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Background: Sex differences in treatment response to intravenous thrombolysis (IVT) are poorly characterized. We compared sex-disaggregated outcomes in patients receiving IVT for acute ischemic stroke in the Alteplase compared to Tenecteplase (AcT) trial, a Canadian multicentre, randomised trial. Methods: In this post-hoc analysis, the primary outcome was excellent functional outcome (modified Rankin Score [mRS] 0-1) at 90 days. Secondary and safety outcomes included return to baseline function, successful reperfusion (eTICI≥2b), death and symptomatic intracerebral hemorrhage. Results: Of 1577 patients, there were 755 women and 822 men (median age 77 [68-86]; 70 [59-79]). There were no differences in rates of mRS 0-1 (aRR 0.95 [0.86-1.06]), return to baseline function (aRR 0.94 [0.84-1.06]), reperfusion (aRR 0.98 [0.80-1.19]) and death (aRR 0.91 [0.79-1.18]). There was no effect modification by treatment type on the association between sex and outcomes. The probability of excellent functional outcome decreased with increasing onset-to-needle time. This relation did not vary by sex (pinteraction 0.42). Conclusions: The AcT trial demonstrated comparable functional, safety and angiographic outcomes by sex. This effect did not differ between alteplase and tenecteplase. The pragmatic enrolment and broad national participation in AcT provide reassurance that there do not appear to be sex differences in outcomes amongst Canadians receiving IVT.
Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.
Background: Canadian Stroke Guidelines recommend that Transient Ischemic Attack (TIA) patients at highest risk of stroke recurrence should undergo immediate vascular imaging. Computed tomography angiography (CTA) of the head and neck is recommended over carotid doppler because it allows for enhanced visualization of the intracranial and posterior circulation vasculature. Imaging while patients are in the emergency department (ED) is optimal for high-risk patients because the risk of stroke recurrence is highest in the first 48 hours. Aim Statement: At our hospital, a designated stroke centre, less than 5% of TIA patients meet national recommendations by undergoing CTA in the ED. We sought to increase the rate of CTA in high risk ED TIA patients from less than 5% to at least 80% in 10 months. Measures & Design: We used a multi-faceted approach to improve our adherence to guidelines including: 1) education for staff ED physicians; 2) agreements between ED and radiology to facilitate rapid access to CTA; 3) agreements between ED and neurology for consultations regarding patients with abnormal CTA; and 4) the creation of an electronic decision support tool to guide ED physicians as to which patients require CTA. We measured the rate of CTA in high risk patients biweekly using retrospective chart review of patients referred to the TIA clinic from the ED on a biweekly basis. As a balancing measure, we also measured the rate of CTA in non-high risk patients. Evaluation/Results: Data collection is ongoing. An interim run chart at 19 weeks shows a complete shift above the median after implementation, with CTA rates between 70 and 100%. At the time of submission, we had no downward trends below 80%, showing sustained improvement. The CTA rate in non-high risk patients did also increase. Disucssion/Impact: After 19 weeks of our intervention, 112 (78.9%) of high risk TIA patients had a CTA, compared to 10 (9.8%) in the 19 weeks prior to our intervention. On average, 10-15% of high risk patients will have an identifiable lesion on CTA, leading to immediate change in management (at minimum, an inpatient consultation with neurology). Our multi-faceted approach could be replicated in any ED with the engagement and availability of the same multi-disciplinary team (ED, radiology, and neurology), access to CTA, and electronic orders.
This article, which emphasizes the importance of transnational history, tracks the influence of E. Stanley Jones, a missionary to India in the early twentieth century, on evangelicals in the United States. It contends that global encounters pushed Jones to hold integrated ashrams, conduct evangelistic crusades, and participate in the Congress on Racial Equality. During his time abroad, he discovered that racial segregation at home hurt the causes of missions and democracy abroad. Using this Cold War logic, Jones in turn provoked American evangelicals to consider more fully questions of racial inequality.
Between 2008 and 2010, 27 acoustic tags were applied to various age and reproductive classes of grey whales in Laguna San Ignacio, Mexico, a part of the Biosphere Reserve ‘El Vizcaino’. Besides previously described S1 and S3 calls, two additional calls were identified: the impulsive S8 call and the slightly frequency-modulated S9 call. These two additional S8 and S9 calls are by far the most common grey whale sounds detected on tags, even though contemporary bottom-mounted acoustic recordings also collected from the lagoon in 2008 yielded no S8 or S9 calls. The new S8 and old S3 calls display similar spectral maxima, even though the S3 is a frequency-modulated harmonic call and the S8 is a broadband impulsive call. This spectral analysis provides evidence that these new call types are not artefacts arising from mechanical vibration or flow noise.
The public health, public safety and clinical implications of violent events among adults with mental illness are significant; however, the causes and consequences of violence and victimization among adults with mental illness are complex and not well understood, which limits the effectiveness of clinical interventions and risk management strategies. This study examined interrelationships between violence, victimization, psychiatric symptoms, substance use, homelessness and in-patient treatment over time.
Available data were integrated from four longitudinal studies of adults with mental illness. Assessments took place at baseline, and at 1, 3, 6, 9, 12, 15, 18, 24, 30 and 36 months, depending on the parent studies’ protocol. Data were analysed with the autoregressive cross-lag model.
Violence and victimization were leading indicators of each other and affective symptoms were a leading indicator of both. Drug and alcohol use were leading indicators of violence and victimization, respectively. All psychiatric symptom clusters – affective, positive, negative, disorganized cognitive processing – increased the likelihood of experiencing at least one subsequent symptom cluster. Sensitivity analyses identified few group-based differences in the magnitude of effects in this heterogeneous sample.
Violent events demonstrated unique and shared indicators and consequences over time. Findings indicate mechanisms for reducing violent events, including trauma-informed therapy, targeting internalizing and externalizing affective symptoms with cognitive–behavioral and psychopharmacological interventions, and integrating substance use and psychiatric care. Finally, mental illness and violence and victimization research should move beyond demonstrating concomitant relationships and instead focus on lagged effects with improved spatio-temporal contiguity.
There is limited evidence on the acceptability, feasibility and cost-effectiveness of task-sharing interventions to narrow the treatment gap for mental disorders in sub-Saharan Africa. The purpose of this article is to describe the rationale, aims and methods of the Africa Focus on Intervention Research for Mental health (AFFIRM) collaborative research hub. AFFIRM is investigating strategies for narrowing the treatment gap for mental disorders in sub-Saharan Africa in four areas. First, it is assessing the feasibility, acceptability and cost-effectiveness of task-sharing interventions by conducting randomised controlled trials in Ethiopia and South Africa. The AFFIRM Task-sharing for the Care of Severe mental disorders (TaSCS) trial in Ethiopia aims to determine the acceptability, affordability, effectiveness and sustainability of mental health care for people with severe mental disorder delivered by trained and supervised non-specialist, primary health care workers compared with an existing psychiatric nurse-led service. The AFFIRM trial in South Africa aims to determine the cost-effectiveness of a task-sharing counselling intervention for maternal depression, delivered by non-specialist community health workers, and to examine factors influencing the implementation of the intervention and future scale up. Second, AFFIRM is building individual and institutional capacity for intervention research in sub-Saharan Africa by providing fellowship and mentorship programmes for candidates in Ethiopia, Ghana, Malawi, Uganda and Zimbabwe. Each year five Fellowships are awarded (one to each country) to attend the MPhil in Public Mental Health, a joint postgraduate programme at the University of Cape Town and Stellenbosch University. AFFIRM also offers short courses in intervention research, and supports PhD students attached to the trials in Ethiopia and South Africa. Third, AFFIRM is collaborating with other regional National Institute of Mental Health funded hubs in Latin America, sub-Saharan Africa and south Asia, by designing and executing shared research projects related to task-sharing and narrowing the treatment gap. Finally, it is establishing a network of collaboration between researchers, non-governmental organisations and government agencies that facilitates the translation of research knowledge into policy and practice. This article describes the developmental process of this multi-site approach, and provides a narrative of challenges and opportunities that have arisen during the early phases. Crucial to the long-term sustainability of this work is the nurturing and sustaining of partnerships between African mental health researchers, policy makers, practitioners and international collaborators.
Anxiety disorders are associated with abnormalities in amygdala function and prefrontal cortex–amygdala connectivity. The majority of functional magnetic resonance imaging studies have examined mean group differences in amygdala activation or connectivity in children and adolescents with anxiety disorders relative to controls, but emerging evidence suggests that abnormalities in amygdala function are dependent on the timing of the task and may vary across the course of a scanning session. The goal of the present study was to extend our knowledge of the dynamics of amygdala dysfunction by examining whether changes in amygdala activation and connectivity over scanning differ in pediatric anxiety disorder patients relative to typically developing controls during an emotion processing task. Examining changes in activation over time allows for a comparison of how brain function differs during initial exposure to novel stimuli versus more prolonged exposure. Participants included 34 anxiety disorder patients and 19 controls 7 to 19 years old. Participants performed an emotional face-matching task during functional magnetic resonance imaging scanning, and the task was divided into thirds in order to examine change in activation over time. Results demonstrated that patients exhibited an abnormal pattern of amygdala activation characterized by an initially heightened amygdala response relative to controls at the beginning of scanning, followed by significant decreases in activation over time. In addition, controls evidenced greater context-modulated prefrontal cortex–amygdala connectivity during the beginning of scanning relative to patients. These results indicate that differences in emotion processing between the groups vary from initial exposure to novel stimuli relative to more prolonged exposure. Implications are discussed regarding how this pattern of neural activation may relate to altered early-occurring or anticipatory emotion-regulation strategies and maladaptive later-occurring strategies in children and adolescents with anxiety disorders.
In the early 1970s, a group of progressive evangelicals challenged the mid-century cultural conservatism of their tradition. Activists associated with Reformed, Anabaptist, and neo-evangelical institutions denounced militarism, racism, sexism, economic injustice, and President Richard Nixon's “lust for and abuse of power.” When this coalition met in 1973 to issue the Chicago Declaration, delegates effused a profound sense of optimism. The evangelical left held very real potential for political impact.
Within a decade, however, the movement seemed to be in disarray. This article suggests the centrality of identity politics to evangelicalism in the 1970s and outlines the fragmentation of the progressive evangelical coalition along gender, racial, and theological lines. The formation of the Evangelical Women's Caucus, the growing stridency of the National Black Evangelical Association, and the divergence of Anabaptist-oriented Evangelicals for Social Action and the Reformed-oriented Association for Public Justice sapped the evangelical left of needed resources and contributed to its impotence into the 1980s. The forces of identity politics, which also plagued the broader political left, were powerful enough to sabotage even a group of evangelicals with remarkably similar theological convictions, religious cultures, and critiques of conservative politics. The story of the fragmenting evangelical left, however, reflects more than broader culture's preoccupation with identity. It points to often-overlooked religious elements of the broader left. And alongside the New Left and the New Right, the evangelical left's debates over racial, sexual, and theological difference added to the disruptions of the liberal consensus in the 1960s and 1970s.
General population data are presented on the prevalence and correlates of comorbidity between DSM–III–R major depressive disorder (MDD) and other DSM–III–R disorders. The data come from the US National Comorbidity Survey, a large general population survey of persons aged 15–54 years in the non-institutionalised civilian population. Diagnoses are based on a modified version of the Composite International Diagnostic Interview (CIDI). The analysis shows that most cases of lifetime MDD are secondary, in the sense that they occur in people with a prior history of another DSM–III–R disorder. Anxiety disorders are the most common primary disorders. The time-lagged effects of most primary disorders on the risk of subsequent MDD continue for many years without change in magnitude. Secondary MDD is, in general, more persistent and severe than pure or primary MDD. This has special public health significance because lifetime prevalence of secondary MDD has increased in recent cohorts, while the prevalence of pure and primary depression has remained unchanged.
Zinc selenide films have been grown heteroepitaxially on Si(100) substrates by molecular beam epitaxy. The initial stages of growth are dominated by the reaction of Se and Si atoms to form the compound SiSe2- The compound formation disrupts epitaxy, and several growth methods which avoid this are described and compared. We find that room temperature deposition plus solid phase epitaxy does not lead to significant SiSex formation and yields uniformly thick films which are misoriented with respect to the substrate and contain large regions of twinned ZnSe. The use of an As monolayer on the Si surface before the start of ZnSe growth allows good ZnSe epitaxy without any Si-Se reaction or any misorientation. ZnSe films have also been used as interlayers for GaAs growth on Si. This has allowed us to obtain uniform GaAs films at thicknesses which typically manifest a coalesced island morphology for GaAs grown directly on Si.
Lead-zirconate-titanate, Pb(Zr0.53Ti0.47)O3, films were produced by the sol-gel method from alkoxide and acetate precursors in a 2-methoxyethanol solvent system. The PZT films were deposited on platinized silicon and single-crystal SrTiO3 substrates for electrical and optical characterization, respectively. The processing parameters, especially excess PbO content and annealing conditions, were shown to have a significant effects on the properties of PZT films. Epitaxial PZT films deposited on SrTiO3 waveguided over 10 mm distances with propagation losses as low as 5.9 dB/cm at 783 nm and a linear electro-optic effect was also demonstrated.
Sol-gel processing is a candidate ferroelectric thin-film deposition method for electronic and electro-optic applications. At Battelle, sol-gel PbTiO3 and Pb(Zr,Ti)O3 films have been prepared on sapphire and single-crystal SrTiO3 substrates. Films deposited and annealed on sapphire substrates are crystalline with the perovksite structure and minimal crystallographic orientation, whereas films deposited on isostructural and lattice-matched SrTiO3 substrates exhibit a high degree of orientation. Guided-mode refractive index measurements were made using a single-prism method and film indices were computed. Refractive index values measured for PbTiO3 films (n = 2.58) and PZT films (n = 2.50) were slightly lower than values expected on the basis of bulk measurements. In double-prism experiments, optical wavcguiding was achieved over distances up to 10 mm in oriented PZT films on  SrTiO3substrates. Optical loss of 19 dB/cm was measured on one of these film samples. Such films, given requisite improvement in optical quality, may be suitable for useful optical waveguide devices. An approach is presented for the integration of ferroelectric waveguides onto silicon and/or GaAs substrates.
An improvement in the quantum efficiency of the 1.3 μm transition of Pr3+ has been acheived as a result of doping alternative halide glasses. An increase from 3.4% in ZBLAN  to 9.9% in a multicomponent halide glass is reported.
Zinc selenide films have been grown heteroepitaxially on Si(100) substrates by molecular beam epitaxy. The growth has been carried out for raised substrate temperatures and also at room temperature followed by solid-phase epitaxial (SPE) regrowth. The ZnSe films have been characterized by a number of surface-sensitive techniques and both the interface and the bulk material have been examined with high resolution transmission electron microscopy (HRTEM). We find that an interlayer, which is most likely SiSex, is present between the ZnSe film and the Si substrate for growths made at 300 °C and causes loss of epitaxy. In the case of room temperature deposition and SPE, it is absent, leading to good epitaxy. In the latter situation, the films are very uniform and there is a 4° rotation of the ZnSe crystal axes relative to those of the Si substrate.