Combined Effect of Pore Water Overpressure, Far-Field Stresses, and Strength Parameters in Wellbore Stability

Studying the stability of wellbores drilled to access reservoirs can be a challenging issue in overpressured basins because accurate estimation of the far-field stresses, overpressure, and rock strength parameters can be difficult to achieve. Unexpected overpressures can induce tensile stresses around the wellbore, and the selection of an appropriate strength criterion and rock properties play an important role in determining the limit mud pressures. This study focuses on the stability analysis of wellbores by considering the mutual interaction of far-field stresses, fluid overpressure, and strength parameters of isotropic rock. We performed sensitivity analyses with the Mohr–Coulomb and Hoek–Brown criteria in two overpressured fields (North Sea basin and Browse basin) to highlight the influence of the uncertainties related to the rock strength. We defined an effective stress path (ESP) failure line to analyze the failure limit condition in the tension and compression zone. The analysis results indicated that the Hoek–Brown criterion better describes rock failure conditions, especially in the tension zone. Furthermore, we suggested using two different frictional components of strength for the tension and compression zone because it is a conservative approach, particularly at high overpressures. The mud pressures obtained from the uniaxial radial/tangential (HF) conventional analysis give different failure limits with respect to the ESP approach suggested in this study. These differences are low, and the mud weight margin can be low. In addition, we carried out numerical simulations with FLAC to investigate the extent of failure. The results indicated that the mud weight margin between the onset of local failure and borehole collapse is very low at high overpressures. Finally, the geomechanical analysis of wellbore stability in overpressured basins indicated the need for improving the accuracy in determining the strength parameters of the rock

Multipartite entanglement detection for hypergraph states

We study the entanglement properties of quantum hypergraph states of $n$ qubits, focusing on multipartite entanglement. We compute multipartite entanglement for hypergraph states with a single hyperedge of maximum cardinality, for hypergraph states endowed with all possible hyperedges of cardinality equal to $n-1$ and for those hypergraph states with all possible hyperedges of cardinality greater than or equal to $n-1$. We then find a lower bound to the multipartite entanglement of a generic quantum hypergraph state. We finally apply the multipartite entanglement results to the construction of entanglement witness operators, able to detect genuine multipartite entanglement in the neighbourhood of a given hypergraph state. We first build entanglement witnesses of the projective type, then propose a class of witnesses based on the stabilizer formalism, hence called stabilizer witnesses, able to reduce the experimental effort from an exponential to a linear growth in the number of local measurement settings with the number of qubits

Applicazione della Psicofisica al Dolore Neuropatico

Il dolore neuropatico è una condizione cronica, definita dall’ International Association for the Study of Pain (IASP) come “quella forma di dolore scatenato o mantenuto da una lesione primaria di un nervo o da una disfunzione del sistema nervoso”(Merskey & Bogduck,1994). Esso può essere distinto in dolore neuropatico periferico (dovuto a alterazioni che interessano principalmente il sistema nervoso periferico) e dolore neuropatico centrale (caratterizzato da alterazioni che riguardano il sistema nervoso centrale) (Bonezzi, 2000). I dati della letteratura riportano una valutazione del paziente con dolore neuropatico prevalentemente di tipo qualitativa, ma è sempre più frequente l’integrazione con strumenti di misurazione quantitativa della sensibilità, come il Quantitative Sensory Testing o QST. La loro applicazione si basa sulle leggi della psicofisica, branca della psicologia che mira a valutare il legame tra il mondo fisico e quello psicologico (Zambianchi,1994). Attraverso le misurazioni psicofisiche è possibile, dunque, quantificare la sensibilità e la percezione del dolore. La ricerca, classificabile in uno studio osservazionale trasversale, ha come obiettivi l'indagine psicofisica del dolore neuropatico e le sue relazioni con le componenti psicologiche. Nel primo caso la nostra indagine mira a esaminare le differenze nelle soglie sensoriali e dolorifiche, tra una area corporea in cui viene riferito dolore con caratteristiche neuropatiche ed un’area senza dolore, nel secondo,si propone di valutare la relazione tra soglie percettive, e variabili cliniche e psicopatologiche associate al dolore neuropatico. Il campione esaminato è costituito da 28 soggetti di cui 15 soggetti mielolesi, scelti come gruppo omogeneo rappresentanti il dolore neuropatico centrale, e 13 soggetti affetti da dolore neuropatico periferico dovuto a differenti quadri clinici. Ciascun soggetto è stato sottoposto a valutazioni psicofisiche, nella sede del dolore ed in una zona di controllo senza dolore, mediante Thermal Sensory Analyzer (TSA), per la valutazione delle soglie termiche e dolorifiche al freddo e caldo, con successiva esplorazione del fenomeno del Wind up e DNIC (Diffusion Noxious Inhibitory control). Per la valutazione clinica del dolore sono stati utilizzati come strumenti di autovalutazione il QUID (Questionario italiano del dolore De Benedittis et al., 1988) e LANSS (Leeds Assessment of Neuropathic Symptoms and Sign Pain Scale di Bennet, 2001) mentre la valutazione psicologica è stata eseguita mediante la somministrazione della SSAS (Somatosensory Amplification Scale, Barsky, et al. 1990), GHQ- 12 (General Health Questionnaire, Bellantuomo, 1987) HADS (Hospital Anxiety and Depression Scale, Zigmond & Snaith, 1999).Come analisi statistiche sono state utilizzate analisi non parametriche, in quanto i dati del campione non presentavano una distribuzione gaussiana al k-s Normality test. Dall’analisi dei primi dati (la ricerca è attualmente in corso) emerge che le manifestazioni si modificano in relazione alla persistenza del dolore nel tempo. Questa variazione, tuttavia, influisce maggiormente sulle componenti cliniche piuttosto che percettive, delle soglie. A differenza della letteratura, in questo piccolo gruppo di pazienti non è stato riscontrato il fenomeno tipico del dolore neuropatico definito Wind up (indice di una sensibilizzazione centrale) anche quando il campione viene distinto in base alla sede di origine del dolore. Le soglie sensoriali, più che quelle dolorifiche, distinguono il territorio leso da quello esente da lesioni, a dimostrazione che la percezione del dolore è un fenomeno molto complesso e multidimensionale. I nostri dati apportano nuove evidenze, che meritano, ampliando il campione, di essere suffragate da ulteriori indagini riguardanti la relazione tra dolore e componenti psicologiche. Dai nostri dati emerge, infatti, che se le variabili psicologiche quali la depressione, l’ansia, il distress si correlano con le variabili cliniche del dolore, la dimensione dell’amplificazione somatica sembra essere quella maggiormente correlata alla soglia percettiva sensoriale e dolorifica. Parole chiave: Dolore neuropatico, Psicofisica, Sensibilizzazione, QST, psicopatologi

The tower of London (tol) in Italy. standardization of the tol test in an Italian population

Deficit in planning and problem-solving, affecting a wide range of neuropsychological patients, has been widely investigated using the Tower of London (ToL) test, as developed by Shallice (Philos Trans R Soc Lond Ser B Biol Sci 298:199-209, 1). The ToL taps on several executive functions (EF), such as planning, time for planning or rule breaks, which may be usefully indexed by different ToL measurements. However, in its original version, the different aspects involved in ToL are not evaluated in a specific way.Here, we report the standardization of the ToL, on 896 individuals aged 15-86 years, taking in account individual factors (i.e. gender, age, years of education) which may affect performances on ToL. We computed several indexes on the ToL including score, planning and execution times, perseverations, rule breaks and self-monitoring. We found that these indexes were affected by individual factors such as gender, age and education. Present results not only provide extensive normative data according to gender, as well as different age and education ranges, but also represent a very useful instrument for a more fine-grained diagnosis of EF deficits in a wide range of neuropsychological patients, including traumatic brain injury and brain-damaged patients, as well as Alzheimer's disease and Parkinson's disease patients

Anti-CD20 Therapy Acts via FcγRIIIA to Diminish Responsiveness of Human Natural Killer Cells

Natural killer (NK) immune cells mediate antibody-dependent cellular cytotoxicity (ADCC) by aggregating FcγRIIIA/CD16, contributing significantly to the therapeutic effect of CD20 monoclonal antibodies (mAb). In this study, we show that CD16 ligation on primary human NK cells by the anti-CD20 mAb rituximab or ofatumumab stably impairs the spontaneous cytotoxic response attributable to cross-tolerance of several unrelated NK-activating receptors (including NKG2D, DNAM-1, NKp46, and 2B4). Similar effects were obtained from NK cells isolated from patients with chronic lymphocytic leukemia in an autologous setting. NK cells rendered hyporesponsive in this manner were deficient in the ability of these cross-tolerized receptors to phosphorylate effector signaling molecules critical for NK cytotoxicity, including SLP-76, PLCγ2, and Vav1. These effects were associated with long-lasting recruitment of the tyrosine phosphatase SHP-1 to the CD16 receptor complex. Notably, pharmacologic inhibition of SHP-1 with sodium stibogluconate counteracted CD20 mAb-induced NK hyporesponsiveness, unveiling an unrecognized role for CD16 as a bifunctional receptor capable of engendering long-lasting NK cell inhibitory signals. Our work defines a novel mechanism of immune exhaustion induced by CD20 mAb in human NK cells, with potentially negative implications in CD20 mAb-treated patients where NK cells are partly responsible for clinical efficacy. Cancer Res; 75(19); 1-12. ©2015 AACR

A time-independent reliability based design approach for debris flow flexible barriers

The design of debris flow protective structures has represented a challenge since the last decades. The design process might consider several variables related to actions and resistances, mainly linked to impact pressure and dynamic pressure resistance. Debris flow events do not have always the same magnitude, and small events can occur with a high probability. Therefore, an events frequency-magnitude relationship might be considered in the design of protective structures. In the Eurocodes framework, the fixed partial safety factors design approach not considering the intrinsic site variability of these phenomena, does not allow obtaining a specific probability of failure. Reliability-based approaches reveal to be compelling solutions. Focusing on flexible barriers, the paper presents a novel time-independent reliability approach, which considers all the possible debris flow events and provides the failure probability of a barrier in a given temporal interval

Treatment of Bloodstream Infections Due to Gram-Negative Bacteria with Difficult-to-Treat Resistance

The rising incidence of bloodstream infections (BSI) due to Gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) has been recognized as a global emergency. The aim of this review is to provide a comprehensive assessment of the mechanisms of antibiotic resistance, epidemiology and treatment options for BSI caused by GNB with DTR, namely extended-spectrum Beta-lactamase-producing Enterobacteriales; carbapenem-resistant Enterobacteriales; DTR Pseudomonas aeruginosa; and DTR Acinetobacter baumannii

Open building and flexibility in healthcare: strategies for shaping spaces for social aspects

Introduction. The fast development of technology and medicine influences the functioning of healthcare facilities as health promoter for the society, making the flexibility a fundamental requirement. Among the many ways to ensure adaptability, one that allows change without increasing the building’s overall size is the Open Building approach. Methodology. Starting from the analysis of the State-of-the-Art and many case-studies, eight parameters of evaluation were defined, appraising their relative importance through a weighting system defined with several experts. The resulting evaluation tool establishes in what measure healthcare facilities follow the Open Building principles. Results and discussion. The tool is tested to ten case-studies, chosen for their flexible features, in order to determine his effectiveness and to identify projects’ weaknesses and strengths. Conclusions. The results suggest that many Open Building’s principles are already in use but, only through a good design thinking, it will be possible to guarantee architectures for health adaptable for future social challenges

Iron chelating properties of Eltrombopag: Investigating its role in thalassemia-induced osteoporosis

Chronic blood transfusions are responsible to cause iron overload, which leads to several complications to end organs and osteoporosis. Iron chelation is needed to remove iron excess and to contain bone-mass loss. Deferasirox is the most recent oral iron chelator that prevents transfusion related iron overload complications. Recently Eltrombopag (ELT) iron chelating properties are emerging. ELT is an agonist at Thrombopoietin receptor, used in treatment of thrombocytopenia. We tested ELT and Deferasirox in iron overloaded osteoclasts from thalassemic patients and donors measuring intracellular iron, TRAP expression and osteoclast activity. We confirmed ELT iron chelation capacity also in bone tissue and a synergic effect when used with Deferasirox. Moreover, having demonstrated its effects on osteoclast activity, we suggest for the first time that ELT could ameliorate bone tissue’s health reducing bone mass loss

Measuring the contribution of higher education to innovation capacity in the EU. Executive Summary

There has been a massive expansion of higher education in recent decades as part of attempts to create workforces with the skills to be able to compete successfully in the context of the knowledge based economy. This emerging context demands new kinds of skills and approaches from workers to feed into industries that are evolving rapidly. Economic strength in the knowledge-based economy is driven by innovation, taking existing resources and assets and using them to do new things better and increase overall welfare levels. Whilst innovation is necessary across government, business, and civil society, universities are at the heart of attempts to improve the overall knowledge capital endowments that provide the feedstock for innovation as well as a proving ground for future innovators. At the same time, there is widespread unrest that universities are failing to respond to these new demands and are continuing to act as ‘ivory towers’ outside of rather than driving forward society (Galan-Muros, 2016). Particular concern lies on perceptions that universities have tended to expand their existing activities rather than to create new courses, pedagogies, and learning environments that best meet these needs. Where universities contribute effectively to innovation, then they can create whole new industries and sectors, and transform the fortunes of particular places. But at the moment, these conflicting narratives make it hard for policy-makers to determine whether universities (and indeed, which kinds of universities) are a boost to or a drag upon innovation capacities. A key challenge for European policy-makers is therefore distinguishing the extent to which universities are realising their potential to contribute to the emergence of the knowledge-based economy. By distinguishing which institutions are and are not realising this potential, policy-makers can developed a more nuanced set of engagement stimuli that can help to maximise this contribution and optimise the returns that European societies receive for their substantial public investments in higher education. This means that are providing the necessary education and knowledge base to deliver the ambitions of Europe 2020 and support Europe’s transition towards a successful, just and sustainable economy. This requires dealing with the uncertainty of the extent to which universities’ contribute to supporting the development of the emerging knowledge economy. Here we define ‘innovation’ as the result of the set of activities by which different kinds of knowledge are combined to create solutions and interventions to solve problems, ultimately making society a better place (a form of Schumpeterian perspective). Those societal improvements may be through: (a) raising competitiveness and creating new markets and sectors, (b) improving the delivery of public services, particularly to vulnerable social groups, or (c) reducing our environmental impacts. We seek to understand the extent to which universities are supporting ‘innovation’ as here defined to distinguish between good and bad performances, as the first step in a process by which policy-makers actively intervene to improve the performance of universities overall