Summary This paper presents a unified formulation for the kinematics, singularity and workspace analyses of parallel delta robots with prismatic actuation. Unlike the existing studies, the derivations presented in this paper are made by assuming variable angles and variable link lengths. Thus, the presented scheme can be used for all of the possible linear delta robot configurations including the ones with asymmetric kinematic chains. Referring to a geometry-based derivation, the paper first formulates the position and the velocity kinematics of linear delta robots with non-iterative exact solutions. Then, all of the singular configurations are identified assuming a parametric content for the Jacobian matrix derived in the velocity kinematics section. Furthermore, a benchmark study is carried out to determine the linear delta robot configuration with the maximum cubic workspace among symmetric and semi-symmetric kinematic chains. In order to show the validity of the proposed approach, two sets of experiments are made, respectively, on the horizontal and the Keops type of linear delta robots. The experiment results for the confirmation of the presented kinematic analysis and the simulation results for the determination of the maximum cubic workspace illustrate the efficacy and the flexible applicability of the proposed framework.

Transition period from preschool years to school years is a time of rapid changes in children’s development. Children with intellectual disability lag behind their peers without disabilities in their school readiness skills, especially in math skills. Thus, there is a great importance of school preparation programs for children with intellectual disability in improving their math abilities. The aim of the present research was to compare the effectiveness of two preschool programs in improving math abilities of children prior to their enrollment in elementary schools. The sample for this research comprised 90 children aged 60-72 months. Of those, there were 60 children with intellectual disability and 30 typically developing children. Math abilities were assessed with a subscale from Peabody Individual Achievement Test. The results of this research indicated that children with intellectual disability attending special education preschool program achieved significantly better math results than children with intellectual disability attending inclusive preschool program. Some suggestions to preschool teachers on how to improve the effectiveness of their work with children with intellectual disability were given. Keywords: children with intellectual disability, inclusive education preschool programs, math abilities, quasi-experimental design, school readiness, special education preschool programs.

BackgroundStigma is associated with health conditions that drive disease burden in low- and middle-income countries (LMICs), including HIV, tuberculosis, mental health problems, epilepsy, and substance use disorders. However, the literature discussing the relationship between stigma and health outcomes is largely fragmented within disease-specific siloes, thus limiting the identification of common moderators or mechanisms through which stigma potentiates adverse health outcomes as well as the development of broadly relevant stigma mitigation interventions.MethodsWe conducted a scoping review to provide a critical overview of the breadth of research on stigma for each of the five aforementioned conditions in LMICs, including their methodological strengths and limitations.ResultsAcross the range of diseases and disorders studied, stigma is associated with poor health outcomes, including help- and treatment-seeking behaviors. Common methodological limitations include a lack of prospective studies, non-representative samples resulting in limited generalizability, and a dearth of data on mediators and moderators of the relationship between stigma and health outcomes.ConclusionsImplementing effective stigma mitigation interventions at scale necessitates transdisciplinary longitudinal studies that examine how stigma potentiates the risk for adverse outcomes for high-burden health conditions in community-based samples in LMICs.

Endotoxemia is associated by dysregulated apoptosis of immune and non-immune cells. We investigated whether simvastatin has anti-apoptotic effects, and induces hepatocytes and lymphocytes survival signaling in endotoxin-induced liver and spleen injuries. Wistar rats were divided into the groups pretreated with simvastatin (20 or 40 mg/kg, orally) prior to a non-lethal dose of lipopolysaccharide (LPS), the LPS group, and the control. The severity of tissue inflammatory injuries was expressed as hepatic damage scores (HDS) and spleen damage scores (SDS), respectively. The apoptotic cell was detected by TUNEL (Terminal deoxynucleotidyl transferase dUTP Nick End Labeling) and immunohistochemical staining (expression of cleaved caspase-3, and anti-apoptotic Bcl-xL, survivin and NF-κB/p65). Simvastatin dose-dependently abolished HDS and SDS induced by LPS (p < 0.01), respectively. Simvastatin 40 mg/kg significantly decreased apoptotic index and caspase-3 cleavage in hepatocytes and lymphocytes (p < 0.01 vs. LPS group, respectively), while Bcl-XL markedly increased accordingly with simvastatin doses. In the simvastatin, groups were determined markedly increased cytoplasmic expression of survivin associated with nuclear positivity of NF-κB, in both hepatocytes and lymphocytes (p < 0.01 vs. LPS group). Cell-protective effects of simvastatin against LPS seemed to be mediated by up-regulation of survivin, which leads to reduced caspase-3 activation and inhibition of hepatocytes and lymphocytes apoptosis.

ABSTRACT Introduction: In January 2018 the European Commission published a Proposal for a Regulation on Health Technology Assessment (HTA): ‘Proposal for a Regulation on health technology assessment and amending Directive 2011/24/EU’. A number of stakeholders, including some Member States, welcomed this initiative as it was considered to improve collaboration, reduce duplication and improve efficiency. There were however a number of concerns including its legal basis, the establishment of a single managing authority, the preservation of national jurisdiction over HTA decision-making and the voluntary/mandatory uptake of joint assessments by Member States. Areas covered: This paper presents the consolidated views and considerations on the original Proposal as set by the European Commission of a number of policy makers, payers, experts from pricing and reimbursement authorities and academics from across Europe. Expert commentary: The Proposal has since been extensively discussed at Council and while good progress has been achieved, there are still divergent positions. The European Parliament gave a number of recommendations for amendments. If the Proposal is approved, it is important that a balanced, improved outcome is achieved for all stakeholders. If not approved, the extensive contribution and progress attained should be sustained and preserved, and the best alternative solutions found.

Alzheimer's disease represents the most common age-related neurodegenerative disorder and a leading cause of progressive cognitive impairment. Predicting cognitive decline is challenging but would be invaluable in an increasingly aging population which also experiences a rising cardiovascular risk. In order to examine whether plasma measurements of one of the established biomarkers of heart failure, brain natriuretic peptide (BNP), reflect a decline in cognitive function, associated with Alzheimer's disease neurodegeneration, BNP levels were analysed, by using a novel assay called a SOMAscan, in 1. cognitively healthy, control subjects; 2. subjects with mild cognitive impairment, and 3. subjects with Alzheimer's disease. The results of our study show that the levels of the BNP were significantly different between the three types of diagnoses (p < 0.05), whereby subjects with mild cognitive impairment had the lowest mean BNP value, and healthy subjects had the highest BNP value. Importantly, our results show that the levels of the BNP are influenced by the presence of at least one APOE4 allele in the healthy (p < 0.05) and in the Alzheimer's disease groups of subjects (p < 0.1). As the levels of the BNP appear to be independent of the APOE4 genotype in subjects with mild cognitive impairment, the results of our study support inclusion of measurements of plasma levels of the BNP in the list of the core Alzheimer's disease biomarkers for identification of the mild cognitive impairment group of patients. In addition, the results of our study warrant further investigations into molecular links between Alzheimer's disease-type cognitive decline and cardiovascular disorders.

Objectives Cocaine use is increasing and many cocaine users engage in polysubstance use. Within polysubstance use, relationships among use of individual substances are necessarily complex. To address this complexity, we used latent class analysis (LCA) to identify patterns of polysubstance use among lifetime cocaine users and examine associations among these patterns, demographics, and risk profiles. Methods Members of HealthStreet, an ongoing community engagement program, were asked about lifetime and past 30-day use of cocaine, alcohol, tobacco, marijuana, and prescription medications, mental health conditions, recent Emergency Department (ED) visits and demographics. LCA was used to identify classes of past 30-day polysubstance use among individuals who endorsed lifetime cocaine use. Multinomial logistic regression identified factors associated with these classes. Results Among 1797 lifetime cocaine users, a five-class LCA model was identified: 1) past 30-day tobacco use only (45%), 2) past 30-day alcohol, marijuana and tobacco use (31%), 3) past 30-day tobacco, prescription opioid and sedative use (13%), 4) past 30-day cocaine, alcohol, marijuana and tobacco use (9%), 5) past 30-day cocaine and multiple polysubstance use (2%). Demographics, ED visits and mental health conditions were associated with class membership. Conclusions Approximately 11% of lifetime cocaine users used cocaine in the past 30 days with two different concurrent substance use patterns. Prescription medication (opioids and sedatives) and complex polysubstance use patterns were stronger indicators of negative outcomes than current cocaine use. Cocaine was not used frequently with other stimulants. In addition to polysubstance use, prescription medication use should be targeted for intervention among lifetime cocaine users.

PurposeMarketing accountability is currently receiving increased attention from scholars and practitioners alike, with its usage mostly being linked to the improved position of marketing within the firm and to better firm performance. The purpose of this study is to assess whether a supplier’s marketing accountability also has an unobserved signaling effect on customer perceived value.Design/methodology/approachBased on a survey of advertising agency-client dyads, the authors develop and test a multilevel model that assesses the relationship between the supplier’s marketing accountability and perceived value of the client.FindingsEmpirical results indicate that marketing accountability of the agency is positively related to client-firm perceived value, that is marketing accountability also has a positive signaling effect on customers’ value perceptions.Originality/valueThis study provides novel insights on how perceptions of customer value are created in business relationships. More specifically, it highlights that marketing accountability of a supplier positively contributes to shaping clients’ value perceptions. Implications for marketing theory and practice, focused on the need for building, improving and sustaining marketing accountability within the firm and its relevance for value, are discussed and future research directions are identified.