Spatial attention in cognitive healthy ageing

In young adults, spatial attention typically manifests in a processing advantage for the left side of space (“pseudoneglect”)(Bowers & Heilman, 1980), whereas older adults tend to display no strongly lateralised bias, or a preference towards the right side of space (Benwell, Thut, Grant, & Harvey, 2014; Schmitz & Peigneux, 2011). However in addition, in recent studies, pseudoneglect has also been found to be maintained into old age (Brooks, Darling, Malvaso, & Della Sala, 2016; Brooks, Sala, & Darling, 2014; Friedrich, Hunter, & Elias, 2018). This suggests that the traditional view of an attenuated spatial asymmetry bias with increasing age may be too simplistic and that the spatial biases observed could be sensitive to a range of influences besides age. In addition, the traditionally observed shifts in spatial asymmetry in older adults have been attributed to neuroanatomical changes in the right hemisphere (with age), however as yet, there is limited evidence linking neurophysiological results to such behavioural shifts. To this end, for older adults, spatial attention research lacks systematic investigation of intra- and inter-task consistency. In the first of the four experiments of this thesis, I built on an earlier study which investigated young adults (Learmonth, Gallagher, Gibson, Thut, & Harvey, 2015, see 2018), and addressed this issue by investigating the magnitude and direction of spatial asymmetry in older adults aged between 60 to 86 years in five commonly used spatial tasks (line bisection, landmark, grey and grating scales and lateralised visual detection). I also compared the obtained spatial biases to a driving task. Results confirmed a stable retest reliability of all spatial tasks across two testing days in older adults. The line bisection and greyscales tasks elicited significant left spatial biases, in accordance with pseudoneglect, while the other tasks showed no significant biases to either side of space. Interestingly, in the driving task a right bias emerged for older adult and was stable across testing sessions. Yet, it failed to correlate with the other spatial measures. In comparison to the young adults’ sample from Learmonth et al. (2015, 2018), only the landmark task was age sensitive. However, none of the task showed significant inter task correlations. This replicates the findings of Learmonth et al. (2015, 2018) for an older age group. So in view of my findings of no significant inter-task correlations, as well as the inconsistent directions of the observed spatial biases for the older adults, I present supporting evidence that pseudoneglect is a multi-component phenomenon and highly task sensitive. Each task may reflect a distinct neural mechanism, likely to be impacted differently by age or other non- spatial modulators. In fact, the influence of other non -spatial modulators on spatial attention was the central topic of the other three experiments presented in Chapters 3 and 4. I employed a dual task paradigm (Chapters 3 and 4) and electroencephalography (EEG) (Chapter 4 only) to investigate behaviourally as well as neurophysiologically if an increase in attentional load has a reducing effect on spatial asymmetry and whether this would be more pronounced with old age. Interestingly, for the last experiment including EEG (Chapter 4) in particular, results showed that although older adults perform similarly well to young adults on a behavioural level, changes are visible on a neuronal level. Specifically, I found that older adults showed an age related reduction in the right hemisphere, for right lateralized targets at the early stages of stimuli processing, indexed by the N1 component, which was absent in young adults. Moreover, the results suggest that older adults used additional neuronal recruitment in the later stages of stimuli processing (P3), to compensate for increased task difficulty and increased resource allocation, likely improving the behavioural results of the older adults so that they were similar to young adults. The work presented in this thesis thus suggest that ageing per se does not result in an attenuated spatial asymmetry (that would be seen as equal to a decline in spatial attention ability). Instead I would argue that, independently of age, a set of underlying non spatial factors (such as load for example) influence the magnitude and direction of spatial asymmetry. In addition, additional neuronal recruitment and intrinsic mechanisms are used in older adults to compensate for possible deficits and this results in maintained performance in this age group

Development and Characterization of Hot-melt Extruded Biodegradable Poly(lactide-co-glycolide) Implants

The influence of three different extrusion methods as well as extrusion temperature and screw speed on drug release from PLGA-based implants were investigated. Comparing biodegradable implants prepared with the Haake MiniLab under extrusion parameters of 85 °C/ 30 rpm and 105 °C/ 120 rpm, an increase in processing temperature and screw speed resulted in extrudates of uneven surface with a so-called “sharkskin effect”. The increased surface area led to a higher burst release of drug and ultimately resulted in a shorter release phase due to an increased PLGA-degradation. Biodegradable implants prepared with the ThreeTec ZE9 at a similar extrusion temperature of 105 °C/ 100 rpm had a lower burst and an even surface morphology. Due to the absence of mixing elements in ram-extrusion processes, the syringe-die method had a poor drug incorporation and thus a high burst release. Nevertheless, drug release phases from implants prepared with the syringe-die method were comparable to those of implants prepared with the ThreeTec ZE9, making it an attractive tool for formulation screening due to low processing times, small amounts of formulation blends needed, and the comparability to implants prepared with the ThreeTec ZE9. Therefore, the syringe-die method as a screening tool for hot-melt extruded implants was utilized. For the establishment of an applicability map the influence on dexamethasone release from PLGA-based implants was investigated in terms of PLGA end groups, PLGA lactic acid to glycolic acid (L:G) ratio, polymer’s average molecular weight, and drug loading. Dexamethasone release from implants follows the typical drug release curve of PLGA-based drug delivery systems (DDS). A small burst release from excess drug on the implant’s surface, followed by a lag phase and the release phase, which is designated to the start of polymer degradation. Lag phases of dexamethasone release from implants prepared with 502H, 503H, and 502 were independent of the drug loading, while lag phases for dexamethasone release from 752S implants were influenced by drug loading. The release time after the lag phase was shorter for 752S implants containing higher drug loadings. Plotting the release phase over the lag phase, dexamethasone release was visualized in an applicability map. This applicability map was successfully utilized to develop a biodegradable dexamethasone implant with a desired release consisting of a lag phase of maximum 7 days and a release phase of approximately 14 days. This could be achieved by the preparation of a dexamethasone implant with 50%/ 60% drug loading and a PLGA mixture of 502H/ 502 in a 3:1 ratio. Next, a formulation of a biodegradable implant for the application of brimonidine base was developed. The requirement for the implant was that it released the active substance to the same extend as dexamethasone was released from the already developed implant in order to possibly enable a simultaneous injection. Brimonidine release from biodegradable PLGA implants was investigated in terms of PLGA end groups, polymer molecular weight, L:G ratio, and drug loading. Release data was again collected in an applicability map, containing lag phase plotted against release phase, to develop the desired release implant as previously with dexamethasone implants. However, a biodegradable implant was successfully developed that released brimonidine from PLGA implants with a 1:1 mixture of 752S/ 503H with a 3-day longer lag phase and almost the same release time compared to the developed dexamethasone implant. Combination implants with both drugs released brimonidine within several days, but dexamethasone release was incomplete for all formulations. Since simultaneous release from single dexamethasone and brimonidine implants was complete for both drugs, a drug – drug or drug – drug – PLGA interaction was assumed but not further investigated. Nevertheless, a combination implant containing both drugs could be possible using alternative preparation methods like co-extrusion. In order to achieve a reliable release test method to obtain drug release curves from biodegradable implants after a short time period, an accelerated release test method was established by investigating the influence of temperature and pH of 106 the release medium on dexamethasone release from PLGA implants. The change of the release medium from aqueous sodium chloride (0.9%, saline) to phosphate buffered saline pH 2 (PBS, USP) did not accelerate PLGA degradation and thus dexamethasone release from the implants. The use of PBS pH 12 (USP) provides an accelerated PLGA degradation through basic catalyzed hydrolysis. PLGA implants degraded completely at temperatures of 37 °C, 45 °C, and 65 °C. Unfortunately, lag phases of dexamethasone release could not be observed at pH 12 due to the rapid PLGA degradation. This makes it difficult to compare different formulations or estimate drug releases under standard release test conditions. The best conditions for accelerated release tests of dexamethasone implants herein were at an elevated temperature of 45 °C in the standard release medium, saline. By increasing the temperature at release tests, dexamethasone release from PLGA implants took only half the time of drug release at 37 °C while still be able to observe differences between the formulations. Dexamethasone release from 502H/ 502 implants was investigated in terms of implant sterilization by gamma irradiation and storage time at room temperature in a silica gel desiccator. The storage time of 2 years for implants prepared with the ThreeTec ZE9 resulted in a slight dexamethasone release during the lag phase but was declared as acceptable since the drug release was still similar to those of implants directly after HME. Dexamethasone release from implants prepared with the Haake MiniLab Compounder significantly changed after 3 years of storage. Although the typical sigmoidal release curve was still seen, the burst release increased, dexamethasone was released during the lag phase, and finally the release phase was decreased. Overall, a 2-years storage of gamma irradiated, PLGA-based dexamethasone implants was acceptable when it comes to drug release. Ultimately, the mechanical properties of biodegradable PLGA implants were investigated in terms of drug loading, molecular weight of polymer matrix, implant dimensions such as length and diameter and moisture content. It was possible to measure and characterize the mechanical properties of biodegradable PLGA implants with a texture analyzer in terms of drug loading, polymer molecular weight, implant dimensions and moisture content by implementing an easy-to-use three-point bending test method. Especially peak forces, but also elongations, and AUC are sufficient parameters to describe differences in formulation properties while the slope of the curves have no beneficial correlations in terms of molecular weight and length of PLGA implants. Without the necessity of a complex method setup or converting measured parameters into tensile strengths, this method could be a simple alternative for the quality control of biodegradable implant formulations

Right-lateralised lane keeping in young and older British drivers

Young adults demonstrate a small, but consistent, asymmetry of spatial attention favouring the left side of space (“pseudoneglect”) in laboratory-based tests of perception. Conversely, in more naturalistic environments, behavioural errors towards the right side of space are often observed. In the older population, spatial attention asymmetries are generally diminished, or even reversed to favour the right side of space, but much of this evidence has been gained from lab-based and/or psychophysical testing. In this study we assessed whether spatial biases can be elicited during a simulated driving task, and secondly whether these biases also shift with age, in line with standard lab-based measures. Data from 77 right-handed adults with full UK driving licences (i.e. prior experience of left-lane driving) were analysed: 38 young (mean age = 21.53) and 39 older adults (mean age = 70.38). Each participant undertook 3 tests of visuospatial attention: the landmark task, line bisection task, and a simulated lane-keeping task. We found leftward biases in young adults for the landmark and line bisection tasks, indicative of pseudoneglect, and a mean lane position towards the right of centre. In young adults the leftward landmark task biases were negatively correlated with rightward lane-keeping biases, hinting that a common property of the spatial attention networks may have influenced both tasks. As predicted, older adults showed no group-level spatial asymmetry on the landmark nor the line bisection task, but they maintained a mean rightward lane position, similar to young adults. The 3 tasks were not inter-correlated in the older group. These results suggest that spatial biases in older adults may be elicited more effectively in experiments involving complex behaviour rather than abstract, lab-based measures. More broadly, these results confirm that lateral biases of spatial attention are linked to driving behaviour, and this could prove informative in the development of future vehicle safety and driving technology

Das «Prohemium longum» des Erfurter Kartaeuserkatalogs aus der Zeit um 1475

Als herausragendes Beispiel mittelalterlicher Bibliothekskataloge gilt der um 1475 angelegte Katalog der Erfurter Kartause. Für ihn entstand zeitgleich ein einführendes Prohemium longum. Das Prohemium longum ist ein wichtiger Text geistlicher Literatur und erweist sich als bedeutender Beitrag zum Verständnis kartäusischer Spiritualität am Ausgang des Mittelalters. Die vorliegende Arbeit liefert die erstmalige und vollständige Edition seines lateinischen Texts. Ergänzt wird diese mit Untersuchungen zu Fragen des Textverständnisses: Was weiss man über den Verfasser? Mit welcher Intention schrieb er? Ein Kapitel widmet sich der Kompilationsmethode, mit der das Prohemium verfasst wurde, ein weiteres der Darstellungsweise. Schliesslich gehen drei umfangreiche Abschnitte zentralen Begriffen des Texts und deren zeitgenössischer Bewertung nach: ignorancia, theologia mistica und lectio et studium

Dye-sensitized CdSe quantum dot hybrid materials: A new approach for optical patterning

In this work, CdSe based quantum dots (QD) are functionalized with β tetraaminophthalocyanine dye molecules to create a functional organic-inorganic semiconductor hybrid material. This process is optimized to achieve a solution-processable material, allowing for the controlled preparation of highly homogenous QD films. The dual nature of the material leads to two individually addressable optical resonances, which are exploited in an optical read/ optical write process, creating complex optical patterns. During this process, a positive and negative fluorescence contrast are created depending on the employed excitation wavelength. This is enabled by a fluorescence enhancement of the quantum dot under excitation, in conjunction with a fluorescence bleaching of the organic dye under ambient excitation conditions. The result of the patterning process is strongly dependent on the excitation wavelength used during writing and read out of the pattern, allowing for the use of both positive and negative fluorescence contrast simultaneously depending on the wavelength. Further investigations reveal that the presence of the organic dye not only enables negative optical patterning, but also enhances the contrast during positive patterning. We show a new approach to functionalize inorganic semiconductor QDs with functional organic molecules and highlight the possibilities arising from this combination

„Wie die Zinnsoldaten“: Altbestandspflege durch Magazinverdichtung in der UB Leipzig

Die UB Leipzig verstärkt mit einer mehrere Monate dauernden Magazinumstellung den Bestandsschutz. Sie hat in den vergangenen Jahren die Bücher, die vor 1600 erschienen sind, in ein Sondersammlungsmagazin umgestellt. Die danach erschienenen Bücher (bis 1940) werden in den nächsten Monaten in sachlichen Gruppen zusammengefasst. Die Kapselschriften werden in neue, säurefreie Kartons gelagert

Der ‚gefrorene Augenblick‘ darf nicht vergehen: Die Restaurierung seltener Daguerreotypien der Universitätsbibliothek Leipzig

Als die Fotografie noch in der Wiege lag, wurde von dem französischen Theatermaler Louis Jaques Mandé Daguerre (1787 –1851) die Daguerreotypie erfunden. (Da das Fachwort „Daguerreotypie“ ein Zungenbrecher ist, spricht man in Insiderkreisen kurz von „Dago“.) Seit der Erfindung 1839 war ihr ein steiler Aufstieg mit kurzer Blüte um die Mitte des Jahrhunderts bestimmt. Neben Paris wurde schon bald Berlin ein Zentrum der bestaunten und umjubelten ersten fotografischen Technik. Aber auch Leipzig gehört zu den wichtigen Orten der frühen Fotografie in Deutschland