Premature cardiovascular events and mortality in south Asians with type 2 diabetes in the United Kingdom Asian Diabetes Study - effect of ethnicity on risk

Background/Aim - People of south Asian origin have an excessive risk of morbidity and mortality from cardiovascular disease. We examined the effect of ethnicity on known risk factors and analysed the risk of cardiovascular events and mortality in UK south Asian and white Europeans patients with type 2 diabetes over a 2 year period. Methods - A total of 1486 south Asian (SA) and 492 white European (WE) subjects with type 2 diabetes were recruited from 25 general practices in Coventry and Birmingham, UK. Baseline data included clinical history, anthropometry and measurements of traditional risk factors – blood pressure, total cholesterol, HbA1c. Multiple linear regression models were used to examine ethnicity differences in individual risk factors. Ten-year cardiovascular risk was estimated using the Framingham and UKPDS equations. All subjects were followed up for 2 years. Cardiovascular events (CVD) and mortality between the two groups were compared. Findings - Significant differences were noted in risk profiles between both groups. After adjustment for clustering and confounding a significant ethnicity effect remained only for higher HbA1c (0.50 [0.22 to 0.77]; P?=?0.0004) and lower HDL (-0.09 [-0.17 to -0.01]; P?=?0.0266). Baseline CVD history was predictive of CVD events during follow-up for SA (P?event or death from CVD was greater but not significantly so in SA than in WE (OR 1.4 [0.9 to 2.2]). Limitations - Fewer events in both groups and short period of follow-up are key limitations. Longer follow-up is required to see if the observed differences between the ethnic groups persist. Conclusion - South Asian patients with type 2 diabetes in the UK have a higher cardiovascular risk and present with cardiovascular events at a significantly younger age than white Europeans. Enhanced and ethnicity specific targets and effective treatments are needed if these inequalities are to be reduced.

Neurodegeneration is an early event in diabetic retinopathy:therapeutic implications

Diabetic retinopathy (DR) remains the leading cause of blindness among working-age individuals in developed countries. Current treatments for DR are indicated in advanced stages of the disease and are associated with significant adverse effects. Therefore, new pharmacological treatments for the early stages of DR are needed. DR has been classically considered to be a microcirculatory disease of the retina. However, there is growing evidence to suggest that retinal neurodegeneration is an early event in the pathogenesis of DR, which participates in the microcirculatory abnormalities that occur in DR. Therefore, the study of the underlying mechanisms that lead to neurodegeneration will be essential for identifying new therapeutic targets. From the clinical point of view, the identification of those patients in whom retinal neurodegeneration appears will be crucial for implementing early treatment based on neuroprotective drugs. When the early stages of DR are the therapeutic target, it would be inconceivable to recommend an aggressive treatment such as intravitreous injections. By contrast, topical administration of neuroprotective drugs by using eye drops is a possible option. However, clinical trials to determine the safety and effectiveness of this non-invasive route, as well as a standardisation of the methods for monitoring neurodegeneration, are needed.

Towards a unified understanding of event-related changes in the EEG:the Firefly model of synchronization through cross-frequency phase modulation

Although event-related potentials (ERPs) are widely used to study sensory, perceptual and cognitive processes, it remains unknown whether they are phase-locked signals superimposed upon the ongoing electroencephalogram (EEG) or result from phase-alignment of the EEG. Previous attempts to discriminate between these hypotheses have been unsuccessful but here a new test is presented based on the prediction that ERPs generated by phase-alignment will be associated with event-related changes in frequency whereas evoked-ERPs will not. Using empirical mode decomposition (EMD), which allows measurement of narrow-band changes in the EEG without predefining frequency bands, evidence was found for transient frequency slowing in recognition memory ERPs but not in simulated data derived from the evoked model. Furthermore, the timing of phase-alignment was frequency dependent with the earliest alignment occurring at high frequencies. Based on these findings, the Firefly model was developed, which proposes that both evoked and induced power changes derive from frequency-dependent phase-alignment of the ongoing EEG. Simulated data derived from the Firefly model provided a close match with empirical data and the model was able to account for i) the shape and timing of ERPs at different scalp sites, ii) the event-related desynchronization in alpha and synchronization in theta, and iii) changes in the power density spectrum from the pre-stimulus baseline to the post-stimulus period. The Firefly Model, therefore, provides not only a unifying account of event-related changes in the EEG but also a possible mechanism for cross-frequency information processing.

The SECURE study:long-term safety of Ranibizumab 0.5 mg in neovascular age-related macular degeneration

Objective - To evaluate long-term safety of intravitreal ranibizumab 0.5-mg injections in neovascular age-related macular degeneration (nAMD). Design - Twenty-four–month, open-label, multicenter, phase IV extension study. Participants - Two hundred thirty-four patients previously treated with ranibizumab for 12 months in the EXCITE/SUSTAIN study. Methods - Ranibizumab 0.5 mg administered at the investigator's discretion as per the European summary of product characteristics 2007 (SmPC, i.e., ranibizumab was administered if a patient experienced a best-corrected visual acuity [BCVA] loss of >5 Early Treatment Diabetic Retinopathy Study letters measured against the highest visual acuity [VA] value obtained in SECURE or previous studies [EXCITE and SUSTAIN], attributable to the presence or progression of active nAMD in the investigator's opinion). Main Outcome Measures - Incidence of ocular or nonocular adverse events (AEs) and serious AEs, mean change in BCVA from baseline over time, and the number of injections. Results - Of 234 enrolled patients, 210 (89.7%) completed the study. Patients received 6.1 (mean) ranibizumab injections over 24 months. Approximately 42% of patients had 7 or more visits at which ranibizumab was not administered, although they had experienced a VA loss of more than 5 letters, indicating either an undertreatment or that factors other than VA loss were considered for retreatment decision by the investigator. The most frequent ocular AEs (study eye) were retinal hemorrhage (12.8%; 1 event related to study drug), cataract (11.5%; 1 event related to treatment procedure), and increased intraocular pressure (6.4%; 1 event related to study drug). Cataract reported as serious due to hospitalization for cataract surgery occurred in 2.6% of patients; none was suspected to be related to study drug or procedure. Main nonocular AEs were hypertension and nasopharyngitis (9.0% each). Arterial thromboembolic events were reported in 5.6% of the patients. Five (2.1%) deaths occurred during the study, none related to the study drug or procedure. At month 24, mean BCVA declined by 4.3 letters from the SECURE baseline. Conclusions - The SECURE study showed that ranibizumab administered as per a VA-guided flexible dosing regimen recommended in the European ranibizumab SmPC at the investigator's discretion was well tolerated over 2 years. No new safety signals were identified in patients who received ranibizumab for a total of 3 years. On average, patients lost BCVA from the SECURE study baseline, which may be the result of disease progression or possible undertreatment.

A simulation study of the shift system at a UK police communications centre

The UK Police Force is required to operate communications centres under increased funding constraints. Staff represent the main cost in operating the facility and the key issue for the efficient deployment of staff, in this case call handler staff, is to try to ensure sufficient staff are available to make a timely response to customer calls when the timing of individual calls is difficult to predict. A discrete-event simulation study is presented of an investigation of a new shift pattern for call handler staff that aims to improve operational efficiency. The communications centre can be considered a specialised case of a call centre but an important issue for Police Force management is the particularly stressful nature of the work staff are involved with when responding to emergency calls. Thus decisions regarding changes to the shift system were made in the context of both attempting to improve efficiency by matching staff supply with customer demand, but also ensuring a reasonable workload pattern for staff over time.

Antecedents, mechanisms and processes of deinstitutionalization and institutional change:a case study approach to understanding enterprise under duress

Adopting a grounded theory methodology, the study describes how an event and pressure impact upon a process of deinstitutionalization and institutional change. Three case studies were theoretically sampled in relation to each other. They yielded mainly qualitative data from methods that included interviews, observations, participant observations, and document reviews. Each case consisted of a boundaried cluster of small enterprises that were not industry specific and were geographically dispersed. Overall findings describe how an event, i.e. a stimulus, causes disruption, which in turn may cause pressure. Pressure is then translated as a tension within the institutional environment, which is characterized by opposing forces that encourage institutional breakdown and institutional maintenance. Several contributions are made: Deinstitutionalization as a process is inextricable from the formation of institutions – both are needed to make sense of institutional change on a conceptual level but are also inseparable experientially in the field; stimuli are conceptually different to pressures; the historical basis of a stimulus may impact on whether pressure and institutional change occurs; pressure exists in a more dynamic capacity rather than only as a catalyst; institutional breakdown is a non-linear irregular process; ethical and survival pressures as new types were identified; institutional current, as an underpinning mechanism, influences how the tension between institutional breakdown and maintenance plays out.

Small businesses and flood impacts:the case of the 2009 flood event in Cockermouth

Flooding can have a devastating impact on businesses, especially on small- and medium-sized enterprises (SMEs) who may be unprepared and vulnerable to the range of both direct and indirect impacts. SMEs may tend to focus on the direct tangible impacts of flooding, limiting their ability to realise the true costs of flooding. Greater understanding of the impacts of flooding is likely to contribute towards increased uptake of flood protection measures by SMEs, particularly during post-flood property reinstatement. This study sought to investigate the full range of impacts experienced by SMEs located in Cockermouth following the floods of 2009. The findings of a questionnaire survey of SMEs revealed that businesses not directly affected by the flooding experienced a range of impacts and that short-term impacts were given a higher significance. A strong correlation was observed between direct, physical flood impacts and post-flood costs of insurance. Significant increases in the costs of property insurance and excesses were noted, meaning that SMEs will be exposed to increased losses in the event of a future flood event. The findings from the research will enable policy makers and professional bodies to make informed decisions to improve the status of advice given to SMEs. The study also adds weight to the case for SMEs to consider investing in property-level flood risk adaptation measures, especially during the post flood reinstatement process. © 2012 Blackwell Publishing Ltd and The Chartered Institution of Water and Environmental Management (CIWEM).

Reinstatement of flood affected properties:experiences of SMEs affected by the 2009 Cockermouth flood event

Recent policy changes in the UK encourage at-risk communities to learn to live with and adapt to flooding. Adaptation of individual properties by embracing resilient and resistant measures is an important aspect endorsed therein. Uptake of such protection measures by property owners, including that of Small and Medium-sized Enterprises (SMEs), has traditionally been low. A post-flood situation offers an opportunity to reinstate / reconstruct by integrating flood protection measures, in such a way that reduce damage and enhance the ability to recover in the event of a future flood incidence. In order to investigate the reinstatement / reconstruction experiences of flood affected SMEs, those affected by the 2009 Cockermouth flood event were studied. The results of a questionnaire survey revealed that many SMEs have opted for traditional reinstatement rather than resilient reinstatement. A detailed case study revealed requirements of getting the business back and running as soon as possible, a lack of guidance and advice from professionals and financial concerns as some of the barriers faced by SMEs. It is important that SMEs are provided with necessary guidance during the post-flood reinstatement stage, in order to make sure that the opportunity to build back better, integrating flood-protection measures is grasped by the SME owners. Stakeholders related to the construction industry, who are actively involved with post-flood reinstatement work, have an important role to play in this regard, providing necessary guidance and expertise to flooded SMEs.

Combining an enterprise resource planning system and informality:a study of efficiency and flexibility complmentarity [sic]

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT One of the current research trends in Enterprise Resource Planning (ERP) involves examining the critical factors for its successful implementation. However, such research is limited to system implementation, not focusing on the flexibility of ERP to respond to changes in business. Therefore, this study explores a combination system, made up of an ERP and informality, intended to provide organisations with efficient and flexible performance simultaneously. In addition, this research analyses the benefits and challenges of using the system. The research was based on socio-technical system (STS) theory which contains two dimensions: 1) a technical dimension which evaluates the performance of the system; and 2) a social dimension which examines the impact of the system on an organisation. A mixed method approach has been followed in this research. The qualitative part aims to understand the constraints of using a single ERP system, and to define a new system corresponding to these problems. To achieve this goal, four Chinese companies operating in different industries were studied, all of which faced challenges in using an ERP system due to complexity and uncertainty in their business environments. The quantitative part contains a discrete-event simulation study that is intended to examine the impact of operational performance when a company implements the hybrid system in a real-life situation. Moreover, this research conducts a further qualitative case study, the better to understand the influence of the system in an organisation. The empirical aspect of the study reveals that an ERP with pre-determined business activities cannot react promptly to unanticipated changes in a business. Incorporating informality into an ERP can react to different situations by using different procedures that are based on the practical knowledge of frontline employees. Furthermore, the simulation study shows that the combination system can achieve a balance between efficiency and flexibility. Unlike existing research, which emphasises a continuous improvement in the IT functions of an enterprise system, this research contributes to providing a definition of a new system in theory, which has mixed performance and contains both the formal practices embedded in an ERP and informal activities based on human knowledge. It supports both cost-efficiency in executing business transactions and flexibility in coping with business uncertainty.This research also indicates risks of using the system, such as using an ERP with limited functions; a high cost for performing informally; and a low system acceptance, owing to a shift in organisational culture. With respect to practical contribution, this research suggests that companies can choose the most suitable enterprise system approach in accordance with their operational strategies. The combination system can be implemented in a company that needs to operate a medium amount of volume and variety. By contrast, the traditional ERP system is better suited in a company that operates a high-level volume market, while an informal system is more suitable for a firm with a requirement for a high level of variety.

A double-blind randomized study comparing the effects of continuing or not continuing rosiglitazone + metformin therapy when starting insulin therapy in people with type 2 diabetes

Aims: To compare the efficacy and safety of either continuing or discontinuing rosiglitazone + metformin fixed-dose combination when starting insulin therapy in people with Type 2 diabetes inadequately controlled on oral therapy. Methods: In this 24-week double-blind study, 324 individuals with Type 2 diabetes inadequately controlled on maximum dose rosiglitazone + metformin therapy were randomly assigned to twice-daily premix insulin therapy (target pre-breakfast and pre-evening meal glucose ≤ 6.5 mmol/l) in addition to either rosiglitazone + metformin (8/2000 mg) or placebo. Results: Insulin dose at week 24 was significantly lower with rosiglitazone + metformin (33.5 ± 1.5 U/day, mean ± se) compared with placebo [59.0 ± 3.0 U/day; model-adjusted difference -26.6 (95% CI -37.7, -15,5) U/day, P < 0.001]. Despite this, there was greater improvement in glycaemic control [HbA 1c rosiglitazone + metformin vs. placebo 6.8 ± 0.1 vs. 7.5 ± 0.1%; difference -0.7 (-0.8, -0.5)%, P < 0.001] and more individuals achieved glycaemic targets (HbA1c < 7.0% 70 vs. 34%, P < 0.001). The proportion of individuals reporting at least one hypoglycaemic event during the last 12 weeks of treatment was similar in the two groups (rosiglitazone + metformin vs. placebo 25 vs. 27%). People receiving rosiglitazone + metformin in addition to insulin reported greater treatment satisfaction than those receiving insulin alone. Both treatment regimens were well tolerated but more participants had oedema [12 (7%) vs. 4 (3%)] and there was more weight gain [3.7 vs. 2.6 kg; difference 1.1 (0.2, 2.1) kg, P = 0.02] with rosiglitazone + metformin. Conclusions: Addition of insulin to rosiglitazone + metformin enabled more people to reach glycaemic targets with less insulin, and was generally well tolerated. © 2007 The Authors.

Performance management of event processing systems

This thesis is a study of performance management of Complex Event Processing (CEP) systems. Since CEP systems have distinct characteristics from other well-studied computer systems such as batch and online transaction processing systems and database-centric applications, these characteristics introduce new challenges and opportunities to the performance management for CEP systems. Methodologies used in benchmarking CEP systems in many performance studies focus on scaling the load injection, but not considering the impact of the functional capabilities of CEP systems. This thesis proposes the approach of evaluating the performance of CEP engines’ functional behaviours on events and develops a benchmark platform for CEP systems: CEPBen. The CEPBen benchmark platform is developed to explore the fundamental functional performance of event processing systems: filtering, transformation and event pattern detection. It is also designed to provide a flexible environment for exploring new metrics and influential factors for CEP systems and evaluating the performance of CEP systems. Studies on factors and new metrics are carried out using the CEPBen benchmark platform on Esper. Different measurement points of response time in performance management of CEP systems are discussed and response time of targeted event is proposed to be used as a metric for quality of service evaluation combining with the traditional response time in CEP systems. Maximum query load as a capacity indicator regarding to the complexity of queries and number of live objects in memory as a performance indicator regarding to the memory management are proposed in performance management of CEP systems. Query depth is studied as a performance factor that influences CEP system performance.

CEPBen:a benchmark for complex event processing systems

Complex Event processing (CEP) has emerged over the last ten years. CEP systems are outstanding in processing large amount of data and responding in a timely fashion. While CEP applications are fast growing, performance management in this area has not gain much attention. It is critical to meet the promised level of service for both system designers and users. In this paper, we present a benchmark for complex event processing systems: CEPBen. The CEPBen benchmark is designed to evaluate CEP functional behaviours, i.e., filtering, transformation and event pattern detection and provides a novel methodology of evaluating the performance of CEP systems. A performance study by running the CEPBen on Esper CEP engine is described and discussed. The results obtained from performance tests demonstrate the influences of CEP functional behaviours on the system performance. © 2014 Springer International Publishing Switzerland.

Holonic supply chain:a study from family-based manufacturing perspective

In the contemporary business environment, to adhere to the need of the customers, caused the shift from mass production to mass-customization. This necessitates the supply chain (SC) to be effective flexible. The purpose of this paper is to seek flexibility through adoption of family-based dispatching rules under the influence of inventory system implemented at downstream echelons of an industrial supply chain network. We compared the family-based dispatching rules in existing literature under the purview of inventory system and information sharing within a supply chain network. The dispatching rules are compared for Average Flow Time performance, which is averaged over the three product families. The performance is measured using extensive discrete event simulation process. Given the various inventory related operational factors at downstream echelons, the present paper highlights the importance of strategically adopting appropriate family-based dispatching rule at the manufacturing end. In the environment of mass customization, it becomes imperative to adopt the family-based dispatching rule from the system wide SC perspective. This warrants the application of intra as well as inter-echelon information coordination. The holonic paradigm emerges in this research stream, amidst the holistic approach and the vital systemic approach. The present research shows its novelty in triplet. Firstly, it provides leverage to manager to strategically adopting a dispatching rule from the inventory system perspective. Secondly, the findings provide direction for the attenuation of adverse impact accruing from demand amplification (bullwhip effect) in the form of inventory levels by appropriately adopting family-based dispatching rule. Thirdly, the information environment is conceptualized under the paradigm of Koestler's holonic theory.

Does start-up financing influence start-up speed? Evidence from the panel study of entrepreneurial dynamics

Why are some entrepreneurs able to start a new firm more quickly than others in the venture creation process? Drawing on pecking order and agency theory, this study investigates how start-up capital structure influences the time to either new firm founding or quitting the start-up process. The temporal aspect of the start-up process is one that is often discussed, but rarely studied. Therefore, we utilize competing risk and Cox regression event history analysis on a nationally representative sample of US entrepreneurs to investigate how start-up capital structure impacts the time in gestation to particular kinds of start-up outcomes. Our findings suggest that external equity has an appreciable impact on new firm emergence over time, and that the percentage of ownership held by the founders attenuates the benefits of external equity.

Take up of property-level flood protection:an exploratory study in Worcester

Significant numbers of homes within the UK are at risk of flooding. Although community level flood protection schemes are the first line of defence for mitigating flood risk, not all properties are protectable. Property-Level Flood Protection (PLFP) provides those unprotected homeowners with an approach for protecting their homes from flooding. This study sought to establish why property-level flood protection is needed and secondly assess the extent of take up using Worcester as the study area. An exploratory questionnaire survey was conducted to achieve these objectives. After consultation of available literature it was established that the introduction of PLFP protection provided numerous benefits including limiting the health & psychological effects flooding poses, the direct financial benefits and also the possible influence on gaining flood insurance. Despite the benefits and the recognition given to PLFP by the government it was found that the overall take up of the measures was low, findings which were further backed up by data collected in the study area of Worcester with only 23% of the sample having introduced PLFP measures. Reasoning for the low take up numbers typically included; unawareness of the measures, low risk of flood event, installation costs and inability to introduce due to tenancy. Age was noted as a significant impacting factor in the study area with none of the respondents under 25 suggesting they had “a good amount of knowledge of PLFP measures” even when they claimed their properties to be at risk of flooding. Guidance and support is especially recommended to those who are unable to manage their own flood risk for e.g. social housing/rental tenants.