Acute and long-term effects of metformin on the function and insulin secretory responsiveness of clonal β-cells

Functional effects of acute and prolonged (48 h) exposure to the biguanide drug metformin were examined in the clonal pancreatic ß-cell line, BRIN-BD11. Effects of metformin on prolonged exposure to excessive increased concentrations of glucose and palmitic acid were also assessed. In acute 20-min incubations, 12.5-50 µm metformin did not alter basal (1.1 mm glucose) or glucose-stimulated (16.7 mm glucose) insulin secretion. However, higher concentrations of metformin (100-1000 µm) increased (1.3-1.5-fold; p

Acute and long-term effects of peroxisome proliferator-activated receptor-γ activation on the function and insulin secretory responsiveness of clonal beta-cells

Thiazolidinediones (TZDs) are used as antidiabetic therapy. The purpose of the present study was to examine whether the TZD rosiglitazone has direct actions on pancreatic beta-cells that contribute to its overall effects. Effects of acute and prolonged (48 h) exposure to rosiglitazone, as a model glitazone compound, were assessed in clonal pancreatic BRIN-BD11 beta-cells maintained in standard, glucotoxic and lipotoxic cultures. In acute 20-min incubations, rosiglitazone (0.2-100 M) did not alter basal or glucose-stimulated insulin secretion. However, rosiglitazone (6.25 M) enhanced (p

Retail restructuring and consumer choice 1:long term local changes in consumer behaviour : Portsmouth 1980-2002

Over the last two decades fundamental changes have taken place in the global supply and local structure of provision of British food retailing. Consumer lifestyles have also changed markedly. Despite some important studies of local interactions between new retail developments and consumers, we argue in this paper that there is a critical need to gauge the cumulative effects of these changes on consumer behaviour over longer periods. In this, the first of two papers, we present the main findings of a study of the effects of long-term retail change on consumers at the local level. We provide in this paper an overview of the changing geography of retail provision and patterns of consumption at the local level. We contextualise the Portsmouth study area as a locality that typifies national changes in retail provision and consumer lifestyles; outline the main findings of two large-scale surveys of food shopping behaviour carried out in 1980 and 2002; and reveal the impacts of retail restructuring on consumer behaviour. We focus in particular on choice between stores at the local level and end by problematising our understanding of how consumers experience choice, emphasising the need for qualitative research. This issue is then dealt with in our complementary second paper, which explores choice within stores and how this relates to the broader spatial context.

In search of a theory of list memory: an inquiry into the efects of long-term information on short-term recall

Over recent years, evidence has been accumulating in favour of the importance of long-term information as a variable which can affect the success of short-term recall. Lexicality, word frequency, imagery and meaning have all been shown to augment short term recall performance. Two competing theories as to the causes of this long-term memory influence are outlined and tested in this thesis. The first approach is the order-encoding account, which ascribes the effect to the usage of resources at encoding, hypothesising that word lists which require less effort to process will benefit from increased levels of order encoding, in turn enhancing recall success. The alternative view, trace redintegration theory, suggests that order is automatically encoded phonologically, and that long-term information can only influence the interpretation of the resultant memory trace. The free recall experiments reported here attempted to determine the importance of order encoding as a facilitatory framework and to determine the locus of the effects of long-term information in free recall. Experiments 1 and 2 examined the effects of word frequency and semantic categorisation over a filled delay, and experiments 3 and 4 did the same for immediate recall. Free recall was improved by both long-term factors tested. Order information was not used over a short filled delay, but was evident in immediate recall. Furthermore, it was found that both long-term factors increased the amount of order information retained. Experiment 5 induced an order encoding effect over a filled delay, leaving a picture of short-term processes which are closely associated with long-term processes, and which fit conceptions of short-term memory being part of language processes rather better than either the encoding or the retrieval-based models. Experiments 6 and 7 aimed to determine to what extent phonological processes were responsible for the pattern of results observed. Articulatory suppression affected the encoding of order information where speech rate had no direct influence, suggesting that it is ease of lexical access which is the most important factor in the influence of long-term memory on immediate recall tasks. The evidence presented in this thesis does not offer complete support for either the retrieval-based account or the order encoding account of long-term influence. Instead, the evidence sits best with models that are based upon language-processing. The path urged for future research is to find ways in which this diffuse model can be better specified, and which can take account of the versatility of the human brain.

Short-term changes in ocular biometry and refraction after discontinuation of long-term orthokeratology

OBJECTIVE: To assess refractive and biometric changes 1 week after discontinuation of lens wear in subjects who had been wearing orthokeratology (OK) contact lenses for 2 years. METHODS: Twenty-nine subjects aged 6 to 12 years and with myopia of -0.75 to -4.00 diopters (D) and astigmatism of ≤1.00 D participated in the study. Measurements of axial length and anterior chamber depth (Zeiss IOLMaster), corneal power and shape, and cycloplegic refraction were taken 1 week after discontinuation and compared with those at baseline and after 24 months of lens wear. RESULTS: A hyperopic shift was found at 24 months relative to baseline in spherical equivalent refractive error (+1.86±1.01 D), followed by a myopic shift at 1 week relative to 24 months (-1.93±0.92 D) (both P<0.001). Longer axial lengths were found at 24 months and 1 week in comparison to baseline (0.47±0.18 and 0.51±0.18 mm, respectively) (both P<0.001). The increase in axial length at 1 week relative to 24 months was statistically significant (0.04±0.06 mm; P=0.006). Anterior chamber depth did not change significantly over time (P=0.31). Significant differences were found between 24 months and 1 week relative to baseline and between 1-week and 24-month visits in mean corneal power (-1.68±0.80, -0.44±0.32, and 1.23±0.70 D, respectively) (all P≤0.001). Refractive change at 1 week in comparison to 24 months strongly correlated with changes in corneal power (r=-0.88; P<0.001) but not with axial length changes (r=-0.09; P=0.66). Corneal shape changed significantly between the baseline and 1-week visits (0.15±0.10 D; P<0.001). Corneal shape changed from a prolate to a more oblate corneal shape at the 24-month and 1-week visits in comparison to baseline (both P≤0.02) but did not change significantly between 24 months and 1 week (P=0.06). CONCLUSIONS: The effects of long-term OK on ocular biometry and refraction are still present after 1-week discontinuation of lens wear. Refractive change after discontinuation of long-term OK is primarily attributed to the recovery of corneal shape and not to an increase in the axial length.

The Long-Term impact of Business Support? - Exploring the Role of Evaluation Timing using Micro Data

The original contribution of this work is threefold. Firstly, this thesis develops a critical perspective on current evaluation practice of business support, with focus on the timing of evaluation. The general time frame applied for business support policy evaluation is limited to one to two, seldom three years post intervention. This is despite calls for long-term impact studies by various authors, concerned about time lags before effects are fully realised. This desire for long-term evaluation opposes the requirements by policy-makers and funders, seeking quick results. Also, current ‘best practice’ frameworks do not refer to timing or its implications, and data availability affects the ability to undertake long-term evaluation. Secondly, this thesis provides methodological value for follow-up and similar studies by using data linking of scheme-beneficiary data with official performance datasets. Thus data availability problems are avoided through the use of secondary data. Thirdly, this thesis builds the evidence, through the application of a longitudinal impact study of small business support in England, covering seven years of post intervention data. This illustrates the variability of results for different evaluation periods, and the value in using multiple years of data for a robust understanding of support impact. For survival, impact of assistance is found to be immediate, but limited. Concerning growth, significant impact centres on a two to three year period post intervention for the linear selection and quantile regression models – positive for employment and turnover, negative for productivity. Attribution of impact may present a problem for subsequent periods. The results clearly support the argument for the use of longitudinal data and analysis, and a greater appreciation by evaluators of the factor time. This analysis recommends a time frame of four to five years post intervention for soft business support evaluation.

The long-term impact of business support? - Exploring the role of evaluation timing using micro data

The original contribution of this work is threefold. Firstly, this thesis develops a critical perspective on current evaluation practice of business support, with focus on the timing of evaluation. The general time frame applied for business support policy evaluation is limited to one to two, seldom three years post intervention. This is despite calls for long-term impact studies by various authors, concerned about time lags before effects are fully realised. This desire for long-term evaluation opposes the requirements by policy-makers and funders, seeking quick results. Also, current ‘best practice’ frameworks do not refer to timing or its implications, and data availability affects the ability to undertake long-term evaluation. Secondly, this thesis provides methodological value for follow-up and similar studies by using data linking of scheme-beneficiary data with official performance datasets. Thus data availability problems are avoided through the use of secondary data. Thirdly, this thesis builds the evidence, through the application of a longitudinal impact study of small business support in England, covering seven years of post intervention data. This illustrates the variability of results for different evaluation periods, and the value in using multiple years of data for a robust understanding of support impact. For survival, impact of assistance is found to be immediate, but limited. Concerning growth, significant impact centres on a two to three year period post intervention for the linear selection and quantile regression models – positive for employment and turnover, negative for productivity. Attribution of impact may present a problem for subsequent periods. The results clearly support the argument for the use of longitudinal data and analysis, and a greater appreciation by evaluators of the factor time. This analysis recommends a time frame of four to five years post intervention for soft business support evaluation.