Grouping and the pitch of a mistuned fundamental component:effects of applying simultaneous multiple mistunings to the other harmonics

Mistuning a harmonic produces an exaggerated change in its pitch. This occurs because the component becomes inconsistent with the regular pattern that causes the other harmonics (constituting the spectral frame) to integrate perceptually. These pitch shifts were measured when the fundamental (F0) component of a complex tone (nominal F0 frequency = 200 Hz) was mistuned by +8% and -8%. The pitch-shift gradient was defined as the difference between these values and its magnitude was used as a measure of frame integration. An independent and random perturbation (spectral jitter) was applied simultaneously to most or all of the frame components. The gradient magnitude declined gradually as the degree of jitter increased from 0% to ±40% of F0. The component adjacent to the mistuned target made the largest contribution to the gradient, but more distant components also contributed. The stimuli were passed through an auditory model, and the exponential height of the F0-period peak in the averaged summary autocorrelation function correlated well with the gradient magnitude. The fit improved when the weighting on more distant channels was attenuated by a factor of three per octave. The results are consistent with a grouping mechanism that computes a weighted average of periodicity strength across several components. © 2006 Elsevier B.V. All rights reserved.

Sustained delivery by leucine-modified chitosan spray-dried respirable powders

The controlled co-delivery of multiple agents to the lung offers potential benefits to patients. This study investigated the preparation and characterisation of highly respirable spray-dried powders displaying the sustained release of two chemically distinct therapeutic agents. Spray-dried powders were produced from 30% (v/v) aqueous ethanol formulations that contained hydrophilic (terbutaline sulphate) and hydrophobic (beclometasone dipropionate) model drugs, chitosan (as a drug release modifier) and leucine (aerosolisation enhancer). The influence of chitosan molecular weight on spray-drying thermal efficiency, aerosol performance and drug release profile was investigated. Resultant powders were physically characterised: with in vitro aerosolisation performance and drug release profile investigated by the Multi-Stage Liquid Impinger and modified USP II dissolution apparatus, respectively. It was found that increased chitosan molecular weight gave increased spray-drying thermal efficiency. The powders generated were of a suitable size for inhalation—with emitted doses over 90% and fine particle fractions up to 72% of the loaded dose. Sustained drug release profiles were observed in dissolution tests for both agents: increased chitosan molecular weight associated with increased duration of drug release. The controlled co-delivery of hydrophilic and hydrophobic entities underlines the capability of spray drying to produce respirable particles with sustained release for delivery to the lung. (c) 2009 Elsevier B.V. All rights reserved.

Patient adherence to medication requirements for therapy of type 2 diabetes

Type 2 diabetes is a complex, progressive endocrine and metabolical disease that typically requires substantial lifestyle changes and multiple medications to lower blood glucose, reduce cardiovascular risk and address comorbidities. Despite an extensive range of available and effective treatments, <50% of patients achieve a glycaemical target of HbA <7.0% and about two-thirds die of premature cardiovascular disease. Adherence to prescribed therapies is an important factor in the management of type 2 diabetes that is often overlooked. Inadequate adherence to oral antidiabetes agents, defined as collecting <80% of prescribed medication, is variously estimated to apply to between 36% and 93% of patients. All studies affirm that a significant proportion of type 2 diabetes patients exhibit poor adherence that will contribute to less than desired control. Identified factors that impede adherence include complex dosing regimens, clinical inertia, safety concerns, socioeconomic issues, ethnicity, patient education and beliefs, social support and polypharmacy. This review explores these factors and potential strategies to improve adherence in patients with type 2 diabetes. © 2011 Blackwell Publishing Ltd.

The need for wider supply chain management adoption:empirical results from Ireland

Purpose - This paper aims to provide empirical results which suggest that there is a need for more widespread adoption of supply chain management among Irish firms. Design/methodology/approach - The Republic of Ireland is a small, open, trade-dependent economy and is one of the fastest growing economies in the developed world. However, due to rising costs, there is an increasing trend in Ireland to outsource lower function manufacturing processes to lower-cost locations but to retain high-skill functions (such as R&D). This trend, together with other factors such as its peripheral location, suggests that supply chain management is critical from an Irish perspective. In order to gain unique insights of current levels of awareness/adoption of SCM and the potential impact SCM could have on competitiveness, a survey was conducted among 776 Irish firms. Findings - Overall, the findings suggest that many firms in Ireland pay lip-service to the importance of SCM elements and objectives but the majority of firms, about two thirds, have only a passing understanding of what constitutes SCM. Only 25 per cent adopt SCM programmes and only 9 per cent of Irish companies have a specialised SCM or logistics manager. The gaps in their understanding of SCM are matched by the gaps in their awareness of key costs (e.g. 59 per cent of companies do not know their total supply chain costs). While there are supply chain management adopters in Ireland that are already well up the s-curve of innovation transfer, it is the larger group of less aware companies that must become better at how they manage their supply chains. Originality/value - The paper offers a useful insight into supply chain management and its role in Irish industry. © Emerald Group Publishing Limited.

Consumer trial, continuous use, and economic benefits of a retail service innovation:the case of the personal shopping assistant

Service innovations in retailing have the potential to benefit consumers as well as retailers. This research models key factors associated with the trial and continuous use of a specific self-service technology (SST), the personal shopping assistant (PSA), and estimates retailer benefits from implementing that innovation. Based on theoretical insights from prior SST studies, diffusion of innovation literature, and the technology acceptance model (TAM), this study develops specific hypotheses and tests them on a sample of 104 actual users of the PSA and 345 nonusers who shopped at the retail store offering the PSA device. Results indicate that factors affecting initial trial are different from those affecting continuous use. More specifically, consumers' trust toward the retailer, novelty seeking, and market mavenism are positively related to trial, while technology anxiety hinders the likelihood of trying the PSA. Perceived ease of use of the device positively impacts continuous use while consumers' need for interaction in shopping environments reduces the likelihood of continuous use. Importantly, there is evidence on retailer benefits from introducing the innovation since consumers using the PSA tend to spend more during each shopping trip. However, given the high costs of technology, the payback period for recovery of investments in innovation depends largely upon continued use of the innovation by consumers. Important implications are provided for retailers considering investments in new in-store service innovations. Incorporation of technology within physical stores affords opportunities for the retailer to reduce costs, while enhancing service provided to consumers. Therefore, service innovations in retailing have the potential to benefit consumers as well as retailers. This research models key factors associated with the trial and continuous use of a specific SST in the retail context, the PSA, and estimates retailer benefits from implementing that innovation. In so doing, the study contributes to the nascent area of research on SSTs in the retail sector. Based on theoretical insights from prior SST studies, diffusion of innovation literature, and the TAM, this study develops specific hypotheses regarding the (1) antecedent effects of technological anxiety, novelty seeking, market mavenism, and trust in the retailer on trial of the service innovation; (2) the effects of ease of use, perceived waiting time, and need for interaction on continuous use of the innovation; and (3) the effect of use of innovation on consumer spending at the store. The hypotheses were tested on a sample of 104 actual users of the PSA and 345 nonusers who shopped at the retail store offering the PSA device, one of the early adopters of PSA in Germany. Data were analyzed using logistic regression (antecedents of trial), multiple regression (antecedents of continuous use), and propensity score matching (assessing retailer benefits). Results indicate that factors affecting initial trial are different from those affecting continuous use. More specifically, consumers' trust toward the retailer, novelty seeking, and market mavenism are positively related to trial, while technology anxiety hinders the likelihood of trying the PSA. Perceived ease of use of the device positively impacts continuous use, while consumers' need for interaction in shopping environments reduces the likelihood of continuous use. Importantly, there is evidence on retailer benefits from introducing the innovation since consumers using the PSA tend to spend more during each shopping trip. However, given the high costs of technology, the payback period for recovery of investments in innovation depends largely upon continued use of the innovation by consumers. Important implications are provided for retailers considering investments in new in-store service innovations. The study contributes to the literature through its (1) simultaneous examination of antecedents of trial and continuous usage of a specific SST, (2) the demonstration of economic benefits of SST introduction for the retailer, and (3) contribution to the stream of research on service innovation, as against product innovation.

Protein modification and phospholipid oxidation

Phospholipid oxidation can generate reactive and electrophilic products that are capable of modifying proteins, especially at cysteine, lysine and histidine residues. Such lipoxidation reactions are known to alter protein structure and function, both with gain of function and loss of activity effects. As well as potential importance in the redox regulation of cell behaviour, lipoxidation products in plasma could also be useful biomarkers for stress conditions. Although studies with antibodies suggested the occurrence of lipoxidation adducts on ApoB-100, these products had not previously been characterized at a molecular level. We have developed new mass spectrometry-based approaches to detect and locate adducts of oxidized phospholipids in plasma proteins, as well as direct oxidation modifications of proteins, which avoid some of the problems typically encountered with database search engines leading to erroneous identifications of oxidative PTMs. This approach uses accurate mass extracted ion chromatograms (XICs) of fragment ions from peptides containing oxPTMs, and allows multiple modifications to be examined regardless of the protein that contains them. For example, a reporter ion at 184.074 Da/e corresponding to phosphocholine indicated the presence of oxidized phosphatidylcholine adducts, while 2 reporter ions at 100.078 and 82.025 Da/e were selective for allysine. ApoB-100-oxidized phospholipid adducts were detected even in healthy human samples, as well as LDL from patients with inflammatory disease. Lipidomic studies showed that more than 350 different species of lipid were present in LDL, and were altered in disease conditions. LDL clearly represents a very complex carrier system and one that offers a rich source of information about systemic conditions, with potential as indicators of oxidative damage in ageing or inflammatory diseases.

Accounting and the 'insoluble' problem of health care costs

Health service accounting reforms are frequently promoted, explained or justified with reference to ageing populations, expensive medical technologies and their purported implications for the cost of health care. Drawing on Foucault’s genealogical method, we examine the emergence of concerns regarding health expenditure in the wake of the creation of the British National Health Service in 1948, and their relationship with health service accounting practices. We argue that concerns regarding the cost of health care are historically contingent rather than inescapable consequences of demographic and technological change, and that health service accounting practices are both constitutive and reflective of such concerns. We conclude by relating our analysis to current attempts to control costs and increase efficiency in the health services.

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.

Performance optimisation of the MAC protocol with multiple contention slots in MIMO ad hoc networks

The multiple-input multiple-output (MIMO) technique can be used to improve the performance of ad hoc networks. Various medium access control (MAC) protocols with multiple contention slots have been proposed to exploit spatial multiplexing for increasing the transport throughput of MIMO ad hoc networks. However, the existence of multiple request-to-send/clear-to-send (RTS/CTS) contention slots represents a severe overhead that limits the improvement on transport throughput achieved by spatial multiplexing. In addition, when the number of contention slots is fixed, the efficiency of RTS/CTS contention is affected by the transmitting power of network nodes. In this study, a joint optimisation scheme on both transmitting power and contention slots number for maximising the transport throughput is presented. This includes the establishment of an analytical model of a simplified MAC protocol with multiple contention slots, the derivation of transport throughput as a function of both transmitting power and the number of contention slots, and the optimisation process based on the transport throughput formula derived. The analytical results obtained, verified by simulation, show that much higher transport throughput can be achieved using the joint optimisation scheme proposed, compared with the non-optimised cases and the results previously reported.