The impact of plasticizer and degree of hydrolysis on free volume of poly (vinyl alcohol) films

The effect of plasticizer species and the degree of hydrolysis (DH) on the free volume properties of poly(vinyl alcohol) (PVA) were studied using positron annihilation lifetime spectroscopy. Both glycerol and propylene glycol caused an increase in the free volume cavity radius, although exhibited distinct plasticization behavior, with glycerol capable of occupying existing free volume cavities in the PVA to some extent. The influence of water, normally present in PVA film under atmospheric conditions, was also isolated. Water added significantly to the measured free volume cavity radius in both plasticized and pure PVA matrices. Differences in plasticization behavior can be attributed to the functionality of each plasticizing additive and its hydrogen bonding capability. The increase in cavity radii upon plasticizer loading shows a qualitative link between the free volume of voids and the corresponding reduction in Tg and crystallinity. Cavity radius decreases with increasing DH, due to PVA network tightening in the absence of acetate groups. This corresponds well with the higher Tg observed in the resin with the higher DH. DH was also shown to impact the plasticization of PVA with glycerol, indicating that the larger cavities—created by the weaker hydrogen bonding acetate groups—are capable of accommodating glycerol molecules with negligible effect on the cavity dimensions

Predictive performance of a competing risk cardiovascular prediction tool CRISK compared to QRISK3 in older people and those with comorbidity:population cohort study

BACKGROUND: Recommended cardiovascular disease (CVD) prediction tools do not account for competing mortality risk and over-predict incident CVD in older and multimorbid people. The aim of this study was to derive and validate a competing risk model (CRISK) to predict incident CVD and compare its performance to that of QRISK3 in UK primary care. METHODS: We used UK linked primary care data from the Clinical Practice Research Datalink (CPRD) GOLD to identify people aged 25–84 years with no previous CVD or statin treatment split into derivation and validation cohorts. In the derivation cohort, we derived models using the same covariates as QRISK3 with Fine-Gray competing risk modelling alone (CRISK) and with Charlson Comorbidity score (CRISK-CCI) as an additional predictor of non-CVD death. In a separate validation cohort, we examined discrimination and calibration compared to QRISK3. Reclassification analysis examined the number of patients recommended for treatment and the estimated number needed to treat (NNT) to prevent a new CVD event. RESULTS: The derivation and validation cohorts included 989,732 and 494,865 women and 946,784 and 473,392 men respectively. Overall discrimination of CRISK and CRISK-CCI were excellent and similar to QRISK3 (for women, C-statistic = 0.863/0.864/0.863 respectively; for men 0.833/0.819/0.832 respectively). CRISK and CRISK-CCI calibration overall and in younger people was excellent. CRISK over-predicted in older and multimorbid people although performed better than QRISK3, whilst CRISK-CCI performed the best. The proportion of people reclassified by CRISK-CCI varied by QRISK3 risk score category, with 0.7–9.7% of women and 2.8–25.2% of men reclassified as higher risk and 21.0–69.1% of women and 27.1–57.4% of men reclassified as lower risk. Overall, CRISK-CCI recommended fewer people for treatment and had a lower estimated NNT at 10% risk threshold. Patients reclassified as higher risk were younger, had lower SBP and higher BMI, and were more likely to smoke. CONCLUSIONS: CRISK and CRISK-CCI performed better than QRISK3. CRISK-CCI recommends fewer people for treatment and has a lower NNT to prevent a new CVD event compared to QRISK3. Competing risk models should be recommended for CVD primary prevention treatment recommendations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02349-6

Real-world impact of fremanezumab on migraine symptoms and resource utilization in the United States

BACKGROUND: Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for migraine prevention in adults. Real-world data on the effectiveness of fremanezumab are limited. This retrospective, observational cohort study assessed patient-reported migraine symptoms, health care resource utilization (HCRU), and direct medical costs before and after fremanezumab treatment initiation. METHODS: Data were extracted from September 2018 through June 2020 from the Midwest component of EMRClaims+®, an integrated health services database containing \u3e 20 million medical records from national commercial insurance claims, Medicare claims, and regional electronic medical records. Patients included in the cohort analysis were aged ≥ 18 years and were administered fremanezumab, with enrollment or treatment history for ≥ 6 months prior (pre-index) to initiating fremanezumab (index date) and ≥ 1 month after the index date (post-index), and without pregnancy or pregnancy-related encounters during the study period. Patient-reported headache frequency, migraine pain intensity (MPI), composite migraine symptoms, and HCRU were assessed pre-index and ≥ 1 month after fremanezumab initiation. Wilcoxon signed-rank tests were used to compare means of migraine symptoms and outcomes and HCRU before and after fremanezumab initiation. RESULTS: Overall, 172 patients were eligible for analysis. Of patients who self-reported (n = 129), 83.7% reported improvement in headache frequency or symptoms after fremanezumab treatment. Specifically, headache frequency decreased by 63% after fremanezumab initiation: mean (standard deviation) headache frequency was 22.24 (9.29) days per month pre-index versus 8.24 (7.42) days per month post-index (P \u3c 0.0001). Mean MPI also decreased by 18% after fremanezumab initiation: MPI was 5.47 (3.19) pre-index versus 4.51 (3.34) post-index (P = 0.014). Mean emergency room (ER) visits per month decreased from 0.72 to 0.54 (P = 0.003), and mean outpatient visits per month decreased from 1.04 to 0.81 (P \u3c 0.001). Mean hospitalizations per month decreased, but the results did not reach statistical significance (P = 0.095). Hospitalization and ER costs decreased, while outpatient costs increased, from pre-index to post-index, but differences were not statistically significant (P ≥ 0.232). CONCLUSIONS: Significant reductions in headache frequency, MPI, and HCRU were observed after fremanezumab initiation in patients with migraine in a US real-world setting

Towards Molecular Simulations that are Transparent, Reproducible, Usable By Others, and Extensible (TRUE)

Systems composed of soft matter (e.g., liquids, polymers, foams, gels, colloids, and most biological materials) are ubiquitous in science and engineering, but molecular simulations of such systems pose particular computational challenges, requiring time and/or ensemble-averaged data to be collected over long simulation trajectories for property evaluation. Performing a molecular simulation of a soft matter system involves multiple steps, which have traditionally been performed by researchers in a "bespoke" fashion, resulting in many published soft matter simulations not being reproducible based on the information provided in the publications. To address the issue of reproducibility and to provide tools for computational screening, we have been developing the open-source Molecular Simulation and Design Framework (MoSDeF) software suite. In this paper, we propose a set of principles to create Transparent, Reproducible, Usable by others, and Extensible (TRUE) molecular simulations. MoSDeF facilitates the publication and dissemination of TRUE simulations by automating many of the critical steps in molecular simulation, thus enhancing their reproducibility. We provide several examples of TRUE molecular simulations: All of the steps involved in creating, running and extracting properties from the simulations are distributed on open-source platforms (within MoSDeF and on GitHub), thus meeting the definition of TRUE simulations

Real-world Use of Mold-Active Triazole Prophylaxis in the Prevention of Invasive Fungal Diseases: Results From a Subgroup Analysis of a Multicenter National Registry

BACKGROUND: Antifungal prophylaxis can prevent invasive fungal diseases (IFDs) in high-risk, immunocompromised patients. This study assessed the real-world use of mold-active triazoles (MATs) for the prevention of IFDs. METHODS: This subgroup analysis of a multicenter, observational, prospective registry in the United States from March 2017 to April 2020 included patients who received MATs for prophylaxis (isavuconazole, posaconazole, and voriconazole) at study index/enrollment. The primary objective was to describe patient characteristics and patterns of MAT use. Exploratory assessments included the frequency of breakthrough IFDs and MAT-related adverse drug reactions (ADRs). RESULTS: A total of 1177 patients (256 isavuconazole, 397 posaconazole, 272 voriconazole, and 252 multiple/sequenced MATs at/after index/enrollment) were included in the prophylaxis subgroup analysis. Patient characteristics were similar across MAT groups, but risk factors varied. Hematological malignancy predominated (76.5%) across all groups. Breakthrough IFDs occurred in 7.1% (73/1030) of patients with an investigator\u27s assessment (5.0% [11/221] isavuconazole; 5.3% [20/374] posaconazole; 4.0% [9/226] voriconazole; and 15.8% [33/209] multiple/sequenced MATs). CONCLUSIONS: Breakthrough IFDs were uncommon in patients who received MATs for prophylaxis

Major mergers going Notts: challenges for modern halo finders

Merging haloes with similar masses (i.e. major mergers) pose significant challenges for halo finders. We compare five halo-finding algorithms’ (ahf, hbt, rockstar, subfind, and velociraptor) recovery of halo properties for both isolated and cosmological major mergers. We find that halo positions and velocities are often robust, but mass biases exist for every technique. The algorithms also show strong disagreement in the prevalence and duration of major mergers, especially at high redshifts (z > 1). This raises significant uncertainties for theoretical models that require major mergers for, e.g. galaxy morphology changes, size changes, or black hole growth, as well as for finding Bullet Cluster analogues. All finders not using temporal information also show host halo and subhalo relationship swaps over successive timesteps, requiring careful merger tree construction to avoid problematic mass accretion histories. We suggest that future algorithms should combine phase-space and temporal information to avoid the issues presented

Genomic analysis of male puberty timing highlights shared genetic basis with hair colour and lifespan.

The timing of puberty is highly variable and is associated with long-term health outcomes. To date, understanding of the genetic control of puberty timing is based largely on studies in women. Here, we report a multi-trait genome-wide association study for male puberty timing with an effective sample size of 205,354 men. We find moderately strong genomic correlation in puberty timing between sexes (rg = 0.68) and identify 76 independent signals for male puberty timing. Implicated mechanisms include an unexpected link between puberty timing and natural hair colour, possibly reflecting common effects of pituitary hormones on puberty and pigmentation. Earlier male puberty timing is genetically correlated with several adverse health outcomes and Mendelian randomization analyses show a genetic association between male puberty timing and shorter lifespan. These findings highlight the relationships between puberty timing and health outcomes, and demonstrate the value of genetic studies of puberty timing in both sexes

The mediated innovation model: a framework for researching media influence in language change

Linguistic innovations that arise contemporaneously in highly distant locations, such as quotative be like, have been termed ‘global linguistic variants’. This is not necessarily to suggest fully global usage, but to invoke more general themes of globalisation vis-à-vis space and time. This research area has grown steadily in the last twenty years, and by asserting a role for mass media, researchers have departed intrepidly from sociolinguistic convention. Yet they have largely relied on quite conventional sociolinguistic methodologies, only inferring media influence post hoc. This methodological conservatism has been overcome recently, but uncertainty remains about the overall shape of the new epistemological landscape. In this paper, I review existing research on global variants, and propose an epistemological model for researching media influence in language change: the mediated innovation model. I also analyse the way arguments are constructed in existing research, including the use of rhetorical devices to plug empirical gaps – a worthy sociolinguistic topic in its own right