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Urban spaces are important components within cities that improve urban competitiveness in the context of intercity competition. The notion of urban space in today's increasingly globalizin...

Supplemental Digital Content is available in the text., GlaxoSmithKline (GSK) conducted pharmacogenetic (PGx) analyses to determine whether genetic variants influence response to belimumab treatment in patients with systemic lupus erythematosus (SLE). We conducted an exploratory genome-wide meta-analysis (GWAS) of 10.9 million genetic variants and the efficacy data from 816 belimumab-treated SLE patients in three phase 3 belimumab clinical studies. Two highly correlated variants, rs293983 and rs364370, in the ANO3 (anoctamin 3) gene region were significantly associated with efficacy as measured by the SLE Response Index (SRI4) with a per-T-allele odds ratio (OR) of 2.15 [95% confidence interval (CI): 1.66–2.79, P=8.0×10−9]. In contrast, there was no association with SRI4 response in 577 placebo-treated patients (per-T-allele OR: 0.98; 95% CI: 0.74–1.29, P=0.87). A post-hoc analysis by geographic region revealed a strong SRI4 response signal in 157 belimumab-treated patients from Asia (per-T-allele OR=2.85, 95% CI: 1.41–5.74, P=0.0021). On the basis of this encouraging finding in Asian patients, we conducted a confirmatory analysis of the SRI4 end point in an independent phase 3 study of SLE patients from northeast Asia. We found no evidence of an association between rs293983 and SRI4 response in 204 belimumab-treated patients (per-T-allele OR: 0.90, 95% CI: 0.52–1.57, P=0.64). The inability to replicate the observed GWAS effect suggests this was a false positive result; hence, we failed to identify any genetic variants significantly associated with belimumab efficacy.

During recent decades, and especially after the economic downturn that began in the late 2000s, many U.S. state and local governments have intensified their pro‐growth efforts to promote corporate investment and jobs, including ever higher incentives (such as tax breaks and grants) in their bidding wars for big businesses. This paper draws an analogy—between bidding for big businesses and bidding on eBay—to highlight the drawbacks of high‐profile bidding wars among governments given that the large corporations establish the bidding rules in their favor. The main consideration raised is whether state and local government bidding for big businesses, which operates analogously to an auction, should be more like eBay, whose rules are fair not only for sellers but also for bidders.

Osteoarthritis is the most common musculoskeletal disease and the leading cause of disability globally. Here, we perform the largest genome-wide association study for osteoarthritis to date (77,052 cases and 378,169 controls), analysing 4 phenotypes: knee osteoarthritis, hip osteoarthritis, knee and/or hip osteoarthritis, and any osteoarthritis. We discover 64 signals, 52 of them novel, more than doubling the number of established disease loci. Six signals fine map to a single variant. We identify putative effector genes by integrating eQTL colocalization, fine-mapping, human rare disease, animal model, and osteoarthritis tissue expression data. We find enrichment for genes underlying monogenic forms of bone development diseases, and for the collagen formation and extracellular matrix organisation biological pathways. Ten of the likely effector genes, including TGFB1, FGF18, CTSK and IL11 have therapeutics approved or in clinical trials, with mechanisms of action supportive of evaluation for efficacy in osteoarthritis.

Introduction: Hospitals have increasing numbers of emergency department attendances each year. We need to treat these patients more quickly and avoid emergency over-crowding thus allowing patients to flow freely through the acute hospital. Hospitals require timely and efficient discharge processes to achieve adequate patient flow. In a previous quality improvement project to reduce readmissions, we had highlighted the importance of supporting patients with complex discharge needs at the time of discharge. Achieving safe, timely and person-centred discharge from hospital to home is an important indicator of quality and a measure of effective integrated care. At a time when building new acute beds is not feasible innovative new ideas are required to attain this goal. Practice change: We planned and commissioned a new off-site 18-bedded transitional care unit (TCU). The nursing and therapy team of the TCU are part of our acute hospital nursing service. The medical model is a unique hybrid with a local general practice providing day-to-day medical input supported by the consultant geriatricians from the acute hospital. Active daily discharge planning and creating links with community is a primary goal of the TCU. There is a weekly multidisciplinary meeting including the GPs and geriatricians with the unit team. Aim: Our TCU was developed to support the smooth flow of patients with complex discharge needs from the acute hospital back to home in a safe and timely manner. The goal of the TCU is to reduce the patients’ stay in acute care and provide effective discharge planning. Targeted population: The TCU is designed to care for patients who no longer require active acute hospital facilities but are not yet ready to discharge directly home. Patients requiring multidisciplinary assessment, a short reablement programme or social care set-up before discharge are suitable. All patients come directly from our acute hospital. Highlights: The TCU opened in September 2016 after nine-months of planning and refurbishment. The TCU is now admitting about 50 patients per month with an average length of stay of 9.1 days. The identification of appropriate patients for the TCU is sustained by a daily “discharge support meeting” and senior staff assessment in the acute hospital. The TCU has developed increasingly close links with other community discharge support services Discussion & Conclusions: Our TCU has been successfully opened and is achieving its goals. Successful discharge involves far more than a move from hospital to home. Appropriate discharge planning emphasises patient support and communication. Success and sustainability of the TCU is possible with a dynamic nursing and therapy team. Acute hospital identification and assessment of appropriate patients is vital for the TCU. The hybrid model of medical care has been a positive innovation that could be replicated elsewhere. Lessons learned: Social & non-clinical problems are often involved in complex discharges Discharge planning is not started early enough in acute hospitals Communication and information transfer between acute wards and TCU is critical Complex operational issues emerge is organising and running an off-site unit

Much of the research on industrialization in less developed countries like China focus on top-down globalization processes associated with foreign direct investment from transnational corporations. This paper attempts to augment that literature with greater attention for bottom-up processes, which are also important in China. This case study of the Shiling leather industrial district was chosen because of the importance of bottom-up initiated local processes that began independently of global forces, yet evolved to become tied into larger processes of globalization: a process we term “logalization”. Our conceptual framework is illustrated using our general model of how this kind of industrial district links into the world market; it includes the importance of “regional structure” comprising not just the industrial district itself but also wholesale markets as well as trade fairs that connect industrial production into the global economy. We examine how the Shiling industrial district was initiated by loca...

To investigate the association between genetic risk variants for age-related macular degeneration (AMD) and response to intravitreal ranibizumab in Korean patients with neovascular AMD.This prospective study included 273 treatment-naive patients (273 eyes) who underwent 5 monthly injections (Months 0, 1, 2, 3, and 4) of intravitreal ranibizumab for neovascular AMD. Patients were genotyped for 23 single-nucleotide polymorphisms within 12 AMD-relevant genes. For each polymorphism, genotypic association with good response at Month 5, predetermined as visual improvement of ≥ 8 Early Treatment Diabetic Retinopathy Study letters from baseline, was investigated with logistic regression analysis adjusted for age, gender, smoking, baseline Early Treatment Diabetic Retinopathy Study letter, central retinal thickness, lesion area, and type of choroidal neovascularization.At Month 5, visual acuity improved by 9.1 ± 17.6 letters from baseline, and 136 patients (49.8%) were classified as good responders. In logistic regression, no tested polymorphism showed statistically significant association with favorable visual outcome at Month 5. When unadjusted for multiple tests, AA genotype for VEGF rs699947 had an increased chance of good response compared with other genotypes (odds ratio, 3.61; 95% confidence interval, 1.42-9.18; P = 0.0071).In this Korean neovascular AMD cohort, there was no statistically significant effect of genotype on early visual outcome after ranibizumab treatment.

Regional cooperation involves cooperative networks of local and regional public, private, and nonprofit bodies, working with higher levels of government, that focus their economic development efforts for the benefit of their region or group of regions as a whole. The assumption is that regional cooperation is “good” and may be able to address some of the shortcomings of competition for private investment among individual localities. This article seeks to evaluate that assumption by critically examining the opportunities and challenges for government involvement in regional cooperation through a comparative review of the urban economic development literature for the United States and Western Europe.

Brownfields are abandoned or under-utilised sites with known or suspected environmental contamination. Public-sector efforts to promote brownfields redevelopment face a dual land-use policy challenge. On the one hand, government agencies must help reduce the barriers to private-sector reuse by addressing the uncertainties created by four major issues: legal liability for contamination; uncertain cleanup standards; availability of funding for redevelopment; and complicated regulatory requirements. On the other hand, brownfields reuse must be connected to wider community efforts to achieve environmental protection, central city revitalisation and reduced suburban sprawl. This involves tackling sustainable development and environmental justice issues: the marketability of brownfields; the social costs and benefits of developing greenfields versus redeveloping brownfields and meaningful community participation. This paper examines the progress by US local, state and federal agencies during the last decade in addressing this dual challenge. It is based on a review of the interdisciplinary brownfields literature, and evidence from Toledo, Ohio, whose experience promoting cleanup and reuse reflects that of many Midwestern and Northeastern cities.

(2002). Review of the Year's Publication in Social Justice Education. Equity & Excellence in Education: Vol. 35, No. 1, pp. 79-85.

Purpose The purpose of this study was to examine emergency department (ED) nurses' attitudes towards individuals presenting with deliberate self-harm (DSH), including the relationship between attitudes and factors such as age, academic achievements, length of experience, and self-harm education. Method The study adopted a quantitative descriptive and correlational design. ED nurses' attitudes, working in a level 1 trauma ED in the Republic of Ireland, were surveyed, using an amended version of McAllister's et al. [McAllister, M., Creedy, D., Moyle, W., Farrugia, C., 2002. Nurses' attitudes towards clients who self-harm. Journal of Advanced Nursing 40(5), 578–586.] Attitude Towards Deliberate Self-Harm Questionnaire (ADSHQ). The survey yielded an 85% ( n =68) response rate. Results The study found that ED nurses held positive attitudes towards individuals presenting with DSH. No correlation was found between total scores and gender, ED experience, or a history of self-harm education, although older nurses and hospital trained nurses had less positive attitudes. Age and length of clinical experience produced a trend in which attitudes increased, reached a peak and then declined. Conclusion Although ED nurses in this study hold positive attitudes, ongoing continuing education, which was identified as a key theme in the study, remains an important strategy to maintain and further improve attitudes. The need for research into aspects of care such as knowledge, awareness and empathy is recommended, as is the need to evaluate the extent to which the National Strategy for Suicide Prevention 2005–2014 recommendations [Department of Health and Children, Health Service Executive, National Suicide Review Group 2005. Reach Out – Irish National Strategy for Action on Suicide Prevention 2005–2014. (accessed 22.02.08)] have been implemented.

Objectives To determine the proportion of patients who died as a result of the withdrawal or withholding of life support (WD/WHLS) in the intensive care units (ICUs) of three teaching hospitals and to describe the process involved by determining: a) why the decision was made to withdraw support (WDLS); b) when WDLS took place; and c) how the WDLS process was conducted. Design Retrospective cohort study. Setting Three university-affiliated ICUs. Patients Four hundred nineteen patients who died in one of three academic, tertiary care ICUs over a 1-yr period. Interventions Retrospective chart review. Data collected included age, gender, admitting diagnoses, comorbid disease, Acute Physiology and Chronic Health Evaluation II score, and mode of death (brain death, death due to withholding of life support, death due to WDLS, or death despite ongoing therapy). For those patients dying due to WDLS, the reason for WDLS, person initiating discussion, timing of WDLS, degree of organ dysfunction, order of withdrawal of life support modalities, and the use of sedatives and analgesics were recorded. Measurements and Main Results Seventy percent of patients died by WD/WHLS and 8.4% were brain dead. Patients undergoing WD/WHLS were older and had a longer length of stay than patients dying from other causes. Poor prognosis was the most common reason given for WDLS, reflected by significant organ dysfunction at the time of WDLS. Future quality of life was a less frequently cited reason. Most patients undergoing WDLS did so early in their ICU stay, although time to WDLS appeared to reflect diagnostic group. Few meetings occurred before WDLS and death occurred soon after initiating WDLS. There was a preference of withdrawing mechanical ventilation last and large amounts of morphine (mean 21 +/- 33 [SD] mg/hr) and benzodiazepines (mean 8.6 +/- 11 mg/hr) were used. Little variability in practice was apparent among the studied ICUs. Conclusions Similar to other studies, WD/WHLS was the most common cause of death in academic ICUs and poor patient prognosis was considered the most important factor in deciding on WDLS. However, in contrast to other studies, future quality of life was not as frequently cited a reason for WDLS and larger amounts of morphine were used during WDLS. These discrepancies suggest areas for potential future research. (Crit Care Med 1997; 25:1324-1331)

Purpose To develop comprehensive predictive models for choroidal neovascularization (CNV) and geographic atrophy (GA) incidence within 3 years that can be applied realistically to clinical practice. Design Retrospective evaluation of data from a longitudinal study to develop and validate predictive models of CNV and GA. Methods The predictive performance of clinical, environmental, demographic, and genetic risk factors was explored in regression models, using data from both eyes of 2011 subjects from the Age-Related Eye Disease Study (AREDS). The performance of predictive models was compared using 10-fold cross-validated receiver operating characteristic curves in the training data, followed by comparisons in an independent validation dataset (1410 AREDS subjects). Bayesian trial simulations were used to compare the usefulness of predictive models to screen patients for inclusion in prevention clinical trials. Results Logistic regression models that included clinical, demographic, and environmental factors had better predictive performance for 3-year CNV and GA incidence (area under the receiver operating characteristic curve of 0.87 and 0.89, respectively), compared with simple clinical criteria (AREDS simplified severity scale). Although genetic markers were associated significantly with 3-year CNV ( CFH : Y402H; ARMS2 : A69S) and GA incidence ( CFH : Y402H), the inclusion of genetic factors in the models provided only marginal improvements in predictive performance. Conclusions The logistic regression models combine good predictive performance with greater flexibility to optimize clinical trial design compared with simple clinical models (AREDS simplified severity scale). The benefit of including genetic factors to screen patients for recruitment to CNV prevention studies is marginal and is dependent on individual clinical trial economics.

Health and social care partnership working is often predicated on the notion that it improves outcomes for service users. Yet there is a lack of evidence linking partnerships to changes in outcomes. Against this background, the Health Services Management Centre at the University of Birmingham designed the Partnership Outcomes Evaluation Toolkit (POET) specifically to evaluate health and social care partnerships in terms of service user outcomes. This paper reports on the field testing of POET with Sandwell Integrated Support Service. This research provided a number of interesting insights into this service, and indicated some dissonance between staff and service user and carer expectations.