A true concurrent model of smart contracts executions

The development of blockchain technologies has enabled the trustless execution of so-called smart contracts, i.e. programs that regulate the exchange of assets (e.g., cryptocurrency) between users. In a decentralized blockchain, the state of smart contracts is collaboratively maintained by a peer-to-peer network of mutually untrusted nodes, which collect from users a set of transactions (representing the required actions on contracts), and execute them in some order. Once this sequence of transactions is appended to the blockchain, the other nodes validate it, re-executing the transactions in the same order. The serial execution of transactions does not take advantage of the multi-core architecture of modern processors, so contributing to limit the throughput. In this paper we propose a true concurrent model of smart contract execution. Based on this, we show how static analysis of smart contracts can be exploited to parallelize the execution of transactions.Comment: Full version of the paper presented at COORDINATION 202

Vicious circles in contracts and in logic

Contracts are formal promises on the future interactions of participants, which describe the causal dependencies among their actions. An inherent feature of contracts is that such dependencies may be circular: for instance, a buyer promises to pay for an item if the seller promises to ship it, and vice versa. We establish a bridge between two formal models for contracts, one based on games over event structures, and the other one on Propositional Contract Logic. In particular, we show that winning strategies in the game-theoretic model correspond to proofs in the logi

Identification of recurrent genetic patterns from targeted sequencing panels with advanced data science: a case-study on sporadic and genetic neurodegenerative diseases

open8noThis work is funded by the University of Bologna, the IRCCS Institute of Neurological sciences of Bologna, and by the European Grants H2020 GenoMed4All [AM1] (Grant N. 101017549) and H2020 MSCA-ITN IMforFUTURE (Grant N. 721815).Background Targeted Next Generation Sequencing is a common and powerful approach used in both clinical and research settings. However, at present, a large fraction of the acquired genetic information is not used since pathogenicity cannot be assessed for most variants. Further complicating this scenario is the increasingly frequent description of a poli/oligogenic pattern of inheritance showing the contribution of multiple variants in increasing disease risk. We present an approach in which the entire genetic information provided by target sequencing is transformed into binary data on which we performed statistical, machine learning, and network analyses to extract all valuable information from the entire genetic profile. To test this approach and unbiasedly explore the presence of recurrent genetic patterns, we studied a cohort of 112 patients affected either by genetic Creutzfeldt–Jakob (CJD) disease caused by two mutations in the PRNP gene (p.E200K and p.V210I) with different penetrance or by sporadic Alzheimer disease (sAD). Results Unsupervised methods can identify functionally relevant sources of variation in the data, like haplogroups and polymorphisms that do not follow Hardy–Weinberg equilibrium, such as the NOTCH3 rs11670823 (c.3837 + 21 T > A). Supervised classifiers can recognize clinical phenotypes with high accuracy based on the mutational profile of patients. In addition, we found a similar alteration of allele frequencies compared the European population in sporadic patients and in V210I-CJD, a poorly penetrant PRNP mutation, and sAD, suggesting shared oligogenic patterns in different types of dementia. Pathway enrichment and protein–protein interaction network revealed different altered pathways between the two PRNP mutations. Conclusions We propose this workflow as a possible approach to gain deeper insights into the genetic information derived from target sequencing, to identify recurrent genetic patterns and improve the understanding of complex diseases. This work could also represent a possible starting point of a predictive tool for personalized medicine and advanced diagnostic applications.openTarozzi, M.; Bartoletti-Stella, A.; Dall’Olio, D.; Matteuzzi, T.; Baiardi, S.; Parchi, P.; Castellani, G.; Capellari, S.Tarozzi, M.; Bartoletti-Stella, A.; Dall’Olio, D.; Matteuzzi, T.; Baiardi, S.; Parchi, P.; Castellani, G.; Capellari, S

Pollen extract in association with vitamins provides early pain relief in patients affected by chronic prostatitis/chronic pelvic pain syndrome

The therapeutic efficacy for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is currently unsatisfactory. The aim of the present study was to assess the safety and efficacy of pollen extract in association with vitamins (DEPROX 500®) in males with CP/CPPS. All patients with a diagnosis of CP/CPPS attending the same urologic centre between March and October 2012 were enrolled in this randomised controlled phase III study. Participants were randomised to receive oral capsules of DEPROX 500® (two capsules every 24 h) or ibuprofen (600 mg, one tablet three times a day) for four weeks. The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), International Prostate Symptom Score and Quality of Well-Being (QoL) questionnaires were used. In the intention-to-treat analysis, 87 males (25 class IIIa and 62 class IIIb) with a mean age of 33.6±5.9 years were randomly allocated to the DEPROX 500® (n=41) or ibuprofen (n=46) treatment groups. At the follow-up examination (following one month of treatment), in the DEPROX 500® group, 31/41 patients (75.6%) reported an improvement in quality of life, defined as a reduction of the NIH-CPSI total score by ≥25%, compared with 19/46 (41.3%) in the control group (P=0.002). The greater improvement in the DEPROX 500® group compared with the ibuprofen group was statistically significant (treatment difference in the NIH-CPSI pain domain, -2.14±0.51, P<0.001; QoL scores, P=0.002). All patients were negative at the Meares-Stamey test evaluation. Adverse events were less frequent in the DEPROX 500® group than in the ibuprofen group. The DEPROX 500® treatment significantly improved total symptoms, pain and quality of life compared with ibuprofen in patients with CP/CPPS, without severe side-effects

The characterization of AD/PART co-pathology in CJD suggests independent pathogenic mechanisms and no cross-seeding between misfolded Aβ and prion proteins

Current evidence indicating a role of the human prion protein (PrP) in amyloid-beta (Aβ) formation or a synergistic effect between Aβ and prion pathology remains controversial. Conflicting results also concern the frequency of the association between the two protein misfolding disorders and the issue of whether the apolipoprotein E gene (APOE) and the prion protein gene (PRNP), the major modifiers of Aβ- and PrP-related pathologies, also have a pathogenic role in other proteinopathies, including tau neurofibrillary degeneration. Here, we thoroughly characterized the Alzheimer's disease/primary age-related tauopathy (AD/PART) spectrum in a series of 450 cases with definite sporadic or genetic Creutzfeldt-Jakob disease (CJD). Moreover, we analyzed: (i) the effect of variables known to affect CJD pathogenesis and the co-occurring Aβ- and tau-related pathologies; (II) the influence of APOE genotype on CJD pathology, and (III) the effect of AD/PART co-pathology on the clinical CJD phenotype. AD/PART characterized 74% of CJD brains, with 53.3% and 8.2% showing low or intermediate-high levels of AD pathology, and 12.4 and 11.8% definite or possible PART. There was no significant correlation between variables affecting CJD (i.e., disease subtype, prion strain, PRNP genotype) and those defining the AD/PART spectrum (i.e., ABC score, Thal phase, prevalence of CAA and Braak stage), and no difference in the distribution of APOE ε4 and ε2 genotypes among CJD subtypes. Moreover, AD/PART co-pathology did not significantly affect the clinical presentation of typical CJD, except for a tendency to increase the frequency of cognitive symptoms. Altogether, the present results seem to exclude an increased prevalence AD/PART co-pathology in sporadic and genetic CJD, and indicate that largely independent pathogenic mechanisms drive AD/PART and CJD pathology even when they coexist in the same brain

Antimicrobial resistance in urosepsis: outcomes from the multinational, multicenter global prevalence of infections in urology (GPIU) study 2003–2013

Primary objective was to identify the (1) relationship of clinical severity of urosepsis with the pathogen spectrum and resistance and (2) appropriateness of using the pathogen spectrum and resistance rates of health-care-associated urinary tract infections (HAUTI) as representative of urosepsis. The secondary objective was to provide an overview of the pathogens and their resistance profile in patients with urosepsis. POPULATION AND METHODS: A point prevalence study carried out in 70 countries (2003-2013). Population studied included; 408 individuals with microbiologically proven urosepsis, 1606 individuals with microbiological proof of HAUTI and 27,542 individuals hospitalised in urology wards. Main outcomes are pathogens and resistance identified in HAUTIs and urosepsis including its clinical severity. A statistical model that included demographic factors (study year, geographical location, hospital setting) was used for analysis. RESULTS: Amongst urology practices, the prevalence of microbiologically proven HAUTI and urosepsis was 5.8 and 1.5 %, respectively. Frequent pathogens in urosepsis were E. coli (43 %), Enterococcus spp. (11 %), P. aeruginosa (10 %) and Klebsiella spp. (10 %). Resistance to commonly prescribed antibiotics was high and rates ranged from 8 % (imipenem) to 62 % (aminopenicillin/β lactamase inhibitors); 45 % of Enterobacteriaceae and 21 % of P. aeruginosa were multidrug-resistant. Resistance rates in urosepsis were higher than in other clinical diagnosis of HAUTI (Likelihood ratio <0.05). CONCLUSIONS: It is not appropriate to use the pathogen spectrum and resistance rates of other HAUTIs as representative of urosepsis to decide on empirical treatment of urosepsis. Resistance rates in urosepsis are high, and precautions should be made to avoid further increas

Regulating Data Exchange in Service Oriented Applications

We define a type system for COWS, a formalism for specifying and combining services, while modelling their dynamic behaviour. Our types permit to express policies constraining data exchanges in terms of sets of service partner names attachable to each single datum. Service programmers explicitly write only the annotations necessary to specify the wanted policies for communicable data, while a type inference system (statically) derives the minimal additional annotations that ensure consistency of services initial configuration. Then, the language dynamic semantics only performs very simple checks to authorize or block communication. We prove that the type system and the operational semantics are sound. As a consequence, we have the following data protection property: services always comply with the policies regulating the exchange of data among interacting services. We illustrate our approach through a simplified but realistic scenario for a service-based electronic marketplace

The global prevalence of infections in urology study. a long term worldwide surveillance study on urological infections

The Global Prevalence of Infections in Urology (GPIU) study is a worldwide-performed point prevalence study intended to create surveillance data on antibiotic resistance, type of urogenital infections, risk factors and data on antibiotic consumption, specifically in patients at urological departments with healthcare-associated urogenital infections (HAUTI). Investigators registered data through a web-based application (http://gpiu.esiu.org/). Data collection includes the practice and characteristics of the hospital and urology ward. On a certain day in November, each year, all urological patients present in the urological department at 8:00 a.m. are screened for HAUTI encompassing their full hospital course from admission to discharge. Apart from the GPIU main study, several side studies are taking place, dealing with transurethral resection of the prostate, prostate biopsy, as well as urosepsis. The GPIU study has been annually performed since 2003. Eight-hundred fifty-six urology units from 70 countries have participated so far, including 27,542 patients. A proxy for antibiotic consumption is reflected by the application rates used for antibiotic prophylaxis for urological interventions. Resistance rates of most uropathogens against antibiotics were high, especially with a note of multidrug resistance. The severity of HAUTI is also increasing, 25% being urosepsis in recent years. KEYWORDS

Session Types with Linearity in Haskell

Type systems with parametric polymorphism can encode a significant pro- portion of the information contained in session types. This allows concurrent programming with session-type-like guarantees in languages like ML and Java. However, statically enforcing the linearity properties of session types, in a way that is also natural to program with, is more challenging. Haskell provides various language features that can capture concurrent programming with session types, with full linearity invariants and in a mostly idiomatic style. This chapter overviews various approaches in the literature for session typed programming in Haskell. As a starting point, we use polymorphic types and simple type-level functions to provide session-typed communication in Haskell without linearity. We then overview and compare the varying approaches to implementing session types with static linearity checks. We conclude with a discussion of the remaining open problems. The code associated with this chapter can be found at http://github. com/dorchard/betty-book-haskell-sessions