Is it more feeling or thinking? The influence of affective and cognitive attitude on adolescents' intention to engage in binge drinking

Previous work has revealed that interventions aiming to reduce adolescent binge drinking commonly focus on cognitive attitudes, but are insufficiently effective in changing binge-drinking intentions. The focus on these cognitive attitudes might be the reason for this insufficient success. That is, other work has revealed that affective attitudes have a stronger influence on binge-drinking intention than cognitive attitudes. However, this relation has so far only been found among traditional college students and pre-vocational school students, therewith neglecting another important population at risk, namely vocational community college students. This study examines whether affective attitudes are also significantly stronger influencers of binge-drinking intentions among vocational community college students. Using a sample of 298 vocational community college students (Mage = 17.63), the current study shows that affective attitudes were more strongly related to vocational community college students' intention to engage in binge drinking than cognitive attitudes. This finding indicates that the effectiveness of interventions targeting adolescent binge drinking can be improved by incorporating content elements concerning affective attitudes

Labeling Uncertainty in Multitarget Tracking

In multitarget tracking, the problem of track labeling (assigning labels to tracks) is an ongoing research topic. The existing literature, however, lacks an appropriate measure of uncertainty related to the assigned labels that has a sound mathematical basis as well as clear practical meaning to the user. This is especially important in a situation where well separated targets move in close proximity with each other and thereafter separate again; in such a situation, it is well known that there will be confusion on target identities, also known as "mixed labeling." In this paper, we specify comprehensively the necessary assumptions for a Bayesian formulation of the multitarget tracking and labeling (MTTL) problem to be meaningful. We provide a mathematical characterization of the labeling uncertainties with clear physical interpretation. We also propose a novel labeling procedure that can be used in combination with any existing (unlabeled) MTT algorithm to obtain a Bayesian solution to the MTTL problem. One advantage of the resulting solution is that it readily provides the labeling uncertainty measures. Using the mixed labeling phenomenon in the presence of two targets as our test bed, we show with simulation results that an unlabeled multitarget sequential Monte Carlo (M-SMC) algorithm that employs sequential importance resampling (SIR) augmented with our labeling procedure performs much better than its "naive" extension, the labeled SIR M-SMC filter

First clinical experiences with inclisiran in a real-world setting

Background and objective: Inclisiran is the first-in-class small interfering RNA (siRNA) PCSK9 inhibitor. In clinical trials inclisiran showed effective and sustained LDL-C reduction of ± 50 %. As data in clinical setting are scarce, we aim to investigate the efficacy and safety in clinical practice. Methods:We describe a registry of consecutive patients who started with inclisiran at a lipid clinic of a university hospital. Patients were eligible if they fulfilled the reimbursement criteria in the Netherlands. Patients were included if they started with inclisiran as first line (group 1) or switched from PCSK9 monoclonal antibody (mAbs) to inclisiran (group 2). LDL-C levels were measured at 3 and 9 months after initiation of inclisiran. Median change of LDL-C levels was calculated on an individual and group level. Results: We analysed 65 patients (36 women), median [25th percentile; 75th percentile] age of 63 [54; 68] years. Of these, 44 patients had both a 3 month and 9 month visit. At 3 months, patients who newly started inclisiran (group 1, n = 45) showed a LDL-C decrease of 38 [-49;-33] %. Patients who used statins as co-medication (n = 15) had a higher median LDL-C decrease compared to those without statin use (n=30; 45 % vs 38 %). However, patients who switched from mAbs to inclisiran (group 2, n = 20) had an increase in LDL-C of 38 [+4; +97] %. Adverse effects associated with inclisiran were mild and consisted of mild injection site reactions. Efficacy was slightly less whereas safety results were similar at 9 months. Conclusion: Our initial experience of inclisiran in a clinical setting showed less reduction in LDL-C levels compared to clinical trials but a similar safety profile. Moreover, patients who switched from PCSK9 mAbs to inclisiran generally showed an increase in LDL-C levels implying that inclisiran is less potent in LDL-C reduction compared to PCSK9 mAbs.</p

Achieving consensus on minimum data items (including core outcome domains) for a longitudinal observational cohort study in rheumatoid arthritis

Objectives: To obtain consensus on minimum data items for an observational cohort study in rheumatoid arthritis (RA) in the UK and to make available the process for similar studies and other rheumatic conditions. Methods: Individuals with a diverse range of expertise and backgrounds were invited to participate in a process to propose a minimal core dataset (MCD) for research studies, commissioned by Arthritis Research UK as part of the larger INBANK project. The group included patients and representatives from clinical and academic rheumatology, outcomes science, stratified medicine, health economics, national professional and academic bodies/ committees. A process was devised based on Outcome Measures in Rheumatology Clinical Trials (OMERACT) principles to review aims/objectives, definition of scope, identification of important research questions, and selection of key domains. Results: Following the initial multi-stakeholder meeting, subsequent teleconferences and email communications, consensus was obtained on: 1. Most important and relevant research questions; 2. Agreement on how the OMERACT Core Areas (life impact, pathophysiological manifestations, resource use and death) could form the basis of a MCD; 3. Consensus on 22 items for inclusion into a MCD. Workshops were undertaken for two essential items which required further exploration: work/social participation and co-morbidity. Conclusions: Consensus for proposed minimal data items for long-term observational cohort studies of RA in the UK posed novel challenges and opportunities, and was largely successful. Further work is needed to select instruments for two important items and to achieve compatibility with other UK national initiatives, and more widely across Europe

Covid-19 and maternal and perinatal outcomes

Background: Alveolar capillary dysplasia with or without misalignment of the pulmonary veins (ACD/MPV) is a lethal congenital lung disorder associated with a variety of heterozygous genomic alterations in the FOXF1 gene or its 60 kb enhancer. Cases without a genomic alteration in the FOXF1 locus have been described as well. The mechanisms responsible for FOXF1 haploinsufficiency and the cause of ACD/MPV in patients without a genomic FOXF1 variant are poorly understood, complicating the search for potential therapeutic targets for ACD/MPV. To investigate the contribution of aberrant DNA methylation, genome wide methylation patterns of ACD/MPV lung tissues were compared with methylation patterns of control lung tissues using the recently developed technique Methylated DNA sequencing (MeD-seq). Results: Eight ACD/MPV lung tissue samples and three control samples were sequenced and their mutual comparison resulted in identification of 319 differentially methylated regions (DMRs) genome wide, involving 115 protein coding genes. The potentially upregulated genes were significantly enriched in developmental signalling pathways, whereas potentially downregulated genes were mainly enriched in O-linked glycosylation. In patients with a large maternal deletion encompassing the 60 kb FOXF1 enhancer, DNA methylation patterns in this FOXF1 enhancer were not significantly different compared to controls. However, two hypermethylated regions were detected in the 60 kb FOXF1 enhancer of patients harbouring a FOXF1 point mutation. Lastly, a large hypermethylated region overlapping the first FOXF1 exon was found in one of the ACD/MPV patients without a known pathogenic FOXF1 variation. Conclusion: This is the first study providing genome wide methylation data on lung tissue of ACD/MPV patients. DNA methylation analyses in the FOXF1 locus excludes maternal imprinting of the 60 kb FOXF1 enhancer. Hypermethylation at the 60 kb FOXF1 enhancer might contribute to FOXF1 haploinsufficiency caused by heterozygous mutations in the FOXF1 coding region. Interestingly, DNA methylation analyses of patients without a genomic FOXF1 variant suggest that abnormal hypermethylation of exon 1 might play a role in some ACD/MPV in patients.</p

Sex differences in efficacy and safety of PCSK9 monoclonal antibodies:A real-world registry

Background and aims: Proprotein convertase subtilisin/kexin 9 monoclonal antibodies (PCSK9 mAbs) reduce low-density lipoprotein (LDL-c) with a favourable safety profile. Available data from PCSK9 antibody trials suggest LDL-c reduction is lower in women compared to men. Data in real-world setting is scarce. The aim of this study was to assess sex differences in efficacy and safety of PCSK9 antibodies in clinical care. Methods: All patients starting with evolocumab or alirocumab in our lipid clinic were included in a prospective registry. We collected clinical information, including baseline and follow-up mean LDL-C levels after initiation of PCSK9 mAbs treatment. In addition, side effects and PCSK9 mAbs discontinuation were recorded. Results: We analysed 436 patients (209 women), mean age 58 ± 11 years. Women had higher baseline LDL-c levels compared to men (4.7 ± 1.6 mmol/L vs 4.1 ± 1.4 mmol/L, p &lt; 0.01). PCSK9 mAbs resulted in less relative LDL-c reduction in women compared to men (50% vs 61% p&lt;0.01), but equal absolute LDL-c reduction (respectively 2.3 ± 1.3 mmol/L vs 2.5 ± 1.1 mmol/L, p = 0.087). Women less often reached LDL-c target levels than men (50% vs 72%). No sex differences were observed in reporting of side effects (women 32% vs men 27% p = 0.26) or PCSK9 mAbs discontinuation (women 13% vs men 10%, p = 0.46). Conclusions: In clinical practice, PCSK9 mAbs are less effective in reducing LDL-c levels in women compared to men and equally safe, implying the importance of sex differences in PCSK9 metabolism.</p

In vitro replication capacity of HIV-2 variants from long-term aviremic individuals

AbstractTo establish whether efficient suppression of virus replication in HIV-2-infected individuals is associated with low replicative capacity of HIV-2, replication kinetics of HIV-2 variants from long-term aviremic individuals was analyzed and compared with that of the relatively slow-replicating HIV-1 variants from asymptomatics and long-term nonprogressors (AS/LTNP). On average, HIV-2 from aviremic individuals had lower replication rates than HIV-1 variants from AS/LTNP in cells of 8 donors (0.45 log10 [range 0.14–0.77] vs. 0.58 log10 [range 0.32–0.99] pg RT/ml/day, P = 0.036). The relatively low replication rate of HIV-2 compared to HIV-1 variants was not related to different sensitivities to inhibition by CD8+ T cells or different degrees of infectivity. HIV-2 replication rates increased with progressive infection and with switch from CCR5 to CXCR4 usage.The relatively low replicative capacity of HIV-2 variants from aviremic individuals likely contributes to the low viral load and benign course of infection in these individuals

A Comparative In Vitro Study of the Effects of Separate and Combined Products of Citrus e fructibus and Cydonia e fructibus on Immunological Parameters of Seasonal Allergic Rhinitis

This paper examined the effects of the combined product, Citrus e fructibus/Cydonia e fructibus (Citrus/Cydonia; Citrus and Cydonia: each 0.01 g/mL), and separate products of Citrus (0.01 g/mL) and Cydonia (0.01 g/mL) on the immunological pathways involved in seasonal allergic rhinitis (SAR). Peripheral blood mononuclear cells (PBMCs) from five healthy and five grass pollen-allergic donors were isolated and analyzed in vitro after polyclonal and allergen-specific stimulation of T cells in the presence of the three extracts. The analyses demonstrated acceptable cell survival with no signs of toxicity. Citrus mainly had a selective effect on reducing allergen-specific chronic inflammatory (TNF-α; Citrus compared to Cydonia and Citrus/Cydonia: −87.4 (P < 0.001) and −68.0 (P < 0.05), resp.) and Th2 pathway activity (IL-5; Citrus compared to Cydonia: −217.8 (P < 0.01); while, both Cydonia and Citrus/Cydonia mainly affected the induction of the allergen-specific Th1 pathway (IFN-γ; Cydonia and Citrus/Cydonia compared to Citrus: 3.8 (P < 0.01) and 3.0 (P < 0.01), resp.). Citrus and Cydonia demonstrated different working mechanisms in the treatment of SAR and the combination product did not demonstrate larger effects than the separate preparations. Further effectiveness and efficacy studies comparing the effects of the products on SAR in vivo are indicated