Implementing post-normal science with or for EU policy actors: using quantitative story-telling.

There is increasing recognition of the wicked nature of the intertwined climate, biodiversity and economic crises, and the need for adaptive, multi-scale approaches to understanding the complexity of both the problems and potential responses. Most science underpinning policy responses to sustainability issues, however, remains overtly apolitical and focussed on technical innovation; at odds with a critical body of literatures insisting on the recognition of systemic problem framing when supporting policy processes. This paper documents the experience of implementing a mixed method approach called quantitative story-telling (QST) to policy analysis that explicitly recognises this normative dimension, as the methodology is part of a post-normal science (PNS) toolkit. The authors reflect on what was learnt when considering how QST fared as a tool for science-policy interaction, working with European Union (EU) level policy actors interested in sustainable agriculture and sustainable development goal 2. These goals-also known as UN Agenda 2030-are the latest institutionalisation of the pursuit of sustainable development and the EU has positioned itself as taking a lead in its implementation. Thus, the paper illustrates our experience of using PNS as an approach to science policy interfaces in a strategic policy context; and illustrates how the challenges identified in the science-policy literature are amplified when working across multiple policy domains and taking a complex systems approach. Our discussion on lessons learnt may be of interest to researchers seeking to work with policy-makers on complex sustainability issues.

Caring for the woman with migraine headaches.

About 16% of American women experience migraine headaches. These debilitating headaches cause lost time from family, social activities, and work. Although migraines are thought to be a result of shifting menstrual and perimenopausal hormones, a physiologic connection has not been well established. This article approaches premenstrual and perimenopausal migraine headaches from a chronic disease perspective, focusing on self-care and the use of prescription and nonprescription therapies. Implications for practice and future research also are discussed.

Caring for the woman with migraine headaches.

Approximately 16% of American women experience migraine headaches. These debilitating headaches cause lost time from family, social activities, and work. Although migraines are thought to be a result of shifting menstrual and perimenopausal hormones, a physiologic connection has not been well established. Despite the lack of certainty regarding migraine cause, several theories have been postulated and a significant amount of literature has been published addressing the management of premenstrual migraines. Fewer articles have been published regarding the management of perimenopausal migraines, which are treated somewhat differently. This article approaches both premenstrual and perimenopausal migraine headaches from a chronic disease perspective, focusing on self-care and the use of prescription and nonprescription therapies. Implications for practice and future research are also discussed.

von Willebrand factor activity detected in a monoclonal antibody-based ELISA: an alternative to the ristocetin cofactor platelet agglutination assay for diagnostic use.

The monoclonal antibody RFF-VIII:R/1 recognises an epitope on von Willebrand factor involved in its interaction with GPIb alpha. A two-site, solid phase ELISA has been established using RFF-VIII:R/1 as the solid-phase, capture antibody and an enzyme-conjugated, polyclonal antibody to human VWF, which provides an assay for VWF functional activity with a detection limit of 0.5 U/dl VWF and an interassay %CV < 10. Plasma from 192 VWD patients (48 studied retrospectively; 144 prospectively) showed VWF levels of < 50 U/dl in type 1 patients (n = 156), < 25 U/dl in type 2A (n = 26) and < 35 U/dl in type 2B (n = 8) which, in type 1 and 2A patients, correlated with RiCoF activity (r > or = 0.82). In plasma from patients with type 1 VWD values of VWF in the Mab-based ELISA were similar to levels of VWF:Ag measured in a polyclonal antibody-based ELISA (r > or = 0.87) but were significantly lower than VWF:Ag in type 2A and 2B plasmas (p < or = 0.0005), allowing discrimination of variant VWD. The Mab-based ELISA has advantages of sensitivity and reproducibility over the RiCoF assay to measure VWF activity and can be used to analyse stored samples. In conjunction with an ELISA for VWF:Ag and VWF multimer analysis, it provides a reliable method for the laboratory diagnosis of VWD.

The impact of climate change on the soil/moisture regime of Scottish mineral soils.

The likely impact of climate change on the moisture regime of Scottish soils and consequently on agriculture and land use has been addressed using a novel Geographic Information Systems (GIS) approach. Current estimates of changes in summer precipitation by the year 2030 are 0% with an associated uncertainty of +/- 11%. This study considers the worst case scenario of a decrease in rainfall by 11% which will lead to some low rainfall areas experiencing an increased drought risk, particularly on lighter soils. Wet areas with heavy soils could benefit from an increase in the accessibility period for machinery. As the major agricultural land in Scotland is located on the relatively dry east coast where localised problems due to drought are not uncommon even under the present climate, the detrimental effects of a decrease in rainfall for the whole of Scotland are therefore likely to outweigh the benefits. Approximately 8% of Scotland has been identified in this study as soil/climate combinations which will be susceptible to drought should summer rainfall decrease by 11% and summer temperature increase by 1.4 degrees C.

Hypothyroidism as a cause of acquired von Willebrand's disease.

Three patients with bleeding tendency who met the criteria for type 1 von Willebrand's disease are described. In two patients, hypothyroidism was suspected and confirmed at presentation, and in the third hypothyroidism became apparent 4 years later. In all three, the history and clinical course after treatment with thyroxine indicated acquired von Willebrand's disease secondary to hypothyroidism. The possibility of hypothyroidism should be considered in patients presenting with von Willebrand's disease.

Disappearance of antibodies to Factor VIII in a patient with acquired haemophilia and carcinoma of the pancreas during cytotoxic therapy with fluorouracil and CCNU.

An inhibitor to clotting factor VIII (anti-VIII:C) developed in a 70 year old woman with carcinoma of the pancreas three months after palliative by-pass surgery. A life-threatening sublingual haemorrhage was controlled by infusion of human factor VIII concentrate in high dosage. With the objective of reducing pancreatic tumour size, combination cytotoxic therapy with fluorouracil and CCNU was given. Reduction in the size of the tumour was associated with disappearance of anti-VIII:C, reappearance of normal quantities of clotting factor VIII (VIII:C) in the plasma and resolution of the bleeding tendency. The anti-VIII:C was characterised as being predominantly of the IgG4 sub-class with k light chains. In vitro and in vivo studies showed the inactivation of VIII:C by anti-VIII:C was markedly non-linear. Normal quantities of factor VIII coagulant antigen (VIII:CAg) were detected in the patient's plasma when VIII:C levels were negligible.

Clinical experience with polyelectrolyte-fractionated porcine factor VIII concentrate in the treatment of hemophiliacs with antibodies to factor VIII.

Circulating antibodies to factor VIII (anti-VIII, "inhibitors") occurring in patients with hemophilia neutralize porcine factor VIII less readily than human factor VIII in vitro. Over an 18-mo period, 8 patients with anti-VIII were treated with 45 courses (297 infusions) of polyelectrolyte-fractionated porcine factor VIII concentrate (PE porcine VIII). Where no anti-PE porcine VIII was detectable, mean post-infusion rise in plasma factor VIII was 1.29 U/dl/units infused/kg. Above 13 Old Oxford units of anti-PE porcine VIII and 48 Bethesda units of anti-human VIII, there were no postinfusion rises in plasma factor VIII. Where postinfusion rises were detected, clinical responses were good and conventional methods could be used to guide dosage. Ten percent of infusions were followed by febrile reactions, but these were usually mild and decreased in frequency and severity with increasing exposure. Multiple and prolonged courses of therapy were given to some patients without evidence of loss of clinical or laboratory efficacy. PE porcine VIII could provoke anamnestic rises of anti-VIII in susceptible patients, but appeared to have a lower immunogenic potential than human VIII. PE porcine VIII is a rational and effective therapeutic alternative for patients with anti-VIII, particularly those with intermediate level inhibitors who cannot be managed effectively using human factor VIII.

A maximum likelihood estimate of the sex ratio of mutation rates in haemophilia A.

Carrier detection tests were carried out on 21 mothers of isolated cases of severe Haemophilia A, according to WHO recommendations. A maximum likelihood estimate of the male to female mutation ratio of 9.6 (95% confidence limits 2.2-41.5) was obtained.

Coagulation activation and hyperviscosity in infection.

A serial study of coagulation activation and whole-blood viscosity was performed on 37 patients with local or systemic bacterial infection, malaria, or a viral infection. Thrombocytopenia, without consumption of coagulation factors, was the main feature of benign tertian malaria and viral infection, whereas in septicaemia and malignant tertian malaria it was associated with activation of coagulation and fibrinolysis. Patients with evidence of intravascular coagulation showed the highest levels of factor VIII related antigen which did not correlate with fibrinogen and probably reflected vascular endothelial cell damage rather than an acute-phase protein reaction. Hyperviscosity, which has been implicated in the pathogenesis of endotoxic shock and cerebral malaria, occurred in parallel with the acute-phase rise in plasma fibrinogen. There was, however, no evidence to implicate hyperviscosity as a major causative factor in the pathogenesis of septic shock or severe infective illness.

Serial changes in coagulation and viscosity during sickle-cell crisis.

Coagulation activity and whole-blood viscosity were measured in the steady state, and serially during painful crisis, in eight patients with sickle-cell anaemia. Platelet and coagulation activation occurred in the steady state and became more pronounced early in crisis. Whole-blood viscosity increased during crisis in parallel with plasma fibrinogen. Similar changes were found in a parallel study of 20 patients with localized bacterial or viral infection who did not have sickle-cell anaemia. Reports of platelet activation, hypercoagulability, and hyperviscosity during painful crisis therefore reflect secondary changes arising from vascular stasis, precipitating infection, and an acute-phase protein reaction. Although secondary, these changes may contribute to vascular occlusion by an additive effect in vessels already partially occluded by sickled cells.

Coagulation and fibrinolytic activity of cerebrospinal fluid.

Fibrin/fibrinogen degradation products (fragments D and E) were detected in cerebrospinal fluid in 23.4% of 252 patients admitted to a neurological/neurosurgical unit. Other coagulation proteins of low molecular weight (plasminogen and factor IX) were also present but larger proteins (fibrinogen and factor V) were not. These findings are consistent with protein leakage across a blood-CSF barrier damaged by inflammatory, vascular, or neoplastic disease. Fibrin/fibrinogen degradation products in cerebrospinal fluid after subarachnoid haemorrhage may not, therefore, be a reliable index of increased fibrinolytic activity in the subarachnoid space and may be misleading when selecting patients for fibrinolytic blockade.