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Background
In isometric muscle function, there are subjectively two different modes of performance: one can either hold isometrically – thus resist an impacting force – or push isometrically – therefore work against a stable resistance. The purpose of this study is to investigate whether or not two different isometric muscle actions – the holding vs. pushing one (HIMA vs PIMA) – can be distinguished by objective parameters.
Methods
Ten subjects performed two different measuring modes at 80% of MVC realized by a special pneumatic system. During HIMA the subject had to resist the defined impacting force of the pneumatic system in an isometric position, whereby the force of the cylinder works in direction of elbow flexion against the subject. During PIMA the subject worked isometrically in direction of elbow extension against a stable position of the system. The signals of pressure, force, acceleration and mechanomyography/-tendography (MMG/MTG) of the elbow extensor (MMGtri/MTGtri) and the abdominal muscle (MMGobl) were recorded and evaluated concerning the duration of maintaining the force level (force endurance) and the characteristics of MMG-/MTG-signals. Statistical group differences comparing HIMA vs. PIMA were estimated using SPSS.
Results
Significant differences between HIMA and PIMA were especially apparent regarding the force endurance: During HIMA the subjects showed a decisively shorter time of stable isometric position (19 ± 8 s) in comparison with PIMA (41 ± 24 s; p = .005). In addition, during PIMA the longest isometric plateau amounted to 59.4% of the overall duration time of isometric measuring, during HIMA it lasted 31.6% (p = .000). The frequency of MMG/MTG did not show significant differences. The power in the frequency ranges of 8–15 Hz and 10–29 Hz was significantly higher in the MTGtri performing HIMA compared to PIMA (but not for the MMGs). The amplitude of MMG/MTG did not show any significant difference considering the whole measurement. However, looking only at the last 10% of duration time (exhaustion), the MMGtri showed significantly higher amplitudes during PIMA.
Conclusion
The results suggest that under holding isometric conditions muscles exhaust earlier. That means that there are probably two forms of isometric muscle action. We hypothesize two potential reasons for faster yielding during HIMA: (1) earlier metabolic fatigue of the muscle fibers and (2) the complexity of neural control strategies.
forum:logopädie 31.2017, 2
(2017)
During the drug discovery & development process, several phases encompassing a number of preclinical and clinical studies have to be successfully passed to demonstrate safety and efficacy of a new drug candidate. As part of these studies, the characterization of the drug's pharmacokinetics (PK) is an important aspect, since the PK is assumed to strongly impact safety and efficacy. To this end, drug concentrations are measured repeatedly over time in a study population. The objectives of such studies are to describe the typical PK time-course and the associated variability between subjects. Furthermore, underlying sources significantly contributing to this variability, e.g. the use of comedication, should be identified. The most commonly used statistical framework to analyse repeated measurement data is the nonlinear mixed effect (NLME) approach. At the same time, ample knowledge about the drug's properties already exists and has been accumulating during the discovery & development process: Before any drug is tested in humans, detailed knowledge about the PK in different animal species has to be collected. This drug-specific knowledge and general knowledge about the species' physiology is exploited in mechanistic physiological based PK (PBPK) modeling approaches -it is, however, ignored in the classical NLME modeling approach.
Mechanistic physiological based models aim to incorporate relevant and known physiological processes which contribute to the overlying process of interest. In comparison to data--driven models they are usually more complex from a mathematical perspective. For example, in many situations, the number of model parameters outrange the number of measurements and thus reliable parameter estimation becomes more complex and partly impossible. As a consequence, the integration of powerful mathematical estimation approaches like the NLME modeling approach -which is widely used in data-driven modeling -and the mechanistic modeling approach is not well established; the observed data is rather used as a confirming instead of a model informing and building input.
Another aggravating circumstance of an integrated approach is the inaccessibility to the details of the NLME methodology so that these approaches can be adapted to the specifics and needs of mechanistic modeling. Despite the fact that the NLME modeling approach exists for several decades, details of the mathematical methodology is scattered around a wide range of literature and a comprehensive, rigorous derivation is lacking. Available literature usually only covers selected parts of the mathematical methodology. Sometimes, important steps are not described or are only heuristically motivated, e.g. the iterative algorithm to finally determine the parameter estimates.
Thus, in the present thesis the mathematical methodology of NLME modeling is systemically described and complemented to a comprehensive description,
comprising the common theme from ideas and motivation to the final parameter estimation. Therein, new insights for the interpretation of different approximation methods used in the context of the NLME modeling approach are given and illustrated; furthermore, similarities and differences between them are outlined. Based on these findings, an expectation-maximization (EM) algorithm to determine estimates of a NLME model is described.
Using the EM algorithm and the lumping methodology by Pilari2010, a new approach on how PBPK and NLME modeling can be combined is presented and exemplified for the antibiotic levofloxacin. Therein, the lumping identifies which processes are informed by the available data and the respective model reduction improves the robustness in parameter estimation. Furthermore, it is shown how apriori known factors influencing the variability and apriori known unexplained variability is incorporated to further mechanistically drive the model development. Concludingly, correlation between parameters and between covariates is automatically accounted for due to the mechanistic derivation of the lumping and the covariate relationships.
A useful feature of PBPK models compared to classical data-driven PK models is in the possibility to predict drug concentration within all organs and tissue in the body. Thus, the resulting PBPK model for levofloxacin is used to predict drug concentrations and their variability within soft tissues which are the site of action for levofloxacin. These predictions are compared with data of muscle and adipose tissue obtained by microdialysis, which is an invasive technique to measure a proportion of drug in the tissue, allowing to approximate the concentrations in the interstitial fluid of tissues. Because, so far, comparing human in vivo tissue PK and PBPK predictions are not established, a new conceptual framework is derived. The comparison of PBPK model predictions and microdialysis measurements shows an adequate agreement and reveals further strengths of the presented new approach.
We demonstrated how mechanistic PBPK models, which are usually developed in the early stage of drug development, can be used as basis for model building in the analysis of later stages, i.e. in clinical studies. As a consequence, the extensively collected and accumulated knowledge about species and drug are utilized and updated with specific volunteer or patient data. The NLME approach combined with mechanistic modeling reveals new insights for the mechanistic model, for example identification and quantification of variability in mechanistic processes. This represents a further contribution to the learn & confirm paradigm across different stages of drug development.
Finally, the applicability of mechanism--driven model development is demonstrated on an example from the field of Quantitative Psycholinguistics to analyse repeated eye movement data. Our approach gives new insight into the interpretation of these experiments and the processes behind.
Mathematical models of bacterial growth have been successfully applied to study the relationship between antibiotic drug exposure and the antibacterial effect. Since these models typically lack a representation of cellular processes and cell physiology, the mechanistic integration of drug action is not possible on the cellular level. The cellular mechanisms of drug action, however, are particularly relevant for the prediction, analysis and understanding of interactions between antibiotics. Interactions are also studied experimentally, however, a lacking consent on the experimental protocol hinders direct comparison of results. As a consequence, contradictory classifications as additive, synergistic or antagonistic are reported in literature.
In the present thesis we developed a novel mathematical model for bacterial growth that integrates cell-level processes into the population growth level. The scope of the model is to predict bacterial growth under antimicrobial perturbation by multiple antibiotics in vitro.
To this end, we combined cell-level data from literature with population growth data for Bacillus subtilis, Escherichia coli and Staphylococcus aureus. The cell-level data described growth-determining characteristics of a reference cell, including the ribosomal concentration and efficiency. The population growth data comprised extensive time-kill curves for clinically relevant antibiotics (tetracycline, chloramphenicol, vancomycin, meropenem, linezolid, including dual combinations).
The new cell-level approach allowed for the first time to simultaneously describe single and combined effects of the aforementioned antibiotics for different experimental protocols, in particular different growth phases (lag and exponential phase). Consideration of ribosomal dynamics and persisting sub-populations explained the decreased potency of linezolid on cultures in the lag phase compared to exponential phase cultures. The model captured growth rate dependent killing and auto-inhibition of meropenem and - also for vancomycin exposure - regrowth of the bacterial cultures due to adaptive resistance development. Stochastic interaction surface analysis demonstrated the pronounced antagonism between meropenem and linezolid to be robust against variation in the growth phase and pharmacodynamic endpoint definition, but sensitive to a change in the experimental duration.
Furthermore, the developed approach included a detailed representation of the bacterial cell-cycle. We used this representation to describe septation dynamics during the transition of a bacterial culture from the exponential to stationary growth phase. Resulting from a new mechanistic understanding of transition processes, we explained the lag time between the increase in cell number and bacterial biomass during the transition from the lag to exponential growth phase. Furthermore, our model reproduces the increased intracellular RNA mass fraction during long term exposure of bacteria to chloramphenicol.
In summary, we contribute a new approach to disentangle the impact of drug effects, assay readout and experimental protocol on antibiotic interactions. In the absence of a consensus on the corresponding experimental protocols, this disentanglement is key to translate information between heterogeneous experiments and also ultimately to the clinical setting.
Carbohydrate-protein interactions are ubiquitous in nature. They provide the initial molecular contacts in many cell-cell processes as for example immune responses, signal transduction, egg fertilization and infection processes of pathogenic viruses and bacteria. Furthermore, bacteria themselves are infected by bacteriophages, viruses which can cause the bacterial lysis, but do not affect other hosts. The infection process of a bacteriophage involves the specific detection and binding of the bacterium, which can be based on a carbohydrate-protein interaction. The mechanism of specific detection of pathogenic bacteria can thereby be useful for the development of bacteria sensors in the food industry or for tools in diagnostics.
Bacteriophages of the Podoviridae family use tailspike proteins for the specific detection of enteritis causing bacteria as Escherichia coli, Salmonella spp. or Shigella flexneri. The tailspike protein provides the first contact by binding to the carbohydrate containing O-antigen part of lipopolysaccharide in the Gram-negative cell wall. After binding to O-antigen repeating units, the enzymatic activity of tailspike proteins leads to cleavage of the carbohydrate chains, which enables the bacteriophage to approach the bacterial surface for DNA injection. Tailspike proteins thereby exhibit a relatively low affinity to the oligosaccharide structures of O-antigen due to the necessary binding, cleavage and release cycle, compared for example to antibodies. In this work it was aimed to study the determinants that influence carbohydrate affinity in the extended TSP binding grooves. This is a prerequisite to design a high-affinity tailspike protein based bacteria sensor.
For this purpose the tailspike protein of the bacteriophage Sf6 (Sf6 TSP) was used, which specifically binds Shigella flexneri Y O-antigen with two tetrasaccharide repeating units at the intersubunits of the trimeric β-helix protein. The Sf6 TSP endorhamnosidase cleaves the O-antigen, which leads to an octasaccharide as the main product. The binding affinity of inactive Sf6 TSP towards polysaccharide was characterized by fluorescence titration experiments and surface plasmon resonance (SPR).
Moreover, cysteine mutations were introduced into the Sf6 TSP binding site for the covalent thiol-coupling of an environment-sensitive fluorescent label to obtain a sensor for Shigella flexneri Y based on TSP-O-antigen recognition. This sensor showed a more than 100 % amplitude increase of a visible light fluorescence upon the binding of a polysaccharide test solution. Improvements of the TSP sensor can be achieved by increasing the tailspike affinity towards the O-antigen. Therefore molecular dynamics simulations evaluating ligand flexibility, hydrogen bond occupancies and water network distributions were used for affinity prediction on the available cysteine mutants of Sf6 TSP. The binding affinities were experimentally analyzed by SPR. This combined computational and experimental set-up for the design of a high-affinity carbohydrate binding protein could successfully distinguish strongly increased and decreased affinities of single amino acid mutants.
A thermodynamically and structurally well characterized set of another tailspike protein HK620 TSP with high-affinity mutants was used to evaluate the influence of water molecules on binding affinity. The free enthalpy of HK620 TSP oligosaccharide complex formation thereby either derived from the replacement of a conserved water molecule or by immobilization of two water molecules upon ligand binding. Furthermore, the enthalpic and entropic contributions of water molecules in a hydrophobic binding pocket could be assigned by free energy calculations. The findings in this work can be helpful for the improvement of carbohydrate docking and carbohydrate binding protein engineering algorithms in the future.
Purpose: Comparison of the dissociation kinetics of rapid-acting insulins lispro, aspart, glulisine and human insulin under physiologically relevant conditions.
Methods: Dissociation kinetics after dilution were monitored directly in terms of the average molecular mass using combined static and dynamic light scattering. Changes in tertiary structure were detected by near-UV circular dichroism.
Results: Glulisine forms compact hexamers in formulation even in the absence of Zn2+. Upon severe dilution, these rapidly dissociate into monomers in less than 10 s. In contrast, in formulations of lispro and aspart, the presence of Zn2+ and phenolic compounds is essential for formation of compact R6 hexamers. These slowly dissociate in times ranging from seconds to one hour depending on the concentration of phenolic additives. The disadvantage of the long dissociation times of lispro and aspart can be diminished by a rapid depletion of the concentration of phenolic additives independent of the insulin dilution. This is especially important in conditions similar to those after subcutaneous injection, where only minor dilution of the insulins occurs.
Conclusion: Knowledge of the diverging dissociation mechanisms of lispro and aspart compared to glulisine will be helpful for optimizing formulation conditions of rapid-acting insulins.
Mosses are a major component of the arctic vegetation, particularly in wetlands. We present C / N atomic ratio, delta C-13 and delta N-15 data of 400 brown-moss samples belonging to 10 species that were collected along hydrological gradients within polygonal mires located on the southern Taymyr Peninsula and the Lena River delta in northern Siberia. Additionally, n-alkane patterns of six of these species (16 samples) were investigated. The aim of the study is to see whether the inter-and intraspecific differences in C / N, isotopic compositions and n-alkanes are indicative of habitat, particularly with respect to water level. Overall, we find high variability in all investigated parameters for two different moisture-related groups of moss species. The C / N ratios range between 11 and 53 (median: 32) and show large variations at the intraspecific level. However, species preferring a dry habitat (xero-mesophilic mosses) show higher C / N ratios than those preferring a wet habitat (meso-hygrophilic mosses). The delta C-13 values range between 37.0 and 22.5% (median D 27.8 %). The delta N-15 values range between 6.6 and C 1.7%(median D 2.2 %). We find differences in delta C-13 and delta N-15 compositions between both habitat types. For some species of the meso-hygrophilic group, we suggest that a relationship between the individ-ual habitat water level and isotopic composition can be inferred as a function of microbial symbiosis. The n-alkane distribution also shows differences primarily between xeromesophilic and meso-hygrophilic mosses, i. e. having a dominance of n-alkanes with long (n-C29, n-C31 /and intermediate (n-C25 /chain lengths, respectively. Overall, our results reveal that C / N ratios, isotopic signals and n-alkanes of studied brown-moss taxa from polygonal wetlands are characteristic of their habitat.
Rehabilitation after autologous chondrocyte implantation for isolated cartilage defects of the knee
(2017)
Autologous chondrocyte implantation for treatment of isolated cartilage defects of the knee has become well established. Although various publications report technical modifications, clinical results, and cell-related issues, little is known about appropriate and optimal rehabilitation after autologous chondrocyte implantation. This article reviews the literature on rehabilitation after autologous chondrocyte implantation and presents a rehabilitation protocol that has been developed considering the best available evidence and has been successfully used for several years in a large number of patients who underwent autologous chondrocyte implantation for cartilage defects of the knee.
Background
Back pain patients (BPP) show delayed muscle onset, increased co-contractions, and variability as response to quasi-static sudden trunk loading in comparison to healthy controls (H). However, it is unclear whether these results can validly be transferred to suddenly applied walking perturbations, an automated but more functional and complex movement pattern. There is an evident need to develop research-based strategies for the rehabilitation of back pain. Therefore, the investigation of differences in trunk stability between H and BPP in functional movements is of primary interest in order to define suitable intervention regimes. The purpose of this study was to analyse neuromuscular reflex activity as well as three-dimensional trunk kinematics between H and BPP during walking perturbations.
Methods
Eighty H (31m/49f;29±9yrs;174±10cm;71±13kg) and 14 BPP (6m/8f;30±8yrs;171±10cm;67±14kg) walked (1m/s) on a split-belt treadmill while 15 right-sided perturbations (belt decelerating, 40m/s2, 50ms duration; 200ms after heel contact) were randomly applied. Trunk muscle activity was assessed using a 12-lead EMG set-up. Trunk kinematics were measured using a 3-segment-model consisting of 12 markers (upper thoracic (UTA), lower thoracic (LTA), lumbar area (LA)). EMG-RMS ([%],0-200ms after perturbation) was calculated and normalized to the RMS of unperturbed gait. Latency (TON;ms) and time to maximum activity (TMAX;ms) were analysed. Total motion amplitude (ROM;[°]) and mean angle (Amean;[°]) for extension-flexion, lateral flexion and rotation were calculated (whole stride cycle; 0-200ms after perturbation) for each of the three segments during unperturbed and perturbed gait. For ROM only, perturbed was normalized to unperturbed step [%] for the whole stride as well as the 200ms after perturbation. Data were analysed descriptively followed by a student´s t-test to account for group differences. Co-contraction was analyzed between ventral and dorsal muscles (V:R) as well as side right:side left ratio (Sright:Sleft). The coefficient of variation (CV;%) was calculated (EMG-RMS;ROM) to evaluate variability between the 15 perturbations for all groups. With respect to unequal distribution of participants to groups, an additional matched-group analysis was conducted. Fourteen healthy controls out of group H were sex-, age- and anthropometrically matched (group Hmatched) to the BPP.
Results
No group differences were observed for EMG-RMS or CV analysis (EMG/ROM) (p>0.025). Co-contraction analysis revealed no differences for V:R and Srigth:Sleft between the groups (p>0.025). BPP showed an increased TON and TMAX, being significant for Mm. rectus abdominus (p = 0.019) and erector spinae T9/L3 (p = 0.005/p = 0.015). ROM analysis over the unperturbed stride cycle revealed no differences between groups (p>0.025). Normalization of perturbed to unperturbed step lead to significant differences for the lumbar segment (LA) in lateral flexion with BPP showing higher normalized ROM compared to Hmatched (p = 0.02). BPP showed a significant higher flexed posture (UTA (p = 0.02); LTA (p = 0.004)) during normal walking (Amean). Trunk posture (Amean) during perturbation showed higher trunk extension values in LTA segments for H/Hmatched compared to BPP (p = 0.003). Matched group (BPP vs. Hmatched) analysis did not show any systematic changes of all results between groups.
Conclusion
BPP present impaired muscle response times and trunk posture, especially in the sagittal and transversal planes, compared to H. This could indicate reduced trunk stability and higher loading during gait perturbations.
Background
Foot orthoses are usually assumed to be effective by optimizing mechanically dynamic rearfoot configuration. However, the effect from a foot orthosis on kinematics that has been demonstrated scientifically has only been marginal. The aim of this study was to examine the effect of different heights in medial arch-supported foot orthoses on rear foot motion during gait.
Methods
Nineteen asymptomatic runners (36±11years, 180±5cm, 79±10kg; 41±22km/week) participated in the study. Trials were recorded at 3.1 mph (5 km/h) on a treadmill. Athletes walked barefoot and with 4 different not customized medial arch-supported foot orthoses of various arch heights (N:0 mm, M:30 mm, H:35 mm, E:40mm). Six infrared cameras and the `Oxford Foot Model´ were used to capture motion. The average stride in each condition was calculated from 50 gait cycles per condition. Eversion excursion and internal tibia rotation were analyzed. Descriptive statistics included calculating the mean ± SD and 95% CIs. Group differences by condition were analyzed by one factor (foot orthoses) repeated measures ANOVA (α = 0.05).
Results
Eversion excursion revealed the lowest values for N and highest for H (B:4.6°±2.2°; 95% CI [3.1;6.2]/N:4.0°±1.7°; [2.9;5.2]/M:5.2°±2.6°; [3.6;6.8]/H:6.2°±3.3°; [4.0;8.5]/E:5.1°±3.5°; [2.8;7.5]) (p>0.05). Range of internal tibia rotation was lowest with orthosis H and highest with E (B:13.3°±3.2°; 95% CI [11.0;15.6]/N:14.5°±7.2°; [9.2;19.6]/M:13.8°±5.0°; [10.8;16.8]/H:12.3°±4.3°; [9.0;15.6]/E:14.9°±5.0°; [11.5;18.3]) (p>0.05). Differences between conditions were small and the intrasubject variation high.
Conclusion
Our results indicate that different arch support heights have no systematic effect on eversion excursion or the range of internal tibia rotation and therefore might not exert a crucial influence on rear foot alignment during gait.
Background
Much of the organismal variation we observe in nature is due to differences in organ size. The observation that even closely related species can show large, stably inherited differences in organ size indicates a strong genetic component to the control of organ size. Despite recent progress in identifying factors controlling organ growth in plants, our overall understanding of this process remains limited, partly because the individual factors have not yet been connected into larger regulatory pathways or networks. To begin addressing this aim, we have studied the upstream regulation of expression of BIG BROTHER (BB), a central growth-control gene in Arabidopsis thaliana that prevents overgrowth of organs. Final organ size and BB expression levels are tightly correlated, implying the need for precise control of its expression. BB expression mirrors proliferative activity, yet the gene functions to limit proliferation, suggesting that it acts in an incoherent feedforward loop downstream of growth activators to prevent over-proliferation.
Results
To investigate the upstream regulation of BB we combined a promoter deletion analysis with a phylogenetic footprinting approach. We were able to narrow down important, highly conserved, cis-regulatory elements within the BB promoter. Promoter sequences of other Brassicaceae species were able to partially complement the A. thaliana bb-1 mutant, suggesting that at least within the Brassicaceae family the regulatory pathways are conserved.
Conclusions
This work underlines the complexity involved in precise quantitative control of gene expression and lays the foundation for identifying important upstream regulators that determine BB expression levels and thus final organ size.
Despite the ongoing progress in nanotechnology and its applications, the development of strategies for connecting nano-scale systems to micro- or macroscale elements is hampered by the lack of structural components that have both, nano- and macroscale dimensions. The production of nano-scale wires with macroscale length is one of the most interesting challenges here. There are a lot of strategies to fabricate long nanoscopic stripes made of metals, polymers or ceramics but none is suitable for mass production of ordered and dense arrangements of wires at large numbers. In this paper, we report on a technique for producing arrays of ordered, flexible and free-standing polymer nano-wires filled with different types of nano-particles. The process utilizes the strong response of photosensitive polymer brushes to irradiation with UV-interference patterns, resulting in a substantial mass redistribution of the polymer material along with local rupturing of polymer chains. The chains can wind up in wires of nano-scale thickness and a length of up to several centimeters. When dispersing nano-particles within the film, the final arrangement is similar to a core-shell geometry with mainly nano-particles found in the core region and the polymer forming a dielectric jacket.
The aim was to analyze the risk of hip fracture in German primary care patients with dementia. This study included patients aged 65-90 from 1072 primary care practices who were first diagnosed with dementia between 2010 and 2013. Controls were matched (1:1) to cases for age, sex, and type of health insurance. The primary outcome was the diagnosis of hip fracture during the three-year follow-up period. A total of 53,156 dementia patients and 53,156 controls were included. A total of 5.3% of patients and 0.7% of controls displayed hip fracture after three years. Hip fracture occurred more frequently in dementia subjects living in nursing homes than in those living at home (9.2% versus 4.3%). Dementia, residence in nursing homes, and osteoporosis were risk factors for fracture development. Antidementia, antipsychotic, and antidepressant drugs generally had no significant impact on hip fracture risk when prescribed for less than six months. Dementia increased hip fracture risk in German primary care practices.
Age-related decline in executive functions and postural control due to degenerative processes in the central nervous system have been related to increased fall-risk in old age. Many studies have shown cognitive-postural dual-task interference in old adults, but research on the role of specific executive functions in this context has just begun. In this study, we addressed the question whether postural control is impaired depending on the coordination of concurrent response-selection processes related to the compatibility of input and output modality mappings as compared to impairments related to working-memory load in the comparison of cognitive dual and single tasks. Specifically, we measured total center of pressure (CoP) displacements in healthy female participants aged 19–30 and 66–84 years while they performed different versions of a spatial one-back working memory task during semi-tandem stance on an unstable surface (i.e., balance pad) while standing on a force plate. The specific working-memory tasks comprised: (i) modality compatible single tasks (i.e., visual-manual or auditory-vocal tasks), (ii) modality compatible dual tasks (i.e., visual-manual and auditory-vocal tasks), (iii) modality incompatible single tasks (i.e., visual-vocal or auditory-manual tasks), and (iv) modality incompatible dual tasks (i.e., visual-vocal and auditory-manual tasks). In addition, participants performed the same tasks while sitting. As expected from previous research, old adults showed generally impaired performance under high working-memory load (i.e., dual vs. single one-back task). In addition, modality compatibility affected one-back performance in dual-task but not in single-task conditions with strikingly pronounced impairments in old adults. Notably, the modality incompatible dual task also resulted in a selective increase in total CoP displacements compared to the modality compatible dual task in the old but not in the young participants. These results suggest that in addition to effects of working-memory load, processes related to simultaneously overcoming special linkages between input- and output modalities interfere with postural control in old but not in young female adults. Our preliminary data provide further evidence for the involvement of cognitive control processes in postural tasks.
Working memory (WM) performance declines with age. However, several studies have shown that WM training may lead to performance increases not only in the trained task, but also in untrained cognitive transfer tasks. It has been suggested that transfer effects occur if training task and transfer task share specific processing components that are supposedly processed in the same brain areas. In the current study, we investigated whether single-task WM training and training-related alterations in neural activity might support performance in a dual-task setting, thus assessing transfer effects to higher-order control processes in the context of dual-task coordination. A sample of older adults (age 60–72) was assigned to either a training or control group. The training group participated in 12 sessions of an adaptive n-back training. At pre and post-measurement, a multimodal dual-task was performed in all participants to assess transfer effects. This task consisted of two simultaneous delayed match to sample WM tasks using two different stimulus modalities (visual and auditory) that were performed either in isolation (single-task) or in conjunction (dual-task). A subgroup also participated in functional magnetic resonance imaging (fMRI) during the performance of the n-back task before and after training. While no transfer to single-task performance was found, dual-task costs in both the visual modality (p < 0.05) and the auditory modality (p < 0.05) decreased at post-measurement in the training but not in the control group. In the fMRI subgroup of the training participants, neural activity changes in left dorsolateral prefrontal cortex (DLPFC) during one-back predicted post-training auditory dual-task costs, while neural activity changes in right DLPFC during three-back predicted visual dual-task costs. Results might indicate an improvement in central executive processing that could facilitate both WM and dual-task coordination.
This dissertation explores whether the processing of ellipsis is affected by changes in the complexity of the antecedent, either due to added linguistic material or to the presence of a temporary ambiguity. Murphy (1985) hypothesized that ellipsis is resolved via a string copying procedure when the antecedent is within the same sentence, and that copying longer strings takes more time. Such an account also implies that the antecedent is copied without its structure, which in turn implies that recomputing its syntax and semantics may be necessary at the ellipsis gap. Alternatively, several accounts predict null effects of antecedent complexity, as well as no reparsing. These either involve a structure copying mechanism that is cost-free and whose finishing time is thus independent of the form of the antecedent (Frazier & Clifton, 2001), treat ellipsis as a pointer into content-addressable memory with direct access (Martin & McElree, 2008, 2009), or assume that one structure is ‘shared’ between antecedent and gap (Frazier & Clifton, 2005).
In a self-paced reading study on German sluicing, temporarily ambiguous garden-path clauses were used as antecedents, but no evidence of reparsing in the form of a slowdown at the ellipsis site was found. Instead, results suggest that antecedents which had been reanalyzed from an initially incorrect structure were easier to retrieve at the gap. This finding that can be explained within the framework of cue-based retrieval parsing (Lewis & Vasishth, 2005), where additional syntactic operations on a structure yield memory reactivation effects.
Two further self-paced reading studies on German bare argument ellipsis and English verb phrase ellipsis investigated if adding linguistic content to the antecedent would increase processing times for the ellipsis, and whether insufficiently demanding comprehension tasks may have been responsible for earlier null results (Frazier & Clifton, 2000; Martin & McElree, 2008). It has also been suggested that increased antecedent complexity should shorten rather than lengthen retrieval times by providing more unique memory features (Hofmeister, 2011). Both experiments failed to yield reliable evidence that antecedent complexity affects ellipsis processing times in either direction, irrespectively of task demands.
Finally, two eye-tracking studies probed more deeply into the proposed reactivation-induced speedup found in the first experiment. The first study used three different kinds of French garden-path sentences as antecedents, with two of them failing to yield evidence for reactivation. Moreover, the third sentence type showed evidence suggesting that having failed to assign a structure to the antecedent leads to a slowdown at the ellipsis site, as well as regressions towards the ambiguous part of the sentence. The second eye-tracking study used the same materials as the initial self-paced reading study on German, with results showing a pattern similar to the one originally observed, with some notable differences.
Overall, the experimental results are compatible with the view that adding linguistic material to the antecedent has no or very little effect on the ease with which ellipsis is resolved, which is consistent with the predictions of cost-free copying, pointer-based approaches and structure sharing. Additionally, effects of the antecedent’s parsing history on ellipsis processing may be due to reactivation, the availability of multiple representations in memory, or complete failure to retrieve a matching target.