The best-kept secret(s) of evidence based policing

This paper draws on the work of the Evidence and Insight Team, a dedicated research function based within the Metropolitan Police Service for over a decade. The aim of the paper is to make readers aware of the obliquely hidden data goldmine that exists within UK policing. Such data captures the decisions police make routinely, the kinds of situations police encounter and with whom. This rich data seam goes beyond crime – and should be used more outside of policing. The authors argue that interested academics need a better roadmap of the data in order to stimulate basic knowledge and usage. Three case studies are presented that illustrate the scope and challenges of working with such data

The best-kept secret(s) of evidence based policing

This paper draws on the work of the Evidence and Insight Team, a dedicated research function based within the Metropolitan Police Service for over a decade. The aim of the paper is to make readers aware of the obliquely hidden data goldmine that exists within UK policing. Such data captures the decisions police make routinely, the kinds of situations police encounter and with whom. This rich data seam goes beyond crime – and should be used more outside of policing. The authors argue that interested academics need a better roadmap of the data in order to stimulate basic knowledge and usage. Three case studies are presented that illustrate the scope and challenges of working with such data

Evidence-based selection of environmental factors and datasets for measuring multiple environmental deprivation in epidemiological research

This Environment and Human Health project aims to develop a health-based summary measure of multiple physical environmental deprivation for the UK, akin to the measures of multiple socioeconomic deprivation that are widely used in epidemiology. Here we describe the first stage of the project, in which we aimed to identify health-relevant dimensions of physical environmental deprivation and acquire suitable environmental datasets to represent population exposure to these dimensions at the small-area level. We present the results of this process: an evidence-based list of environmental dimensions with population health relevance for the UK, and the spatial datasets we obtained and processed to represent these dimensions. This stage laid the foundations for the rest of the project, which will be reported elsewhere

Genetics and pathophysiology of mammalian sulfate biology

Nutrient sulfate is essential for numerous physiological functions in mammalian growth and development. Accordingly, disruptions to any of the molecular processes that maintain the required biological ratio of sulfonated and unconjugated substrates are likely to have detrimental consequences for mammalian physiology. Molecular processes of sulfate biology can be broadly grouped into four categories: firstly, intracellular sulfate levels are maintained by intermediary metabolism and sulfate transporters that mediate the transfer of sulfate across the plasma membrane; secondly, sulfate is converted to 3′-phosphoadenosine 5′-phosphosulfate (PAPS), which is the universal sulfonate donor for all sulfonation reactions; thirdly, sulfotransferases mediate the intracellular sulfonation of endogenous and exogenous substrates; fourthly, sulfate is removed from substrates via sulfatases. From the literature, we curated 91 human genes that encode all known sulfate transporters, enzymes in pathways of sulfate generation, PAPS synthetases and transporters, sulfotransferases and sulfatases, with a focus on genes that are linked to human and animal pathophysiology. The predominant clinical features linked to these genes include neurological dysfunction, skeletal dysplasias, reduced fecundity and reproduction, and cardiovascular pathologies. Collectively, this review provides reference information for genetic investigations of perturbed mammalian sulfate biology

Stable transformation of an episomal protein-tagging shuttle vector in the piscine diplomonad Spironucleus vortens

<p>Abstract</p> <p>Background</p> <p>Diplomonads are common free-living inhabitants of anoxic aquatic environments and are also found as intestinal commensals or parasites of a wide variety of animals. <it>Spironucleus vortens </it>is a putatively commensal diplomonad of angelfish that grows to high cell densities in axenic culture. Genomic sequencing of <it>S. vortens </it>is in progress, yet little information is available regarding molecular and cellular aspects of <it>S. vortens </it>biology beyond descriptive ultrastructural studies. To facilitate the development of <it>S. vortens </it>as an additional diplomonad experimental model, we have constructed and stably transformed an episomal plasmid containing an enhanced green fluorescent protein (GFP) tag, an AU1 epitope tag, and a tandem affinity purification (TAP) tag. This construct also contains selectable antibiotic resistance markers for both <it>S. vortens </it>and <it>E. coli</it>.</p> <p>Results</p> <p>Stable transformants of <it>S. vortens </it>grew relatively rapidly (within 7 days) after electroporation and were maintained under puromycin selection for over 6 months. We expressed the enhanced GFP variant, eGFP, under transcriptional control of the <it>S. vortens </it>histone H3 promoter, and visually confirmed diffuse GFP expression in over 50% of transformants. Next, we generated a histone H3::GFP fusion using the <it>S. vortens </it>conventional histone H3 gene and its native promoter. This construct was also highly expressed in the majority of <it>S. vortens </it>transformants, in which the H3::GFP fusion localized to the chromatin in both nuclei. Finally, we used fluorescence <it>in situ </it>hybridization (FISH) of the episomal plasmid to show that the transformed plasmid localized to only one nucleus/cell and was present at roughly 10–20 copies per nucleus. Because <it>S. vortens </it>grows to high densities in laboratory culture, it is a feasible diplomonad from which to purify native protein complexes. Thus, we also included a TAP tag in the plasmid constructs to permit future tagging and subsequent purification of protein complexes by affinity chromatography via a two-step purification procedure.</p> <p>Conclusion</p> <p>Currently, progress in protistan functional and comparative genomics is hampered by the lack of free-living or commensal protists in axenic culture, as well as a lack of molecular genetic tools with which to study protein function in these organisms. This stable transformation protocol combined with the forthcoming genome sequence allows <it>Spironucleus vortens </it>to serve as a new experimental model for cell biological studies and for comparatively assessing protein functions in related diplomonads such as the human intestinal parasite, <it>Giardia intestinalis</it>.</p

Retinoids regulate TGFβ signaling at the level of Smad2 phosphorylation and nuclear accumulation

AbstractIndirect regulation of transforming growth factor (TGF)-β signaling by retinoids occurs on a long-term timescale, secondary to transcriptional events. Studies by our group show loss of retinoid X receptor (RXR) alpha results in increased TGFβ2 in the midgestational heart, which may play a role in the cardiac defects seen in this model [S.W. Kubalak, D.R. Hutson, K.K. Scott and R.A. Shannon, Elevated transforming growth factor beta2 enhances apoptosis and contributes to abnormal outflow tract and aortic sac development in retinoic X receptor alpha knockout embryos, Development 129 (2002) 733–746.]. Acute and direct interactions between retinoid and TGFβ signaling, however, are not clearly understood. Treatment of dispersed hearts and NIH3T3 cells for 1 h with TGFβ and retinoids (dual treatment) resulted in increased phosphorylated Smad2 and Smad3 when compared to treatment with TGFβ alone. Of all dual treatments, those with the RXR agonist Bexarotene, resulted in the highest level of phosphorylated Smad2, a 7-fold increase over TGFβ2 alone. Additionally, during dual treatment phosphorylation of Smad2 occurs via the TGFβ type I receptor but not by increased activation of the receptor. As loss of RXRα results in increased levels of Smad2 phosphorylation in response to TGFβ treatment and since nuclear accumulation of phosphorylated Smad2 is decreased during dual treatment, we propose that RXRα directly regulates the activities of Smad2. These data show retinoid signaling influences the TGFβ pathway in an acute and direct manner that has been unappreciated until now

Systemic lobar shunting induces advanced pulmonary vasculopathy

AbstractObjectives: We characterized the morphology and vasomotor responses of a localized, high-flow model of pulmonary hypertension. Methods: An end-to-side anastomosis was created between the left lower lobe pulmonary artery and the aorta in 23 piglets. Control animals had a thoracotomy alone or did not have an operation. Eight weeks later, hemodynamic measurements were made. Then shunted and/or nonshunted lobes were removed for determination of vascular resistance and compliance by occlusion techniques under conditions of normoxia, hypoxia (FIO2 = 0.03), and inspired nitric oxide administration. Quantitative histologic studies of vessel morphology were performed. Results: Eighty-three percent of animals having a shunt survived to final study. Aortic pressure, main pulmonary artery and wedge pressures, cardiac output, blood gases, and weight gain were not different between control pigs and those receiving a shunt. Six of 9 shunted lobes demonstrated systemic levels of pulmonary hypertension in vivo. Arterial resistance was higher (24.3 ± 12.0 vs 1.3 ± 0.2 mm Hg · mL–1 · s–1, P =.04) and arterial compliance was lower (0.05 ± 0.01 vs 0.16 ± 0.03 mL/mm Hg, P =.02) in shunted compared with nonshunted lobes. Hypoxic vasoconstriction was blunted in shunted lobes compared with nonshunted lobes (31% ± 13% vs 452% ± 107% change in arterial resistance, during hypoxia, P <.001). Vasodilation to inspired nitric oxide was evident only in shunted lobes (34% ± 6% vs 1.8% ± 8.2% change in arterial resistance during administration of inspired nitric oxide, P =.008). Neointimal and medial proliferation was found in shunted lobes with approximately a 10-fold increase in wall/luminal area ratio. Conclusions: An aorta–lobar pulmonary artery shunt produces striking vasculopathy. The development of severe pulmonary hypertension within a short time frame, low mortality, and localized nature of the vasculopathy make this model highly attractive for investigation of mechanisms that underlie pulmonary hypertension. (J Thorac Cardiovasc Surg 2000; 120:88-98

Safe and just operating spaces for regional social-ecological systems

Humanity faces a major global challenge in achieving wellbeing for all, while simultaneously ensuring that the biophysical processes and ecosystem services that underpin wellbeing are exploited within scientifically informed boundaries of sustainability. We propose a framework for defining the safe and just operating space for humanity that integrates social wellbeing into the original planetary boundaries concept (Rockström et al., 2009a,b) for application at regional scales. We argue that such a framework can: (1) increase the policy impact of the boundaries concept as most governance takes place at the regional rather than planetary scale; (2) contribute to the understanding and dissemination of complexity thinking throughout governance and policy-making; (3) act as a powerful metaphor and communication tool for regional equity and sustainability. We demonstrate the approach in two rural Chinese localities where we define the safe and just operating space that lies between an environmental ceiling and a social foundation from analysis of time series drawn from monitored and palaeoecological data, and from social survey statistics respectively. Agricultural intensification has led to poverty reduction, though not eradicated it, but at the expense of environmental degradation. Currently, the environmental ceiling is exceeded for degraded water quality at both localities even though the least well-met social standards are for available piped water and sanitation. The conjunction of these social needs and environmental constraints around the issue of water access and quality illustrates the broader value of the safe and just operating space approach for sustainable development