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Obiettivi. Lo scopo principale di questo lavoro è di evidenziare i motivi per cui un approccio sistemico è necessario per meglio comprendere le dinamiche economiche e sociali in condizioni di complessità, come l’Approccio Sistemico Vitale può supportare il processo decisionale in condizioni di complessità e come la discussione sulla complessità e sulla sopravvivenza dei sistemi vitali in uno scenario complesso, implica inevitabilmente una discussione sulla sostenibilità. Metodologia. Una panoramica della letteratura sui contributi radicati nel pensiero sistemico è fornita per illustrare il ruolo dell’Approccio Sistemico Vitale nel supportare la comprensione e la gestione della complessità e delle sfide della sostenibilità. Risultati. Il lavoro sottolinea la soggettività della complessità e propone un modello a Tripla Elica per rileggere le sfide della sostenibilità nelle dinamiche sociali ed economiche. Limiti della ricerca. Il contributo del documento al dibattito in corso sulla complessità e sulle sfide della sostenibilità si limita al dominio concettuale. Il quadro interpretativo proposto potrebbe trarre beneficio da studi di casi e da evidenze empiriche. Implicazioni pratiche. Questo lavoro stimola sia i ricercatori che i professionisti a ripensare radicalmente il loro approccio alla complessità e alla sostenibilità allo scopo di identificare nuovi strumenti e modelli manageriali per reagire alle emergenti sfide sociali ed economiche. Originalità del lavoro. Il contributo arricchisce gli studi manageriali richiamando alcuni concetti chiave radicati nel pensiero sistemico e sistematizzandoli attraverso la definizione di un quadro interpretativo olistico in grado di spiegare il contributo dell’Approccio Sistemico Vitale alla comprensione e gestione della complessità e delle sfide imposte dalla sostenibilità.

Drug-induced blockade of the human ether-à-go-go-related gene (hERG) channel is today considered the main cause of cardiotoxicity in postmarketing surveillance. Hence, several ligand-based approaches were developed in the last years and are currently employed in the early stages of a drug discovery process for in silico cardiac safety assessment of drug candidates. Herein, we present the first structure-based classifiers able to discern hERG binders from nonbinders. LASSO regularized support vector machines were applied to integrate docking scores and protein-ligand interaction fingerprints. A total of 396 models were trained and validated based on: (i) high-quality experimental bioactivity information returned by 8337 curated compounds extracted from ChEMBL (version 25) and (ii) structural predictor data. Molecular docking simulations were performed using GLIDE and GOLD software programs and four different hERG structural models, namely, the recently published structures obtained by cryoelectron microscopy (PDB codes: 5VA1 and 7CN1) and two published homology models selected for comparison. Interestingly, some classifiers return performances comparable to ligand-based models in terms of area under the ROC curve (AUCMAX = 0.86 ± 0.01) and negative predictive values (NPVMAX = 0.81 ± 0.01), thus putting forward the herein proposed computational workflow as a valuable tool for predicting hERG-related cardiotoxicity without the limitations of ligand-based models, typically affected by low interpretability and a limited applicability domain. From a methodological point of view, our study represents the first example of a successful integration of docking scores and protein-ligand interaction fingerprints (IFs) through a support vector machine (SVM) LASSO regularized strategy. Finally, the study highlights the importance of using hERG structural models accounting for ligand-induced fit effects and allowed us to select the best-performing protein conformation (made available in the Supporting Information, SI) to be employed for a reliable structure-based prediction of hERG-related cardiotoxicity.

Ikujiro Nonaka and Hirotaka Takeuchi are widely recognized as among the most impactful scholars in the field of knowledge management. Not surprisingly for us, one of their recent works, published in Harvard Business Review in 2011, was listed as a contribution about ‘Ethics’. It was titled “The Big Idea: The Wise Leader” and the incipit sentence was as follows: “In an era when discontinuity is the only constant, the ability to lead wisely has nearly vanished. All the knowledge in the world did not prevent the collapse of the global financial system three years ago or stop institutions like Lehman Brothers and Washington Mutual from failing.” Hence, what Nonaka and Takeuchi considered ‘big’ was the idea of embedding leaders with a wisdom that was clearly long lacking. The impact of their message has been probably lower than that of their previous works. In fact, in the subsequent years, attention has been increasingly put on the challenge of managing ever bigger among of data; accordingly, the topic of ‘Big Data’ is attracting increasing interest. Just one year later, in 2012, Andrew McAfee and Brynjolfsson, discussing about Big Data as a ‘Management Revolution” and envisioning “Smart leaders across industries” dealing with this revolution, argued that: “as with any other major change in business, the challenges of becoming a big data–enabled organization can be enormous and require hands-on – or in some cases hands-off – leadership.” (McAfee and Brynjolfsson, 2012: 62). We would put the accent on the “hands-off” word, as we recognize and deeply agree not only on the revolutionary impact of Big Data on management but manly on the necessity to change the “decision making culture” of organizations (McAfee and Brynjolfsson, 2012: 61). Hence, discussion shifts again on different requirements, like a change in ‘culture’ and in the management ‘style’, that do not currently appear adequately embedded into the knowledge management framework, especially considering major trend like that of ‘Big Data’. Undoubtedly, data management represents one of the most relevant challenges both for decision makers and researchers interested in the governance of social and economic dynamics (Yew Wong & Aspinwall, 2005; Espejo & Reyes, 2011; Barile & Saviano, 2011; Chen et al., 2013). Fast progresses in Computer Science are increasing opportunities to acquire and manage big amounts of data in really short time. Of course, although requiring appropriate techniques and tools (Maimon & Rokach, 2005; Carayannis et al., 2006a, 2006b; Hey et al., 2009; Del Giudice et al., 2016), almost any disciplinary domain has an interest in the use of data that are at the basis of information and knowledge management (Beer, 1979; Espejo, 1996; Carayannis, 1999, 2010; Del Giudice et al., 2012; Di Nauta et al., 2015; Caputo et al. 2016; Caputo & Walletzký, 2017). However, it seems that this increasing focus on producing new data (i.e. the means) is attracting more interest than solving the problems (the goals) (Linoff & Berry, 2011): new data are produced to explain other data, giving rise to a circular dynamic that may not help solving the problems (Boyd & Crawford, 2012). The capability of humans to solve problems appears constantly improved despite the evidence of big failures in facing the most relevant humans’ issues. This situation is well synthesized by Schumacher who, analyzing the ‘problem of production’ in the modern era, argued that “the changes of the last twenty-five years, both in the quantity and in the quality of man’s industrial processes, have produced an entirely new situation – a situation resulting not from our failures but from what we thought were our greatest successes” (Schumacher, 2010: 6). This is the reality of our ever-smarter knowledge society. In this context of reflection, we wonder: Given the complex nature of the main issues to face on our planet, are ever-bigger amount of data and ever-smarter technologies what we only need? Would managing big data really help to better solve complex humans’ problems? Acknowledging the increasing relevance of managing big data, this paper does not neglect their importance as well as the value of ‘smart’ technologies to efficiently manage them. However, given the emblematic evidence highlighted by Nonaka and Takeuchi about the uselessness of all the knowledge available in the world to prevent the last collapse of the global financial system, the aim of this work is to stimulate reflections upon the kind of knowledge that is required to first prevent and then solve the big issues of humanity, i.e. complex issues for which decision makers seem to lack the support of useful information (Barile, 2009b).

Purpose – Innovation and Information and Communications Technologies (ICTs) are new levers on which act for redesigning social and economic relations and structures. The technology shifts produce disruptive effects on business models, having revolutionary impacts on internal growth strategies for the future of manufacturing. Joining the vibrant debate about the role of Innovation and ICTs in ensuring companies’ viable survival, the paper aims at investigating Open Innovation and Industry 4.0 using an interpretative framework rooted in Service and Systems research highlighting new opportunities to advance knowledge about value co-creation. Methodology/approach – A brief literature review on Open Innovation and Industry 4.0 is conducted using the interpretative lens provided by the Service and Systems perspectives. A deductive approach is adopted for interpreting key processes of Open Innovation and Industry 4.0 as drivers for enhancing value co-creation. Findings – The findings direct to identify Technology Readiness, Cognitive Alignment, Collaborative Orientation, and Shared Strong Beliefs as possible drivers that enhance the value co-creation potential created by Open Innovation and Industry 4.0. A framework of synthesis is outlined that can represent a useful reference for exploiting the value co-creation opportunities of Open Innovation and Industry 4.0. Research implications/limitations – The paper contributes to the multi- and inter- disciplinary research stream aimed at overcoming the limitations of a still dominant reductionist view by adopting systems approaches. Analyzing Open Innovation and Industry 4.0 as potential paths for addressing future evolutions in value co-creation studies, the paper enriches previous managerial researches. Nevertheless, the work is currently a preliminary study mainly directed to share ideas and views within the multi-perspective context of the Naples Forum on Service. Practical implications – Valorizing the opportunities for value co-creation linked to Open Innovation and Industry 4.0 practices, the paper provides decision makers with a road map for better understanding and managing critical drivers for effectively implementing value co-creation logics. Originality/value – The paper enriches the ongoing debate about Open Innovation and Industry 4.0 providing new insights through the interpretative lens of the Service and Systems perspectives that highlight the great potential for value co-creation linked to these new technologies.

Purpose – The increasing variety and variability of social and economic dynamics is pushing both researchers and practitioners in developing approaches, models, and tools for supporting decision makers in observing, interpreting, understanding and managing emergent dynamics. For contributing to the ongoing debate, the paper aims at discussing possible paths for facing the challenges of the increasing complexity through flexible decisional and behavioral approaches. Methodology/approach – The paper adopts a qualitative approach for systematizing and refreshing the interpretative role of existing literature within managerial and organizational fields. Through the interpretative contributions provided by the systems thinking, a multi-disciplinarity literature review is conducted for identifying possible constructs through which addressing the development of flexible managerial and organizational models. Findings – Managerial and organizational fields are enriched through the concepts of exaptation and bricolage as explicative domains able to provide useful indications to decision makers interested in building more flexible decisional and behavioral approaches. A possible path for managing the increasing social and economic complexity is depicting in the light of systems perspective, and a system based interpretative framework is defined for explaining actors’ reciprocal adaptation as a way for supporting value co-creation. Research implications – The paper provides possible pillars on which acting to build managerial and organizational approaches able to enhance actors’ contributions through the definition of shared processes. The concepts of exaptation and bricolage enrich previous managerial and organizational literature promoting research on value co-creation as a driver for ensuring systems’ viability in dynamic ecosystems. Practical implications – The paper calls the attention of decision makers on the need for the systems’ flexibility trough the enhancement of actors’ contributions for facing the challenges of increasing social and economic complexity. Acting on exaptation and bricolage, a possible model is provided for clarifying managerial and organizational paths for increasing the systems’ flexibility and for supporting practitioners in defining approaches able to support actors’ collaboration as a required condition for value co-creation. Originality/value – Adopting a multi-disciplinary perspective the paper enriches previous managerial and organizational literature trough the definition of concepts, processes, and approaches able to support both researchers and practitioners for better understanding and managing increasing social and economic complexity by acting on exaptation and bricolage. Thanks to the interpretative lens provided by the systems studies, a conceptual model for addressing systems’ decisions and behaviors in the light of value co-creation is proposed.

This paper proposes a possible reference model to analyse the link between sustainability and business strategy. The study delved on the evaluation of the 2017 Non-Financial Statements of 30 companies listed in the Italian market according to the Legislative Decree n. 254/2016. A multi-sector analysis was conducted, and it involves companies from Media and Communications, Utility and Multi-Utility, Industrial and Financial sectors. Due to the fact that substantial differences between the national and European laws still exist among EU member states, the requirements of non-financial information are often considered unclear and ineffective. To counteract this situation, the EU harmonized the legislation, enacting the directive 2014/95/EU that establishes the main requirements for the reporting on social, economic and environmental topics. In such a vein, Italian government established that listed companies have to regularly disclose their non-financial information through non-financial statement. Drawing on authoritative academic literature, non-financial reports of the companies analysed, current articles and documents, an investigation model has been developed for assessing companies’ strategic orientation towards sustainability. To this end, the model was structured in the following six main themes: 1) Strategy, 2) Governance, 3) Operations, 4) Performance, 5) Risk management, 6) Politics. The analysis highlights companies’ approach in sustainability reports and its interconnections with company strategy, organizational structures, management policies, and risk management models.

Obiettivo del presente contributo è fornire una analisi dell’evoluzione del concetto di sostenibilità nell’ambito degli studi manageriali di matrice sistemica con particolare riferimento al filone di studi che può ricondursi all’approccio sistemico vitale (asv).. Il concetto di sostenibilità, introdotto nel 1987 dal Rapporto “Our Common Future”, ha assunto, nel tempo, un ruolo centrale nella definizione delle scelte di governo, non solo delle istituzioni ma anche delle organizzazioni imprenditoriali e sociali. Adottare un’ottica di sostenibilità, infatti, significa, per il decisore, valutare le possibili alternative che emergono dalle rappresentazioni di vincoli e regole dei contesti di natura economico, sociale e ambientale in cui ciascuna organizzazione vive ed opera. Tanto premesso, i tradizionali approcci alla sostenibilità si sono spesso concentrati sull’affrontare ed esaminare tematiche riconducibili ad uno o più dei tre citati contesti in maniera separata , senza considerare le interdipendenze che, invece, tra tali contesti esistono. Ciò ha portato, in molti casi, alla definizione di linee strategiche e prassi operative che hanno tralasciato i possibili effetti che una mancanza di visione sistemica implica. Nella consapevolezza di tali limiti, il contributo traccia gli avanzamenti che il pensiero sistemico, e in particolare l’approccio sistemico vitale, ha fornito allo studio del concetto di sostenibilità, con specifico riferimento agli effetti sinergici che emergono dall’interazione e contemporanea considerazione delle istanze che provengono da ciascuno degli ambiti della sostenibilità, così come definiti da Elkington nellla triple bottom line.

The present global situation recalls us the two walls in which the Red Sea had split to allow that Pharaoh follow the people beloved by God. On one wall stays the economic crisis, that is tout court the capitalist crisis, on the other wall there is the predicament of environment. Then, it is reasonable to wonder if the walls will tumble down with severe damages to all the characters, this time, of this representation; unless a “modest proposal”, of the kind that we will try to formulate in this paper, be intensively pursued. Several of the themes here gathered have already been object of reflection in some previous works. In this paper we collect and enrich those ideas, and put a special attention to the so called economic “cycle” and a stationary ecological-economic model in a sustainability scenario. Some years ago, the financial “bubble”, burst with its destructive and lasting economic and social consequences, the bloody geopolitics of oil of the last decades, one sixth of the humankind under the threshold of surviving, the plunder of the resources of the Earth – from the rare ores up to the great pluvial forests –, the general environment crisis, dramatic for the climate change, exemplified in an also too much persuasive way that capitalist democracies as well as totalitarian States, those which have chosen the free market economy, were not able to face the two crises of our title.INGLESE

OBJECTIVE: To identify predictive risk factors for conversion to open splenectomy and postoperative complications in patients undergoing elective laparoscopic splenectomy. BACKGROUND: The laparoscopic approach represents the "gold standard" for splenectomy, but its use in the treatment of splenomegaly and malignant disease is controversial. Factors that influence immediate outcome are clinical, anatomic, and pathologic. METHODS: Univariate and multivariate analyses of data from the Italian Registry of Laparoscopic Surgery of the Spleen, a multicenter database supported by 25 referral centers. Analysis of data (1993-2007) was performed on a series of patients (n = 676) undergoing elective laparoscopic splenectomy. Demographic data, the operative indications, the surgical technique applied, and any intra- and/or postoperative complications with respect to the patients were assessed. Records were analyzed retrospectively using the Student t test, the chi test, and logistic regression. RESULTS: Conversion to open splenectomy was necessary in 39 cases (5.8%). Perioperative deaths occurred in 3 cases (0.4%). There were no complications in 560 patients (82.8%), with a mean hospital stay of 5 days (range, 2-54). Overall, morbidity occurred in 116 patients (17.2%). Multivariate analysis found that the body mass index (P = 0.01) and the presence of hematologic malignancy (P < 0.001) were independent predictors for intraoperative complications and surgical conversion. Spleen longitudinal diameter (P = 0.001) and surgical conversion (P = 0.001) were independent predictors for the occurrence of postoperative complications. CONCLUSIONS: This large multicenter study provides evidence for the significance of predictive risk factors for intra- and postoperative complications in laparoscopic splenic surgery. Besides splenic dimensions, other factors like the patient's habitus and the specific underlying hematologic pathology should be recognized by the surgeon to reduce complications and initiate adequate treatment.

Peptide and proteins with one or more beta-sheet strands exhibit the extraordinary ability to assemble into long fibrillar nanostructures via intermolecular hydrogen bonding. While designed alfa-helical proteins have been extensively studied, the design of beta-sheet structures remained a challenge for many year, because of their tendency to form unsoluble aggregates. The tendency to aggregate is manifested most clearly in nature in the formation of fibrils that follow upon extensive beta-sheet formations in proteins. The origin of the stability of beta-sheet folding has been attributed to interstrand hydrogen bonding and/or side chain hydrophobic interactions. Peptide models have proved valuable in probing the relationship between local sequence information and folded conformation in the absence of the tertiary interactions found in the native state of proteins, allowing intrinsic secondary structure propensities to be investigated in isolation. In synthetic model systems the turn/loop units are combined with peptide to form parallel or antiparallel ?-sheet. For reason of design and synthesis we report on antiparallel double strand. Several factors are of key importance including: (1) the nature and role of beta-turn in stabilizing dimeric structure formation, (2) propensities of different residues in the pre-organization of beta-strands, (3) the role of co-operativity in beta-sheet folding and stability, (4) insights into the nature of the stabilizing weak interactions. Recent studies revealed that the beta-turn sequence and its allowed geometry appears to be crucial in dictating the ?-strand alignment, and also that side chain interactions can have a significant stabilising effect on antiparallel double strand conformation. Here we centered the attention on sequences having high beta-sheet propensity.

Multipoint LV Pacing Improves Mid-Term CRT Response Introduction Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing in a single coronary sinus branch improves acute LV function. We hypothesized that multipoint pacing (MPP) can improve midterm echocardiographic and clinical response compared with conventional CRT. Methods and Results Consecutive patients receiving a CRT implant (Unify Quadra MP™ or Quadra Assura MP™ CRT-D and Quartet™ LV lead, St. Jude Medical, Sylmar, CA, USA) were randomized to receive biventricular (BiV) pacing with either conventional LV pacing (CONV group) or MPP (MPP group). For each patient, an optimal pacing configuration for the assigned pacing mode was programmed based on intraoperative pressure-volume (PV) loop measurements. A clinical evaluation and transthoracic echocardiogram were performed before implant (BASELINE) and at 3 months postimplant and analyzed by a blinded observer. A reduction in end-systolic volume (ESV) of ≥15% relative to BASELINE was prospectively defined as response to CRT. Forty-four patients (NYHA Class III, EF 29 ± 6%, QRS duration 152 ± 17 milliseconds) were enrolled and randomized. One patient in the MPP group was lost to follow-up and excluded from further analysis. After 3 months, 11 of 22 (50%) CONV patients and 16 of 21 (76%) MPP patients were classified as responders. ESV reduction, EF increase, and NYHA class reduction relative to BASELINE were significantly greater in the MPP group than in the CONV group (ESV: -21.0 ± 13.9 vs. -12.6 ± 11.1%, P = 0.03; EF: +9.8 ± 5.1 vs. +2.0 ± 7.8 percentage points, P < 0.001; ΔNYHA: -1.05 ± 0.22 vs. -0.72 ± 0.46 functional classes, P = 0.006). Conclusion PV loop optimized BiV pacing with MPP resulted in an improved rate of response to CRT.