Paroxysmal mechanical aortic valve prosthesis dysfunction: capturing the right moment

Cardiolog

Age- and Disease-Specific Changes of the Kynurenine Pathway in Parkinson's and Alzheimer's Disease

The Kynurenine (Kyn) pathway, which regulates neuroinflammation and n-methyl-d-aspartate (NMDA) receptor activation, is implicated in Parkinson's disease (PD) and Alzheimer's disease (AD). Age-related changes in Kyn metabolism and altered cerebral Kyn uptake along large-neutral amino acid (LNAA) transporters, could contribute to these diseases. To gain further insight into the role and prognostic potential of the Kyn pathway in PD and AD, we investigated systemic and cerebral Kyn metabolite production and estimations of their transporter-mediated uptake in the brain. Kyn metabolites and LNAAs were retrospectively measured in serum and cerebrospinal fluid (CSF) of clinically well-characterized PD patients (n=33), AD patients (n=33) and age-matched controls (n=39) using solid-phase extraction-liquid chromatographic-tandem mass spectrometry. Aging was disease-independently associated with increased Kyn, kynurenic acid and quinolinic acid in serum and CSF. Concentrations of kynurenic acid were reduced in CSF of PD and AD patients (p=.001; p=.002) but estimations of Kyn brain uptake did not differ between diseased and controls. Furthermore, serum Kyn and quinolinic acid levels strongly correlated with their respective content in CSF and Kyn in serum negatively correlated with AD disease severity (p=.002). Kyn metabolites accumulated with aging in serum and CSF similarly in PD patients, AD patients and control subjects. In contrast, kynurenic acid was strongly reduced in CSF of PD and AD patients. Differential transporter-mediated Kyn uptake is unlikely to majorly contribute to these cerebral Kyn pathway disturbances. We hypothesize that the combination of age- and disease-specific changes in cerebral Kyn pathway activity could contribute to reduced neurogenesis and increased excitotoxicity in neurodegenerative disease. This article is protected by copyright. All rights reserved

The Effect of Tryptophan 2,3-Dioxygenase Inhibition on Kynurenine Metabolism and Cognitive Function in the APP23 Mouse Model of Alzheimer's Disease

Alzheimer's disease (AD) is associated with progressive endogenous neurotoxicity and hampered inflammatory regulation. The kynurenine (Kyn) pathway, which is controlled by tryptophan 2,3-dioxygenase (TDO), produces neuroactive and anti-inflammatory metabolites. Age-related Kyn pathway activation might contribute to AD pathology in humans, and inhibition of TDO was found to reduce AD-related cellular toxicity and behavioral deficits in animal models. To further explore the effect of aging on the Kyn pathway in the context of AD, we analyzed Kyn metabolite profiles in serum and brain tissue of the APP23 amyloidosis mouse model. We found that aging had genotype-independent effects on Kyn metabolite profiles in serum, cortex, hippocampus and cerebellum, whereas serum concentrations of many Kyn metabolites were reduced in APP23 mice. Next, to further establish the role of TDO in AD-related behavioral deficits, we investigated the effect of long-term pharmacological TDO inhibition on cognitive performance in APP23 mice. Our results indicated that TDO inhibition reversed recognition memory deficits without producing measurable changes in cerebral Kyn metabolites. TDO inhibition did not affect spatial learning and memory or anxiety-related behavior. These data indicate that age-related Kyn pathway activation is not specific for humans and could represent a cross-species phenotype of aging. These data warrant further investigation on the role of peripheral Kyn pathway disturbances and cerebral TDO activity in AD pathophysiology

Cost-effectiveness of a vocational enablement protocol for employees with hearing impairment; design of a randomized controlled trial

Background: Hearing impairment at the workplace, and the resulting psychosocial problems are a major health problem with substantial costs for employees, companies, and society. Therefore, it is important to develop interventions to support hearing impaired employees. The objective of this article is to describe the design of a randomized controlled trial evaluating the (cost-) effectiveness of a Vocational Enablement Protocol (VEP) compared with usual care. Methods/Design. Participants will be selected with the 'Hearing and Distress Screener'. The study population will consist of 160 hearing impaired employees. The VEP intervention group will be compared with usual care. The VEP integrated care programme consists of a multidisciplinary assessment of auditory function, work demands, and personal characteristics. The goal of the intervention is to facilitate participation in work. The primary outcome measure of the study is 'need for recovery after work'. Secondary outcome measures are coping with hearing impairment, distress, self-efficacy, psychosocial workload, job control, general health status, sick leave, work productivity, and health care use. Outcome measures will be assessed by questionnaires at baseline, and 3, 6, 9, and 12 months after baseline. The economic evaluation will be performed from both a societal and a company perspective. A process evaluation will also be performed. Discussion. Interventions addressing occupational difficulties of hearing impaired employees are rare but highly needed. If the VEP integrated care programme proves to be (cost-) effective, the intervention can have an impact on the well-being of hearing impaired employees, and thereby, on the costs for the company as well for the society. Trial registration. Netherlands Trial Register (NTR): NTR2782. © 2012 Gussenhoven et al; BioMed Central Ltd

A theoretical framework to describe communication processes during medical disability assessment interviews

BACKGROUND: Research in different fields of medicine suggests that communication is important in physician-patient encounters and influences satisfaction with these encounters. It is argued that this also applies to the non-curative tasks that physicians perform, such as sickness certification and medical disability assessments. However, there is no conceptualised theoretical framework that can be used to describe intentions with regard to communication behaviour, communication behaviour itself, and satisfaction with communication behaviour in a medical disability assessment context. OBJECTIVE: The objective of this paper is to describe the conceptualization of a model for the communication behaviour of physicians performing medical disability assessments in a social insurance context and of their claimants, in face-to-face encounters during medical disability assessment interviews and the preparation thereof. CONCEPTUALIzATION: The behavioural model, based on the Theory of Planned Behaviour (TPB), is conceptualised for the communication behaviour of social insurance physicians and claimants separately, but also combined during the assessment interview. Other important concepts in the model are the evaluation of communication behaviour (satisfaction), intentions, attitudes, skills, and barriers for communication. CONCLUSION: The conceptualization of the TPB-based behavioural model will help to provide insight into the communication behaviour of social insurance physicians and claimants during disability assessment interviews. After empirical testing of the relationships in the model, it can be used in other studies to obtain more insight into communication behaviour in non-curative medicine, and it could help social insurance physicians to adapt their communication behaviour to their task when performing disability assessment

Design of line-start permanent magnet synchronous machines using the Taguchi Method

Thesis (PhD)--Stellenbosch University, 2017.ENGLISH ABSTRACT: Future energy challenges and global environmental concerns urge the world to focus on energy efficiency programs more than ever. Energy efficiency improvement is an important way to address these challenges. Since motor-driven systems are responsible for approximately 40-50% of all electricity consumption in industry, a huge amount of energy saving can be realised by increasing electrical motor efficiency. Induction motors are still the most common electric machines used in industry. Although the performance of induction motors have been significantly improved over the years, the inherent limitation of induction motors such as relatively poor efficiency and power factor cannot be easily remedied. With the introduction of more stringent energy efficiency standard, electrical motor manufacturers worldwide increasingly focuses on alternative motor technologies. Amongst others, line start permanent magnet synchronous motor (LS PMSM) technology has received considerable attention. The distinct advantages of LS PMSMs such as self-start capability, high efficiency and power factor have made this type of motor very attractive. There has been extensive research work on LS PMSMs in literature, which mainly focused on the development of rotor topologies, improving the steady-state analytical model and the utilisation of transient time-step finite element method (FEM) for synchronisation analysis. Since an LS PMSM has a hybrid rotor containing both cage winding and PM arrays, the torque components for the transient start-up and steady state operation modes are different. To validate the synchronisation capability of an LS PMSM design, transient time-step FEM simulations are usually employed. However, this verification method is computationally expensive, thus limiting the possibility for designers to incorporate it into an optimisation procedure. There have been limited attempts to develop a design strategy which enabled machine designers to consider both transient and steady-states objectives. This study focuses on formulating a comprehensive design approach for LS PMSMs that can consider both steady-state and transient performance objectives in a multiobjective design optimisation procedure. This was achieved by incorporating the Taguchi method for robust design methodology in an iterative optimisation structure. The use of Taguchi method in electrical machine design is relatively new. The method differs from commonly used optimisation methods in that it analyses the results to locate a region where the performance objectives are most stable rather than searching for a definite point in the domain. Some key advantages of the Taguchi method are reduced sensitivity to initial conditions, lower parameter complexity and the relative ease in determining the subsequent conditions of the parameters in an iterative process. Traditionally, the Taguchi method is unsuitable for iterative and multi-objective design optimisation (MODO) problems. To address this limitation, an improved version of the regression rate methodology is incorporated into the Taguchi method for LS PMSM designs. It is shown that the proposed method can effectively take into account both steady-state and transient synchronisation performance in the design of LS PMSMs. The Taguchi based regression rate (TBRR) framework as presented in this thesis possesses the ability to simultaneous optimise both steady-state and transient performances of LS PMSMs. The MODO was solved by first establishing the competing relationship between the selected steady-state and transient performance objectives using a Pareto front solution, and then identifying the balanced design using the objective function for each topology. The successful implementation of the TBRR method using its robust design approach can be seen as the first use of this method to solve electrical machine related design problem. To validate the proposed method a prototype machine was designed, manufactured and experimentally evaluated. It shows that the proposed method can effectively take into account both steady-state and transient synchronisation performance in the design of LS PMSMs. The analytical calculation of the transient performance index shows good agreement with that of the measured one close to rated load conditions. It confirmed that the performance index of an LS PMSM could be used as a performance objective in design optimisation method. This thesis presented an alternative way of viewing machine design through the use of the Taguchi method for robust design. The unique attributes of this method and the effects it may have on machine design is still less known. The implementation capabilities of this method in various optimisation methods along with Dr Taguchi’s methodology is very promising. The TBRR method as presented in this thesis is just one of many possible design variants relying on the fundamentals of the Taguchi method to realise improved designs. The TBRR method as presented could find even broader applications in electrical machine design.AFRIKAANSE OPSOMMING: Toekomstige energie-uitdagings en omgewingskwessies vra die wêreld om nou, meer as ooit tevore op energie-doeltreffendheidsprogramme te fokus. Verbetering van energiedoeltreffendheid is ’n belangrike manier om hierdie uitdagings aan te spreek. Aangesien motor-aangedrewe stelsels verantwoordelik is vir ongeveer 40-50% van alle elektrisiteitsverbruik, kan ’n groot hoeveelheid energiebesparing gerealiseer word deur die verhoging van elektriese motors se doeltreffendheid. Induksiemotors is steeds die mees algemene elektriese masjiene wat in industrie gebruik word. Alhoewel die effektiviteit van induksiemotors oor die jare aansienlik verbeter het, kan die inherente beperking van die motors soos relatief swak doeltreffendheid en arbeidsfaktor nie maklik verbeter word nie. Met die bekendstelling van strenger energie-doeltreffendheidstandaarde, fokus elektriese motorvervaardigers wêreldwyd toenemend op alternatiewe motor tegnologië. Die direk-aan-lyn permanente magneet sinchrone masjien (DAL-PMSM) tegnologie het onder andere aansienlike aandag geniet. Die duidelike voordele van DAL-PMSMs soos self-begin vermoë, hoë doeltreffendheid en hoë arbeidsfaktor maak hierdie tipe motor baie aantreklik. Literatuur toon aan dat daar reeds baie navorsing gedoen is op DAL-PMSM’s, wat hoofsaaklik gefokus het op die ontwikkeling van rotor topologieë, die verbetering van die bestendige analitiese model en die gebruik van die eindige-element-metode (EEM) vir sinchronisasie-analise. Aangesien ’n DAL-PMSM ’n hibriede rotor het, wat beide n kourotor en permanente magnete bevat, is die wringkragkomponente vir die oorgangsen bestendige toestande verskillend. Om die sinkronisasievermoë van ’n DAL-PMSMontwerp te bevestig, word oorgangstyd-EEM-simulasies gewoonlik gebruik. Hierdie verifikasie metode gebruik baie bewerkingstyd, wat die moontlikheid vir gebruik in optimaliseringsprosedure beprek. Daar was egter enkele pogings in die verlede om ontwerpstrategië te ontwikkel wat masjienontwerpers in staat stel om beide toestande se doelwitte te oorweeg. Hierdie studie fokus op die formulering van ’n omvattende ontwerpbenadering vir DALPMSMs wat beide bestendige en oorgangse prestasie doelwitte in ’n multi-objektiewe ontwerps optimaliseringsprosedure kan oorweeg. Dit is behaal deur die Taguchi-metode vir robuuste ontwerpmetodologie in ’n iteratiewe optimaliseringsstruktuur in te sluit. Die gebruik van Taguchi-metode in elektriese masjienontwerp is relatief nuut. Die metode verskil van algemeen gebruikte optimaliseringsmetodes, omdat dit die resultate ontleed om ’n area te vind waar die doelwitte die mees stabiel is, eerder as om ’n bepaalde punt in die domein te soek. Enkele belangrike voordele van die Taguchi-metode is die verminderde sensitiwiteit van aanvanklike toestande, laer parameterkompleksiteit en die relatiewe gemak met die bepaling van die daaropvolgende toestande van die parameters in ’n iteratiewe proses. Tradisioneel is die Taguchi-metode onvanpas vir iteratiewe en multiobjektiewe ontwerpoptimalisering (MOO) probleme. Om hierdie beperking aan te spreek, vir DAL-PMSM-ontwerpe. Daar word aangetoon dat die voorgestelde metode effektief beide toestande se doelwitte in die ontwerp van DAL-PMSMs in ag kan neem. Die Taguchi gebaseer regressie-tempo (TGRT) raamwerk wat in hierdie proefskrif aangebied word, beskik oor die vermoë om gelyktydig beide die bestadigde en oorgangse doelwitte van DAL-PMSMs te optimaliseer. Die MOO is opgelos deur eers die mededingende verhouding tussen die geselekteerde doelwitte te vestig deur gebruik te maak van ’n Paretofront oplossing. Die gebalanseerde ontwerp is daarna geidentifiseer deur die doelwit funksie vir elke topologie te gebruik. Die suksesvolle implementering van die TGRT-metode met behulp van ’n robuuste ontwerpbenadering is die eerste gebruik van hierdie metode om elektriese masjienverwante ontwerpprobleme op te los. Om die voorgestelde metode te valideer, is ’n prototipe masjien ontwerp, vervaardig en eksperimenteel geëvalueer. Dit toon dat die voorgestelde metode beide die arbiedsfaktor en sinkronisasieprestasie kan optimeer in die ontwerp van DAL-PMSMs. Die analitiese berekening van die sinkronisasieprestasie-indeks toon goeie ooreenkoms met die gemete resultate by die gegewe lasvoorwaardes. Dit het bevestig dat die prestasie-indeks van ’n DAL-PMSM gebruik kan word as ’n prestasiedoelwit in ontwerpoptimaliseringsmetodes. Hierdie proefskrif het ’n alternatiewe manier van masjienontwerp bekyk deur die gebruik van die Taguchi-metode vir robuuste ontwerp te gebruik. Die unieke eienskappe van hierdie metode en die impak wat dit op masjienontwerp kan hê, is nog minder bekend. Die implementeringsvermoë van hierdie metode in verskeie optimaliseringsmetodes saam met Dr Taguchi se metodologie is baie belowend. Die TGRT-metode wat in hierdie proefskrif aangebied word, is net een van die vele moontlike ontwerpvariante wat staatmaak op die beginsels van die Taguchi-metode om verbeterde ontwerpe te realiseer. Die TGRT-metode soos aangebied kan selfs groter masjienontwerp toepassings vind

DIREKTE KOSTEBEREKENING NADER ONDERSOEK

DIREKTE KOSTEBEREKENING NADER ONDERSOE

Multiobjective design of a line-start PM motor using the Taguchi method

This paper investigates the use of the Taguchi method for the design of line-start permanent magnet synchronous motors (LS-PMSMs). To address the inherent limitation of the Taguchi method in solving multiresponse optimization problems, an improved regression rate methodology and a weighted factor multiobjective technique are incorporated to form a Taguchi method based multiobjective design framework. To validate the proposed method, a prototype machine has been designed, constructed, and experimentally evaluated. It shows that the proposed method can effectively take into account both steady-state and transient synchronization performances in the design of LS-PMSM