Long-term inhibition of return of attention

During search of the environment, the inhibition of the return (IOR) of attention to already-examined information ensures that the target will ultimately be detected. Until now, inhibition was assumed to support search of information during one processing episode. However, in some situations search may have to be completed long after it was begun. We therefore propose that inhibition can be associated with an episode encoded into memory such that later retrieval reinstates inhibitory processing and encourages examination of new information. In two experiments in which attention was drawn to face stimuli with an exogenous cue, we demonstrated for the first time the existence of long-term IOR. Interestingly, this was the case only for faces in the left visual field, perhaps because more efficient processing of faces in the right hemisphere than the left hemisphere results in richer, more retrievable memory representations.

Paradox lost? Exploring the role of alpha oscillations during externally vs. internally directed attention and the implications for idling and inhibition hypotheses

Although slow waves of the electroencephalogram (EEG) have been associated with attentional processes, the functional significance of the alpha component in the EEG (8.1–12 Hz) remains uncertain. Conventionally, synchronisation in the alpha frequency range is taken to be a marker of cognitive inactivity, i.e. ‘cortical idling’. However, it has been suggested that alpha may index the active inhibition of sensory information during internally directed attentional tasks such as mental imagery. More recently, this idea has been amended to encompass the notion of alpha synchronisation as a means of inhibition of non-task relevant cortical areas irrespective of the direction of attention. Here we test the adequacy of the one idling and two inhibition hypotheses about alpha. In two experiments we investigated the relation between alpha and internally vs. externally directed attention using mental imagery vs. sensory-intake paradigms. Results from both experiments showed a clear relationship between alpha and both attentional factors and increased task demands. At various scalp sites alpha amplitudes were greater during internally directed attention and during increased load, results incompatible with alpha reflecting cortical idling and more in keeping with suggestions of active inhibition necessary for internally driven mental operations.

Center of shelf attention:understanding the role of visual attention on product choice

Two eye-tracking studies and an offline experiment explored the effect of central shelf location on attention and choice. Investigation of the attention process revealed that the central gaze cascade effect, progressively increasing attention focused on the central option predicted choice.

To which extent can attention and/or modulation explains deficits in dyslexia?

This thesis investigates the visual deficits associated with developmental dyslexia, particularly that of visual attention. Visual attention has previously been investigated in a wide array of behavioural and psychophysical (amongst others) studies but not many have produced consistent findings. Attention processes are believed to play an integral part in depicting the overall "extent" of reading deficits in dyslexia, so it was of paramount importance to aim at such attention mechanisms in this research. The experiments in this thesis focused on signal enhancement and noise (distractor) exclusion. Given the flexibility of the visual search paradigms employed in this research, factors such as visual crowding and attention distribution was also investigated. The experiments systematically manipulated noise (by increasing distractor count, i.e. set-size), crowding (varying the spacing between distractors), attention allocation (use of peripheral cues to direct attention), and attention distribution (influence of one visual field over the other), all of which were tied to a critical factor, the "location/spatial/decisional uncertainty". Adults with dyslexia were: (i) able to modulate attention appropriately using peripheral pre-cues, (ii) severely affected by crowding, and (iii) unable to counteract increased set-sizes when post or un-cued, the latter signifying poor distractor (noise) suppression. By controlling for location uncertainty, the findings confirmed that adults with dyslexia were yet again affected by crowding and set-size, in addition to an asymmetric attention distribution. Confounding effects of ADHD symptoms did not explain a significant independent variance in performance, suggesting that the difficulty shown by adult dyslexics were not accounted for by co-morbid ADHD. Furthermore, the effects of crowding, set-size and asymmetric attention correlated significantly with literacy, but not ADHD measures. It is believed that a more diffuse and an asymmetric attention system (in dyslexia) to be the limiting factor concerning noise exclusion and attention distribution. The findings from this thesis add to the current understanding of the potential role of deficits in visual attention in dyslexia and in the literacy difficulties experienced by this population.

Adults with dyslexia can use cues to orient and constrain attention but have a smaller and weaker attention spotlight

We report results from two experiments assessing distribution of attention and cue use in adults with dyslexia (AwD) and in a group of typically reading controls. Experiment 1 showed normal effects of cueing in AwD, with faster responses when probes were presented within a cued area and normal effects of eccentricity and stimulus onset asynchrony (SOA). In addition, AwD showed stronger benefits of a longer SOA when they had to move attention farther, and stronger effects of inclusion on the left, suggesting that cueing is particularly important in more difficult conditions. Experiment 2 tested the use of cues in a texture detection task involving a wider range of eccentricities and a shorter SOA. In this paradigm, focused attention at the central location is actually detrimental and cueing further reduces performance. Thus, if AwD have a more distributed attention, they should show a reduced performance drop at central locations and, if they do not use cues, they should show less negative effects of cueing. In contrast, AwD showed a larger drop and a positive effect of cueing. These results are better accounted for by a smaller and weaker spotlight of attention. Performance does not decrease at central locations because the attentional spotlight is already deployed with maximum intensity, which cannot be further enhanced at central locations. Instead, use of cueing helps to focus limited resources. Cues orient attention to the right area without enhancing it to the point where this is detrimental for texture detection. Implications for reading are discussed.

New approaches to North Korean politics after reunification:the search for a common Korean identity

Whilst most of the literature focusing on the Korean peninsula has concentrated on how to achieve unification through confidence-building measures, dialogues, negotiation and diplomacy, little attention has been paid to how a unified Korean identity, a core component of any potential reunification scheme could develop and be sustained. The paper addresses this gap by: (1) defining what national identity is, and how Korean identities have been formed, (2) outlining how both South and North Korea have understood and used the concept of national identity, (3) suggesting possible grounds on which the two Koreas could build a new, common national identity. © 2014 The Regents of the University of California.

Poly(glycerol adipate-co-ω-pentadecalactone) spray-dried microparticles as sustained release carriers for pulmonary delivery

Purpose: The aim of this work was to optimize biodegradable polyester poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL, microparticles as sustained release (SR) carriers for pulmonary drug delivery. Methods: Microparticles were produced by spray drying directly from double emulsion with and without dispersibility enhancers (L-arginine and L-leucine) (0.5-1.5%w/w) using sodium fluorescein (SF) as a model hydrophilic drug. Results: Spray-dried microparticles without dispersibility enhancers exhibited aggregated powders leading to low fine particle fraction (%FPF) (28.79±3.24), fine particle dose (FPD) (14.42±1.57 μg), with a mass median aerodynamic diameter (MMAD) 2.86±0.24 μm. However, L-leucine was significantly superior in enhancing the aerosolization performance ( L-arginine:%FPF 27.61±4.49-26.57±1.85; FPD 12.40±0.99-19.54±0.16 μg and MMAD 2.18±0.35-2. 98±0.25 μm, L-leucine:%FPF 36.90±3.6-43.38±5. 6; FPD 18.66±2.90-21.58±2.46 μg and MMAD 2.55±0.03-3. 68±0.12 μm). Incorporating L-leucine (1.5%w/w) reduced the burst release (24.04±3.87%) of SF compared to unmodified formulations (41.87±2.46%), with both undergoing a square root of time (Higuchi's pattern) dependent release. Comparing the toxicity profiles of PGA-co-PDL with L-leucine (1.5%w/w) (5 mg/ml) and poly(lactide-co-glycolide), (5 mg/ml) spray-dried microparticles in human bronchial epithelial 16HBE14o-cell lines, resulted in cell viability of 85.57±5.44 and 60.66±6.75%, respectively, after 72 h treatment. Conclusion:The above data suggest that PGA-co-PDL may be a useful polymer for preparing SR microparticle carriers, together with dispersibility enhancers, for pulmonary delivery. © Springer Science+Business Media, LLC 2011.

Sustained delivery of salbutamol and beclometasone from spray-dried double emulsions

The sustained delivery of multiple agents to the lung offers potential benefits to patients. This study explores the preparation of highly respirable dual-loaded spray-dried double emulsions. Spray-dried powders were produced from water-in-oil-in-water (w/o/w) double emulsions, containing salbutamol sulphate and/or beclometasone dipropionate in varying phases. The double emulsions contained the drug release modifier polylactide co-glycolide (PLGA 50 : 50) in the intermediate organic phase of the original micro-emulsion and low molecular weight chitosan (Mw<190 kDa: emulsion stabilizer) and leucine (aerosolization enhancer) in the tertiary aqueous phase. Following spray-drying resultant powders were physically characterized: with in vitro aerosolization performance and drug release investigated using a Multi-Stage Liquid Impinger and modified USP II dissolution apparatus, respectively. Powders generated were of a respirable size exhibiting emitted doses of over 95% and fine particle fractions of up to 60% of the total loaded dose. Sustained drug release profiles were observed during dissolution for powders containing agents in the primary aqueous and secondary organic phases of the original micro-emulsion; the burst release of agents was witnessed from the tertiary aqueous phase. The novel spray-dried emulsions from this study would be expected to deposit and display sustained release character in the lung.

The effect of disfiguring features on covert and overt attention to faces

It is well documented that facial disfigurements can generate avoidance responses in observers towards the afflicted person, yet less is known about the effect of a facial disfigurement on attention to and perception of faces. In two experiments we studied overt and covert attention to laterally presented face stimuli when these contained a unilateral disfiguring feature (a simulated portwine stain), an occluding feature, or no salient feature. In Experiment 1, observers’ eye movements were tracked while they explored laterally presented faces which they had to rate for attractiveness. Overt attention, as measured by the patterns of fixations on the face, was found to be significantly affected by the presence of a facial disfigurement or an occluder. In Experiment2, we used a covert orienting task with bilaterally presented target and distractor to measure the interference effect induced by a distractor face (disfigured, occluded, or normal) on a non facetarget discrimination task. The presence of a face increased response times to the target stimulus,but this interference was not modulated by the presence of a salient feature (disfigurement or occluder). Together, these results suggest that the presence of salient features affect overt but not the covert processing of faces.

Sustained efficacy of dapagliflozin when added to metformin in type 2 diabetes inadequately controlled by metformin monotherapy

Background and aims: The selective SGLT2 inhibitor dapagliflozin (DAPA) reduces hyperglycaemia independently of insulin secretion or action by inhibiting renal glucose reabsorption. This study (MB102014) is a randomised double-blind, placebo (PBO)-controlled trial of DAPA added to metformin (MET) in T2DM (n=546) inadequately controlled with MET alone. Previously reported short-term data at week 24 showed significant mean reductions in the primary [HbA1c] and secondary [fasting plasma glucose (FPG) and weight] endpoints with DAPA compared to PBO. Here we report efficacy and safety results at week 102 of the long-term extension. Materials and methods: Patients aged 18-77 years with HbA1c 7-10% received DAPA 2.5 mg, 5 mg, 10 mg or PBO, plus open-label MET (≥1500mg/d). Exploratory endpoints at week 102 included changes from baseline in HbA1c, FPG and weight, and were analyzed by longitudinal repeated measures analysis. Results: Overall 71.2% of patients completed 102 weeks of the study; fewer on PBO (63.5%) than on DAPA 2.5 mg, 5 mg, and 10 mg (68.3%, 73.0%, 79.8%), due mainly to more patients on PBO discontinuing for lack of efficacy. At week 102, all DAPA groups showed greater mean reductions from baseline in HbA1c, FPG and weight compared to PBO (table), effects that were similar to those observed at week 24 and maintained throughout the trial. More patients at week 102 also achieved a therapeutic response of HbA1c<7% with DAPA 2.5 mg, 5 mg, and 10 mg (20.7%, 26.4%, 31.5%) than with PBO (15.4%). Adverse events (AEs), serious AEs and AEs leading to discontinuation were balanced across all groups. Signs and symptoms suggestive of genital infection (GenInf) were reported in 11.7%, 14.6%, 12.6% (DAPA 2.5 mg, 5 mg, 10 mg) and 5.1% (PBO) of patients, with 1 discontinuation due to GenInf. Signs and symptoms suggestive of urinary tract infection (UTI) were reported in 8.0%, 8.8%, 13.3% (DAPA 2.5 mg, 5 mg, 10 mg) and 8.0% (PBO), with 1 discontinuation due to UTI. No event of pyelonephritis was reported. Conclusion: In comparison to PBO, DAPA added to MET over 102 weeks demonstrated greater and sustained improvements in glycaemic control, clinically meaningful reduction in weight, and no increased risk of hypoglycaemia in patients with T2DM inadequately controlled with MET alone.