CYP2D6 genotypes in revolving door patients with bipolar disorders: A case series

RATIONALE: In psychiatric disorders, interindividual differences in cytochrome P450 (CYP)2D6 (CYP2D6) enzymatic activity could be responsible of adverse drug reactions (ADRs) and therapeutic failures (TFs) for CYP2D6-metabolized drugs, contributing to the periodical hospital readmissions of the revolving door (RD) condition.PATIENT CONCERNS: We investigated CYP2D6 genotypes in a controlled series of 5 consecutive RD patients with Bipolar Disorder (BD).DIAGNOSES: Psychiatric patients affected by Bipolar Disorder.INTERVENTIONS: We defined TFs as a difference at the Brief Psychiatric Rating Scale score \u394BPRS\u200a<\u200a25% at each 1-week of stable treatment, and ADRs as the onset of extrapyramidal symptoms and/or metabolic impairment with weight gain.OUTCOMES: At 3 months, a mean number of 2.75\u200a\ub1\u200a1.26 ADR and a mean \u394BPRS score of 16.07\u200a\ub1\u200a0.05% were observed. At 6 months of follow-up, compared to the only patient without BD (\u394BPRS\u200a<\u200a32.10%), BD patients (n\u200a=\u200a4) showed TFs (\u394BPRS\u200a<\u200a25%). CYP2D6 genotyping revealed intermediate metabolizer phenotypes for BD patients and an extensive metabolizer phenotype for the patient without BD. In BD patients, the ratio of drugs maintained/discontinued for TFs or ADRs was 1.75 for non-CYP2D6 versus 0.33 for CYP2D6 interacting drugs, while the proportion of ADR:TF was 0:4 versus 6:3.LESSONS: Our findings may suggest that CYP2D6 clinically relevant genotypes may be involved in the unwanted outcomes observed in RD patients with BD

Damage tolerant design of additively manufactured metallic components subjected to cyclic loading:State of the art and challenges

none21siUndoubtedly, a better understanding and the further development of approaches for damage tolerant component design of AM parts are among the most significant challenges currently facing the use of these new technologies. This article presents a thorough overview of the workshop discussions. It aims to provide a review of the parameters affecting the damage tolerance of parts produced by additive manufacturing (shortly, AM parts) with special emphasis on the process parameters intrinsic to the AM technologies, the resulting defects and the residual stresses. Based on these aspects, basic concepts are reviewed and critically discussed specifically for AM materials: - Criteria for damage tolerant component design; - Criteria for the determination of fatigue and fracture properties; - Strategies for the determination of the fatigue life in dependence of different manufacturing conditions; - Methods for the quantitative characterization of microstructure and defects; - Methods for the determination of residual stresses; - Effect of the defects and the residual stresses on the fatigue life and behaviour. We see that many of the classic concepts need to be expanded in order to fit with the particular microstructure (grain size and shape, crystal texture) and defect distribution (spatial arrangement, size, shape, amount) present in AM (in particular laser powder bed fusion). For instance, 3D characterization of defects becomes essential, since the defect shapes in AM are diverse and impact the fatigue life in a different way than in the case of conventionally produced components. Such new concepts have immediate consequence on the way one should tackle the determination of the fatigue life of AM parts; for instance, since a classification of defects and a quantification of the tolerable shapes and sizes is still missing, a new strategy must be defined, whereby theoretical calculations (e.g. FEM) allow determining the maximum tolerable defect size, and non-destructive testing (NDT) techniques are required to detect whether such defects are indeed present in the component. Such examples show how component design, damage and failure criteria, and characterization (and/or NDT) become for AM parts fully interlinked. We conclude that the homogenization of these fields represents the current challenge for the engineer and the materials scientist.noneZerbst, Uwe; Bruno, Giovanni; Buffiere, Jean-Yves; Wegener, Thomas; Niendorf, Thomas; Wu, Tao; Zhang, Xiang; Kashaev, Nikolai; Meneghetti, Giovanni; Hrabe, Nik; Madia, Mauro; Werner, Tiago; Hilgenberg, Kai; Koukolíková, Martina; Procházka, Radek; Džugan, Jan; Möller, Benjamin; Beretta, Stefano; Evans, Alexander; Wagener, Rainer; Schnabel, KaiZerbst, Uwe; Bruno, Giovanni; Buffiere, Jean-Yves; Wegener, Thomas; Niendorf, Thomas; Wu, Tao; Zhang, Xiang; Kashaev, Nikolai; Meneghetti, Giovanni; Hrabe, Nik; Madia, Mauro; Werner, Tiago; Hilgenberg, Kai; Koukolíková, Martina; Procházka, Radek; Džugan, Jan; Möller, Benjamin; Beretta, Stefano; Evans, Alexander; Wagener, Rainer; Schnabel, Ka

Fracture mechanics based determination of the fatigue strength of weldments.

AbstractA fracture mechanics model which shall be applied to the fatigue strength determination of weldments has to focus on various aspects such as: (a) the description of mechanical and physical short fatigue crack extension which is characterised by yielding conditions which do not permit the application of the common ΔK concept and by the gradual build-up of the crack closure effect, (b) a consistent methodology for determining the initial crack size, (c) based on this, the determination of a fatigue limit, (d) the treatment of multiple crack propagation at load levels above this limit, (e) the variation of the local geometry along the weld toe, and (f) statistical effects.The paper gives alimited overview of the work the authors did in this field during the last years within the German project cluster IBESS. A model is presented and briefly discussed which covers the questions above