30 research outputs found
Phase transitions, memory and frustration in a Sznajd-like model with synchronous updating
We introduce a consensus model inspired by the Sznajd Model. The updating is
synchronous and memory plays here a decisive role in making possible the
reaching of total consensus. We study the phase transition between the state
with no-consensus to the state with total consensus.Comment: to be published in the IJMP
Non-monotonic spontaneous magnetization in a Sznajd-like Consensus Model
Ising or Potts models of ferromagnetism have been widely used to describe
locally interacting social or economic systems. We consider a related model,
introduced by Sznajd to describe the evolution of consensus in a society. In
this model, the opinion or state of any spins can only be changed through the
influence of neighbouring pairs of similarly aligned spins. Such pairs can
polarize their neighbours. We show that, assuming the global dynamics evolve in
a synchronous manner, the two-state Sznajd model exhibits a non-monotonically
decreasing overall orientation that has a maximum value when the system is
subject to a finite value of noise. Reinterpreting the model in terms of
opinions within a society we predict that consensus can be increased by the
addition of an appropriate amount of random noise. These features are explained
by the presence of islands of complete orientation that are stable in the
absence of noise but removed via the presence of added noise.Comment: 6 pages, 6 figure
Langevin processes, agent models and socio-economic systems
We review some approaches to the understanding of fluctuations in some models
used to describe socio and economic systems. Our approach builds on the
development of a simple Langevin equation that characterises stochastic
processes. This provides a unifying approach that allows first a
straightforward description of the early approaches of Bachelier. We generalise
the approach to stochastic equations that model interacting agents. Using a
simple change of variable, we show that the peer pressure model of Marsilli and
the wealth dynamics model of Solomon are closely related. The methods are
further shown to be consistent with a global free energy functional that
invokes an entropy term based on the Boltzmann formula. A more recent approach
by Michael and Johnson maximised a Tsallis entropy function subject to simple
constraints. We show how this approach can be developed from an agent model
where the simple Langevin process is now conditioned by local rather than
global noise. The approach yields a BBGKY type hierarchy of equations for the
system correlation functions. Of especial interest is that the results can be
obtained from a new free energy functional similar to that mentioned above
except that a Tsallis like entropy term replaces the Boltzmann entropy term. A
mean field approximation yields the results of Michael and Johnson. We show how
personal income data for Brazil, the US, Germany and the UK, analysed recently
by Borgas can be qualitatively understood by this approach.Comment: 1 figur
An ALS-associated mutation in the FUS 3′-UTR disrupts a microRNA–FUS regulatory circuitry
While the physiologic functions of the RNA-binding protein FUS still await thorough characterization, the pathonegetic role of FUS mutations in amyotrophic lateral sclerosis (ALS) is clearly established. Here we find that a human FUS mutation that leads to increased protein expression, and was identified in two ALS patients with severe outcome, maps to the seed sequence recognized by miR-141 and miR-200a in the 3'-UTR of FUS. We demonstrate that FUS and these microRNAs are linked by a feed-forward regulatory loop where FUS upregulates miR-141/200a, which in turn impact FUS protein synthesis. We also show that Zeb1, a target of miR-141/200a and transcriptional repressor of these two microRNAs, is part of the circuitry and reinforces it. Our results reveal a possible correlation between deregulation of this regulatory circuit and ALS pathogenesis, and open interesting perspectives in the treatment of these mutations through ad hoc-modified microRNAs
Burden of hospitalizations and outpatient visits associated with moderate and severe acute graft-versus-host disease in Finland and Sweden : a real-world data study
Purpose The aim of this study was to describe patient characteristics and quantify hospital stays and outpatient visits (H&OV) following diagnosis with moderate-to-severe acute graft-versus-host disease (aGVHD) in Finland and Sweden. Methods A retrospective chart audit collected data from patient medical records of 3 specialized centers performing allogeneic hematopoietic stem cell transplantation (HSCT; Finland, n = 2; Sweden, n = 1). Eligible patients received allogeneic HSCT (January 1, 2016-June 30, 2017) from any donor source, were diagnosed with grade II-IV aGVHD (MAGIC or modified Glucksberg criteria) at any time from transplantation to 12 months before data collection, and were >= 18 years old at diagnosis. Criteria for comparing patients graded with modified Glucksberg and MAGIC severity scales were defined. Results Fifty-five patients (Finland, n = 45; Sweden, n = 10) were included. Myeloablative conditioning was the most common conditioning regimen (81.8%); immunosuppression regimens were based on combinations of methotrexate (96.4%), in vivo T-cell depletion (80.0%), cyclosporine (63.6%), mycophenolate (40.0%), and tacrolimus (34.5%). Sixteen patients (29.1%) developed grade III/IV aGVHD; skin was the most common organ involved (80.0%). Most patients required >= 1 hospital stay (89.1%; median of 2 hospitalizations per patient); 7 patients (14.3%) required admission to an intensive care unit. Median hospitalization duration from HSCT to discharge was 26 days. Most patients also required outpatient or emergency department visits (90.9%). Subgroup analyses showed longer hospital stays for patients receiving multiple treatment lines; no clear differences in H&OV were observed between prophylactic regimens. Conclusion Based on this retrospective study, moderate-to-severe aGVHD is associated with considerable healthcare resource utilization in Finland and Sweden, particularly in patients who received multiple lines of therapy.Peer reviewe
A cost-effectiveness analysis of denosumab for the prevention of skeletal-related events in patients with multiple myeloma in the United States of America
Objective: A large, pivotal, phase 3 trial in patients with newly diagnosed multiple myeloma (MM) demonstrated that denosumab, compared with zoledronic acid, was non-inferior for the prevention of skeletal-related events (SREs), extended the observed median progression-free survival (PFS) by 10.7 months, and showed significantly less renal toxicity. The cost-effectiveness of denosumab vs zoledronic acid in MM in the US was assessed from societal and payer perspectives.
Methods: The XGEVA Global Economic Model was developed by integrating data from the phase 3 trial comparing the efficacy of denosumab with zoledronic acid for the prevention of SREs in MM. SRE rates were adjusted to reflect the real-world incidence. The model included utility decrements for SREs, administration, serious adverse events (SAEs), and disease progression. Drug, administration, SRE management, SAEs, and anti-MM treatment costs were based on data from published studies. For the societal perspective, the model additionally included SRE-related direct non-medical costs and indirect costs. The net monetary benefit (NMB) was calculated using a willingness-to-pay threshold of US26,329 and an incremental quality-adjusted life-year (QALY) of 0.2439, translating into a cost per QALY gained of US10,259 in favor of denosumab. Results were sensitive to SRE rates and PFS parameters.
Limitations: Costs were estimated from multiple sources, which varied by tumor type, patient population, country, and other parameters. PFS and overall survival were extrapolated beyond the follow-up of the primary analysis using fitted parametric curves.
Conclusion: Denosumab’s efficacy in delaying or preventing SREs, potential to improve PFS, and lack of renal toxicity make it a cost-effective option for the prevention of SREs in MM compared with zoledronic acid
Assessment of aflatoxin M1 enrichment factor in cheese produced with naturally contaminated milk
Aflatoxin M1 (AFM1) is a well-known carcinogenic compound that may contaminate milk and dairy products. Thus, with the regulation 1881/2006, the European Union established a concentration limit for AFM1 in milk and insisted on the importance of defining enrichment factors (EFs) for cheese. In 2019, the Italian Ministry of Health proposed four different EFs based on cheese’s moisture content on a fat-free basis (MMFB) for bovine dairy products. This study aimed to define the EFs of cheese with different MFFB. The milk used for cheesemaking was naturally contaminated with different AFM1 concentrations. Results showed that all the EF average values from this study were lower than those of the Italian Ministry of Health. Hence, the current EFs might need to be reconsidered for a better categorization of AFM1 risk in cheese
Burden of hospitalizations and outpatient visits associated with moderate and severe acute graft-versus-host disease in Finland and Sweden: a real-world data study
Purpose The aim of this study was to describe patient characteristics and quantify hospital stays and outpatient visits (H&OV) following diagnosis with moderate-to-severe acute graft-versus-host disease (aGVHD) in Finland and Sweden.Methods A retrospective chart audit collected data from patient medical records of 3 specialized centers performing allogeneic hematopoietic stem cell transplantation (HSCT; Finland, n = 2; Sweden, n = 1). Eligible patients received allogeneic HSCT (January 1, 2016-June 30, 2017) from any donor source, were diagnosed with grade II-IV aGVHD (MAGIC or modified Glucksberg criteria) at any time from transplantation to 12 months before data collection, and were >= 18 years old at diagnosis. Criteria for comparing patients graded with modified Glucksberg and MAGIC severity scales were defined.Results Fifty-five patients (Finland, n = 45; Sweden, n = 10) were included. Myeloablative conditioning was the most common conditioning regimen (81.8%); immunosuppression regimens were based on combinations of methotrexate (96.4%), in vivo T-cell depletion (80.0%), cyclosporine (63.6%), mycophenolate (40.0%), and tacrolimus (34.5%). Sixteen patients (29.1%) developed grade III/IV aGVHD; skin was the most common organ involved (80.0%). Most patients required >= 1 hospital stay (89.1%; median of 2 hospitalizations per patient); 7 patients (14.3%) required admission to an intensive care unit. Median hospitalization duration from HSCT to discharge was 26 days. Most patients also required outpatient or emergency department visits (90.9%). Subgroup analyses showed longer hospital stays for patients receiving multiple treatment lines; no clear differences in H&OV were observed between prophylactic regimens.Conclusion Based on this retrospective study, moderate-to-severe aGVHD is associated with considerable healthcare resource utilization in Finland and Sweden, particularly in patients who received multiple lines of therapy.</p
Elevated TGF \u3b22 serum levels in Emery-Dreifuss Muscular Dystrophy: Implications for myocyte and tenocyte differentiation and fibrogenic processes
Among rare diseases caused by mutations in LMNA gene, Emery-Dreifuss Muscular Dystrophy type 2 and Limb-Girdle muscular Dystrophy 1B are characterized by muscle weakness and wasting, joint contractures, cardiomyopathy with conduction system disorders. Circulating biomarkers for these pathologies have not been identified. Here, we analyzed the secretome of a cohort of patients affected by these muscular laminopathies in the attempt to identify a common signature. Multiplex cytokine assay showed that transforming growth factor beta 2 (TGF \u3b22) and interleukin 17 serum levels are consistently elevated in the vast majority of examined patients, while interleukin 6 and basic fibroblast growth factor are altered in subgroups of patients. Levels of TGF \u3b22 are also increased in fibroblast and myoblast cultures established from patient biopsies as well as in serum from mice bearing the H222P Lmna mutation causing Emery-Dreifuss Muscular Dystrophy in humans. Both patient serum and fibroblast conditioned media activated a TGF \u3b22-dependent fibrogenic program in normal human myoblasts and tenocytes and inhibited myoblast differentiation. Consistent with these results, a TGF \u3b22 neutralizing antibody avoided fibrogenic marker activation and myogenesis impairment. Cell intrinsic TGF \u3b22-dependent mechanisms were also determined in laminopathic cells, where TGF \u3b22 activated AKT/mTOR phosphorylation. These data show that TGF \u3b22 contributes to the pathogenesis of Emery-Dreifuss Muscular Dystrophy type 2 and Limb-Girdle muscular Dystrophy 1B and can be considered a potential biomarker of those diseases. Further, the evidence of TGF \u3b22 pathogenetic effects in tenocytes provides the first mechanistic insight into occurrence of joint contractures in muscular laminopathies
Effect of Heterogeneous Mixing and Vaccination on the Dynamics of Anthelmintic Resistance: A Nested Model
Anthelmintic resistance is a major threat to current measures for helminth
control in humans and animals. The introduction of anthelmintic vaccines, as a
complement to or replacement for drug treatments, has been advocated as a
preventive measure. Here, a computer-based simulation, tracking the dynamics of
hosts, parasites and parasite-genes, shows that, depending on the degree of
host-population mixing, the frequency of totally recessive autosomes associated
with anthelmintic resistance can follow either a fast dynamical regime with a
low equilibrium point or a slow dynamical regime with a high equilibrium point.
For fully dominant autosomes, only one regime is predicted. The effectiveness
of anthelminthic vaccines against resistance is shown to be strongly influenced
by the underlying dynamics of resistant autosomes. Vaccines targeting adult
parasites, by decreasing helminth fecundity or lifespan, are predicted to be
more effective than vaccines targeting parasite larvae, by decreasing host
susceptibility to infection, in reducing the spread of resistance. These
results may inform new strategies to prevent, monitor and control the spread of
anthelmintic resistance, including the development of viable anthelmintic
vaccines