UK devolution and the European Union: a tale of cooperative asymmetry?

The post 1999 devolution project has resulted in a major recalibration of the pre-existing arrangements for making European Union policy within the UK. The devolved administrations in Scotland and Wales (but not the English regions) have gained in electoral legitimacy and legislative powers, and thereby a greater claim to consultation with UK central government. Four key characteristics of EU policy making in a devolved UK are identified. The legal contingency of the 'devolveds'' status has not yet impeded traditional cooperative relations between government tiers, but the stability of the new arrangements remains in question. The UK case is compared to EU regionalisation in other member states and a distinction is drawn between a cooperative regionalist approach (the devolveds) and a consultative one (the English regions)

Vascular Dysfunction and Posttraumatic Stress Disorder: Examining the Role of Oxidative Stress and Sympathetic Activity

Purpose: The physiological manifestations of posttraumatic stress disorder (PTSD) have been associated with an increase in risk of cardiovascular disease (CVD) independent of negative lifestyle factors. The goal of the study was to better elucidate the mechanisms behind the increased CVD risk by examining peripheral vascular function, a precursor to CVD. Moreover, this study sought to determine the role of oxidative stress and sympathetic nervous system (SNS) activity in PTSD-induced vascular dysfunction. Methods: Sixteen individuals with PTSD (10 women, 6 men; age 24 ± 4 years), and twenty-four healthy controls (CTRL; 15 women, 9 men, 24 ± 4 years), participated in the study. The PTSD group participated in two visits, consuming either a placebo or antioxidant cocktail (AO - vitamins C and E and alpha lipoic acid) prior to their visits, in a randomized order. Arm vascular function was assessed via the reactive hyperemia- induced flow mediated dilation of the brachial artery (BAFMD) technique and evaluated with Doppler ultrasonography. Brachial artery and arm microvascular function were determined by percent change of diameter from baseline normalized for BA shear rate (BAD/Shear), and blood flow area under the curve (BF AUC), respectively. Heart rate variability (HRV) was used to assess autonomic nervous system activity. Results: BF AUC was significantly lower (p = 0.02) and SNS activity was significantly higher (p = 0.02) in the PTSD group when compared to the CTRL group. BAD/Shear was not different between groups. Following the acute AO supplementation, BF AUC was augmented to which it was no longer significantly different (p = 0.16) when compared to the CTRL group. SNS activity within the PTSD group was significantly reduced (p=.007) following the AO supplementation when compared to the PL condition, and the difference between PTSD and CTRL was no longer significant (p=.41). Conclusion: Young individuals with PTSD demonstrated lower arm microvascular, but not brachial artery, function as well as higher sympathetic activity when compared to healthy controls matched for age, sex, and physical activity level. Furthermore, this microvascular dysfunction and SNS activity was attenuated by an acute AO supplementation to the level of the healthy controls. Taken together, this study revealed that the modulation of oxidative stress, via an acute AO supplementation, improved vascular dysfunction in individuals with PTSD, potentially by reducing the substantial SNS activity associated with this disorder.https://scholarscompass.vcu.edu/gradposters/1084/thumbnail.jp

Pharmacology of Heparin and Related Drugs: An Update

Heparin has been used extensively as an antithrombotic and anticoagulant for close to 100 years. This anticoagulant activity is attributed to the pentasaccharide sequence which potentiates the inhibitory action of antithrombin, a major inhibitor of the coagulation cascade. More recently it has been determined that heparin also has antithrombotic action through interference of the formation of neutrophil extracellular traps which have been determined to play a role in thrombosis. This demonstrated a well-known observation that heparin, given it is a highly negatively charged polysaccharide, interacts with a broad range of biomolecules demonstrating attenuating effect. Since our previous review, there has been an increased interest in these non-anticoagulant effects of heparin, with the beneficial role in patients infected with sars2-coronavirus a highly topical example. This article provides an update on our previous review with more recent developments and observations made for these novel uses of heparin and an overview of the development status of heparin-based drugs. Significance Statement This state of the art review covers recent developments in the use of heparin and heparin-like materials as anticoagulant, now including immuno-thrombosis observations, and as non-anticoagulant including a role in the treatment of sars-coronavirus and inflammatory conditions

Effects of Dietary Sodium Intake on Blood Flow Regulation During Exercise in Salt Resistant Individuals

PURPOSE: Dietary sodium intake guidelines is ≤2,300 mg/day, yet is exceeded by 90% of Americans. This study examined the impact of a high sodium diet on blood flow regulation during exercise. METHODS: Six males (25 ± 2 years) consumed dietary sodium intake guidelines for two weeks, with one week salt-capsule supplemented (HS: 6,900 mg/day of sodium) and the other week placebo-capsule supplemented (LS: 2,300 mg/day of sodium). At the end of each week, peripheral hemodynamic measurements [blood flow (BF), shear rate (SR), and flow mediated dilation (FMD)/SR)] of the brachial and superficial femoral artery were taken during handgrip (HG) and plantar flexion (PF) exercise, respectively. Each exercise workload was 3 minutes and progressed by 8 kilograms until exhaustion. RESULTS: There were no differences between LS and HS in blood pressure (82 ± 4 v 80 ± 5 mmHg; p = 0.3) or heart rate (56 ± 6 v 59 ± 10 bpm; p = 0.4). HG and PF exercise increased BF, SR, and FMD/SR across workload (p \u3c 0.03 for all), but no difference between diets (p \u3e 0.05 for all). CONCLUSION: Despite previous reports that HS impairs resting vascular function, this study revealed that peripheral vascular function and blood flow regulation during exercise is not impacted by a HS diet.https://scholarscompass.vcu.edu/gradposters/1082/thumbnail.jp

Biochemical and functional characterization of glycosaminoglycans released from degranulating rat peritoneal mast cells: insights into the physiological role of endogenous heparin

We acknowledge the support of the Wellcome Trust for a grant to RL, CPP and NVR to support some of this work.The properties of commercially prepared heparin as an anticoagulant and antithrombotic agent in medicine are better understood than is the physiological role of heparin in its native form, where it is uniquely found in the secretory granules of mast cells. In the present study we have isolated and characterised the glycosaminoglycans (GAGs) released from degranulating rat peritoneal mast cells. Analysis of the GAGs by NMR spectroscopy showed the presence of both heparin and the galactosaminoglycan dermatan sulphate; heparinase digestion profiles and measurements of anticoagulant activity were consistent with this finding. The rat peritoneal mast cell GAGs significantly inhibited accumulation of leukocytes in the rat peritoneal cavity in response to IL-1β (p < 0.05, n = 6/group), and inhibited adhesion and diapedesis of leukocytes in the inflamed rat cremasteric microcirculation in response to LPS (p < 0.001, n = 4/group). FTIR spectra of human umbilical vein endothelial cells (HUVECs) were altered by treatment of the cells with heparin degrading enzymes, and restored by the addition of exogenous heparin. In conclusion, we have shown that rat peritoneal mast cells contain a mixture of GAGs that possess anticoagulant and anti-inflammatory properties.PostprintPeer reviewe

MODIFI: protocol for randomised feasibility study of eye-movement desensitisation and reprocessing therapy (EMDR) for functional neurological disorder (FND)

INTRODUCTION: Functional neurological disorder (FND) refers to an involuntary loss of control over and/or aberrant perception of the body. Common presenting symptoms are functional (non-epileptic) seizures, and functional motor disorder, for example, walking difficulties, weakness or tremor. Greater access to effective treatments would lead to reduced distress and disability; and reduce unnecessary healthcare costs.This study will examine eye-movement desensitisation and reprocessing therapy (EMDR) as a treatment for FND. EMDR is an evidence-based treatment for post-traumatic stress disorder (PTSD), but its use for other conditions is growing. An FND-specific EMDR protocol will be tested, and if the intervention proves feasible with promising clinical outcomes, progression to a substantive study could take place. METHODS AND ANALYSIS: Fifty adult patients diagnosed with FND will be recruited. It will be a single-blind randomised controlled trial with two arms: EMDR (plus standard neuropsychiatric care; NPC) and standard NPC. The two groups will be compared at baseline (T0), 3 months (T1), 6 months (T2) and 9 months (T3). Measures of feasibility include safety, recruitment, retention, treatment adherence and acceptability. Clinical outcome measures will assess health-related functioning/quality of life, ratings of FND symptoms and severity, depression, anxiety, PTSD, dissociation, service utilisation and other costs. Improvement and satisfaction ratings will also be assessed. Feasibility outcomes will be summarised using descriptive statistics. Exploratory analyses using (linear/logistic) mixed-effect models will examine the rate of change in the groups' clinical outcome measures across the four time-points.After the intervention period, a sample of participants, and clinicians, will be invited to attend semistructured interviews. The interviews will be analysed using reflexive thematic analysis. ETHICS AND DISSEMINATION: This study has been approved by the NHS West Midlands-Edgbaston Research Ethics Committee. Study findings will be published in open access peer-reviewed journals, presented at conferences, and communicated to participants and other relevant stakeholders. TRIAL REGISTRATION: NCT05455450 (www.gov)

Housing theory, housing research and housing policy

Jim Kemeny in 1992 criticised existing housing research for neglecting social theory and being overly positivist and policy focused. The result has been a strengthening of the conceptual basis of housing research in general, but also a growing schism between researchers who focus on policy relevancy and those that pursue more theoretical work. This paper challenges this schism and argues for theoretically based and policy relevant research. First the paper argues that the policy-making process is complex and can vary between different countries, situations and over time. Therefore, it is argued that many styles of research can influence policy in the right circumstances. Second, the paper challenges the idea that there can be theoretically-free housing research arguing that all research has a theoretical foundation even though in many studies it is not explicit. Finally, the paper engages with the debate about where theory for housing research should come from and what it would look like

MODIFI: protocol for randomised feasibility study of eye-movement desensitisation and reprocessing therapy (EMDR) for functional neurological disorder (FND).

INTRODUCTION: Functional neurological disorder (FND) refers to an involuntary loss of control over and/or aberrant perception of the body. Common presenting symptoms are functional (non-epileptic) seizures, and functional motor disorder, for example, walking difficulties, weakness or tremor. Greater access to effective treatments would lead to reduced distress and disability; and reduce unnecessary healthcare costs.This study will examine eye-movement desensitisation and reprocessing therapy (EMDR) as a treatment for FND. EMDR is an evidence-based treatment for post-traumatic stress disorder (PTSD), but its use for other conditions is growing. An FND-specific EMDR protocol will be tested, and if the intervention proves feasible with promising clinical outcomes, progression to a substantive study could take place. METHODS AND ANALYSIS: Fifty adult patients diagnosed with FND will be recruited. It will be a single-blind randomised controlled trial with two arms: EMDR (plus standard neuropsychiatric care; NPC) and standard NPC. The two groups will be compared at baseline (T0), 3 months (T1), 6 months (T2) and 9 months (T3). Measures of feasibility include safety, recruitment, retention, treatment adherence and acceptability. Clinical outcome measures will assess health-related functioning/quality of life, ratings of FND symptoms and severity, depression, anxiety, PTSD, dissociation, service utilisation and other costs. Improvement and satisfaction ratings will also be assessed. Feasibility outcomes will be summarised using descriptive statistics. Exploratory analyses using (linear/logistic) mixed-effect models will examine the rate of change in the groups' clinical outcome measures across the four time-points.After the intervention period, a sample of participants, and clinicians, will be invited to attend semistructured interviews. The interviews will be analysed using reflexive thematic analysis. ETHICS AND DISSEMINATION: This study has been approved by the NHS West Midlands-Edgbaston Research Ethics Committee. Study findings will be published in open access peer-reviewed journals, presented at conferences, and communicated to participants and other relevant stakeholders. TRIAL REGISTRATION: NCT05455450 (www. CLINICALTRIALS: gov)

The New British Policy Style: From a British to a Scottish Political Tradition?

The new context of coalition government and the &lsquo;Big Society' suggests that the UK government is moving towards a style of politics followed successfully in Scotland, extending a partnership approach from national to local forms of government. Yet the two arenas have never been as far apart as is commonly imagined. The majoritarian (UK) and consensus (Scottish) labels are misleading. British politics is not as exceptional as it is often made out to be, while Scottish politics retains many elements of its British counterpart. This article assesses the state of British politics in this light. It sets out a counter-exceptionalism thesis based on the theory and evidence from public policy. It then summarises the post-devolution evidence, producing insights on the British policy style when compared to the &lsquo;new politics' in Scotland