62 research outputs found
Differences in neurophysiological markers of inhibitory and temporal processing deficits in children and adults with ADHD
We compared ADHD-related temporal processing and response inhibition deficits in children and adults using event-related potentials (ERPs) during cued continuous performance tasks (CPT, O-X-version, plus a more demanding flanker version). ERP markers of temporal processing (Cue CNV) and inhibition (NoGo P300) were obtained in matched groups of children (32 with ADHD, mean age 11.2 years, and 31 controls, mean age 11.1 years) and adults (22 ADHD, mean age 42.7 years, and 22 controls, mean age 44.0 years). ERP markers and performance reflected both age and ADHD status. Performance was poorer, and Cue CNV and NoGo P300 were weaker in ADHD children and adults compared to their matched controls. ADHD-related ERP differences in children were more prominent at posterior scalp sites but more pronounced at anterior scalp sites in adults, paralleling the prominent topographic changes of both ERP markers with development. The fact that differences in the same test and the same processing period appear in both children and adults, but that they present in different aspects of performance and different scalp topographies, leads to the conclusion that some ADHD-related deficits persist into adulthood despite alterations of their qualitative aspects
Action monitoring in boys with attention-deficit/hyperactivity disorder, their nonaffected siblings, and normal control subjects: evidence for an endophenotype
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a very common and highly heritable child psychiatric disorder associated with dysfunctions in fronto-striatal networks that control attention and response organization. The aim of this study was to investigate whether features of action monitoring related to dopaminergic functions represent endophenotypes that are brain functions on the pathway from genes and environmental risk factors to behavior. METHODS: Action monitoring and error processing as indicated by behavioral and electrophysiological parameters during a flanker task were examined in boys with ADHD combined type according to DSM-IV (n = 68), their nonaffected siblings (n = 18), and healthy control subjects with no known family history of ADHD (n = 22). RESULTS: Boys with ADHD displayed slower and more variable reaction-times. Error negativity (Ne) was smaller in boys with ADHD compared with healthy control subjects, whereas nonaffected siblings displayed intermediate amplitudes following a linear model predicted by genetic concordance. The three groups did not differ on error positivity (Pe). The N2 amplitude enhancement due to conflict (incongruent flankers) was reduced in the ADHD group. Nonaffected siblings also displayed intermediate N2 enhancement. CONCLUSIONS: Converging evidence from behavioral and event-related potential findings suggests that action monitoring and initial error processing, both related to dopaminergically modulated functions of anterior cingulate cortex, might be an endophenotype related to ADHD
Genetics of preparation and response control in ADHD : the role of DRD4 and DAT1
Difficulties with performance and brain activity related to attentional orienting (Cue-P3), cognitive or response preparation (Cue-CNV) and inhibitory response control (Nogo-P3) during tasks tapping executive functions are familial in ADHD and may represent endophenotypes. The aim of this study was to clarify the impact of dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) gene polymorphisms on these processes in ADHD and control children.; Behavioural and electrophysiological parameters from cued continuous performance tests with low and high attentional load were assessed in boys with ADHD combined type (N = 94) and controls without family history of ADHD (N = 31). Both groups were split for the presence of at least one DRD4 7-repeat allele and the DAT1 10-6 haplotype.; Children with ADHD showed diminished performance and lower Cue-P3, CNV and Nogo-P3 amplitudes. Children with DRD4 7R showed similar performance problems and lower Cue-P3 and CNV, but Nogo-P3 was not reduced. Children with the DAT1 10-6 haplotype had no difficulties with performance or Cue-P3 and CNV, but contrary to expectations increased Nogo-P3. There were no Genotype by ADHD interactions.; This study detected specific effects of DRD4 7R on performance and brain activity related to attentional orienting and response preparation, while DAT1 10-6 was associated with elevated brain activity related to inhibitory response control, which potentially compensates increased impulsivity. As these genotype effects were additive to the impact of ADHD, the current results indicate that DRD4 and DAT1 polymorphisms are functionally relevant risk factors for ADHD and presumably other disorders sharing these endophenotypes
Familiality of neural preparation and response control in childhood attention deficit-hyperactivity disorder
BACKGROUND: Patients with attention deficit-hyperactivity disorder (ADHD) exhibit difficulties in multiple attentional functions. Although high heritability rates suggest a strong genetic impact, aetiological pathways from genes and environmental factors to the ADHD phenotype are not well understood. Tracking the time course of deviant task processing using event-related electrophysiological brain activity should characterize the impact of familiality on the sequence of cognitive functions from preparation to response control in ADHD. Method Preparation and response control were assessed using behavioural and electrophysiological parameters of two versions of a cued continuous performance test with varying attentional load in boys with ADHD combined type (n = 97), their non-affected siblings (n = 27) and control children without a family history of ADHD (n = 43).
RESULTS: Children with ADHD and non-affected siblings showed more variable performance and made more omission errors than controls. The preparatory Cue-P3 and contingent negative variation (CNV) following cues were reduced in both ADHD children and their non-affected siblings compared with controls. The NoGo-P3 was diminished in ADHD compared with controls whilst non-affected siblings were located intermediate but did not differ from both other groups. No clear familiality effects were found for the Go-P3. Better task performance was further associated with higher CNV and P3 amplitudes.
CONCLUSIONS: Impairments in performance and electrophysiological parameters reflecting preparatory processes and to some extend also for inhibitory response control, especially under high attentional load, appeared to be familially driven in ADHD and may thus constitute functionally relevant endophenotypes for the disorder
Modelling effect of coarse aggregates on oxygen transport and corrosion products precipitation in reinforced concrete
The structure of concrete, in particular the microstructure of the steel-concrete interface (SCI), can significantly affect corrosion of rebars. To support corrosion, oxygen needs to diffuse from the ambient environment to the steel surface. Meanwhile, corrosion products transport through the SCI and precipitate in concrete. Transport properties of concrete play an important role in these two processes. However, the effect of the heterogeneous structure of concrete especially coarse aggregates on oxygen transport and corrosion products precipitation in reinforced concrete is rarely studied in the literature. This study employed a numerical model to investigate such effect. Simulation domains in 2D were created with different aggregate contents and sizes. The model included oxygen diffusion, ions diffusion and migration, corrosion products oxidation and precipitation. The simulation results showed that the presence of aggregates significantly reduces oxygen diffusion. It becomes more pronounced for high aggregate contents which lead to more corrosion products formed at the interface. Furthermore, results showed that the interfacial transition zone (ITZ) around aggregates can enhance oxygen diffusion
Oral rehydration therapy--Qualitative studies of balance between pragmatism and scientific rigour in managing diarrhoea
In the experience of the author, oral rehydration therapy has proven effective at home, in the ambulatory and in the institutional care setting. A series of anecdotal reports on the successful use of oral rehydration on refugees, in famine and poverty, on medical students, prisoners, and the well-off people of western countries, is presented. The essential principles of oral rehydration are identified and we show how these can be adapted to a particular health care setting. A clear understanding of local attitudes and beliefs about diarrhoea is essential to professional health workers if they are to act as agents of change.oral rehydration therapy applied technology qualitative studies
Engineering of cartilage tissue constructs in a 3-dimensional perfusion bioreactor culture system under controlled oxygen tension
The most relevant results generated in this thesis can be summarized as follow:
· Adult human articular chondrocytes (AHAC) from elderly individuals expanded in culture
medium supplemented with the growth factors TGFβ-1, FGF-2 and PDGF and subsequently
cultured in 3-d pellets had an enhanced chondrogenic capacity when exposed to more
physiological (i.e. 5%) oxygen levels.
· In correlation with the enhanced tissue forming capacity of AHAC from elderly donors under
low oxygen tension, the mRNA expression levels of selective matrix degrading enzymes
were reduced as compared to conventional in vitro oxygen culture condition.
· We developed an integrated bioreactor system, which streamlines within a single device the
phases of perfusion cell seeding and prolonged perfusion culture of cell seeded scaffolds in
vitro.
· The culturing of uniformly seeded adult human articular chondrocytes under direct perfusion,
where cells are continuously exposed to a normoxic range of oxygen levels, can maintain a
uniform distribution of viable cells throughout thick porous scaffolds as compared to
statically cultured constructs.
· The culturing of constructs uniformly seeded with adult human articular chondrocytes under
a more physiological range of oxygen resulted in a higher chondrogenic differentiation as
compared to culture under normoxic levels. Anyhow, this effect was less pronounced as
compared to statically cultured cell constructs or micromass cell pellets, possibly due to the
flow induced shear forces.
· Reduced perfusion flow rates applied to chondrocytes on porous scaffolds significantly
induced more cartilaginous tissue in the presents of low vs. high oxygen levels. However the
effects of low oxygen were not as marked as in pellet culture
Modelling of Cathodic Protection of Steel in Concrete Considering Time and Location-dependent Influencing Factors
Cathodic protection (CP) is an electrochemical repair technique for reinforced concrete (RC) structures affected by chloride induced corrosion. The underlying concept is based on a shift of the free corrosion potential of the reinforcement towards negative (cathodic) potentials, in order to force the reinforcement to act as a cathode and therefore suppress the anodic dissolution of iron. This is achieved via the application of an additional CP anode system to the structure. For CP, different types of anode system (galvanic, impressed current, laminar or discrete), made from different materials (e.g. zinc, mixed metal oxide coated titanium, carbon) exist. The protective effect of this method depends on the effective protection current density obtained on the active surfaces of the reinforcement. The continuous construction of the usual reinforcing cages impedes a direct measurement of this parameter. As no reliable test method for the corrosion state of reinforcement during CP exists, the application is based on(semi-) empirical criteria. While this is sufficient for successful application of CP for a wide range of common geometries and CP anode systems, the applicability of CP for unconventional geometrical arrangements of active and passive rebar or the use of new anode materials cannot be assessed this way. For these cases, numerical studies provide the opportunity to predict the current and potential distribution within the structure on a theoretical basis in order to support the design process. Within this thesis, the theoretical background of the numerical simulation of corrosion processes in RC is described and the modifications necessary for the modelling of impressed current cathodic protection (ICCP) are presented. A key focus in this work is the implementation of ICCP anode systems. Proposed models of this author are discussed versus those obtained from the literature. In the course of this work, influencing parameters such as the geometrical arrangement of reinforcement (active/passive) and CP anode system, concrete resistivity and conductivity of the anode material are investigated by means of parametrical studies and discussed IV regarding their specific impact on the applicability of CP against the backdrop of the common protection criteria. An additional focus is set on the implementation of the time-dependency of the current and potential distribution into the numerical models. It is known, that the permanent cathodic polarization of the reinforcement can provide beneficial side effects such as migration of chloride ions away from the surface of the reinforcement, or the evolution of hydroxyl ions caused by the cathodic reaction. A method for the consideration of these processes within a numerical study is proposed and the impact of these side effects versus those of the influencing parameters given above is discussed by means of a parametrical study
The impact of study design and diagnostic approach in a large multi-centre ADHD study. Part 1: ADHD symptom patterns
Background: The International Multi-centre ADHD Genetics (IMAGE) project with 11 participating centres from 7 European countries and Israel has collected a large behavioural and genetic database for present and future research. Behavioural data were collected from 1068 probands with the combined type of attention deficit/hyperactivity disorder (ADHD-CT) and 1446 'unselected' siblings. The aim was to analyse the IMAGE sample with respect to demographic features (gender, age, family status, and recruiting centres) and psychopathological characteristics (diagnostic subtype, symptom frequencies, age at symptom detection, and comorbidities). A particular focus was on the effects of the study design and the diagnostic procedure on the homogeneity of the sample in terms of symptom-based behavioural data, and potential consequences for further analyses based on these data.Methods: Diagnosis was based on the Parental Account of Childhood Symptoms (PACS) interview and the DSM-IV items of the Conners' teacher questionnaire. Demographics of the full sample and the homogeneity of a subsample (all probands) were analysed by using robust statistical procedures which were adjusted for unequal sample sizes and skewed distributions. These procedures included multi-way analyses based on trimmed means and winsorised variances as well as bootstrapping.Results: Age and proband/sibling ratios differed between participating centres. There was no significant difference in the distribution of gender between centres. There was a significant interaction between age and centre for number of inattentive, but not number of hyperactive symptoms. Higher ADHD symptom frequencies were reported by parents than teachers. The diagnostic symptoms differed from each other in their frequencies. The face-to-face interview was more sensitive than the questionnaire. The differentiation between ADHD-CT probands and unaffected siblings was mainly due to differences in hyperactive/impulsive symptoms.Conclusions: Despite a symptom-based standardized inclusion procedure according to DSM-IV criteria with defined symptom thresholds, centres may differ markedly in probands' ADHD symptom frequencies. Both the diagnostic procedure and the multi-centre design influence the behavioural characteristics of a sample and, thus, may bias statistical analyses, particularly in genetic or neurobehavioral studies.<br/
A functional variant of the serotonin transporter gene (SLC6A4) moderates impulsive choice in attention-deficit/hyperactivity disorder boys and siblings
Background: impulsive drive for immediate reward (IDIR) and delay aversion are dissociable elements of the preference for immediate over delayed rewards seen in attention-deficit/hyperactivity disorder (ADHD). We hypothesized that IDIR would be associated with dopamine regulating genes and delay aversion would be associated with serotonin-regulating genes.Methods: impulsive drive for immediate reward and delay aversion were measured in 459 male children and adolescents (328 ADHD and 131 unaffected siblings) with a laboratory choice task. The sample was genotyped for the 5HTT (SLC6A4) promoter serotonin-transporter-linked polymorphic region polymorphism and a DAT1 (SLC6A3) 40-base pair variable number tandem repeat located in the 3?-untranslated region of the gene.Results: there was no effect of dopamine transporter (DAT)1 on IDIR. As predicted, serotonin-transporter-linked polymorphic region s-allele carriers were more delay averse. This effect was driven by the s/l genotype in the ADHD group. These results were not altered by taking account of the rs25531 A/G single nucleotide polymorphism and were independent of age, IQ, and oppositional defiant disorder symptoms.Conclusions: the results support the genetic distinctiveness of IDIR and delay aversion in ADHD and implicate serotonin function in delay aversion. Possible explanations of the heterosis effect in the ADHD cases are presente
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