Measurement of apolipoprotein B-48 in the Svedberg flotation rate (Sf) > 400, Sf 60 – 400 and Sf 20 – 60 lipoprotein fractions reveals novel findings with respect to the effects of dietary fatty acids on triacylglycerol-rich lipoproteins in postmenopausal women

The present study was designed to examine whether the type of fat ingested in an initial test meal influences the response and density distribution of dietary-derived lipoproteins in the Svedberg flotation rate (Sf)>400, Sf 60 - 400 and Sf 20 - 60 lipoprotein fractions. A single-blind randomized within-subject crossover design was used to study the effects of palm oil, safflower oil, a mixture of fish and safflower oil, and olive oil on postprandial apolipoprotein (apo) B-48, retinyl ester and triacylglycerol responses in each lipoprotein fraction following an initial test meal containing one of the oils and a second standardized test meal. For all dietary oils, late postprandial (300min) concentrations of triacylglycerol and apo B-48 were significantly higher in the Sf 60 - 400 fraction than in the Sf>400 fraction (P<0.02). Significantly greater apo B-48 incremental areas under the curve (IAUCs) were also observed in the Sf 60 - 400 fraction than in the Sf>400 fraction following palm oil, safflower oil and olive oil (P<0.04), with a similar non-significant trend for fish/safflower oil. Olive oil resulted in a significantly greater apo B-48 IAUC in the Sf>400 fraction (P<0.02) than did any of the other dietary oils, as well as a tendency for a higher IAUC in the Sf 60 - 400 fraction compared with the palm, safflower and fish/safflower oils. In conclusion, we have found that the majority of intestinally derived lipoproteins present in the circulation following meals enriched with saturated, polyunsaturated or monounsaturated fatty acids are of the density and size of small chylomicrons and chylomicron remnants. Olive oil resulted in a greater apo B-48 response compared with the other dietary oils following sequential test meals, suggesting the formation of a greater number of small (Sf 60 - 400) and large (Sf>400) apo B-48-containing lipoproteins in response to this dietary oil.

Single nucleotide polymorphisms at the ADIPOQ gene locus interact with age and dietary intake of fat to determine serum adiponectin in subjects at risk of the metabolic syndrome

Background: Adiponectin gene expression is modulated by peroxisome proliferator–activated receptor γ, which is a transcription factor activated by unsaturated fatty acids. Objective: We investigated the effect of the interaction between variants at the ADIPOQ gene locus, age, sex, body mass index (BMI), ethnicity, and the replacement of dietary saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) or carbohydrates on serum adiponectin concentrations. Design: The RISCK (Reading, Imperial, Surrey, Cambridge, and Kings) study is a parallel-design, randomized controlled trial. Serum adiponectin concentrations were measured after a 4-wk high-SFA (HS) diet and a 24-wk intervention with reference (HS), high-MUFA (HM), and low-fat (LF) diets. Single nucleotide polymorphisms at the ADIPOQ locus −11391 G/A (rs17300539), −10066 G/A (rs182052), −7734 A/C (rs16861209), and +276 G/T (rs1501299) were genotyped in 448 participants. Results: In white Europeans, +276 T was associated with higher serum adiponectin concentrations (n = 340; P = 0.006) and −10066 A was associated with lower serum adiponectin concentrations (n = 360; P = 0.03), after adjustment for age, BMI, and sex. After the HM diet, −10066 G/G subjects showed a 3.8% increase (95% CI: −0.1%, 7.7%) and G/A+A/A subjects a 2.6% decrease (95% CI: −5.6%, 0.4%) in serum adiponectin (P = 0.006 for difference after adjustment for the change in BMI, age, and sex). In −10066 G/G homozygotes, serum adiponectin increased with age after the HM diet and decreased after the LF diet. Conclusion: In white −10066 G/G homozygotes, an HM diet may help to increase adiponectin concentrations with advancing age. This trial was registered at clinicaltrials.gov as ISRCTN29111298.

Community involvement in urban design: help or hindrance?

This paper examines the realities of community involvement in urban design in the context of a study of the West Itchen Neighbourhood of Southampton, a diverse inner city area accommodating some 7,000 households and 18,000 people. The findings are based on a literature review of community involvement in urban design and case study research into three government supported regeneration projects all located within the study area: a Neighbourhood Renewal Area - designated in 1994; an Estate Action Scheme - implemented between 1993 and 1996; and a Single Regeneration Budget programme - following a successful bid in 1995. The research was undertaken by Helen Gregory in 1997/8 as the basis of a dissertation, supervised by Alan Rowley, submitted for the award of an MPhil in Environmental Planning and Development from The University of Reading.

PPARγ2 gene Pro12Ala and PPARα gene Leu162Val single nucleotide polymorphisms interact with dietary intake of fat in determination of plasma lipid concentrations

Background/Aims: The peroxisome proliferator-activated receptors (PPARs) are transcriptional regulators of lipid metabolism, activated by unsaturated fatty acids. We investigated independent and interactive effects of PPARγ2 gene PPARG Pro12Ala (rs1801282) andPPARαgene PPARA Leu162Val (rs1800206) genotypes with dietary intake of fatty acids on concentrations of plasma lipids in subjects of whom 47.5% had metabolic syndrome. Methods: The RISCK study is a parallel design, randomised controlled trial. Plasma lipids were quantified at baseline after a 4-week high saturated fatty acids diet and after three parallel 24-week interventions with reference (high saturated fatty acids), high monounsaturated fatty acids and low-fat diets. Single nucleotide polymorphisms were genotyped in 466 subjects. Results: At baseline, the PPARG Ala12allele was associated with increased plasma total cholesterol (n = 378; p = 0.04), LDL cholesterol (p = 0.05) and apoB (p =0.05) after adjustment for age, gender and ethnicity. At baseline, PPARA Leu162Val × PPARG Pro12Ala genotype interaction did not significantly influence plasma lipid concentrations. After dietary intervention, gene-gene interaction significantly influenced LDL cholesterol (p =0.0002) and small dense LDL as a proportion of LDL (p = 0.005) after adjustments. Conclusions: Interaction between PPARG Pro12Ala and PPARA Leu162Valgenotypes may influence plasma LDL cholesterol concentration and the proportion as small dense LDL after a high monounsaturated fatty acids diet.

Wernicke’s aphasia reflects a combination of acoustic-phonological and semantic control deficits: A case-series comparison of Wernicke’s aphasia, semantic dementia and semantic aphasia

Wernicke’s aphasia (WA) is the classical neurological model of comprehension impairment and, as a result, the posterior temporal lobe is assumed to be critical to semantic cognition. This conclusion is potentially confused by (a) the existence of patient groups with semantic impairment following damage to other brain regions (semantic dementia and semantic aphasia) and (b) an ongoing debate about the underlying causes of comprehension impairment in WA. By directly comparing these three patient groups for the first time, we demonstrate that the comprehension impairment in Wernicke’s aphasia is best accounted for by dual deficits in acoustic-phonological analysis (associated with pSTG) and semantic cognition (associated with pMTG and angular gyrus). The WA group were impaired on both nonverbal and verbal comprehension assessments consistent with a generalised semantic impairment. This semantic deficit was most similar in nature to that of the semantic aphasia group suggestive of a disruption to semantic control processes. In addition, only the WA group showed a strong effect of input modality on comprehension, with accuracy decreasing considerably as acoustic-phonological requirements increased. These results deviate from traditional accounts which emphasise a single impairment and, instead, implicate two deficits underlying the comprehension disorder in WA.

Digital predistorter design using B-Spline neural network and inverse of De Boor algorithm

This contribution introduces a new digital predistorter to compensate serious distortions caused by memory high power amplifiers (HPAs) which exhibit output saturation characteristics. The proposed design is based on direct learning using a data-driven B-spline Wiener system modeling approach. The nonlinear HPA with memory is first identified based on the B-spline neural network model using the Gauss-Newton algorithm, which incorporates the efficient De Boor algorithm with both B-spline curve and first derivative recursions. The estimated Wiener HPA model is then used to design the Hammerstein predistorter. In particular, the inverse of the amplitude distortion of the HPA's static nonlinearity can be calculated effectively using the Newton-Raphson formula based on the inverse of De Boor algorithm. A major advantage of this approach is that both the Wiener HPA identification and the Hammerstein predistorter inverse can be achieved very efficiently and accurately. Simulation results obtained are presented to demonstrate the effectiveness of this novel digital predistorter design.

Nano structures through self-assembly of protected hydrophobic amino acids: encapsulation of rhodamine B dye by proline-based nanovesicles

The development of novel molecules for the creation of nanometer structures with specific properties has been the current interest of this research. We have developed a set of molecules from hydrophobic omega- and alpha-amino acids by protecting the -NH(2) with Boc (t-butyloxycarbonyl) group and -CO(2)H with para-nitroanilide such as BocHN-Xx-CONH-(p-NO(2))center dot C(6)H(4), where Xx is gamma-aminobutyric acid (gamma-Abu), (L)-isoleucine, alpha-aminoisobutyric acid, proline, etc. These molecules generate various nanometer structures, such as nanofibrils, nanotubes and nanovesicles, in methanol/water through the self-assembly of bilayers in which the nitro benzene moieties are stacked in the middle and the Boc-protected amino acids parts are packed in the outer surface. The bilayers can be further stacked one over the other through hydrophobic interactions to form multilayer structure, which helps to generate different kinds of nanoscopic structures. The formation of the nanostructures has been facilitated through the participation of various noncovalent interactions, such as hydrophobic interactions, hydrogen bonding and aromatic p-stacking interactions. Fluorescence microscopy and UV studies reveal that the nanovesicles generated from pro-based molecule can encapsulate dye molecules which can be released by addition of acid (at pH 2). These single amino acid based molecules are both easy to synthesize and cost-effective and therefore offer novel scaffolds for the future design of nanoscale structures.

A rare case of solution and solid state inter-conversion of two copper(II) dimers and a copper(II) chain

Three Cu(II)-azido complexes of formula [Cu2L2(N-3)(2)] (1), [Cu2L2(N-3)(2)]center dot H2O (2) and [CuL(N-3)](n) (3) have been synthesized using the same tridentate Schiff base ligand HL (2-[(3-methylaminopropylimino)-methyl]-phenol), the condensation product of N-methyl-1,3-propanediamine and salicyldehyde). Compounds 1 and 2 are basal-apical mu-1,1 double azido bridged dimers. The dimeric structure of 1 is centro-symmetric but that of 2 is non-centrommetric. Compound 3 is a mu-1,1 single azido bridged 1D chain. The three complexes interconvert in solution and can be obtained in pure form by carefully controlling the synthetic conditions. Compound 2 undergoes an irreversible transformation to 1 upon dehydration in the solid state. The magnetic properties of compounds 1 and 2 show the presence of weak antiferromagnetic exchange interactions mediated by the double 1,1-N-3 azido bridges (J = -2.59(4) and -0.10(1) cm-(1), respectively). The single 1,1-N-3 bridge in compound 3 mediates a negligible exchange interaction.

Task design and second language performance: the effect of narrative type on learner output

This article reports on a detailed empirical study of the way narrative task design influences the oral performance of second-language (L2) learners. Building on previous research findings, two dimensions of narrative design were chosen for investigation: narrative complexity and inherent narrative structure. Narrative complexity refers to the presence of simultaneous storylines; in this case, we compared single-story narratives with dual-story narratives. Inherent narrative structure refers to the order of events in a narrative; we compared narratives where this was fixed to others where the events could be reordered without loss of coherence. Additionally, we explored the influence of learning context on performance by gathering data from two comparable groups of participants: 60 learners in a foreign language context in Teheran and 40 in an L2 context in London. All participants recounted two of four narratives from cartoon pictures prompts, giving a between-subjects design for narrative complexity and a within-subjects design for inherent narrative structure. The results show clearly that for both groups, L2 performance was affected by the design of the task: Syntactic complexity was supported by narrative storyline complexity and grammatical accuracy was supported by an inherently fixed narrative structure. We reason that the task of recounting simultaneous events leads learners into attempting more hypotactic language, such as subordinate clauses that follow, for example, while, although, at the same time as, etc. We reason also that a tight narrative structure allows learners to achieve greater accuracy in the L2 (within minutes of performing less accurately on a loosely structured narrative) because the tight ordering of events releases attentional resources that would otherwise be spent on finding connections between the pictures. The learning context was shown to have no effect on either accuracy or fluency but an unexpectedly clear effect on syntactic complexity and lexical diversity. The learners in London seem to have benefited from being in the target language environment by developing not more accurate grammar but a more diverse resource of English words and syntactic choices. In a companion article (Foster & Tavakoli, 2009) we compared their performance with native-speaker baseline data and see that, in terms of nativelike selection of vocabulary and phrasing, the learners in London are closing in on native-speaker norms. The study provides empirical evidence that L2 performance is affected by task design in predictable ways. It also shows that living within the target language environment, and presumably using the L2 in a host of everyday tasks outside the classroom, confers a distinct lexical advantage, not a grammatical one.

The prevalence and nature of prescribing and monitoring errors in English general practice – a retrospective case note review

Objective To determine the prevalence and nature of prescribing and monitoring errors in general practices in England. Design Retrospective case note review of unique medication items prescribed over a 12 month period to a 2% random sample of patients. Mixed effects logistic regression was used to analyse the data. Setting Fifteen general practices across three primary care trusts in England. Data sources Examination of 6048 unique prescription items prescribed over the previous 12 months for 1777 patients. Main outcome measures Prevalence of prescribing and monitoring errors, and severity of errors, using validated definitions. Results Prescribing and/or monitoring errors were detected in 4.9% (296/6048) of all prescription items (95% confidence interval 4.4 - 5.5%). The vast majority of errors were of mild to moderate severity, with 0.2% (11/6048) of items having a severe error. After adjusting for covariates, patient-related factors associated with an increased risk of prescribing and/or monitoring errors were: age less than 15 (Odds Ratio (OR) 1.87, 1.19 to 2.94, p=0.006) or greater than 64 years (OR 1.68, 1.04 to 2.73, p=0.035), and higher numbers of unique medication items prescribed (OR 1.16, 1.12 to 1.19, p<0.001). Conclusion Prescribing and monitoring errors are common in English general practice, although severe errors are unusual. Many factors increase the risk of error. Having identified the most common and important errors, and the factors associated with these, strategies to prevent future errors should be developed based on the study findings.

Linking urban water balance and energy balance models to analyse urban design options

Using a water balance modelling framework, this paper analyses the effects of urban design on the water balance, with a focus on evapotranspiration and storm water. First, two quite different urban water balance models are compared: Aquacycle which has been calibrated for a suburban catchment in Canberra, Australia, and the single-source urban evapotranspiration-interception scheme (SUES), an energy-based approach with a biophysically advanced representation of interception and evapotranspiration. A fair agreement between the two modelled estimates of evapotranspiration was significantly improved by allowing the vegetation cover (leaf area index, LAI) to vary seasonally, demonstrating the potential of SUES to quantify the links between water sensitive urban design and microclimates and the advantage of comparing the two modelling approaches. The comparison also revealed where improvements to SUES are needed, chiefly through improved estimates of vegetation cover dynamics as input to SUES, and more rigorous parameterization of the surface resistance equations using local-scale suburban flux measurements. Second, Aquacycle is used to identify the impact of an array of water sensitive urban design features on the water balance terms. This analysis confirms the potential to passively control urban microclimate by suburban design features that maximize evapotranspiration, such as vegetated roofs. The subsequent effects on daily maximum air temperatures are estimated using an atmospheric boundary layer budget. Potential energy savings of about 2% in summer cooling are estimated from this analysis. This is a clear ‘return on investment’ of using water to maintain urban greenspace, whether as parks distributed throughout an urban area or individual gardens or vegetated roofs.

Investigating flavonoids as molecular templates for the design of small-molecule inhibitors of cell signaling

Epidemiological and clinical trials reveal compelling evidence for the ability of dietary flavonoids to lower cardiovascular disease risk. The mechanisms of action of these polyphenolic compounds are diverse, and of particular interest is their ability to function as protein and lipid kinase inhibitors. We have previously described structure-activity studies that reinforce the possibility for using flavonoid structures as templates for drug design. In the present study, we aim to begin constructing rational screening strategies for exploiting these compounds as templates for the design of clinically relevant, antiplatelet agents. We used the platelet as a model system to dissect the structural influence of flavonoids, stilbenes, anthocyanidins, and phenolic acids on inhibition of cell signaling and function. Functional groups identified as relevant for potent inhibition of platelet function included at least 2 benzene rings, a hydroxylated B ring, a planar C ring, a C ring ketone group, and a C-2 positioned B ring. Hydroxylation of the B ring with either a catechol group or a single C-4' hydroxyl may be required for efficient inhibition of collagen-stimulated tyrosine phosphorylated proteins of 125 to 130 kDa, but may not be necessary for that of phosphotyrosine proteins at approximately 29 kDa. The removal of the C ring C-3 hydroxyl together with a hydroxylated B ring (apigenin) may confer selectivity for 37 to 38 kDa phosphotyrosine proteins. We conclude that this study may form the basis for construction of maps of flavonoid inhibitory activity on kinase targets that may allow a multitargeted therapeutic approach with analogue counterparts and parent compounds.

Climate change impacts in the design of drainage systems: case study of Portugal

This paper aims to assess the necessity of updating the intensity-duration-frequency (IDF) curves used in Portugal to design building storm-water drainage systems. A comparative analysis of the design was performed for the three predefined rainfall regions in Portugal using the IDF curves currently in use and estimated for future decades. Data for recent and future climate conditions simulated by a global and regional climate model chain are used to estimate possible changes of rainfall extremes and its implications for the drainage systems. The methodology includes the disaggregation of precipitation up to subhourly scales, the robust development of IDF curves, and the correction of model bias. Obtained results indicate that projected changes are largest for the plains in southern Portugal (5–33%) than for mountainous regions (3–9%) and that these trends are consistent with projected changes in the long-term 95th percentile of the daily precipitation throughout the 21st century. The authors conclude there is a need to review the current precipitation regime classification and change the new drainage systems towards larger dimensions to mitigate the projected changes in extreme precipitation.

Operating models for a multi-polar world: balancing global integration and local responsiveness

Purpose – Multinationals have always needed an operating model that works – an effective plan for executing their most important activities at the right levels of their organization, whether globally, regionally or locally. The choices involved in these decisions have never been obvious, since international firms have consistently faced trade‐offs between tailoring approaches for diverse local markets and leveraging their global scale. This paper seeks a more in‐depth understanding of how successful firms manage the global‐local trade‐off in a multipolar world. Design methodology/approach – This paper utilizes a case study approach based on in‐depth senior executive interviews at several telecommunications companies including Tata Communications. The interviews probed the operating models of the companies we studied, focusing on their approaches to organization structure, management processes, management technologies (including information technology (IT)) and people/talent. Findings – Successful companies balance global‐local trade‐offs by taking a flexible and tailored approach toward their operating‐model decisions. The paper finds that successful companies, including Tata Communications, which is profiled in‐depth, are breaking up the global‐local conundrum into a set of more manageable strategic problems – what the authors call “pressure points” – which they identify by assessing their most important activities and capabilities and determining the global and local challenges associated with them. They then design a different operating model solution for each pressure point, and repeat this process as new strategic developments emerge. By doing so they not only enhance their agility, but they also continually calibrate that crucial balance between global efficiency and local responsiveness. Originality/value – This paper takes a unique approach to operating model design, finding that an operating model is better viewed as several distinct solutions to specific “pressure points” rather than a single and inflexible model that addresses all challenges equally. Now more than ever, developing the right operating model is at the top of multinational executives' priorities, and an area of increasing concern; the international business arena has changed drastically, requiring thoughtfulness and flexibility instead of standard formulas for operating internationally. Old adages like “think global and act local” no longer provide the universal guidance they once seemed to.