Microvascular lesions of diabetic retinopathy: clues towards understanding pathogenesis?

Retinopathy is a major complication of diabetes mellitus and this condition remains a leading cause of blindness in the working population of developed countries. As diabetic retinopathy progresses a range of neuroglial and microvascular abnormalities develop although it remains unclear how these pathologies relate to each other and their net contribution to retinal damage. From a haemodynamic perspective, evidence suggests that there is an early reduction in retinal perfusion before the onset of diabetic retinopathy followed by a gradual increase in blood flow as the complication progresses. The functional reduction in retinal blood flow observed during early diabetic retinopathy may be additive or synergistic to pro-inflammatory changes, leucostasis and vaso-occlusion and thus be intimately linked to the progressive ischaemic hypoxia and increased blood flow associated with later stages of the disease. In the current review a unifying framework is presented that explains how arteriolar dysfunction and haemodynamic changes may contribute to late stage microvascular pathology and vision loss in human diabetic retinopathy.

The role of lipids and protein kinase Cs in the pathogenesis of diabetic retinopathy

Diabetic retinopathy is one of the most common complications of diabetes and is a major cause of new blindness in the working-age population of developed countries. While the exact pathogenic basis of this condition remains ill defined, it is clear that hyperglycaemia is a critical factor in its aetiology. Protein kinase C (PKC) activation is one of the sequelae of hyperglycaemia and it is thought to play an important role in the development of diabetic complications. This review questions the currently held dogma that PKC stimulation in diabetes is solely mediated through the overproduction of palmitate and oleate enriched diacylglycerols. Blood glucose concentrations are closely tracked by changes in the levels of free fatty acids and these, in addition to oxidative stress, may account for the aberrant activation of PKCs in diabetes. Little is known about why PKCs fail to downregulate in diabetes and efforts should be directed towards acquiring such information. Considerable evidence implicates the PKCbeta isoform in the pathogenesis of diabetic retinopathy, but other isoforms may also be of relevance. In addition to PKCs, it is evident that novel diacyglycerol-activated non-kinase receptors could also play a role in the development of diabetic complications. Therapeutic agents have been developed to inhibit specific PKC isoforms and PKCbeta antagonists are currently undergoing clinical trials to test their toxicity and efficacy in suppressing diabetic complications. The likely impact of these drugs in the treatment of diabetic patients is considered.

A systematic review of systematic reviews to improve maternal mental health and well-being

Objective: to identify non-invasive interventions in the perinatal period that could enable midwives to offer effective support to women within the area of maternal mental health and well-being.

Methods: a total of 9 databases were searched: MEDLINE, PubMed, EBSCO (CINAHL/British Nursing Index), MIDIRS Online Database, Web of Science, The Cochrane library, CRD (NHS EED/DARE/HTA), Joanne Briggs Institute and EconLit. A systematic search strategy was formulated using key MeSH terms and related text words for midwifery, study aim, study design and mental health. Inclusion criteria were articles published from 1999 onwards, English language publications and articles originating from economically developed countries, indicated by membership of the Organisation for Economic Co-operation and Development (OECD). Data were independently extracted using a data collection form, which recorded data on the number of papers reviewed, time frame of the review, objectives, key findings and recommendations. Summary data tables were set up outlining key data for each study and findings were organised into related groups. The methodological quality of the reviews was assessed based on predefined quality assessment criteria for reviews.

Findings: 32 reviews were identified as examining interventions that could be used or co-ordinated by midwives in relation to some aspect of maternal mental health and well-being from the antenatal to the postnatal period and met the inclusion criteria. The review highlighted that based on current systematic review evidence it would be premature to consider introducing any of the identified interventions into midwifery training or practice. However there were a number of examples of possible interventions worthy of further research including midwifery led models of care in the prevention of postpartum depression, psychological and psychosocial interventions for treating postpartum depression and facilitation/co-ordination of parent-training programmes. No reviews were identified that supported a specific midwifery role in maternal mental health and well-being in pregnancy, and yet, this is the point of most intensive contact.

Key conclusions and implications for practice: This systematic review of systematic reviews provides a valuable overview of the current strengths and gaps in relation to maternal mental health interventions in the perinatal period. While there was little evidence identified to inform the current role of midwives in maternal mental health, the review provides the opportunity to reflect on what is achievable by midwives now and in the future and the need for high quality randomised controlled trials to inform a strategic approach to promoting maternal mental health in midwifery.

Investigating local relationships between trace elements in soils and cancer data

Medical geology research has recognised a number of potentially toxic elements (PTEs), such as arsenic, cobalt, chromium, copper, nickel, lead, vanadium, uranium and zinc, known to influence human disease by their respective deficiency or toxicity. As the impact of infectious diseases has decreased and the population ages, so cancer has become the most common cause of death in developed countries including Northern Ireland. This research explores the relationship between environmental exposure to potentially toxic elements in soil and cancer disease data across Northern Ireland. The incidence of twelve different cancer types (lung, stomach, leukaemia, oesophagus, colorectal, bladder, kidney, breast, mesothelioma, melanoma and non melanoma(NM) both basal and squamous, were examined in the form of twenty-five coded datasets comprising aggregates over the 12 year period from 1993 to 2006. A local modelling technique,geographically weighted regression (GWR) is usedto explore the relationship between environmental exposure and cancer disease data. The results show comparisons of the geographical incidence of certain cancers (stomach and NM squamous skin cancer) in relation to concentrations of certain PTEs (arsenic levels in soils and radon were identified). Findings from the research have implications for regional human health risk assessments.

Bolivian health and social care professionals' experiences of decision-making in oncology and palliative care

In the UK, end-of-life care strategies recommend patients and families are involved in decision making around treatment and care. In Bolivia, such strategies do not exist, and access to oncology services depends on finance, geography, education and culture. Compared to more developed countries, the delivery of oncology services in Latin America may result in a higher percentage of patients presenting with advanced incurable disease. The objective of this study was to explore decision-making experiences of health and social care professionals who cared for oncology and palliative care patients attending the Instituto Oncológico Nacional, Cochabamba (Bolivia). Patients were predominantly from the Quechua tradition, which has its own ethnic diversity, linguistic distinctions and economic systems. Qualitative data were collected during focus groups. Data analysis was conducted using Interpretative Phenomenological Analysis. Three interrelated themes emerged: (i) making sense of structures of experience and relationality; (ii) frustration with the system; and (iii) the challenges of promoting shared decision making. The study uncovered participants' lived experiences, emotions and perceptions of providing care for Quechua patients. There was evidence of structural inequalities, the marginalisation of Quechua patients and areas of concern that social workers might well be equipped to respond to, such as accessing finances for treatment/care, education and alleviating psychological or spiritual suffering.

Lung cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK:A population-based study, 2004-2007

Background: The authors consider whether differences in stage at diagnosis could explain the variation in lung cancer survival between six developed countries in 2004-2007. Methods: Routinely collected population-based data were obtained on all adults (15-99 years) diagnosed with lung cancer in 2004-2007 and registered in regional and national cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK. Stage data for 57 352 patients were consolidated from various classification systems. Flexible parametric hazard models on the log cumulative scale were used to estimate net survival at 1 year and the excess hazard up to 18 months after diagnosis. Results: Age-standardised 1-year net survival from non-small cell lung cancer ranged from 30% (UK) to 46% (Sweden). Patients in the UK and Denmark had lower survival than elsewhere, partly because of a more adverse stage distribution. However, there were also wide international differences in stage-specific survival. Net survival from TNM stage I non-small cell lung cancer was 16% lower in the UK than in Sweden, and for TNM stage IV disease survival was 10% lower. Similar patterns were found for small cell lung cancer. Conclusions: There are comparability issues when using population-based data but, even given these constraints, this study shows that, while differences in stage at diagnosis explain some of the international variation in overall lung cancer survival, wide disparities in stage-specific survival exist, suggesting that other factors are also important such as differences in treatment. Stage should be included in international cancer survival studies and the comparability of population-based data should be improved.

Regulating Services Trade Agreements - A Comparative Analysis of Regulatory Disciplines Included in EU and US Free Trade Agreements

Developed countries, led by the EU and the US, have consistently called for ‘deeper integration’ over the course of the past three decades i.e., the convergence of ‘behind-the-border’ or domestic polices and rules such as services, competition, public procurement, intellectual property (“IP”) and so forth. Following the collapse of the Doha Development Round, the EU and the US have pursued this push for deeper integration by entering into deep and comprehensive free trade agreements (“DCFTAs”) that are comprehensive insofar as they are not limited to tariffs but extend to regulatory trade barriers. More recently, the EU and the US launched negotiations on a Transatlantic Trade and Investment Partnership (“TTIP”) and a Trade in Services Agreement (“TISA”), which put tackling barriers resulting from divergences in domestic regulation in the area of services at the very top of the agenda. Should these agreements come to pass, they may well set the template for the rules of international trade and define the core features of domestic services market regulation. This article examines the regulatory disciplines in the area of services included in existing EU and US DCFTAs from a comparative perspective in order to delineate possible similarities and divergences and assess the extent to which these DCFTAs can shed some light into the possible outcome and limitations of future trade negotiations in services. It also discusses the potential impact of such negotiations on developing countries and, more generally, on the multilateral process.

Population Mobility Dynamics Estimated from Mobile Telephony Data

In the last decade, mobile phones and mobile devices using mobile cellular telecommunication network connections have become ubiquitous. In several developed countries, the penetration of such devices has surpassed 100 percent. They facilitate communication and access to large quantities of data without the requirement of a fixed location or connection. Assuming mobile phones usually are in close proximity with the user, their cellular activities and locations are indicative of the user's activities and movements. As such, those cellular devices may be considered as a large scale distributed human activity sensing platform. This paper uses mobile operator telephony data to visualize the regional flows of people across the Republic of Ireland. In addition, the use of modified Markov chains for the ranking of significant regions of interest to mobile subscribers is investigated. Methodology is then presented which demonstrates how the ranking of significant regions of interest may be used to estimate national population, results of which are found to have strong correlation with census data.

Beyond Financialisation? Transformative Strategies for More Sustainable Financial Markets in the European Union

The global financial crisis has led many regulators and lawmakers to a rethinking about current versus optimum financial market structures and activities that include a variety and even radical ideas about delevaraging and downsizing finance. This paper focuses on the flaws and shortcomings of regulatory reforms of finance and on the necessity of and scope for more radical transformative strategies. With 'crisis economics' back, the most developed countries, including the EU member states, are still on the edge of disaster and confronted with systemic risk. Changes in financial regulation adopted in the aftermath of the financial meltdown have not been radical enough to transform the overall system of finance-driven capitalism towards a more sustainable system with a more embedded finance. The paper discusses financialisation in order to understand the development trends in finance over the past decades and examines various theories to describe the typical trends and patterns in financial regulation. By focusing on a limited number of regulatory reforms in the European Union, the limitations of current reforms and the need for additional transformative strategies necessary to overcome the finance-driven accumulation regime are explored. Finally, the regulatory space for such transformative strategies and for taming finance in times of crisis, austerity, and increased public protest potential is analysed.

Inequality and Heights

This chapter discusses opportunities and limitations of height inequality, especially the role of social status and income distribution in determining height inequality. The more unequal the income distribution in a society, the more unequal the corresponding height distribution. At one time, the height gap between rich and poor teenagers in industrializing England was as high as 22 cm (8.7 inches); today, height inequality tends to be much lower (on the order of a few centimeters) because the gap between rich and poor in developed countries tends to be smaller. Results presented here suggest that height inequality is driven by differences in purchasing power, education, physical workload, and epidemiological environment. In a modern setting, social safety and redistribution of income is also relevant. An introduction into the literature helps illustrate opportunities this methodology has to offer to understand better the dynamics of the way populations experience economic development.

Replication of the association of GLT6D1 with aggressive periodontitis in a Sudanese population

BACKGROUND: Susceptibility to aggressive periodontitis (AgP) is influenced by genetic as well as environmental factors. Studies linking gene variants to AgP have been mainly centred in developed countries with limited data from Africa.
AIM: To investigate whether previously reported candidate gene associations with AgP could be replicated in a population from Sudan.


METHODS: The investigation was a case-control design. Cases with AgP (n = 132) and controls (n = 136) were identified from patients attending the Periodontal Department in Khartoum Dental Hospital. Genotyping was performed using the Sequenom MassARRAY iPLEX platform. Analysis focused on gene variants with a minor allele frequency (MAF) > 25% in the Sudanese subjects that had previously been reported to be associated with AgP.


RESULTS: One candidate gene rs1537415 (GLT6D1) was significantly associated with AgP, OR = 1.50 (95% CI 1.04-2.17), p = 0.0295 (increasing to p = 0.09 after correction for multiple testing). The association strengthened to OR = 1.56 (95% CI 1.15-2.16), p = 0.0042 when the controls were supplemented with data from the Hap map for the Yoruba in Ibadan (n = 147) and remained significant (p = 0.013) after correction for multiple testing.


CONCLUSION: The study independently replicated the finding that rs1537415, a variant in glycosyl transferase gene GLT6D1, is associated with AgP and provided the first report of genetic associations with AgP in a Sudanese population.

Clinical and Cost-Effectiveness of Procalcitonin Test for Prodromal Meningococcal Disease-A Meta-Analysis

BACKGROUND: Despite vaccines and improved medical intensive care, clinicians must continue to be vigilant of possible Meningococcal Disease in children. The objective was to establish if the procalcitonin test was a cost-effective adjunct for prodromal Meningococcal Disease in children presenting at emergency department with fever without source.

METHODS AND FINDINGS: Data to evaluate procalcitonin, C-reactive protein and white cell count tests as indicators of Meningococcal Disease were collected from six independent studies identified through a systematic literature search, applying PRISMA guidelines. The data included 881 children with fever without source in developed countries.The optimal cut-off value for the procalcitonin, C-reactive protein and white cell count tests, each as an indicator of Meningococcal Disease, was determined. Summary Receiver Operator Curve analysis determined the overall diagnostic performance of each test with 95% confidence intervals. A decision analytic model was designed to reflect realistic clinical pathways for a child presenting with fever without source by comparing two diagnostic strategies: standard testing using combined C-reactive protein and white cell count tests compared to standard testing plus procalcitonin test. The costs of each of the four diagnosis groups (true positive, false negative, true negative and false positive) were assessed from a National Health Service payer perspective. The procalcitonin test was more accurate (sensitivity=0.89, 95%CI=0.76-0.96; specificity=0.74, 95%CI=0.4-0.92) for early Meningococcal Disease compared to standard testing alone (sensitivity=0.47, 95%CI=0.32-0.62; specificity=0.8, 95% CI=0.64-0.9). Decision analytic model outcomes indicated that the incremental cost effectiveness ratio for the base case was £-8,137.25 (US $ -13,371.94) per correctly treated patient.

CONCLUSIONS: Procalcitonin plus standard recommended tests, improved the discriminatory ability for fatal Meningococcal Disease and was more cost-effective; it was also a superior biomarker in infants. Further research is recommended for point-of-care procalcitonin testing and Markov modelling to incorporate cost per QALY with a life-time model.

Public Private Partnerships: A Global Review

This book provides an international perspective on Public Private Partnerships. Through 21 case studies, it investigates the existing and fast developing body of principles and practices from a wide range of countries and is the first book to bring together leading international academics and practitioners under a common framework that enables convenient cross-country comparisons. The authors focus on the impact of the financial crisis has had on how governments have reviewed and overhauled their PPP policies as they have examined or tested new ways of partnering more effectively, efficiently and sustainably with the private sector.
Readers will be able to gauge the level of maturity of PPP development in the book’s case studies, understand similarities and differences in their practices, and gain useful insights into the regulatory framework and institutional infrastructure in place to support implementation of PPP. Finally, the book offers insights into the future challenges and opportunities that PPP offers stakeholders.

Alterations in Circulating Immune Cells in Neovascular Age-Related Macular Degeneration

Neovascular age-related macular degeneration (nAMD) is the leading cause of irreversible blindness in developed countries. Recent advances have highlighted the essential role of inflammation in the development of the disease. In addition to local retinal chronic inflammatory response, systemic immune alterations have also been observed in AMD patients. In this study we investigated the association between the frequency of circulating leukocyte populations and the prevalence as well as clinical presentations of nAMD. Leukocyte subsets of 103 nAMD patients (most of them were receiving anti-VEGF therapy prior to enrolment) and 26 controls were analysed by flow cytometry by relative cell size, granularity and surface markers. Circulating CD11b(+) cells and CD16(hi)HLA-DR(-) neutrophils were significantly increased (P = 0.015 and 0.009 respectively) in nAMD when compared to controls. The percentage of circulating CD4(+) T-cells was reduced in nAMD patients without subretinal fibrosis (P = 0.026) compared to patients with subretinal fibrosis. There was no correlation between the percentage of circulating leukocytes and the responsiveness to anti-VEGF therapy in nAMD patients. Our results suggest that higher levels of circulating CD11b(+) cells and neutrophils are associated with nAMD and that reduced levels of CD4(+) T-cells are associated with the absence of subretinal fibrosis in nAMD.

Five-year incidence and postoperative visual outcome of cataract surgery in urban southern China:The liwan eye study

Purpose. To determine the 5-year incidence and visual outcome of cataract surgery in an adult urban Chinese population. Methods. A comprehensive eye examination was performed at baseline and 5 years later on subjects participating in a population-based study. Incident cataract surgery was defined as having undergone surgery in either eye during the 5-year period. Postoperative visual impairment (PVI) was defined as visual acuity (VA) <6/18 based on both presenting VA (PVA) and best corrected VA (BCVA) in the operated eye. Results. Among the 1405 baseline participants, 75% (924) of survivors were seen at the 5-year follow-up visit. Forty-four returning participants (62 eyes) had undergone incident cataract surgery, an incidence of 4.84% (95% confidence interval [CI] - [3.53, 6.44]). Detailed medical and surgical records were available for 54/62 (87.1%) eyes, and of these, 5/ 54 (24.1%) had an immediate preoperative visual acuity <6/ 120. All recorded surgeries were performed at tertiary-level hospitals with phacoemulsification and foldable intraocular lens implantation. Those undergoing cataract surgery were more educated (P < 0.05) and had poorer baseline PVA in the worse-seeing eye (P < 0.001) than 54 persons with baseline PVA <6/18 due to cataract who had not had surgery. Among the 62 operated eyes, 22.6% (14/62) had PVI based on PVA and 9.6% (6/62) based on BCVA. Conclusions. Despite somewhat lower incidence, outcomes of cataract surgery in urban southern China are comparable with developed countries and better than for rural China. In urban China, emphasis should be on improving access to surgery. (Invest Ophthalmol Vis Sci. 2012;53:7936-7942) © 2012 The Association for Research in Vision and Ophthalmology, Inc.