship between the time course of brain activation during the observation of pictures depic ting scenes associated with the four basic emotion of happiness, sadness, fear and disgust. Twenty-nin e right-handed volunteers (17 male, 12 female; mean age 24.6 years) took part in the study. To stu dy the time course of the affective processing the low resolution brain electromagnetic tomography (LORETA) has been used. Each emotional condition has shown specific activation patterns in different brain regions, changing over time. Our findings are in good agreement with other brain-ima ging studies (PET/fMRI) but with the advantage to investigate the temporal evolution of the emotional process in the millisecond range. The results showed that the time sequence of activa tions is different and characteristic for each emotion conditions

Vertex-regular 11-factorizations in infinite graphs

The existence of $1$-factorizations of an infinite complete equipartite graph $K_m[n]$ (with $m$ parts of size $n$) admitting a vertex-regular automorphism group $G$ is known only when $n=1$ and $m$ is countable (that is, for countable complete graphs) and, in addition, $G$ is a finitely generated abelian group $G$ of order $m$. In this paper, we show that a vertex-regular $1$-factorization of $K_m[n]$ under the group $G$ exists if and only if $G$ has a subgroup $H$ of order $n$ whose index in $G$ is $m$. Furthermore, we provide a sufficient condition for an infinite Cayley graph to have a regular $1$-factorization. Finally, we construct 1-factorizations that contain a given subfactorization, both having a vertex-regular automorphism group

A statistical mechanical problem?

The problem of deriving the processes of perception and cognition or the modes of behaviour from states of the brain appears to be unsolvablein view of the huge numbers of units involved. However, neural activities are not random, but, rather, form spatio-temporal patterns, and thank to these restrictions, which in turn are due to connections among neurons, the problem can at least be approached.The situation is similar to what happens in large physical ensembles, whereglobal behaviour is derived by microscopic properties. Despite the obvious differences between neural and physical systems a statistical mechanics approach is almost inescapable, since dynamics of the brain as a whole are clearly determined by the outputs of single neurons. In this paper it will be shown how, starting from very simple systems, connectivity engenders levels of increasing complexity in thefunctions of the brain depending on specific constraints.Correspondingly levels of explanations must take into account the fundamental role of constraints and assign at each level proper model structures and variables, that, on one hand, emerge from outputs of the lower levels, and yet are specific, in that they ignore irrelevant details

Mission, strategie e valutazione delle performance delle aziende nonprofit in un approccio di stakeholder management

Le aziende non profit (anp) sono particolari organizzazioni che hanno come obiettivo istituzionale non la creazione di profitto in senso economico ma la massimizzazione del valore sociale prodotto a vantaggio della collettività di riferimento. Tale valore è di natura intangibile e la sua definizione e misurazione dipendono in maniera fondamentale dalla percezione dei diversi stakeholder da esso a vario titolo influenzati. Per questo, per le anp il dialogo ed il coinvolgimento dei propri stakeholder nella definizione della missione e poi nelle scelte manageriali che ne conseguono è elemento fondamentale per il raggiungimento di performance soddisfacenti. Le scelte strategiche devono quindi essere orientate al conseguimento degli obiettivi di missione (mission oriented) nel rispetto del modello organizzativo e gestionale di tipo multi-stakeholder. Per queste ragioni nel working paper si sottolinea l’importanza di processi di stakeholder engagement per la definizione e la misurazione degli indicatori di performance: il valore sociale prodotto è tale, infatti, solo se percepito dagli stakeholder coinvolti.******** (Mission, Strategies and Performance Evaluation in Nonprofit Organisations From a Stakeholder Management Approach Nonprofit organisations (NPOs) have emerged as important not-for-profit private actors providing goods or services directly related to their explicit aim to create social value for the community in which they work. In order to maximize its social value creation, an NPO firstly has to define its mission according to stakeholders’ expectations, then it has to carry it out considering how it is defined by stakeholders, and finally it has to measure its performance and account for it related to how their stakeholders evaluate performance achievement. Since the mission achievement and effectiveness of NPOs are not easy to estimate and to assess, it follows that NPO effectiveness is always a matter of comparison, and that NPO effectiveness is a social construction, which depends on the evaluation given by the stakeholders who have an impact on and are impacted by the mission of the organisation. For these reasons, in the present working paper we assert that managers of NPOs have to use strategic stakeholder relationships, and not only adaptive or reactive approaches, in order to negotiate outcomes which reflect win-win situations for different stakeholders.) (This paper is only available in italian)

Analisi delle caratteristiche del processo gestionale dei Centri di Servizio per il Volontariato (CSV) in un’ottica stakeholder management

Partendo dal presupposto che le performance delle Anp dipendono dalla percezione che i vari stakeholder hanno rispetto al raggiungimento della missione, il presente paper analizza il caso dei Centri di Servizio per il Volontariato (CSV). Tali organizzazioni rappresentano una particolare tipologia di azienda non profit (anp) la cui missione è riconducibile ad attività di supporto strategico, organizzativo e tecnico alle piccole organizzazioni di volontariato italiane. L’elaborato presenta i risultati di una ricerca-azione sviluppata con 61 CSV italiani. Scopo della ricerca è stato evidenziare i limiti del sistema di management dei CSV e l’impatto in termini di raggiungimento della missione. Nel paper si ipotizza che tali limiti siano dovuti alla difficoltà di mappare le istanze dei loro stakeholder da parte dei CSV, pertanto si propone un modello di analisi delle stesse, finalizzato a superare gli attuali limiti manageriali dei CSV. ********* (Analysis of the Management Process of Centres for Services for Voluntary Organisations from a Stakeholder Management Perspective Considering the assumption that the performance of Nonprofit Organisations (NPOs) depends upon stakeholders’ perceptions, in an NPO, strategic management of stakeholders entails not only responding to their requests, but also guiding them in order to align their needs, values and objectives with the mission of the organisation. Given the background on the managerial characteristics that distinguish an NPO and a profit organisation, and the different role of a stakeholder approach in these two kinds of organisations, the paper will discuss the strengthens and weaknesses of a particular type of Italian NPO – Centres for Services for Voluntary Organisations (CSVs) – and will suggest that a proactive dialogue between CSVs and their stakeholders could help these organisations align their stakeholders’ claims to the organizational mission and to better define and develop strategies and activities coherent with the mission. The research was carried out using the action research model (Lewin, 1946) and the findings are based on the analysis of a sample of 61 CSVs throughout Italy.) (This paper is only available in italian)

A Mutation Changes Ligand Selectivity and Transmembrane Signaling Preference of the Neurokinin-1 Receptor

Abstract We studied the biochemical properties of a genetically engineered neurokinin-1 receptor (NK1R) in which two residues lying on the extracellular edge of the fourth transmembrane domain were replaced by equivalently located elements of the neurokinin-2 receptor (G166C, Y167F NK1R mutant). The mutation produced two effects. The first is enhancement of the apparent binding affinity for heterologous tachykinins (substance K and neurokinin B) and for N- or C-terminal modified analogues of substance P, but not for substance P itself, its full-length analogues, and several peptide and nonpeptide antagonists. Only two antagonists, as exceptions, were found to exhibit a diminished affinity for the mutant receptor. The second effect is a shift in NK1R preference for distinct G protein-mediated signaling pathways. NK1R-mediated phosphoinositide hydrolysis was enhanced both in transiently and permanently transfected cells, while stimulation of cAMP accumulation did not change in transient expression experiments and was reduced in permanently expressing cells. The effect of the mutation on ligand affinity was not related to any obvious structural commonality, nor to the selectivity for different neurokinin receptors or the agonistic/antagonistic nature of the ligand. However, all ligands responding to the mutation appear to share the ability to induce phosphoinositide signaling more efficiently than cAMP responses when binding to NK1R. We suggest that the mutation shifts the internal equilibria of different functional forms of NK1R. A theoretical analysis according to a multistate allosteric model suggests that the link between binding and biological changes can result from altered stability constants of substates in the conformational space of the receptor