Pentacene in 1,3,5-Tri(1-naphtyl)benzene: A Novel Standard for Transient EPR Spectroscopy at Room Temperature

Testing and calibrating an experimental setup with standard samples is an essential aspect of scientifc research. Single crystals of pentacene in p-terphenyl are widely used for this purpose in transient electron paramagnetic resonance (EPR) spectros copy. However, this sample is not without downsides: the crystals need to be grown and the EPR transitions only appear at particular orientations of the crystal with respect to the external magnetic feld. An alternative host for pentacene is the glass forming 1,3,5-tri(1-naphtyl)benzene (TNB). Due to the high glass transition point of TNB, an amorphous glass containing randomly oriented pentacene molecules is obtained at room temperature. Here we demonstrate that pentacene dissolved in TNB gives a typical “powder-like” transient EPR spectrum of the triplet state fol lowing pulsed laser excitation. From the two-dimensional data set, it is straight forward to obtain the zero-feld splitting parameters and relative populations by spectral simulation as well as the B1 feld in the microwave resonator. Due to the simplicity of preparation, handling and stability, this system is ideal for adjusting the laser beam with respect to the microwave resonator and for introducing students to transient EPR spectroscopy

Faraday instability in small vessels under vertical vibration

The formation of Faraday waves in a liquid inside a cylindrical vessel under the influence of vertical vibration is studied. The stability thresholds and its mode decomposition are obtained using a linear stability analysis. The stability model is validated with a vibration experiment in a vertical vibration table. The Faraday instability threshold is found for accelerations ranging from 0.1 to 1.0 times the gravitational acceleration. The confinement effect by the vessel introduces cut-off the low frequency modes and the allowed frequencies are discretized. The resulting acceleration stability threshold is high at low frequencies and it is the lowest at medium frequencies, 10-70 Hz, where the discretization of the mode k-momenta introduces low stability regions delimited by more stable frequency ranges. The relevance of these characteristics for the agitation of liquids will be discussed

Predictors and correlates of adherence to combination antiretroviral therapy (ART) for chronic HIV infection: a meta-analysis

Adherence to combination antiretroviral therapy (ART) is a key predictor of the success of human immunodeficiency virus (HIV) treatment, and is potentially amenable to intervention. Insight into predictors or correlates of non-adherence to ART may help guide targets for the development of adherence-enhancing interventions. Our objective was to review evidence on predictors/correlates of adherence to ART, and to aggregate findings into quantitative estimates of their impact on adherence. We searched PubMed for original English-language papers, published between 1996 and June 2014, and the reference lists of all relevant articles found. Studies reporting on predictors/correlates of adherence of adults prescribed ART for chronic HIV infection were included without restriction to adherence assessment method, study design or geographical location. Two researchers independently extracted the data from the same papers. Random effects models with inverse variance weights were used to aggregate findings into pooled effects estimates with 95% confidence intervals. The standardized mean difference (SMD) was used as the common effect size. The impact of study design features (adherence assessment method, study design, and the United Nations Human Development Index (HDI) of the country in which the study was set) was investigated using categorical mixed effects meta-regression. In total, 207 studies were included. The following predictors/correlates were most strongly associated with adherence: adherence self-efficacy (SMD = 0.603, P = 0.001), current substance use (SMD = -0.395, P = 0.001), concerns about ART (SMD = -0.388, P = 0.001), beliefs about the necessity/utility of ART (SMD = 0.357, P = 0.001), trust/satisfaction with the HIV care provider (SMD = 0.377, P = 0.001), depressive symptoms (SMD = -0.305, P = 0.001), stigma about HIV (SMD = -0.282, P = 0.001), and social support (SMD = 0.237, P = 0.001). Smaller but significant associations were observed for the following being prescribed a protease inhibitor-containing regimen (SMD = -0.196, P = 0.001), daily dosing frequency (SMD = -0.193, P = 0.001), financial constraints (SMD -0.187, P = 0.001) and pill burden (SMD = -0.124, P = 0.001). Higher trust/satisfaction with the HIV care provider, a lower daily dosing frequency, and fewer depressive symptoms were more strongly related with higher adherence in low and medium HDI countries than in high HDI countries. These findings suggest that adherence-enhancing interventions should particularly target psychological factors such as self-efficacy and concerns/beliefs about the efficacy and safety of ART. Moreover, these findings suggest that simplification of regimens might have smaller but significant effect

Concurrent validity and reliability of the Community Balance and Mobility scale in young-older adults

Background: With the growing number of young-older adults (baby-boomers), there is an increasing demand for assessment tools specific for this population, which are able to detect subtle balance and mobility deficits. Various balance and mobility tests already exist, but suffer from ceiling effects in higher functioning older adults. A reliable and valid challenging balance and mobility test is critical to determine a young-older adult’s balance and mobility performance and to timely initiate preventive interventions. The aim was to evaluate the concurrent validity, inter- and intrarater reliability, internal consistency, and ceiling effects of a challenging balance and mobility scale, the Community Balance and Mobility Scale (CBM), in young-older adults aged 60 to 70 years. Methods: Fifty-one participants aged 66.4 ± 2.7 years (range, 60–70 years) were assessed with the CBM. The Fullerton Advanced Balance scale (FAB), 3-Meter Tandem Walk (3MTW), 8-level balance scale, Timed-Up-and-Go (TUG), and 7-m habitual gait speed were used to estimate concurrent validity, examined by Spearman correlation coefficient (ρ). Inter- and intrarater reliability were calculated as Intra-class-correlations (ICC), and internal consistency by Cronbach alpha and item-total correlations (ρ). Ceiling effects were determined by obtaining the percentage of participants reaching the highest possible score. Results: The CBM significantly correlated with the FAB (ρ = 0.75; p < .001), 3MTW errors (ρ = − 0.61; p < .001), 3MTW time (ρ = − 0.35; p = .05), the 8-level balance scale (ρ = 0.35; p < .05), the TUG (ρ = − 0.42; p < .01), and 7-m habitual gait speed (ρ = 0.46, p < .001). Inter- (ICC2,k = 0.97), intrarater reliability (ICC3,k = 1.00) were excellent, and internal consistency (α = 0.88; ρ = 0.28–0.81) was good to satisfactory. The CBM did not show ceiling effects in contrast to other scales. Conclusions: Concurrent validity of the CBM was good when compared to the FAB and moderate to good when compared to other measures of balance and mobility. Based on this study, the CBM can be recommended to measure balance and mobility performance in the specific population of young-older adults. Trial registration Trial number: ISRCTN37750605 . (Registered on 21/04/2016)

Additional treatment after primary conservative treatment in patients with chronic subdural hematoma—A retrospective study

Objective: Chronic subdural hematoma (CSDH) is a common neurological condition and is typically treated with burr hole craniostomy. Nevertheless, conservative treatment may lead to spontaneous hematoma resolution in some patients. This study aims to describe the characteristics of patients who were treated conservatively without the eventual need for additional treatment. Methods: Data were retrospectively collected from patients who were primarily treated conservatively in three hospitals in the Netherlands from 2008 to 2018. The Primary outcome was the nonnecessity of additional treatment within 3 months after the initial CSDH diagnosis. We used univariable and multivariable logistic regression analyses to identify factors associated with not receiving additional treatment. Results: In this study, 83 patients were included and 61 patients (73%) did not receive additional treatment within 3 months. Upon first presentation, the patients had a Markwalder Grading Scale score (MGS) of 0 (n = 5, 6%), 1 (n = 43, 52%), and 2 (n = 35, 42%). Additional treatment was less often received by patients with smaller hematoma volumes (adjusted odds ratio [aOR] 0.78 per 10 mL; 95% confidence interval [CI] 0.64–0.92). Patients using antithrombotic medication also received less additional treatment, but this association was not significant (aOR 2.02; 95% CI 0.61–6.69). Conclusions: Three quarters of the initially conservatively treated CSDH patients do not receive additional management. Typically, these patients have smaller hematoma volumes. Further, prospective research is needed to distinguish which patients require surgical intervention and in whom primary conservative treatment suffices

GIS-based sales support by company knowledge reuse in the telecommunications sector

A quick and timely response to a customer request provides an important competitive advantage for a company. Experience reuse as intended by experience management facilitates an acceleration of the process of preparing offers. From a technology-oriented point of view, experience is "valuable, stored, specific knowledge that was acquired by a problem solving agent in a problem solving situation" . In the situation of creating an offer in response to a customer request, such valuable knowledge from a company’s experience might include past prices of products or services for a similar customer request. Especially in the telecommunication market such prices are volatile and depend on many impact factors such as the required technology, bandwidth of available lines, or the time period in which the telecommunication service is required. In the run-up for a large sports event, for instance, purchase prices might be significantly higher than after the event when the investment in new infrastructure has provided additional capacities and when there is less demand

Autologous haematopoietic stem cell transplantation for multiple sclerosis: a position paper and registry outline

Background: While substantial progress has been made in the development of disease-modifying medications for multiple sclerosis (MS), a high percentage of treated patients still show progression and persistent inflammatory activity. Autologous haematopoietic stem cell transplantation (AHSCT) aims at eliminating a pathogenic immune repertoire through intense short-term immunosuppression that enables subsequent regeneration of a new and healthy immune system to re-establish immune tolerance for a long period of time. A number of mostly open-label, uncontrolled studies conducted over the past 20 years collected about 4000 cases. They uniformly reported high efficacy of AHSCT in controlling MS inflammatory disease activity, more markedly beneficial in relapsing-remitting MS. Immunological studies provided evidence for qualitative immune resetting following AHSCT. These data and improved safety profiles of transplantation procedures spurred interest in using AHSCT as a treatment option for MS. Objective: To develop expert consensus recommendations on AHSCT in Germany and outline a registry study project. Methods: An open call among MS neurologists as well as among experts in stem cell transplantation in Germany started in December 2021 to join a series of virtual meetings. Results: We provide a consensus-based opinion paper authored by 25 experts on the up-to-date optimal use of AHSCT in managing MS based on the Swiss criteria. Current data indicate that patients who are most likely to benefit from AHSCT have relapsing-remitting MS and are young, ambulatory and have high disease activity. Treatment data with AHSCT will be collected within the German REgistry Cohort of autologous haematopoietic stem CeLl trAnsplantation In MS (RECLAIM). Conclusion: Further clinical trials, including registry-based analyses, are urgently needed to better define the patient characteristics, efficacy and safety profile of AHSCT compared with other high-efficacy therapies and to optimally position it as a treatment option in different MS disease stages. Keywords: Autologous haematopoietic stem cell transplantation (AHSCT), multiple sclerosis, registry study, treatment recommendation

Instructions for Authors

Nonadherence to medical therapy is frequently encountered in patients with inflammatory bowel disease (IBD). We aimed to identify predictors for future (non)adherence in IBD

Facile access to potent antiviral quinazoline heterocycles with fluorescence properties via merging metal-free domino reactions

Most of the known approved drugs comprise functionalized heterocyclic compounds as subunits. Among them, non-fluorescent quinazolines with four different substitution patterns are found in a variety of clinically used pharmaceuticals, while 4,5,7,8-substituted quinazolines and those displaying their own specific fluorescence, favourable for cellular uptake visualization, have not been described so far. Here we report the development of a one-pot synthetic strategy to access these 4,5,7,8-substituted quinazolines, which are fluorescent and feature strong antiviral properties (EC$_{50}$ down to 0.6±0.1 μM) against human cytomegalovirus (HCMV). Merging multistep domino processes in one-pot under fully metal-free conditions leads to sustainable, maximum efficient and high-yielding organic synthesis. Furthermore, generation of artesunic acid–quinazoline hybrids and their application against HCMV (EC$_{50}$ down to 0.1±0.0 μM) is demonstrated. Fluorescence of new antiviral hybrids and quinazolines has potential applications in molecular imaging in drug development and mechanistic studies, avoiding requirement of linkage to external fluorescent markers

Application of AOPs to assist regulatory assessment of chemical risks - Case studies, needs and recommendations

While human regulatory risk assessment (RA) still largely relies on animal studies, new approach methodologies (NAMs) based on in vitro, in silico or non-mammalian alternative models are increasingly used to evaluate chemical hazards. Moreover, human epidemiological studies with biomarkers of effect (BoE) also play an invaluable role in identifying health effects associated with chemical exposures. To move towards the next generation risk assessment (NGRA), it is therefore crucial to establish bridges between NAMs and standard approaches, and to establish processes for increasing mechanistically-based biological plausibility in human studies. The Adverse Outcome Pathway (AOP) framework constitutes an important tool to address these needs but, despite a significant increase in knowledge and awareness, the use of AOPs in chemical RA remains limited. The objective of this paper is to address issues related to using AOPs in a regulatory context from various perspectives as it was discussed in a workshop organized within the European Union partnerships HBM4EU and PARC in spring 2022. The paper presents examples where the AOP framework has been proven useful for the human RA process, particularly in hazard prioritization and characterization, in integrated approaches to testing and assessment (IATA), and in the identification and validation of BoE in epidemiological studies. Nevertheless, several limitations were identified that hinder the optimal usability and acceptance of AOPs by the regulatory community including the lack of quantitative information on response-response relationships and of efficient ways to map chemical data (exposure and toxicity) onto AOPs. The paper summarizes suggestions, ongoing initiatives and third-party tools that may help to overcome these obstacles and thus assure better implementation of AOPs in the NGRA