Risk minimisation methods in shaping the optimal range of treadmills

The article presents a solution to the problem of integrating risk minimisation methods in the process of forming the optimal range of treadmill models in a retail enterprise. The problem of multi-criteria optimisation was solved using the generalised criterion method. The formulated problem was therefore broken down into a number of specific tasks, each of which was solved by selecting specific methods. Risks were minimised by mathematical methods, taking into account the economic performance of the enterprise. Recommendations were also offered for customers wishing to purchase one of the treadmill models chosen from the analysis and the best option for ordering via the online shop with home delivery.

On the Way to the Fluvial Anthroposphere—Current Limitations and Perspectives of Multidisciplinary Research

Floodplains represent a global hotspot of sensitive socioenvironmental changes and early human forcing mechanisms. In this review, we focus on the environmental conditions of preindustrial floodplains in Central Europe and the fluvial societies that operated there. Due to their high land-use capacity and the simultaneous necessity of land reclamation and risk minimisation, societies have radically restructured the Central European floodplains. According to the current scientific consensus, up to 95% of Central European floodplains have been extensively restructured or destroyed. Therefore, question arises as to whether or when it is justified to understand Central European floodplains as a ‘Fluvial Anthroposphere’. The case studies available to date show that human-induced impacts on floodplain morphologies and environments and the formation of specific fluvial societies reveal fundamental changes in the medieval and preindustrial modern periods. We aim to contribute to disentangling the questions of when and why humans became a significant controlling factor in Central European floodplain formation, and how humans in interaction with natural processes and other chains of effects have modified floodplains. As a conclusion, we superimpose emerging fields of research concerning the onset of the Fluvial Anthroposphere and provide 10 specific thematic objectives for future multidisciplinary work.

Molecular fingerprinting by single cell clone analysis in adverse drug reaction (ADR) assessment

: Causality assessment for idiosyncratic ADRs mainly relies on epidemiology, signal detection and less often on proven or plausible mechanistic evidence of the drug at a cellular or organ level. Distinct clones of cells can exist within organs of individual patients, some conferring susceptibility to well recognised adverse drug reactions (ADRs). Recent advances in molecular biology has allowed the development of single cell clonal techniques, including single cell RNA sequencing (scRNA-seq) to molecularly fingerprint ADRs and distinguish between distinct clones of cells within organs in individuals, which may confer differing susceptibilities to ADRs. ScRNA-seq permits molecular fingerprinting of some serious ADRs, mainly in the skin, through identification of directly expressed genes (DEG) of interest within specific clones. Overexpressed DEGs provides an opportunity for targeted treatment strategies to be developed. scRNA-seq could be applied to a number of other ADRs involving tissues that can be biopsied/sampled (including skin, liver, kidney, blood, stem cells) as well as providing a molecular basis for rapid screening of potential therapeutic candidates, which may not otherwise be predictable from class of toxicity/organ involvement. . A framework for putative assessment for ADRs using scRNA-seq is proposed as well as speculating on potential regulatory implications for pharmacovigilance and drug development. Molecular fingerprinting of ADRs using scRNA-seq may allow better targeting for enhanced pharmacovigilance and risk minimisation measures for medicines with appropriate benefit risk profiles, although cost-effectiveness and other factors, such as frequency/severity of individual ADRs and population differences will still be relevant.

Thirsty work: Testing the risk reduction model of mid- to late-Holocene stone points with distance decay from freshwater in northern Australia

A key tenant of risk reduction models in archaeology the world over is that changes in resource availability drove mobility increases and created a need for an extension of stone tool use life. This manuscript directly addresses the question, is retouch intensity of tools related to distance from freshwater, by using extant localities of major Gorges, Rivers and water holes in the southern Kimberley region of northern Australia. Previous research has argued that retouched stone points during the mid to late-Holocene were part of a risk minimisation strategy, within broader technological organisation models. Modelling the distance from primary water sources, in arid to semi-arid regions of the southern Kimberley, reduction intensity of points is found to increase with distance from water sources consistently. This research provides an appropriate test of existing risk minimisation models and highlights global significance for similar studies where retouch tool reduction and forager mobility are linked to environmental change.

Real-world Utilisation of the Rivastigmine Transdermal Patches Accompanying the use of Risk Minimisation Tools in Patients with Dementia

Background: Transdermal patches are convenient to use, especially in patients with Alzheimer’s disease (AD)-associated dementia. However, various identified risks of errors in ad- ministering the patches cannot be disregarded. Patient Reminder Cards (PRCs, included a Medica- tion record sheet [MRS]) have been recently introduced as a risk minimisation tool to prevent incor- rect patch use (IU). Objectives: This study aimed to assess the effectiveness of PRCs to prevent IU and to investigate the dose titration pattern of rivastigmine patches in a real-world setting. Methods: This multinational, observational, 11-month study included patients with AD currently using rivastigmine patches (4.6 mg/day, 9.5 mg/day, 13.3 mg/day) accompanied by a caregiver. Study outcomes were IU, including multiple patch use (MPU), incorrect patch placement, other IUs, perceived usefulness of the PRCs, and titration patterns of the patches. Results: Of the total 614 patients included, most were aged ≥65 years and had mild-to-moderate AD. Before and during the study, 27.7% and 18.0% of patients reported IU, respectively. Most pa- tients used MRS, and 73.5% rated it ‘helpful’ and reported lower rates of IU than those who report- ed it ‘not helpful’ (13.9%–16.5% vs. 20.2%). Overall, 141 patients had dose titrations, with 75.8% being up-titrated from 4.6 mg/day to 9.5 mg/day after a mean duration of 58 days. Safety findings were consistent with the established profile for the rivastigmine patch. Conclusion: PRC was effective as a risk minimisation tool in limiting the inappropriate use of ri- vastigmine patches. The majority of patients requiring dose-change were up-titrated to 9.5 mg/day patches.