135 research outputs found
Parametric estimation of ultrasonic phase velocity and attenuation in dispersive media
ΠΠ°Π΄Π°ΡΡ Π·Π°ΠΎΡΠ½ΠΎΡ ΡΡΠ·ΠΈΠΊΠΎ-ΠΌΠ°ΡΠ΅ΠΌΠ°ΡΠΈΡΠ½ΠΎΡ ΡΠΊΠΎΠ»ΠΈ
Π£ ΠΏΠΎΡΡΠ±Π½ΠΈΠΊΡ Π½Π° ΠΎΡΠ½ΠΎΠ²Ρ ΡΠ·Π°Π³Π°Π»ΡΠ½Π΅Π½Π½Ρ Π΄ΠΎΡΠ²ΡΠ΄Ρ ΡΠΎΠ±ΠΎΡΠΈ Π·Π°ΠΎΡΠ½ΠΎΡ ΡΡΠ·ΠΈΠΊΠΎ-ΠΌΠ°ΡΠ΅ΠΌΠ°ΡΠΈΡΠ½ΠΎΡ ΡΠΊΠΎΠ»ΠΈ ΠΡΡΠΎΠ²ΠΎΠ³ΡΠ°Π΄ΡΡΠΊΠΎΠ³ΠΎ Π΄Π΅ΡΠΆΠ°Π²Π½ΠΎΠ³ΠΎ ΠΏΠ΅Π΄Π°Π³ΠΎΠ³ΡΡΠ½ΠΎΠ³ΠΎ ΡΠ½ΡΠ²Π΅ΡΡΠΈΡΠ΅ΡΡ ΡΠΌΠ΅Π½Ρ ΠΠΎΠ»ΠΎΠ΄ΠΈΠΌΠΈΡΠ° ΠΠΈΠ½Π½ΠΈΡΠ΅Π½ΠΊΠ° ΠΏΠΎΠ΄Π°Π½ΠΎ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΡ ΠΉ Π°Π½Π°Π»ΡΠ· ΡΠΎΠ·Π²βΡΠ·ΡΠ²Π°Π½Π½Ρ ΠΎΡΠ½ΠΎΠ²Π½ΠΈΡ
ΡΠΈΠΏΡΠ² Π·Π°Π²Π΄Π°Π½Ρ Π· ΠΌΠ°ΡΠ΅ΠΌΠ°ΡΠΈΠΊΠΈ ΠΉ ΡΡΠ·ΠΈΠΊΠΈ. ΠΡΠ½ ΠΏΠΎΠΊΠ»ΠΈΠΊΠ°Π½ΠΈΠΉ Π΄ΠΎΠΏΠΎΠΌΠΎΠ³ΡΠΈ ΡΡΠ°ΡΡΠΎΠΊΠ»Π°ΡΠ½ΠΈΠΊΠ°ΠΌ Ρ Π°Π±ΡΡΡΡΡΡΠ½ΡΠ°ΠΌ Ρ ΡΡΠΈΡΠ»Ρ ΡΠ΅ΡΠΌΡΠ½ΠΈ ΡΠΈΡΡΠ΅ΠΌΠ°ΡΠΈΠ·ΡΠ²Π°ΡΠΈ ΡΠ²ΠΎΡ Π·Π½Π°Π½Π½Ρ, ΡΠ΄ΠΎΡΠΊΠΎΠ½Π°Π»ΠΈΡΠΈ Π½Π°Π²ΠΈΡΠΊΠΈ, Π·Π°ΡΡΠ΅ΡΠ΅Π³ΡΠΈ Π²ΡΠ΄ ΠΌΠΎΠΆΠ»ΠΈΠ²ΠΈΡ
ΠΏΠΎΠΌΠΈΠ»ΠΎΠΊ, Π° ΠΎΡΠΆΠ΅ ΠΊΡΠ°ΡΠ΅ ΠΏΡΠ΄Π³ΠΎΡΡΠ²Π°ΡΠΈΡΡ Π΄ΠΎ Π½Π΅Π·Π°Π»Π΅ΠΆΠ½ΠΎΠ³ΠΎ ΡΠ΅ΡΡΡΠ²Π°Π½Π½Ρ Π· ΠΌΠ°ΡΠ΅ΠΌΠ°ΡΠΈΠΊΠΈ ΠΉ ΡΡΠ·ΠΈΠΊΠΈ.
ΠΠΎΡΡΠ±Π½ΠΈΠΊ Π±ΡΠ΄Π΅ ΠΊΠΎΡΠΈΡΠ½ΠΈΠΌ Π²ΠΈΠΏΡΡΠΊΠ½ΠΈΠΊΠ°ΠΌ Π·Π°Π³Π°Π»ΡΠ½ΠΎΠΎΡΠ²ΡΡΠ½ΡΡ
ΡΠΊΡΠ», Π° ΡΠ°ΠΊΠΎΠΆ ΡΡΠΈΡΠ΅Π»ΡΠΌ ΡΠ° ΡΡΡΠ΄Π΅Π½ΡΠ°ΠΌ ΡΡΠ·ΠΈΠΊΠΎ-ΠΌΠ°ΡΠ΅ΠΌΠ°ΡΠΈΡΠ½ΠΈΡ
ΡΠ°ΠΊΡΠ»ΡΡΠ΅ΡΡΠ² ΠΏΠ΅Π΄Π°Π³ΠΎΠ³ΡΡΠ½ΠΈΡ
ΡΠ½ΡΠ²Π΅ΡΡΠΈΡΠ΅ΡΡΠ²
On definition and inference of nonlinear Boolean dynamic networks
Network reconstruction has become particularly important in systems biology, and is now expected to deliver information on causality. Systems in nature are inherently nonlinear. However, for nonlinear dynamical systems with hidden states, how to give a useful definition of dynamic networks is still an open question. This paper presents a useful definition of Boolean dynamic networks for a large class of nonlinear systems. Moreover, a robust inference method is provided. The well-known Millar-10 model in systems biology is used as a numerical example, which provides the ground truth of causal networks for key mRNAs involved in eukaryotic circadian clocks. In addition, as second contribution of this paper, we suggest definitions of linear network identifiability, which helps to unify the available work on network identifiability
Preclinical Pharmacology of [2-(3-Fluoro-5-Methanesulfonyl-phenoxy)Ethyl](Propyl)amine (IRL790), a Novel Dopamine Transmission Modulator for the Treatment of Motor and Psychiatric Complications in Parkinson Disease.
IRL790 ([2-(3-fluoro-5-methanesulfonylphenoxy)ethyl](propyl)amine, mesdopetam) is a novel compound in development for the clinical management of motor and psychiatric disabilities in Parkinson disease. The discovery of IRL790 was made applying a systems pharmacology approach based on in vivo response profiling. The chemical design idea was to develop a new type of DA D3/D2 receptor type antagonist built on agonist rather than antagonist structural motifs. We hypothesized that such a dopamine antagonist with physicochemical properties similar to agonists would exert antidyskinetic and antipsychotic effects in states of dysregulated dopaminergic signaling while having little negative impact on physiologic dopamine transmission and, hence, minimal liability for side effects related to dopamine-dependent functions. At the level of in vivo pharmacology, IRL790 displays balancing effects on aberrant motor phenotypes, reducing l-DOPA-induced dyskinesias in the rodent 6-hydroxydopamine lesion model and reducing psychostimulant-induced locomotor hyperactivity elicited by pretreatment with either d-amphetamine or dizocilpine, without negatively impacting normal motor performance. Thus, IRL790 has the ability to normalize the behavioral phenotype in hyperdopaminergic as well as hypoglutamatergic states. Neurochemical and immediate early gene (IEG) response profiles suggest modulation of DA neurotransmission, with some features, such as increased DA metabolites and extracellular DA, shared by atypical antipsychotics and others, such as increased frontal cortex IEGs, unique to IRL790. IRL790 also increases extracellular levels of acetylcholine in the prefrontal cortex and ventral hippocampus. At the receptor level, IRL790 appears to act as a preferential DA D3 receptor antagonist. Computational docking studies support preferential affinity at D3 receptors with an agonist-like binding mode. SIGNIFICANCE STATEMENT: This paper reports preclinical pharmacology along with molecular modeling results on IRL790, a novel compound in clinical development for the treatment of motor and psychiatric complications in advanced Parkinson disease. IRL790 is active in models of perturbed dopaminergic and glutamatergic signaling, including rodent 6-hydroxydopamine l-DOPA-induced dyskinesias and psychostimulant-induced hyperactivity, in a dose range that does not impair normal behavior. This effect profile is attributed to interactions at dopamine D2/D3 receptors, with a 6- to 8-fold preference for the D3 subtype
Short-term, intermediate-term and long-term risks of acute coronary syndrome in cohorts of patients with RA starting biologic DMARDs : results from four Nordic countries
Objectives To compare the 1-year, 2-year and 5-year incidences of acute coronary syndrome (ACS) in patients with rheumatoid arthritis (RA) starting any of the biologic disease-modifying antirheumatic drugs (bDMARDs) currently available in clinical practice and to anchor these results with a general population comparator. Methods Observational cohort study, with patients from Denmark, Finland, Norway and Sweden starting a bDMARD during 2008-2017. Time to first ACS was identified through register linkages. We calculated the 1-year, 2-year and 5-year incidence rates (IR) (on drug and ever since treatment start) and used Cox regression (HRs) to compare ACS incidences across treatments taking ACS risk factors into account. Analyses were further performed separately in subgroups defined by age, number of previous bDMARDs and history of cardiovascular disease. We also compared ACS incidences to an individually matched general population cohort. Results 24 083 patients (75% women, mean age 56 years) contributing 40 850 treatment courses were included. During the maximum (5 years) follow-up (141 257 person-years (pyrs)), 780 ACS events occurred (crude IR 5.5 per 1000 pyrs). Overall, the incidence of ACS in RA was 80% higher than that in the general population. For all bDMARDs and follow-up definitions, HRs were close to 1 (etanercept as reference) with the exception of the 5-year risk window, where signals for abatacept, infliximab and rituximab were noted. Conclusion The rate of ACS among patients with RA initiating bDMARDs remains elevated compared with the general population. As used in routine care, the short-term, intermediate-term and longer-term risks of ACS vary little across individual bDMARDs.Peer reviewe
Inequalities in income and education are associated with survival differences after out-of-hospital cardiac arrest : nationwide observational study
Published online: 12 November 2021Background:
Despite the acknowledged importance of socioeconomic factors as regards cardiovascular disease onset and survival, the relationship between individual-level socioeconomic factors and survival after out-of-hospital cardiac arrest is not established. Our aim was to investigate whether socioeconomic variables are associated with 30-day survival after out-of-hospital cardiac arrest.
Methods:
We linked data from the Swedish Registry for Cardiopulmonary Resuscitation with individual-level data on socioeconomic factors (ie, educational level and disposable income) from Statistics Sweden. Confounding and mediating variables included demographic factors, comorbidity, and Utstein resuscitation variables. Outcome was 30-day survival. Multiple modified Poisson regression was used for the main analyses.
Results:
A total of 31 373 out-of-hospital cardiac arrests occurring in 2010 to 2017 were included. Crude 30-day survival rates by income quintiles were as follows: Q1 (low), 414/6277 (6.6%); Q2, 339/6276 (5.4%); Q3, 423/6275 (6.7%); Q4, 652/6273 (10.4%); and Q5 (high), 928/6272 (14.8%). In adjusted analysis, the chance of survival by income level followed a gradient-like increase, with a risk ratio of 1.86 (95% CI, 1.65β2.09) in the highest-income quintile versus the lowest. This association remained after adjusting for comorbidity, resuscitation factors, and initial rhythm. A higher educational level was associated with improved 30-day survival, with the risk ratio associated with postsecondary education β₯4 years being 1.51 (95% CI, 1.30β1.74). Survival disparities by income and educational level were observed in both men and women.
Conclusions:
In this nationwide observational study using individual-level socioeconomic data, higher income and higher educational level were associated with better 30-day survival after out-of-hospital cardiac arrest in both sexes
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