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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003ECognitive dysfunction occurs after an aneurysmal subarachnoid hemorrhage, affecting psychosocial behavior, activities of daily living, and return to work. The mechanisms for the cognitive deficits are not understood, but neuroinflammation appears to be one process. New therapies to target neuroinflammation are being studied.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Eaneurysmal subarachnoid hemorrhage\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecognitive dysfunction\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecognitive deficit\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eheparin\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eglibenclamide\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EMini\u2013Mental Status Examination\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EMontreal Cognitive Assessment\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eneuroinflammation\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eneuropsychological tests\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Epsychosocial behavior\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Evasospasm\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003ECognitive function is affected after an aneurysmal subarachnoid hemorrhage (aSAH). A review of 61 studies identified deficits in memory, executive function, and language after an aSAH, which in turn affected activities of daily living, return to work, and quality of life [Al-Khindi T et al. \u003Cem\u003EStroke\u003C\/em\u003E. 2010]. Anxiety and depression were also increased in this patient population (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E) [Morris PG et al. \u003Cem\u003ENeurosurgery.\u003C\/em\u003E 2004]. However, there was a large variation in the proportion of patients who were affected across these studies, stated R. Loch Macdonald, MD, PhD, St Michael\u2019s Hospital, Toronto, Ontario, Canada, which may be a result of the various neuropsychological tests (NPTs) used to assess cognitive functions.\u003C\/p\u003E\n         \u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/2\/17\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Rates of Anxiety and Depression After Aneurysmal Subarachnoid HemorrhageReprinted from Morris PG et al. Anxiety and depression after spontaneous subarachnoid hemorrhage. Neurosurgery. 2004;54:47-54. With permission from Congress of Neurological Surgeons.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1745298829\u0022 data-figure-caption=\u0022\u0026amp;lt;div xmlns=\u0026amp;quot;http:\/\/www.w3.org\/1999\/xhtml\u0026amp;quot;\u0026amp;gt;Rates of Anxiety and Depression After Aneurysmal Subarachnoid HemorrhageReprinted from Morris PG et al. Anxiety and depression after spontaneous subarachnoid hemorrhage. \u0026amp;lt;em\u0026amp;gt;Neurosurgery.\u0026amp;lt;\/em\u0026amp;gt; 2004;54:47-54. With permission from Congress of Neurological Surgeons.\u0026amp;lt;\/div\u0026amp;gt;\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/2\/17\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/2\/17\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/2\/17\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/15260\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-3\u0022 class=\u0022first-child\u0022\u003ERates of Anxiety and Depression After Aneurysmal Subarachnoid Hemorrhage\u003C\/p\u003E\n               \u003Cp id=\u0022p-4\u0022\u003EReprinted from Morris PG et al. Anxiety and depression after spontaneous subarachnoid hemorrhage. \u003Cem\u003ENeurosurgery.\u003C\/em\u003E 2004;54:47-54. With permission from Congress of Neurological Surgeons.\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-5\u0022\u003ENeuropsychological testing is beneficial to help the patient identify and understand the inability to return to work. Additionally, NPTs can be used to target rehabilitation. Within clinical trials, NPTs can be used for outcome assessment and possibly to understand the pathophysiology and mechanisms of the brain damage after an aSAH. However, there is a need for tests that are more sensitive and specific in assessing cognitive function and accurately detecting a treatment effect, compared with the modified Rankin Scale and Glasgow Outcome Scale, for example, which are cruder, broader measures.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EThe Mini\u2013Mental Status Examination (MMSE) is short in duration but does not evaluate executive function after an aSAH. The Montreal Cognitive Assessment (MoCA) was developed to detect mild cognitive impairment, and it includes executive function and visual\/spatial testing. MoCA was found to be more sensitive than MMSE to detect cognitive impairment and predict abnormalities in executive function, among others, in 2 studies [Wong GK et al. \u003Cem\u003EEur J Neurol\u003C\/em\u003E. 2014; Schweizer TA et al. \u003Cem\u003EJ Neurol Sci\u003C\/em\u003E. 2012] but was similar to MMSE in another study [Wong GK et al. \u003Cem\u003EJ Neurol Neurosurg Psychiatry\u003C\/em\u003E. 2012].\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EThe development of additional NPTs may come from the common data elements project initiated by Prof Macdonald and colleagues, to reach consensus on a common set of cognitive tests that are short but comprehensive and validated in multiple languages and countries for multicenter data collection. They also started the Subarachnoid Hemorrhage International Trialists data repository to advance research in understanding cognitive dysfunction after an aSAH.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EMechanisms for Cognitive Dysfunction After an aSAH\u003C\/h2\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EThe inflammatory system appears to play a role in the cognitive dysfunction and delayed onset of memory after an aSAH, but the mechanisms are not fully understood. Although vasospasm can lead to permanent deficit, other mechanisms are involved too, stated Jose Javier Provencio, MD, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA.\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003ESubarachnoid hemorrhage (SAH) inhibits late long-term potentiation, known to affect spatial memory, through changes in the NMDA receptor that occur between days 3 and 6 after the hemorrhagic event. Neutrophils have also been implicated in the delayed deterioration post-SAH. One study showed an 8-fold increased risk of vasospasm in patients with cerebral spinal fluid (CSF) containing\u2009\u0026gt;\u200962% neutrophils on day 3 post-SAH [Provencio JJ et al. \u003Cem\u003ENeurocrit Care\u003C\/em\u003E. 2010]. Neutrophils may cause delayed deterioration through their effects on blood vessels, red cell hemolysis, and reactive oxygen species production and direct effects on the brain and recruitment of more inflammatory cells.\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EThe depletion of myeloid cells with anti-Lys6G\/C antibody ameliorated delayed deterioration and vasospasm and improved behavioral testing in a mouse model [Provencio JJ et al. \u003Cem\u003EJ Neuroimmunol\u003C\/em\u003E. 2011]. More recently, Dr Provencio and colleagues found that the depletion of neutrophils at day 3 post-SAH in a mouse model led to improvement in NMDA receptor function and memory testing.\u003C\/p\u003E\n         \u003Cp id=\u0022p-11\u0022\u003ENeutrophils and monocytes leave the vasculature when an aneurysm ruptures, moving into the CSF in humans and mice. The neutrophils act on the microglial cells, neurons, and NMDA receptor. However, how the neutrophils cross over into the CSF is unknown, and this is the focus of an upcoming study in Dr Provencio\u2019s laboratory. The 3-day delay in this process suggests a possible recruitment of systemic neutrophils as a second wave that is ultimately causing damage.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-3\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EStrategies to Modulate Neuroinflammation Post-SAH\u003C\/h2\u003E\n         \u003Cp id=\u0022p-12\u0022\u003EThe activation of toll-like receptor 4 activates the microglia and release of tumor necrosis factor alpha (TNF-\u03b1), which has been linked to cognitive dysfunction in animal models. Compounds that block the sulfonylurea receptor 1\u2013transient receptor potential melastatin 4 (Sur1-\u003Cem\u003ETrpm4\u003C\/em\u003E) channel have been shown to reduce not only the levels of TNF-\u03b1 and other markers of inflammation but also cognitive dysfunction in animal models of SAH, according to work reviewed by J. Marc Simard, MD, PhD, University of Maryland School of Medicine, Baltimore, Maryland, USA, and conducted in his laboratory. The Sur1-Trpm4 channel is upregulated in microglia, vessels, and astrocytes in animal models, and it was upregulated in neurons and vessels in human autopsy tissue.\u003C\/p\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EGlibenclamide has been shown to inhibit release of TNF-\u03b1 from microglia activated by methemoglobin, and in another model of SAH it reduced TNF-\u03b1, transcription factor p65, and glial fibrillary acidic protein (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E) [Simard JM et al. \u003Cem\u003EJ Cereb Blood Flow.\u003C\/em\u003E 2009]. Glibenclamide also has been shown to reduce induced nitric oxide synthase in microglia, as well as neutrophils and macrophages, and increase interleukin 10 in the entorhinal model of SAH. Notably, cognitive dysfunction was also reduced in the entorhinal model of SAH, with improvement in memory, rapid learning, and preservation of white and gray matter. These improvements are related to the beneficial effect of the anti-inflammatory agent in the hippocampal pathology, with better preservation of myelin and less cell death, stated Dr Simard.\u003C\/p\u003E\n         \u003Cdiv id=\u0022F2\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/2\/17\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Glibenclamide Reduced Markers of Inflammation in a Subarachnoid Hemorrhage ModelGFAP, glial fibrillary acidic protein; GLIB, glibenclamide; p65, transcription factor p65; ROI, region of interest; TNF-\u0026#xF061;, tumor necrosis factor alpha; VEH, vehicle.*P\u0026#x2009;\u0026amp;lt;\u0026#x2009;.05.**P\u0026#x2009;\u0026amp;lt;\u0026#x2009;.01.Adapted by permission from Macmillan Publishers Ltd: J Cereb Blood Flow. Simard JM et al. Glibenclamide reduces inflammation, vasogenic edema, and caspase-3 activation after subarachnoid hemorrhage. 2009;29:317-330. Copyright 2009.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1745298829\u0022 data-figure-caption=\u0022Glibenclamide Reduced Markers of Inflammation in a Subarachnoid Hemorrhage ModelGFAP, glial fibrillary acidic protein; GLIB, glibenclamide; p65, transcription factor p65; ROI, region of interest; TNF-\u0026#xF061;, tumor necrosis factor alpha; VEH, vehicle.*P\u0026#x2009;\u0026amp;amp;lt;\u0026#x2009;.05.**P\u0026#x2009;\u0026amp;amp;lt;\u0026#x2009;.01.Adapted by permission from Macmillan Publishers Ltd: J Cereb Blood Flow. Simard JM et al. Glibenclamide reduces inflammation, vasogenic edema, and caspase-3 activation after subarachnoid hemorrhage. 2009;29:317-330. Copyright 2009.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/2\/17\/F2.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/2\/17\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/2\/17\/F2.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/15261\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \n               \u003Cp id=\u0022p-14\u0022 class=\u0022first-child\u0022\u003EGlibenclamide Reduced Markers of Inflammation in a Subarachnoid Hemorrhage Model\u003C\/p\u003E\n               \u003Cp id=\u0022p-15\u0022\u003EGFAP, glial fibrillary acidic protein; GLIB, glibenclamide; p65, transcription factor p65; ROI, region of interest; TNF-\uf061, tumor necrosis factor alpha; VEH, vehicle.\u003C\/p\u003E\n               \u003Cp id=\u0022p-16\u0022\u003E*P\u2009\u0026lt;\u2009.05.\u003C\/p\u003E\n               \u003Cp id=\u0022p-17\u0022\u003E**P\u2009\u0026lt;\u2009.01.\u003C\/p\u003E\n               \u003Cp id=\u0022p-18\u0022\u003EAdapted by permission from Macmillan Publishers Ltd: J Cereb Blood Flow. Simard JM et al. Glibenclamide reduces inflammation, vasogenic edema, and caspase-3 activation after subarachnoid hemorrhage. 2009;29:317-330. Copyright 2009.\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-19\u0022\u003EHeparin is also a potent anti-inflammatory agent. Beneficial effects on cognitive function with heparin were found in a literature review [Simard JM et al. \u003Cem\u003ENeurocrit Care\u003C\/em\u003E. 2010], in preclinical data, and in patients, according to Robert F. James, MD, University of Louisville, Louisville, Kentucky, USA.\u003C\/p\u003E\n         \u003Cp id=\u0022p-20\u0022\u003EIn a rat model of SAH, heparin inhibited cortical inflammation and transsynaptic apoptosis and reduced demyelination [Simard JM et al. \u003Cem\u003ETransl Stroke Res\u003C\/em\u003E. 2012]. In patients with an aSAH, a retrospective blinded review of 2 series of prospectively enrolled patients found that the incidence of clinical vasospasm (9% vs 47%; \u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.0002) and infarcts on computed tomography (0% vs 21%; \u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.003) was significantly lower in the heparin group compared with the control group, while the incidence of angiographic vasospasm was similar (58% vs 60%) [Simard JM et al. \u003Cem\u003EJ Neurosurg\u003C\/em\u003E. 2013]. The use of rescue therapy for vasospasm was also significantly lower in the heparin group vs the control group (\u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.016 for phenylephrine and \u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.021 for microcatheter-directed therapy). More patients in the heparin group were discharged to home rather than to a rehabilitation center.\u003C\/p\u003E\n         \u003Cp id=\u0022p-21\u0022\u003EThese overall findings have led to a multicenter randomized controlled trial that will evaluate the safety of heparin and its effect on the primary outcome of the mean MoCA score at 90 days and secondary outcomes. The phase 2 open-label blinded adjudication Aneurysmal Subarachnoid Hemorrhage Trial Randomizing Heparin study will begin enrollment in spring 2015.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2015 SAGE Publications\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/15\/2\/17.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzlr0p\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzlr0p\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}