102 research outputs found
Corporate Universities’ Configuration in the Italian Context: An Exploratory Study
The popularity of Corporate Universities (CUs) has grown considerably over the last decades, gaining both scholars and practitioners’ interest. This exploratory study contributes to the CU-related research field adding empirical evidence to the scant literature that examines how the CU configuration is operationalized in the Italian context. Our findings reveal that different features exist with varied prominence among the selected CUs, revealing a great heterogeneity that cannot be explained uniquely by their stage of life cycle. Nevertheless, it is worth noting some common features across the selected cases. First of all, these CUs devote most of their activities exclusively or prominently to their internal audiences. Moreover, although they have relationships with universities and business schools, the level of involvement of external partners is still modest. Together these two aspects denote a low level of openness of these entities that may be explained by institutional and cultural factors characterizing the Italian context
Combined quay crane assignment and quay crane scheduling with crane inter-vessel movement and non-interference constraints
Integrated models of the quay crane assignment problem (QCAP) and the quay crane scheduling problem (QCSP) exist. However, they have shortcomings in that some do not allow movement of quay cranes between vessels, others do not take into account precedence relationships between tasks, and yet others do not avoid interference between quay cranes. Here, an integrated and comprehensive optimization model that combines the two distinct QCAP and QCSP problems which deals with the issues raised is put forward. The model is of the mixed-integer programming type with the objective being to minimize the difference between tardiness cost and earliness income based on finishing time and requested departure time for a vessel. Because of the extent of the model and the potential for even small problems to lead to large instances, exact methods can be prohibitive in computational time. For this reason an adapted genetic algorithm (GA) is implemented to cope with this computational burden. Experimental results obtained with branch-and-cut as implemented in CPLEX and GA for small to large-scale problem instances are presented. The paper also includes a review of the relevant literature
An evolutionary approach to a combined mixed integer programming model of seaside operations as arise in container ports
This paper puts forward an integrated optimisation model that combines three distinct problems, namely berth allocation, quay crane assignment, and quay crane scheduling that arise in container ports. Each one of these problems is difficult to solve in its own right. However, solving them individually leads almost surely to sub-optimal solutions. Hence, it is desirable to solve them in a combined form. The model is of the mixed-integer programming type with the objective being to minimize the tardiness of vessels and reduce the cost of berthing. Experimental results show that relatively small instances of the proposed model can be solved exactly using CPLEX. Large scale instances, however, can only be solved in reasonable times using heuristics. Here, an implementation of the genetic algorithm is considered. The effectiveness of this implementation is tested against CPLEX on small to medium size instances of the combined model. Larger size instances were also solved with the genetic algorithm, showing that this approach is capable of finding the optimal or near optimal solutions in realistic times
Adjunctive cenobamate in people with focal onset seizures: Insights from the Italian Expanded Access Program
Objective: This study was undertaken to assess the effectiveness/tolerability of adjunctive cenobamate, variations in the load of concomitant antiseizure medications (ASMs) and predictors of clinical response in people with focal epilepsy. Methods: This was a retrospective study at 21 centers participating in the Italian Expanded Access Program. Effectiveness outcomes included retention and responder rates (>= 50% and 100% reduction in baseline seizure frequency). Tolerability/safety outcomes included the rate of treatment discontinuation due to adverse events (AEs) and their incidence. Total drug load was quantified as the number of concomitant ASMs and total defined daily dose (DDD). Concomitant ASMs were also classified according to their mechanism of action and pharmacokinetic interactions to perform explorative subgroup analyses. Results: A total of 236 subjects with a median age of 38 (Q(1)-Q(3) = 27-49) years were included. At 12 months, cenobamate retention rate was 78.8% and responders were 57.5%. The seizure freedom rates during the preceding 3 months were 9.8%, 12.2%, 16.3%, and 14.0% at 3, 6, 9, and 12 months. A higher percentage of responders was observed among subjects treated with clobazam, although the difference was not statistically significant. A total of 223 AEs were recorded in 133 of 236 participants, leading to cenobamate discontinuation in 8.5% cases. At 12 months, a reduction of one or two concomitant ASMs occurred in 42.6% and 4.3% of the subjects. The median total DDD of all concomitant ASMs decreased from 3.34 (Q(1)-Q(3) = 2.50-4.47) at baseline to 2.50 (Q(1)-Q(3) = 1.67-3.50) at 12 months (p < .001, median percentage reduction = 22.2%). The highest rates of cotreatment withdrawal and reductions in the DDD were observed for sodium channel blockers and gamma-aminobutyric acidergic modulators (above all for those linked to pharmacokinetic interactions), and perampanel. Significance: Adjunctive cenobamate was associated with a reduction in seizure frequency and in the burden of concomitant ASMs in adults with difficult-to-treat focal epilepsy. The type of ASM associated did not influence effectiveness except for a favorable trend with clobazam
Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes
Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance. Genes encoding ion channels show strong association with multiple epilepsy subtypes, including epileptic encephalopathies, generalized and focal epilepsies, while most other gene discoveries are subtype-specific, highlighting distinct genetic contributions to different epilepsies. Combining results from rare single nucleotide/short indel-, copy number-, and common variants, we offer an expanded view of the genetic architecture of epilepsy, with growing evidence of convergence among different genetic risk loci on the same genes. Top candidate genes are enriched for roles in synaptic transmission and neuronal excitability, particularly postnatally and in the neocortex. We also identify shared rare variant risk between epilepsy and other neurodevelopmental disorders. Our data can be accessed via an interactive browser, hopefully facilitating diagnostic efforts and accelerating the development of follow-up studies
Genome-wide association meta-analyses of drug-resistant epilepsy
Background
Epilepsy is one of the most common neurological disorders, affecting over 50 million people worldwide. One-third of people with epilepsy do not respond to currently available anti-seizure medications, constituting one of the most important problems in epilepsy. Little is known about the molecular pathology of drug resistance in epilepsy, in particular, possible underlying genetic factors are largely unknown.
Methods
We performed a genome-wide association study (GWAS) in two epilepsy cohorts of European ancestry, comparing drug-resistant (N = 4208) to drug-responsive individuals (N = 2618) followed by meta-analyses across the studies. Next, we performed subanalyses split into two broad subtypes: acquired or non-acquired focal and genetic generalized epilepsy.
Findings
Our drug-resistant versus drug-responsive epilepsy GWAS meta-analysis showed no significant loci when combining all epilepsy types. Sub-analyses on individuals with focal epilepsy (FE) identified a significant locus on chromosome 1q42.11-q42.12 (lead SNP: rs35915186, P = 1·51 × 10−8, OR[C] = 0·74). This locus was not associated with any epilepsy subtype in the latest epilepsy GWAS (lowest uncorrected P = 0·009 for FE vs. healthy controls), and drug resistance in FE was not genetically correlated with susceptibility to FE itself. Seven genome-wide significant SNPs within this locus, encompassing the genes CNIH4, WDR26, and CNIH3, were identified to protect against drug-resistant FE. Further transcriptome-wide association studies (TWAS) imply significantly higher expression levels of CNIH3 and WDR26 in drug-resistant FE than in drug-responsive FE. CNIH3 is implicated in AMPA receptor assembly and function, while WDR26 haploinsufficiency is linked to intellectual disability and seizures. These findings suggest that CNIH3 and WDR26 may play a role in mediating drug response in focal epilepsy.
Interpretation
We identified a contribution of common genetic variation to drug-resistant focal epilepsy. These findings provide insights into possible mechanisms underlying drug response variability in epilepsy, offering potential targets for personalised treatment approaches
Inter-organizational knowledge transfer:current issues and future prospects
Many papers have been published recently in the fields of strategy and international business research incorporating the role of organizational knowledge as a basis of firm competitive advantage. While such knowledge is normally developed within the firm, it is important that firms possess the ability to learn from others in order to meet the increasing pace of competition. Knowledge transfer, defined here as an event through which one organization learns from the experience of another, has thus become an important research area within the broader domain of organizational learning and knowledge management. This paper presents a theoretical framework, identifies key themes covered by the six articles included in the Special Issue on Inter-Organizational Knowledge Transfer, and then discusses priorities for future research
Nascondere la conoscenza nuoce alla propria creatività (e non solo a quella degli altri)
Siamo certi di fare il nostro interesse quando scegliamo intenzionalmente di non condividere ciò che sappiamo con i colleghi? Questo articolo suggerisce che nascondere la conoscenza non solo impedisce ai colleghi di generare idee creative, ma riduce anche la nostra stessa creatività.
Le organizzazioni, però, possono lavorare sul clima per diminuire la propensione individuale al knowledge hiding e attenuare i suoi effetti negativi sulla creatività
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