Arbitrarily accurate, nonparametric coarse graining with Markov renewal processes and the Mori-Zwanzig formulation

Stochastic dynamics, such as molecular dynamics, are important in many scientific applications. However, accessing macroscopic dynamical behavior often requires inordinately long simulation times. Coarse graining is a popular technique for addessing this problem. While coarse graining provides computational tractability, it comes at the cost of accuracy. This article shows how to eliminate coarse-graining error using two key ideas. First, we represent coarse-grained dynamics as a Markov renewal process. Second, we outline a data-driven, non-parametric Mori-Zwanzig approach for computing jump times of the renewal process. Numerical tests on a small protein illustrate the method.Comment: 8 pages, 6 figure

On the bifurcation diagram of the capillary-gravity Whitham equation

We study the bifurcation of periodic travelling waves of the capillary-gravity Whitham equation. This is a nonlinear pseudo-differential equation that combines the canonical shallow water nonlinearity with the exact (unidirectional) dispersion for finite-depth capillary-gravity waves. Starting from the line of zero solutions, we give a complete description of all small periodic solutions, unimodal as well bimodal, using simple and double bifurcation via Lyapunov--Schmidt reductions. Included in this study is the resonant case when one wavenumber divides another. Some bifurcation formulas are studied, enabling us, in almost all cases, to continue the unimodal bifurcation curves into global curves. By characterizing the range of the surface tension parameter for which the integral kernel corresponding to the linear dispersion operator is completely monotone (and therefore positive and convex; the threshold value for this to happen turns out to be $T = \frac{4}{\pi^2}$, not the critical Bond number $\frac{1}{3}$), we are able to say something about the nodal properties of solutions, even in the presence of surface tension. Finally, we present a few general results for the equation and discuss, in detail, the complete bifurcation diagram as far as it is known from analytical and numerical evidence. Interestingly, we find, analytically, secondary bifurcation curves connecting different branches of solutions; and, numerically, that all supercritical waves preserve their basic nodal structure, converging asymptotically in L^2(\SM) (but not in $L^\infty$) towards one of the two constant solution curves

An open prospective study evaluating efficacy and safety of a new medical device for rectal application of activated carbon in the treatment of chronic, uncomplicated perianal fistulas

Purpose: It has been proposed that biological/chemical substances in the intestine might play a role in the occurrence and deterioration of perianal fistulas. Elimination of such unidentified factors from the lower gastrointestinal tract might offer a new strategy for the management of anal fistulas. The aim of this study was to evaluate the clinical effects on non-Crohn’s disease perianal fistula healing, and the safety and tolerability of a new medical device that applies high-purity, high-activity granular activated carbon locally into the rectum twice daily of patients with perianal fistulas without any concomitant medication. Methods: An open, single-arm, prospective study with active treatment for 8 weeks and an optional follow-up until week 24 (ClinicalTrial.govidentifier NCT01462747) among patients with chronic, uncomplicated perianal fistulas scheduled for surgery was conducted. Results: Of 28 patients included, 10 patients (35.7%) showed complete fistula healing (closed, no discharge on palpation) after 8 weeks; seven of these patients, corresponding to 25% of the enrolled patients, remained in remission for up to 31 weeks. At week 8, there was a statistically significant reduction in the discharge visual analog scale (p = 0.04), a significant improvement in the patient-perceived quality of life for the category of embarrassment (p = 0.002), and a trend toward improvement in the other assessment categories. Conclusions: The treatment was well tolerated, and patient acceptance was high. The results support the efficacy and safety of locally administered activated carbon for the treatment of patients with chronic uncomplicated perianal fistulas not receiving any other medication for fistula problems

Eurooppalaisen innovaatiopolitiikan uusi vaihde vihreässä siirtymässä jatkaa monitasoisen hallinnon tiellä

Uuden vihreän innovaatiopolitiikan alustaksi muodostuvat alueelliset yhteistyöverkostot älykkään erikoistumisen strategioiden toteuttamisessa. Euroopan komission ja Alueiden komitean aloitteella Partnerships for Regional Innovation Pohjanmaalla haetaan seuraavan vaiheen vihreän siirtymän innovaatiopolitiikkaa

European, randomized, phase 3 study of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivity disorder

AbstractThis study evaluated the efficacy and safety of lisdexamfetamine dimesylate (LDX) compared with placebo in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in Europe. Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference arm. Patients (6–17 years old) with a baseline ADHD Rating Scale version IV (ADHD-RS-IV) total score ≥28 were randomized (1:1:1) to dose-optimized LDX (30, 50, or 70mg/day), OROS-MPH (18, 36, or 54mg/day) or placebo for 7 weeks. Primary and key secondary efficacy measures were the investigator-rated ADHD-RS-IV and the Clinical Global Impressions-Improvement (CGI-I) rating, respectively. Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms, and vital signs. Of 336 patients randomized, 196 completed the study. The difference between LDX and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was −18.6 (95% confidence interval [CI]: −21.5 to −15.7) (p<0.001; effect size, 1.80). The difference between OROS-MPH and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was −13.0 (95% CI: −15.9 to −10.2) (p<0.001; effect size, 1.26). The proportions (95% CI) of patients showing improvement (CGI-I of 1 or 2) at endpoint were 78% (70–86), 14% (8–21), and 61% (51–70) for LDX, placebo, and OROS-MPH. The most common TEAEs for LDX were decreased appetite, headache, and insomnia. Mean changes in vital signs were modest and consistent with the known profile of LDX. LDX was effective and generally well tolerated in children and adolescents with ADHD

Growth and puberty in a 2-year open-label study of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivity disorder

Background: Stimulant medications for the treatment of attention-deficit/hyperactivity disorder have a history of safe and effective use; however, concerns exist that they may adversely affect growth trajectories in children and adolescents. Objective: The objective of this study was to evaluate the longer-term effects of lisdexamfetamine dimesylate on weight, height, body mass index and pubertal development in children and adolescents with attention-deficit/hyperactivity disorder. Methods: Children and adolescents aged 6–17 years with attention-deficit/hyperactivity disorder took open-label lisdexamfetamine dimesylate (30, 50 or 70 mg/day) in this open-label 2-year safety and efficacy study. Safety evaluations included treatment-emergent adverse events, measurement of weight, height and body mass index, and selfreported pubertal status using Tanner staging. Results: The safety analysis population comprised all enrolled participants (N = 314) and 191 (60.8%) completed the study. Weight decrease was reported as a treatmentemergent adverse event in 63 participants (20.1%) and two participants (0.6%) discontinued the study as a result of treatment-emergent adverse events of weight decrease

Steady water waves with multiple critical layers: interior dynamics

We study small-amplitude steady water waves with multiple critical layers. Those are rotational two-dimensional gravity-waves propagating over a perfect fluid of finite depth. It is found that arbitrarily many critical layers with cat's-eye vortices are possible, with different structure at different levels within the fluid. The corresponding vorticity depends linearly on the stream function.Comment: 14 pages, 3 figures. As accepted for publication in J. Math. Fluid Mec

Establishment of reference values for plasma neurofilament light based on healthy individuals aged 5-90 years

The recent development of assays that accurately quantify neurofilament light, a neuronal cytoskeleton protein, in plasma has generated a vast literature supporting that it is a sensitive, dynamic, and robust biomarker of neuroaxonal damage. As a result, efforts are now made to introduce plasma neurofilament light into clinical routine practice, making it an easily accessible complement to its cerebrospinal fluid counterpart. An increasing literature supports the use of plasma neurofilament light in differentiating neurodegenerative diseases from their non-neurodegenerative mimics and suggests it is a valuable biomarker for the evaluation of the effect of putative disease-modifying treatments (e.g. in multiple sclerosis). More contexts of use will likely emerge over the coming years. However, to assist clinical interpretation of laboratory test values, it is crucial to establish normal reference intervals. In this study, we sought to derive reliable cut-offs by pooling quantified plasma neurofilament light in neurologically healthy participants (5-90 years) from eight cohorts. A strong relationship between age and plasma neurofilament light prompted us to define the following age-partitioned reference limits (upper 95th percentile in each age category): 5-17 years = 7 pg/mL; 18-50 years = 10 pg/mL; 51-60 years = 15 pg/mL; 61-70 years = 20 pg/mL; 70 + years = 35 pg/mL. The established reference limits across the lifespan will aid the introduction of plasma neurofilament light into clinical routine, and thereby contribute to diagnostics and disease-monitoring in neurological practice

National cohort of infants born before 24 gestational weeks showed increased survival rates but no improvement in neonatal morbidity

Aim: To describe survival and neonatal morbidities in infants born before 24\ua0weeks of gestation during a 12-year period. Methods: Data were retrieved from national registries and validated in medical files of infants born before 24\ua0weeks of gestation 2007–2018 in Sweden. Temporal changes were evaluated. Results: In 2007–2018, 282\ua0live births were recorded at 22\ua0weeks and 460 at 23\ua0weeks of gestation. Survival to discharge from hospital of infants born alive at 22 and 23\ua0weeks increased from 20% to 38% (p\ua0=\ua00.006) and from 45% to 67% (