The use of humour in diversional therapy

Humour is a natural phenomenon that every human being possesses. But humour is often not fully utilized and often taken for granted. It is only recently that there has been an upsurge in research in the area of humour that has began to highlight and prove the many benefits that come from its effective utilization. Although humour is a natural phenomenon, there are times in our lives when humour needs to be formally initiated such as in times of illness. Diversional Therapists because of the nature of their work, have ample opportunities to initiate humour. Humour is one of the many tools diversional therapists can use to increase the effectiveness of their activities programmes. This paper examines the definitions of humour and laughter, the beneficial functions of humour, why the use of humour is important in diversional therapy practice and the applications of humour in practice. The paper aims to give diversional therapists background information about humour, highlight the many benefits of humour and give some practical ideas of how humour can be formally incorporated into their diversional therapy programmes. It is envisaged that this paper will increase diversional therapists knowledge of humour, encourage the use of formal humour programmes with clients and encourage diversional therapists to research the various ways of using humour in their practice

Editorial Findable Accessible Interoperable Re usable FAIR diffraction data are coming to protein crystallography

The policy of IUCr Journals on diffraction data is defined

Antibody recognition of different staphylococcus aureus wall teichoic acid glycoforms

Wall teichoic acids (WTAs) are glycopolymers decorating the surface of Gram-positive bacteria and potential targets for antibody-mediated treatments against Staphylococcus aureus, including methicillin-resistant (MRSA) strains. Through a combination of glycan microarray, synthetic chemistry, crystallography, NMR, and computational studies, we unraveled the molecular and structural details of fully defined synthetic WTA fragments recognized by previously described monoclonal antibod-ies (mAbs 4461 and 4497). Our results unveiled the structural requirements for the discriminatory recognition of alpha- and beta-GlcNAc-modified WTA glycoforms by the complementarity-determining regions (CDRs) of the heavy and light chains of the mAbs. Both mAbs interacted not only with the sugar moiety but also with the phosphate groups as well as residues in the ribitol phosphate (RboP) units of the WTA backbone, highlighting their significant role in ligand specificity. Using elongated WTA fragments, containing two sugar modifications, we also demonstrated that the internal carbohydrate moiety of alpha-GlcNAc-modified WTA is preferentially accommodated in the binding pocket of mAb 4461 with respect to the terminal moiety. Our results also explained the recently documented cross-reactivity of mAb 4497 for beta-1,3/beta-1,4-GlcNAc-modified WTA, revealing that the flexibility of the RboP backbone is crucial to allow positioning of both glycans in the antibody binding pocket.Bio-organic Synthesi

Molecular characterization of a lizard adenovirus reveals the first atadenovirus with two fiber genes and the first adenovirus with either one short or three long fibers per penton

Although adenoviruses (AdVs) have been found in a wide variety of reptiles, including numerous squamate species, turtles, and crocodiles, the number of reptilian adenovirus isolates is still scarce. The only fully sequenced reptilian adenovirus, snake adenovirus 1 (SnAdV-1), belongs to the Atadenovirus genus. Recently, two new atadenoviruses were isolated from a captive Gila monster (Heloderma suspectum) and Mexican beaded lizards (Heloderma horridum). Here we report the full genomic and proteomic characterization of the latter, designated lizard adenovirus 2 (LAdV-2). The double-stranded DNA (dsDNA) genome of LAdV-2 is 32,965 bp long, with an average G+C content of 44.16%. The overall arrangement and gene content of the LAdV-2 genome were largely concordant with those in other atadenoviruses, except for four novel open reading frames (ORFs) at the right end of the genome. Phylogeny reconstructions and plesiomorphic traits shared with SnAdV-1 further supported the assignment of LAdV-2 to the Atadenovirus genus. Surprisingly, two fiber genes were found for the first time in an atadenovirus. After optimizing the production of LAdV-2 in cell culture, we determined the protein compositions of the virions. The two fiber genes produce two fiber proteins of different sizes that are incorporated into the viral particles. Interestingly, the two different fiber proteins assemble as either one short or three long fiber projections per vertex. Stoichiometry estimations indicate that the long fiber triplet is present at only one or two vertices per virion. Neither triple fibers nor a mixed number of fibers per vertex had previously been reported for adenoviruses or any other virus

Imatinib in patients with severe COVID-19: a randomised, double-blind, placebo-controlled, clinical trial

Background The major complication of COVID-19 is hypoxaemic respiratory failure from capillary leak and alveolar oedema. Experimental and early clinical data suggest that the tyrosine-kinase inhibitor imatinib reverses pulmonary capillary leak.Methods This randomised, double-blind, placebo-controlled, clinical trial was done at 13 academic and non-academic teaching hospitals in the Netherlands. Hospitalised patients (aged >= 18 years) with COVID-19, as confirmed by an RT-PCR test for SARS-CoV-2, requiring supplemental oxygen to maintain a peripheral oxygen saturation of greater than 94% were eligible. Patients were excluded if they had severe pre-existing pulmonary disease, had pre-existing heart failure, had undergone active treatment of a haematological or non-haematological malignancy in the previous 12 months, had cytopenia, or were receiving concomitant treatment with medication known to strongly interact with imatinib. Patients were randomly assigned (1:1) to receive either oral imatinib, given as a loading dose of 800 mg on day 0 followed by 400 mg daily on days 1-9, or placebo. Randomisation was done with a computer-based clinical data management platform with variable block sizes (containing two, four, or six patients), stratified by study site. The primary outcome was time to discontinuation of mechanical ventilation and supplemental oxygen for more than 48 consecutive hours, while being alive during a 28-day period. Secondary outcomes included safety, mortality at 28 days, and the need for invasive mechanical ventilation. All efficacy and safety analyses were done in all randomised patients who had received at least one dose of study medication (modified intention-to-treat population). This study is registered with the EU Clinical Trials Register (EudraCT 2020-001236-10).Findings Between March 31, 2020, and Jan 4, 2021, 805 patients were screened, of whom 400 were eligible and randomly assigned to the imatinib group (n=204) or the placebo group (n=196). A total of 385 (96%) patients (median age 64 years [IQR 56-73]) received at least one dose of study medication and were included in the modified intention-to-treat population. Time to discontinuation of ventilation and supplemental oxygen for more than 48 h was not significantly different between the two groups (unadjusted hazard ratio [HR] 0.95 [95% CI 0.76-1.20]). At day 28, 15 (8%) of 197 patients had died in the imatinib group compared with 27 (14%) of 188 patients in the placebo group (unadjusted HR 0.51 [0.27-0.95]). After adjusting for baseline imbalances between the two groups (sex, obesity, diabetes, and cardiovascular disease) the HR for mortality was 0.52 (95% CI 0.26-1.05). The HR for mechanical ventilation in the imatinib group compared with the placebo group was 1.07 (0.63-1.80; p=0.81). The median duration of invasive mechanical ventilation was 7 days (IQR 3-13) in the imatinib group compared with 12 days (6-20) in the placebo group (p=0.0080). 91 (46%) of 197 patients in the imatinib group and 82 (44%) of 188 patients in the placebo group had at least one grade 3 or higher adverse event. The safety evaluation revealed no imatinib-associated adverse events.Interpretation The study failed to meet its primary outcome, as imatinib did not reduce the time to discontinuation of ventilation and supplemental oxygen for more than 48 consecutive hours in patients with COVID-19 requiring supplemental oxygen. The observed effects on survival (although attenuated after adjustment for baseline imbalances) and duration of mechanical ventilation suggest that imatinib might confer clinical benefit in hospitalised patients with COVID-19, but further studies are required to validate these findings. Copyright (C) 2021 Elsevier Ltd. All rights reserved.Pathogenesis and treatment of chronic pulmonary disease

An application to model traffic behaviour on freeways with Getram.AIMSUN2: A calibration procedure for micro-dynamic traffic modelling

To study traffic flow characteristics at freeways, traffic model s are used. One of these traffic models is the micro-dynamic traffic model Getram/AIMSUN2 (in this study referred to as AIMSUN2) developed at the Barcelona University of Technology (UPC). DHV Environment and Infrastructure is using this software package for traffic modelling in the Netherlands. To achieve sufficient accuracy between simulation outcomes and observations traffic models need to be calibrated. At this moment, a procedure to perform the calibration process for AIMSUN2 does not exist. The objective of this study is to design such as procedure. This study focuses on the driver behaviour on freeways. The objective of a calibration process is to estimate the unknown model parameters and to optimise the overall model performance. By definition, a simulation model generates output on multiple aspects such as flows, density and travel time. Each of these aspects is associated to it is own performance indicator. The overall performance of a model can be defined as a weighted sum of these indicators. The weights depend on the priorities of model experts, but are seldom made explicit. In this study a procedure is applied to determine these weights from revealed preferences of model experts. First, a problem analysis is performed to distinguish typical aspects of the calibration process. Possibilities to estimate unknown model parameters and optimisation processes to compute the distance between simulation outcomes and observations are defined. The optimisation processes is divided into a one dimensional and a multi-criteria analysis. During the one dimensional optimisation single criterion variables are observed while during the multi-criteria analysis the total performance (all examined criterion variables) of a model is examined. Various estimation techniques are distinguished to determine the model parameter values which are used within the mentioned optimisation processes. Next, a description of the micro-dynamic traffic model AIMSUN2 is given. The computation of the driving speed for vehicles at sections is discussed. Also, the sub models defining the individual driver behaviour are described and examined. A qualitative analysis is performed to define the influences of model parameters on criterion variables. Parameters are classified into fixed parameters, model dependent parameters and location dependent parameters. Basic network configurations for simulations are proposed. A stretch, a fork and a join are distinguished as basic configurations By means of this classification, specific driver characterist ics are related to network configurations. An objective function is proposed to compute a distance measure between observations and examined criterion variables. The following criterion variables are included in this objective function: flow, density, speed, travel time and location/ length traffic-jams. It is proposed to compute the mentioned distance measure by a mean absolute error proportional (MAEP) function. Experiences of model experts are used to define the weights of examined criterion variables A sensitivity analysis (quantitative analysis) is performed to define the sensitiveness of model parameter values on criterion variables. A calibration procedure is proposed based on experiences obtained during this calibration study. In later versions of AIMSUN2, it should be possible to combine the findings of this study into a network wide applicable calibration model. An important aspect of this study has been the study of the categories to which model parameters are assigned. In the AIMSUN2 (version 3.2 which is not publicly available and used for this study) various model parameters used in the model implementation are assigned to a category which is less suitable for calibration. This classification implies that there are only limited possibilities for tun i ng the model during the various phases of the calibration process.Transport & PlanningCivil Engineering and Geoscience