Characterization of Nanoparticle Release from Surface Coatings by the Simulation of a Sanding Process

Nanoparticles are used in industrial and domestic applications to control customized product properties. But there are several uncertainties concerning possible hazard to health safety and environment. Hence, it is necessary to search for methods to analyze the particle release from typical application processes. Based on a survey of commercial sanding machines, the relevant sanding process parameters were employed for the design of a miniature sanding test setup in a particle-free environment for the quantification of the nanoparticle release into air from surface coatings. The released particles were moved by a defined airflow to a fast mobility particle sizer and other aerosol measurement equipment to enable the determination of released particle numbers additionally to the particle size distribution. First, results revealed a strong impact of the coating material on the swarf mass and the number of released particles

Temperature-Dependent Charge-Transfer-State Absorption and Emission Reveal the Dominant Role of Dynamic Disorder in Organic Solar Cells

The energetic landscape of charge-transfer (CT) states at the interface of electron donating and electron accepting domains in organic optoelectronic devices is crucial for their performance. Central questions - such as the role of static energetic disorder and vibrational effects - are under ongoing dispute. This study provides an in-depth analysis of temperature-dependent broadening of the spectroscopic absorption and emission features of CT states in devices with small molecule-fullerene blends. We confirm the validity of the electro-optical reciprocity relation between the photovoltaic external quantum efficiency and electroluminescence, enabling us to validate the device temperature during the experiment. The validated temperature allows us to fit our experimental data with several models, and compare extracted CT state energies with the corresponding open-circuit voltage limit at 0 K. Our findings reveal that the absorption and emission characteristics are usually not symmetric, and dominated by temperature-activated broadening (vibrational) effects instead of static disorder

Reducing Non-Radiative Voltage Losses by Methylation of Push–Pull Molecular Donors in Organic Solar Cells

Organic solar cells are approaching power conversion efficiencies of other thin-film technologies. However, in order to become truly market competitive, the still substantial voltage losses need to be reduced. Here, the synthesis and characterization of four novel arylamine-based push-pull molecular donors was described, two of them exhibiting a methyl group at the para-position of the external phenyl ring of the arylamine block. Assessing the charge-transfer state properties and the effects of methylation on the open-circuit voltage of the device showed that devices based on methylated versions of the molecular donors exhibited reduced voltage losses due to decreased non-radiative recombination. Modelling suggested that methylation resulted in a tighter interaction between donor and acceptor molecules, turning into a larger oscillator strength to the charge-transfer states, thereby ensuing reduced non-radiative decay rates

A meta-review of evidence on heart failure disease management programs: the challenges of describing and synthesizing evidence on complex interventions

Background: Despite favourable results from past meta-analyses, some recent large trials have not found Heart Failure (HF) disease management programs to be beneficial. To explore reasons for this, we evaluated evidence from existing meta-analyses. Methods: Systematic review incorporating meta-review was used. We selected meta-analyses of randomized controlled trials published after 1995 in English that examined the effects of HF disease management programs on key outcomes. Databases searched: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews (CDSR), DARE, NHS EED, NHS HTA, Ageline, AMED, Scopus, Web of Science and CINAHL; cited references, experts and existing reviews were also searched. Results: 15 meta-analyses were identified containing a mean of 18.5 randomized trials of HF interventions +/- 10.1 (range: 6 to 36). Overall quality of the meta-analyses was very mixed (Mean AMSTAR Score = 6.4 +/- 1.9; range 2-9). Reporting inadequacies were widespread around populations, intervention components, settings and characteristics, comparison, and comparator groups. Heterogeneity (statistical, clinical, and methodological) was not taken into account sufficiently when drawing conclusions from pooled analyses. Conclusions: Meta-analyses of heart failure disease management programs have promising findings but often fail to report key characteristics of populations, interventions, and comparisons. Existing reviews are of mixed quality and do not adequately take account of program complexity and heterogeneity

p53 Target Gene SMAR1 Is Dysregulated in Breast Cancer: Its Role in Cancer Cell Migration and Invasion

Tumor suppressor SMAR1 interacts and stabilizes p53 through phosphorylation at its serine-15 residue. We show that SMAR1 transcription is regulated by p53 through its response element present in the SMAR1 promoter. Upon Doxorubicin induced DNA damage, acetylated p53 is recruited on SMAR1 promoter that allows activation of its transcription. Once SMAR1 is induced, cell cycle arrest is observed that is correlated to increased phospho-ser-15-p53 and decreased p53 acetylation. Further we demonstrate that SMAR1 expression is drastically reduced during advancement of human breast cancer. This was correlated with defective p53 expression in breast cancer where acetylated p53 is sequestered into the heterochromatin region and become inaccessible to activate SMAR1 promoter. In a recent report we have shown that SMAR1 represses Cyclin D1 transcription through recruitment of HDAC1 dependent repressor complex at the MAR site of Cyclin D1 promoter. Here we show that downmodulation of SMAR1 in high grade breast carcinoma is correlated with upregulated Cyclin D1 expression. We also established that SMAR1 inhibits tumor cell migration and metastases through inhibition of TGFβ signaling and its downstream target genes including cutl1 and various focal adhesion molecules. Thus, we report that SMAR1 plays a central role in coordinating p53 and TGFβ pathways in human breast cancer

Conformation Effects of CpG Methylation on Single-Stranded DNA Oligonucleotides: Analysis of the Opioid Peptide Dynorphin-Coding Sequences

Single-stranded DNA (ssDNA) is characterized by high conformational flexibility that allows these molecules to adopt a variety of conformations. Here we used native polyacrylamide gel electrophoresis (PAGE), circular dichroism (CD) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy to show that cytosine methylation at CpG sites affects the conformational flexibility of short ssDNA molecules. The CpG containing 37-nucleotide PDYN (prodynorphin) fragments were used as model molecules. The presence of secondary DNA structures was evident from differences in oligonucleotide mobilities on PAGE, from CD spectra, and from formation of A-T, G-C, and non-canonical G-T base pairs observed by NMR spectroscopy. The oligonucleotides displayed secondary structures at 4°C, and some also at 37°C. Methylation at CpG sites prompted sequence-dependent formation of novel conformations, or shifted the equilibrium between different existing ssDNA conformations. The effects of methylation on gel mobility and base pairing were comparable in strength to the effects induced by point mutations in the DNA sequences. The conformational effects of methylation may be relevant for epigenetic regulatory events in a chromatin context, including DNA-protein or DNA-DNA recognition in the course of gene transcription, and DNA replication and recombination when double-stranded DNA is unwinded to ssDNA

A review of economic evaluation models for cardiac resynchronization therapy with implantable cardioverter defibrillators in patients with heart failure

Objectives Cardiac resynchronization therapy with a biventricular pacemaker (CRT-P) is an effective treatment for dyssynchronous heart failure (DHF). Adding an implantable cardioverter defibrillator (CRT-D) may further reduce the risk of sudden cardiac death (SCD). However, if the majority of patients do not require shock therapy, the cost-effectiveness ratio of CRT-D compared to CRT-P may be high. The objective of this study was to systematically review decision models evaluating the cost-effectiveness of CRT-D for patients with DHF, compare the structure and inputs of these models and identify the main factors influencing the ICERs for CRT-D. Methods A comprehensive search strategy of Medline (Ovid), Embase (Ovid) and EconLit identified eight cost-effectiveness models evaluating CRT-D against optimal pharmacological therapy (OPT) and/or CRT-P. Results The selected economic studies differed in terms of model structure, treatment path, time horizons, and sources of efficacy data. CRT-D was found cost-effective when compared to OPT but its cost-effectiveness became questionable when compared to CRT-P. Conclusions Cost-effectiveness of CRT-D may increase depending on improvement of all-cause mortality rates and HF mortality rates in patients who receive CRT-D, costs of the device, and battery life. In particular, future studies need to investigate longer-term mortality rates and identify CRT-P patients that will gain the most, in terms of life expectancy, from being treated with a CRT-D.This work was supported by the Center for Translational Molecular Medicine and The Netherlands Heart Foundation under the ‘Biomarkers to predict cardiac failure, arrhythmias and success of treatment’ (COHFAR) projec

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0–1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0–2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4–6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10–2·03]; p=0·011), with low heterogeneity across studies (I2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05–1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06–2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4–6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52–1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03–4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22–25·50]; p=0·024). Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. Funding: None