Lattice model study of the thermodynamic interplay of polymer crystallization and liquid-liquid demixing

We report Monte Carlo simulations of a lattice-polymer model that can account for both polymer crystallization and liquid-liquid demixing in solutions of semiflexible homopolymers. In our model, neighboring polymer segments can have isotropic interactions that affect demixing, and anisotropic interactions that are responsible for freezing. However, our simulations show that the isotropic interactions also have a noticeable effect on the freezing curve, as do the anisotropic interactions on demixing. As the relative strength of the isotropic interactions is reduced, the liquid-liquid demixing transition disappears below the freezing curve. A simple, extended Flory-Huggins theory accounts quite well for the phase behavior observed in the simulations.Comment: Revtex, 7 pages, the content accepted by J. Chem. Phy

Is Categorization in Visual Working Memory a Way to Reduce Mental Effort? A Pupillometry Study

Recent studies on visual working memory (VWM) have shown that visual information can be stored in VWM as continuous (e.g., a specific shade of red) as well as categorical representations (e.g., the general category red). It has been widely assumed, yet never directly tested, that continuous representations require more VWM mental effort than categorical representations; given limited VWM capacity, this would mean that fewer continuous, as compared to categorical, representations can be maintained simultaneously. We tested this assumption by measuring pupil size, as a proxy for mental effort, in a delayed estimation task. Participants memorized one to four ambiguous (boundaries between adjacent color categories) or prototypical colors to encourage continuous or categorical representations, respectively; after a delay, a probe indicated the location of the to‐be‐reported color. We found that, for memory load 1, pupil size was larger while maintaining ambiguous as compared to prototypical colors, but without any difference in memory precision; this suggests that participants relied on an effortful continuous representation to maintain a single ambiguous color, thus resulting in pupil dilation while preserving precision. Strikingly, this effect gradually inverted, such that for memory load 4, pupil size was smaller while maintaining ambiguous and prototypical colors, but memory precision was now substantially reduced for ambiguous colors; this suggests that with increased memory load participants increasingly relied on categorical representations for ambiguous colors (which are by definition a poor fit to any category). Taken together, our results suggest that continuous representations are more effortful than categorical representations and that very few continuous representations (perhaps only one) can be maintained simultaneously

Concurrent guidance of attention by multiple working memory items:Behavioral and computational evidence

During visual search, task-relevant representations in visual working memory (VWM), known as attentional templates, are assumed to guide attention. A current debate concerns whether only one (Single-Item-Template hypothesis; SIT) or multiple (Multiple-Item-Template hypothesis; MIT) items can serve as attentional templates simultaneously. The current study was designed to test these two hypotheses. Participants memorized two colors, prior to a visual-search task in which the target and the distractor could match or not match the colors held in VWM. Robust attentional guidance was observed when one of the memory colors was presented as the target (reduced response times (RTs) on target-match trials) or the distractor (increased RTs on distractor-match trials). We constructed two drift-diffusion models that implemented the MIT and SIT hypotheses, which are similar in their predictions about overall RTs, but differ in their predictions about RTs on individual trials. Critically, simulated RT distributions and error rates revealed a better match of the MIT hypothesis to the observed data than the SIT hypothesis. Taken together, our findings provide behavioral and computational evidence for the concurrent guidance of attention by multiple items in VWM

Total Sulphur Content and N:S Ratio as Indicators for S Deficiency in Grasses

Recently, sulphur (S) deficiencies have been observed throughout Europe (Zaoh et al., 2002). Grassland covers about 50 % of the agricultural area in the European Union. In cutting regimes exports are ca 30 kg S/ha per year. Atmospheric depositions provide, at the present, ca15 kg S/ha per year and S is not considered in fertiliser programmes. Without fertilisation, the S balance at the field scale is negative and therefore some cut swards could be S deficient. Tools for determining whether the grassland is deficient are required. The utilisation of indicators based on S content and N:S ratio was investigated by using S deficient grasses produced in a controlled environment

Study of Soil Characteristics to Estimate Sulphur Supply for Plant Growth

During the last decades, sulphur (S) deficiencies have been observed throughout Europe (Zaoh et al., 2002). Accurate estimation of S supply by the soil-atmosphere system is required to give advice for S fertilisers. Soil is an important S source for plants and it is therefore important to evaluate supply by the soil to avoid deficiencies or excessive S fertilisation. The purpose of this preliminary study was to estimate which soil characteristics could be useful for predicting S supply by soil. Lolium multiflorum was grown on different soils in a growth chamber and S supply was correlated with soil characteristics

Tomographic imaging and scanning thermal microscopy: thermal impedance tomography

The application of tomographic imaging techniques developed for medical applications to the data provided by the scanning thermal microscope will give access to true three-dimensional information on the thermal properties of materials on a mm length scale. In principle, the technique involves calculating and inverting a sensitivity matrix for a uniform isotropic material, collecting ordered data at several modulation frequencies, and multiplying the inverse of the matrix with the data vector. In practice, inversion of the matrix in impractical, and a novel iterative technique is used. Examples from both simulated and real data are given

Medication use during end-of-life care in a palliative care centre

Background In end-of-life care, symptoms of discomfort are mainly managed by drug therapy, the guidelines for which are mainly based on expert opinions. A few papers have inventoried drug prescriptions in palliative care settings, but none has reported the frequency of use in combination with doses and route of administration. Objective To describe doses and routes of administration of the most frequently used drugs at admission and at day of death. Setting Palliative care centre in the Netherlands. Method In this retrospective cohort study, prescription data of deceased patients were extracted from the electronic medical records. Main outcome measure Doses, frequency and route of administration of prescribed drugs Results All regular medication prescriptions of 208 patients, 89 % of whom had advanced cancer, were reviewed. The three most prescribed drugs were morphine, midazolam and haloperidol, to 21, 11 and 23 % of patients at admission, respectively. At the day of death these percentages had increased to 87, 58 and 50 %, respectively. Doses of these three drugs at the day of death were statistically significantly higher than at admission. The oral route of administration was used in 89 % of patients at admission versus subcutaneous in 94 % at the day of death. Conclusions Nearing the end of life, patients in this palliative care centre receive discomfort-relieving drugs mainly via the subcutaneous route. However, most of these drugs are unlicensed for this specific application and guidelines are based on low level of evidence. Thus, there is every reason for more clinical research on drug use in palliative care

In silico evaluation of limited sampling strategies for individualized dosing of extended half-life factor IX concentrates in hemophilia B patients

PURPOSE: Hemophilia B is a bleeding disorder, caused by a factor IX (FIX) deficiency. Recently, FIX concentrates with extended half-life (EHL) have become available. Prophylactic dosing of EHL-FIX concentrates can be optimized by assessment of individual pharmacokinetic (PK) parameters. To determine these parameters, limited sampling strategies (LSSs) may be applied. The study aims to establish adequate LSSs for estimating individual PK parameters of EHL-FIX concentrates using in silico evaluation. METHODS: Monte Carlo simulations were performed to obtain FIX activity versus time profiles using published population PK models for N9-GP (Refixia), rFIXFc (Alprolix), and rIX-FP (Idelvion). Fourteen LSSs, containing three or four samples taken within 8 days after administration, were formulated. Bayesian analysis was applied to obtain estimates for clearance (CL), half-life (t(1/2)), time to 1% (Time(1%)), and calculated weekly dose (Dose(1%)). Bias and precision of these estimates were assessed to determine which LSS was adequate. RESULTS: For all PK parameters of N9-GP, rFIXFc and rIX-FP bias was generally acceptable (range: −5% to 5%). For N9-GP, precision of all parameters for all LSSs was acceptable (< 25%). For rFIXFc, precision was acceptable for CL and Time(1%), except for t(1/2) (range: 27.1% to 44.7%) and Dose(1%) (range: 12% to 29.4%). For rIX-FP, all LSSs showed acceptable bias and precision, except for Dose(1%) using LSS with the last sample taken on day 3 (LSS 6 and 10). CONCLUSION: Best performing LSSs were LSS with samples taken at days 1, 5, 7, and 8 (N9-GP and rFIXFc) and at days 1, 4, 6, and 8 (rIX-FP), respectively

Pharmacokinetic Modelling to Predict FVIII:C Response to Desmopressin and Its Reproducibility in Nonsevere Haemophilia A Patients

Background Nonsevere haemophilia A (HA) patients can be treated with desmopressin. Response of factor VIII activity (FVIII:C) differs between patients and is difficult to predict. Objectives Our aims were to describe FVIII:C response after desmopressin and its reproducibility by population pharmacokinetic (PK) modelling. Patients and Methods Retrospective data of 128 nonsevere HA patients (age 7–75 years) receiving an intravenous or intranasal dose of desmopressin were used. PK modelling of FVIII:C was performed by nonlinear mixed effect modelling. Reprodu

Feasibility of sedation and analgesia interruption following cannulation in neonates on extracorporeal membrane oxygenation

Purpose: In most extracorporeal membrane oxygenation (ECMO) centers patients are heavily sedated to prevent accidental decannulation and bleeding complications. In ventilated adults not on ECMO, daily sedation interruption protocols improve short- and long-term outcome. This study aims to evaluate safety and feasibility of sedation interruption following cannulation in neonates on ECMO. Methods: Prospective observational study in 20 neonates (0.17-5.8 days of age) admitted for ECMO treatment. Midazolam (n = 20) and morphine (n = 18) infusions were discontinued within 30 min after cannulation. Pain and sedation were regularly assessed using COMFORT-B and visual analog scale (VAS) scores. Midazolam and/or morphine were restarted and titrated according to protocolized treatment algorithms. Results: Median (interquartile range, IQR) time without any sedatives was 10.3 h (5.0-24.1 h). Median interruption duration for midazolam was 16.5 h (6.6-29.6 h), and for morphine was 11.2 h (6.7-39.4 h). During this period no accidental extubations, decannulations or bleeding complications occurred. Conclusions: This is the first study to show that interruption of sedatives and analgesics following cannulation in neonates on ECMO is safe and feasible. Interruption times are 2-3 times longer than reported for adult ICU patients not on ECMO. Further trials are needed to substantiate these findings and evaluate short- and long-term outcomes