Chronicle of a referendum foretold: what next for the Malvinas/Falklands?

The announcement of the result of the March 2013 referendum on whether the Falklands/Malvinas should remain a British overseas territory came as no surprise in either Britain or Argentina, or on the South Atlantic islands themselves. Indeed, perhaps the biggest shock of all was the news that three inhabitants actually voted against remaining under British rule. As bewildered Kelpers in the close-knit island community speculated on where the voices of dissent had come from, in the aftermath of the referendum we consider what has really changed and offer insight into what will happen next. In particular, we argue that it is in both British and Argentine self-interest to change their stances in order to resolve the issue

Cariology Clinical Trials:What Are We-and What Should We Be-Looking At?

Randomized control trial (RCT) methodology has compared interventions for the prevention and management of dental caries since the late 1960s. Despite almost 50 years and evidence of significant wastage within the wider biomedical research field, there has been little investigation into what works well and where weaknesses lie. This paper aims to draw attention to areas for improvement within cariology clinical trial methodology by summarizing systematic reviews on interventions and outcomes, and using examples to illustrate some challenges with intervention delivery fidelity, outcome analyses, and intervention co-production. Trial design stage choices are critical to ensure that optimum information is obtained when testing interventions. Intervention choice, outcome choice, and analyses are particularly important, and cariology trials have specific issues associated with them. A systematic search and review of cariology RCTs found 650 RCT reports. Social Network Analysis of interventions revealed a high degree of separation between prevention and management trials, gaps in clinically important comparisons, and a tendency for there to be comparisons within groups; e.g., comparison of interventions within the same, rather than different, levels of invasiveness. Outcomes measured for the same trial reports show: a focus on restoration performance and individual/population caries burden; the growing use of carious lesion activity and economic-related outcomes; and sparse, although an increase in the use of, patient-reported/patient-centered outcomes. Fidelity of adherence to complex interventions can be challenging to measure but is important in interpreting trial findings. Involving target populations in intervention design, delivery, and relating it to the planned rollout, are opportunities to ensure intervention relevance and improved uptake. Outcomes analyses should consider the minimum clinically important differences and outcome relevance measures for the target population. Factors underlying trialists’ comparator and outcome choices need to be identified, and there is a need to ensure that a minimum dataset of outcomes allow for combination and comparisons of trial data for systematic review

Introduction revisiting the Argentine crisis a decade on: changes and continuities

This introductory chapter to the book "Argentina Since the 2001 Crisis Recovering the Past, Reclaiming the Future" analyses crisis and its associated responses and subsequent recovery in the context of Argentina’s multiple implosion of 2001-02 whilst also assessing its legacies for the country’s social, cultural, economic and political realms during the last decade. It recognises that "crisis" is a term that is much used in the post-Lehman Brothers world and that the subsequent responses and associated recoveries (or lack of) have been the subject of a cascade of academic, government, media, and think-tank investigation ever since. The chapter instead seeks to understand the nature of how crisis and its impacts should be investigated and interrogated, by rejecting false dichotomies of ‘old’ and ‘new’ and synthesising understanding to form an analysis that draws both elements of continuity and elements of change. Secondly, it argues that crisis manifests itself in a number of realms, and that heuristic devices employed to investigate them must subsequently also be drawn from across a range of disciplinary perspectives. Thirdly, it examines how the 2001-02 crisis in Argentina led to a series of responses that both rejected the neoliberal model yet also recovered elements of it. Finally it outlines the structure of the rest of the book, briefly summarising the chapters in turn

Inbuilt Mechanisms for Overcoming Functional Problems Inherent in Hepatic Microlobular Structure

This paper is funded by an MRC/EPSRC Discipline Bridging Initiative Grant (G0502256-77947) to W. Wan

Observational study of the association of first insulin type in uncontrolled type 2 diabetes with macrovascular and microvascular disease

<p>Aims: To compare the risk of vascular disease, HbA1c and weight change, between first prescribed insulins in people with type 2 diabetes.</p> <p>Methods: People included in THIN United Kingdom primary care record database who began insulin (2000–2007) after poor control on oral glucose-lowering agents (OGLD) were grouped by the number of OGLDs in their treatment regimen immediately before starting insulin (n = 3,485). Within OGLD group, Cox regression compared macrovascular (all-cause mortality, myocardial infarction, acute coronary syndrome and stroke) and microvascular disease (peripheral neuropathy, nephropathy, and retinopathy) between insulin type (basal, pre-mix or Neutral Protamine Hagedorn, NPH) while ANCOVAs compared haemoglobin A1c (HbA1c) and weight change.</p> <p>Results: Mean follow-up was 3.6 years. Rates of incident macrovascular events were similar when basal insulin was compared to pre-mix or NPH, adjusted hazard ratio versus basal: pre-mix 1.08 (95% CI 0.73, 1.59); NPH 1.00 (0.63, 1.58) after two OGLDs, and pre-mix 0.97 (0.46, 2.02); NPH 0.77 (0.32, 1.86) after three OGLDs. An increased risk of microvascular disease in NPH versus basal after 3 OGLDs, adjusted hazard ratio1.87 (1.04, 3.36), was not seen after two agents or in comparisons of basal and pre-mix. At one year, after two OGLDs, weight increase was less with basal compared with pre-mix. After three OGLDs, mean HbA1c had reduced less in basal versus pre-mix or NPH at 6–8 and at 9–11 months, and versus pre-mix at 12–14 months.</p> <p>Conclusion: We found no difference in the risk of macrovascular events between first insulins in the medium term when started during poor glycaemia control. The increased risk of microvascular events with NPH warrants further study. In certain groups, first use of basal insulin was associated with less gain in weight and decrease in HbA1c compared to other insulins.</p&gt

Towards precision medicine for pain: diagnostic biomarkers and repurposed drugs

We endeavored to identify objective blood biomarkers for pain, a subjective sensation with a biological basis, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design. We studied psychiatric patients, a high risk group for co-morbid pain disorders and increased perception of pain. For discovery, we used a powerful within-subject longitudinal design. We were successful in identifying blood gene expression biomarkers that were predictive of pain state, and of future emergency department (ED) visits for pain, more so when personalized by gender and diagnosis. MFAP3, which had no prior evidence in the literature for involvement in pain, had the most robust empirical evidence from our discovery and validation steps, and was a strong predictor for pain in the independent cohorts, particularly in females and males with PTSD. Other biomarkers with best overall convergent functional evidence for involvement in pain were GNG7, CNTN1, LY9, CCDC144B, and GBP1. Some of the individual biomarkers identified are targets of existing drugs. Moreover, the biomarker gene expression signatures were used for bioinformatic drug repurposing analyses, yielding leads for possible new drug candidates such as SC-560 (an NSAID), and amoxapine (an antidepressant), as well as natural compounds such as pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), and apigenin (a plant flavonoid). Our work may help mitigate the diagnostic and treatment dilemmas that have contributed to the current opioid epidemic

Nonalbuminuric Renal Impairment in Type 2 Diabetic Patients and in the General Population (National Evaluation of the Frequency of Renal Impairment cO-existing with NIDDM [NEFRON] 11)

OBJECTIVE Most diabetic patients with impaired renal function have a urinary albumin excretion rate in the normal range. In these patients, the etiology of renal impairment is unclear, and it is also unclear whether this nonalbumunuric renal impairment is unique to diabetes. RESEARCH DESIGN AND METHODS In this study, we examined the frequency and predictors of nonalbumunuric renal impairment (estimated glomerular filtration rate [eGFR] <60 ml/min per 1.73 m(2)) in a nationally representative cohort of 3,893 patients with type 2 diabetes and compared our findings with rates observed in the general population from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab) survey (n = 11,247). RESULTS Of the 23.1% of individuals with type 2 diabetes who had eGFR <60 ml/min per 1.73 m(2) (95% CI 21.8-24.5%), more than half (55%) had a urinary albumin excretion rate that was persistently in the normal range. This rate of renal impairment was predictably higher than that observed in the general population (adjusted odds ratio 1.3, 95% CI 1.1-1.5, P < 0.01) but was solely due to chronic kidney disease associated with albuminuria. In contrast, renal impairment in the absence of albuminuria was less common in those with diabetes than in the general population, independent of sex, ethnicity, and duration of diabetes (0.6, 0.5-0.7, P < 0.001). CONCLUSIONS Nonalbuminuric renal impairment is not more common in those with diabetes. However, its impact may be more significant. New studies are required to address the pathogenesis, prevention, and treatment of nonalbuminuric renal disease

Leibniz, Acosmism, and Incompossibility

Leibniz claims that God acts in the best possible way, and that this includes creating exactly one world. But worlds are aggregates, and aggregates have a low degree of reality or metaphysical perfection, perhaps none at all. This is Leibniz’s tendency toward acosmism, or the view that there this no such thing as creation-as-a-whole. Many interpreters reconcile Leibniz’s acosmist tendency with the high value of worlds by proposing that God sums the value of each substance created, so that the best world is just the world with the most substances. I call this way of determining the value of a world the Additive Theory of Value (ATV), and argue that it leads to the current and insoluble form of the problem of incompossibility. To avoid the problem, I read “possible worlds” in “God chooses the best of all possible worlds” as referring to God’s ideas of worlds. These ideas, though built up from essences, are themselves unities and so well suited to be the value bearers that Leibniz’s theodicy requires. They have their own value, thanks to their unity, and that unity is not preserved when more essences are added

South Africa, now at 2600 Natta Blvd., Bellmore, NY 11710, USA. § Physical Metallurgy Division, Mintek, Private Bag X3015, Randburg, 2125, South Africa. # School of Process and Materials Engineering

Abstract. Colour and hardness were measured on a series of alloys along the 76 wt % Au line of the Au-Cu-Al system. Complex, non-monotonic behaviour was observed, which is shown to be correlated with microstructural changes. The available colours include reddish, yellow, &apos;apricot&apos;, white and purple. The hardness of as-cast material varies from 150 to 500 Vickers