Melvin G. Marcus, 1929-1997

[This brief biography chronicles the life and achievements of Dr. Mel Marcus, geographer and climatologist, who died 2 March 1997.] ... His copious field work activities included research on glacier environments in Alaska and the Yukon, New Zealand, Mt. Ararat in Turkey, and the mountains of Nepal, Peru and Bolivia, plus vegetation studies in the Grand Canyon and urban environmental studies. He published about one hundred papers, books and book chapters. ... At his death he was about to receive the Cullum Geographic Medal of the American Geographical Society, and the Lifetime Achievement Award of the Association of American Geographers. ..

Characterizing the Use of Telepsychiatry for Patients with Opioid Use Disorder and Cooccurring Mental Health Disorders in Ontario, Canada

Rural patients with opioid use disorder (OUD) face a variety of barriers when accessing opioid agonist therapy (OAT) and psychiatric services, due to the limited supply of physicians and the vast geographic area. The telemedicine allows for contact between patients and their physician—regardless of physical distance. Objective. We characterize the usage of telemedicine to deliver psychiatric services to patients with OUD in Ontario, as well as traits of treatment-seeking patients with opioid dependence and concurrent psychiatric disorders. Methodology. A retrospective cohort study was conducted using an administrative database for patients who received psychiatric services via telemedicine between 2008 and 2014 and who also had OUD. Results. We identified 9,077 patients with concurrent opioid use and other mental health disorders who had received psychiatric services via telemedicine from 2008 to 2014; 7,109 (78.3%) patients lived in Southern Ontario and 1,968 (21.7%) in Northern Ontario. Telemedicine was used more frequently to provide mental health services to patients residing in Northern Ontario than Southern Ontario. Conclusion. Telemedicine is increasingly being utilized throughout Ontario for delivering mental health treatment. There is an opportunity to increase access to psychiatric services for patients with opioid dependence and concurrent psychiatric disorders through the use of the telemedicine

Retreat into scientism, paradoxes of transparency, and corruption in education

Um dos sintomas da razão indolente (SANTOS, 2006) é o recuo ao cientificismo, o qual tem sido, particularmente, acentuado nas políticas, cada vez mais hegemônicas, de avaliação, de prestação de contas e de responsabilização. Por isso, um dos objetivos deste texto é o de colocar em causa este aparente consenso cientificista (ou este consenso supostamente transideológico) e fazer uma breve incursão exploratória ao que aqui se designa de paradoxos da transparência. Considera-se que esses paradoxos traduzem a existência de tensões e contradições relativas a uma dimensão central dos discursos políticos e educacionais contemporâneos. Com isso, o artigo pretende dar continuidade a uma linha de pesquisa que tem procurado sublinhar a relevância da necessidade de complexificar e dar maior rigor teórico-conceptual à accountability em educação. Finalmente, tentando abrir caminho para o desenvolvimento de novas articulações e análises, chama-se a atenção para a corrupção na educação cuja complexidade ainda é insuficientemente conhecida e pesquisada, nomeadamente, nas suas relações com as problemáticas da transparência e da accountability. Admite-se que as práticas de corrupção em educação, em muitas situações, são (paradoxalmente) induzidas pela necessidade de dar resposta à governação baseada nos números, nos rankings e nas (supostas) evidências, anulando completamente as expectativas legítimas em torno da transparência dos processos educacionais e das decisões políticas.One symptom of “indolent reason” (SANTOS, 2006) is the retreat into scientism, which is especially marked in the increasingly hegemonic policies surrounding assessment, reporting and accountability. As such, one of the aims of this paper is to call into question this apparent consensus on scientism (a supposedly trans-ideological consensus), and briefly explore what we define as the paradoxes of transparency. These paradoxes are found to reveal the existence of tensions and contradictions concerning a central aspect of current political and educational discourse. In doing so, the article seeks to continue a line of study which has aimed to emphasize the significance of the need for a more complex, and theoretically and conceptually rigorous understanding of accountability in education. Finally, in an attempt to pave the way for further discussion and analysis, attention is drawn to corruption in education, the complex nature of which remains insufficiently understood and studied, notably in terms of its relationship with the problems of transparency and accountability. It is acknowledged that practices of corruption within education are, in many situations, (paradoxically) caused by the need to answer to a system of governance based on numbers, league tables, and (supposed) truths, completely nullifying legitimate expectations about the transparency of educational processes and policy decisions.Trabalho financiado por Fundos Nacionais através da FCT – Fundação para a Ciência e a Tecnologia – no âmbito do Projeto PEst-OE/CED/UI1661/2014.info:eu-repo/semantics/publishedVersio

Fish-oil supplementation in patients with implantable cardioverter defibrillators: a meta-analysis

Background: A recent Cochrane meta-analysis did not confirm the benefits of fish and fish oil in the secondary prevention of cardiac death and myocardial infarction. We performed a meta-analysis of randomized controlled trials that examined the effect of fish-oil supplementation on ventricular fibrillation and ventricular tachycardia to determine the overall effect and to assess whether heterogeneity exists between trials. Methods: We searched electronic databases (MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, CINAHL) from inception to May 2007. We included randomized controlled trials of fish-oil supplementation on ventricular fibrillation or ventricular tachycardia in patients with implantable cardioverter defibrillators. The primary outcome was implantable cardioverter defibrillator discharge. We calculated relative risk [RR] for outcomes at 1-year follow-up for each study. We used the DerSimonian and Laird random-effects methods when there was significant heterogeneity between trials and the Mantel-Hanzel fixed-effects method when heterogeneity was negligible. Results: We identified 3 trials of 1–2 years' duration. These trials included a total of 573 patients who received fish oil and 575 patients who received a control. Meta-analysis of data collected at 1 year showed no overall effect of fish oil on the relative risk of implantable cardioverter defibrillator discharge. There was significant heterogeneity between trials. The second largest study showed a significant benefit of fish oil (relative risk [RR] 0.74, 95% confidence interval [CI] 0.56–0.98). The smallest showed an adverse tendency at 1 year (RR 1.23, 95% CI 0.92–1.65) and significantly worse outcome at 2 years among patients with ventricular tachycardia at study entry (log rank p = 0.007). Conclusion: These data indicate that there is heterogeneity in the response of patients to fish-oil supplementation. Caution should be used when prescribing fish-oil supplementation for patients with ventricular tachycardia

Video directly-observed therapy for patients receiving office-based buprenorphine - a pilot randomized controlled trial

Background and Aims: Video directly-observed therapy (DOT) delivered through a mobile health platform has potential to improve buprenorphine adherence and opioid use disorder (OUD) treatment outcomes. We conducted a pilot study to assess feasibility of using video DOT for patients initiating buprenorphine to evaluate whether it is associated with better OUD treatment outcomes when compared to treatment-as-usual (TAU). Design: Pilot randomized controlled trial. Setting: Two medical centers (Seattle, WA and Boston, MA) from January 2019 to May 2020. Participants: Adult patients with OUD initiating treatment with buprenorphine (n=78). Intervention: Video DOT using a HIPAA-compliant smartphone application to record ingestion of daily buprenorphine. Daily text reminders to upload a video were sent, and calendar summaries of video DOT adherence were provided to patients and providers. Study smartphones were provided. Measurements: Main outcomes were 1) percentage of 12 weekly urine drug tests (UDT) negative for illicit opioids and 2) engagement in treatment at week 12 (i.e., having an active prescription for buprenorphine within the last 7 days). Findings: Of 78 enrolled, 20 (26%) were female; 29 (37%) non-white; and 31 (40%) reported homelessness. The mean (standard deviation) number of doses confirmed by video was 31% (34%). In intention-to-treat analysis, the average percentage of weekly opioid negative UDT was 50% (95% CI: 40-63%) in the intervention arm versus 64% (95% CI: 55-74%) among controls; RR=0.78 (95% CI: 0.60-1.02, p=0.07). Engagement at week 12 was 69% (95% CI: 56-86%) v. 82% (95% CI: 71-95%) in the intervention vs. TAU arms, respectively; RR=0.84 (95% CI: 0.65-1.10, p=0.20). Conclusions: The intervention among recently enrolled patients did not result in improvements in illicit opioid use and treatment engagement compared to controls. The study was limited by low rates of intervention use which could be addressed by adding patient incentives (e.g., financial or reduced need for in-person visits)

Müller glia-derived PRSS56 is required to sustain ocular axial growth and prevent refractive error.

A mismatch between optical power and ocular axial length results in refractive errors. Uncorrected refractive errors constitute the most common cause of vision loss and second leading cause of blindness worldwide. Although the retina is known to play a critical role in regulating ocular growth and refractive development, the precise factors and mechanisms involved are poorly defined. We have previously identified a role for the secreted serine protease PRSS56 in ocular size determination and PRSS56 variants have been implicated in the etiology of both hyperopia and myopia, highlighting its importance in refractive development. Here, we use a combination of genetic mouse models to demonstrate that Prss56 mutations leading to reduced ocular size and hyperopia act via a loss of function mechanism. Using a conditional gene targeting strategy, we show that PRSS56 derived from Müller glia contributes to ocular growth, implicating a new retinal cell type in ocular size determination. Importantly, we demonstrate that persistent activity of PRSS56 is required during distinct developmental stages spanning the pre- and post-eye opening periods to ensure optimal ocular growth. Thus, our mouse data provide evidence for the existence of a molecule contributing to both the prenatal and postnatal stages of human ocular growth. Finally, we demonstrate that genetic inactivation of Prss56 rescues axial elongation in a mouse model of myopia caused by a null mutation in Egr1. Overall, our findings identify PRSS56 as a potential therapeutic target for modulating ocular growth aimed at preventing or slowing down myopia, which is reaching epidemic proportions

Lineage tracing of <i>Prss56</i> expressing cells during ocular development.

<p><b>(A)</b><i>Prss56</i>^<i>Cre/+</i> mice were crossed to <i>R26</i>^{<i>tdTomato/+</i>} reporter mice that express tdTomato following CRE-mediated excision of a stop codon to label <i>Prss56</i> expressing cells and their derivatives. (<b>B</b>-<b>F)</b> Representative images showing lineage tracing of <i>Prss56</i> expressing cells (red) in <i>Prss56</i>^<i>Cre/+</i>; <i>R26</i>^{<i>tdTomato/+</i>} eyes throughout ocular development. (<b>B</b>) tdTomato expression is first detected in the retina at embryonic day (E) 16.5 in retinal progenitor cells (RPCs). (<b>C</b>, <b>D</b>) The number of tdTomato positive RPCs increases with age, shown are (<b>C</b>) E18.5 and (<b>D</b>) P2 retinas. (<b>E</b>) By P7, when retinal laminar organization is visible, tdTomato expression was predominantly observed in cells exhibiting characteristic features of Müller glia, with cell bodies located in the inner nuclear layer and apicobasal processes extending across the retina. tdTomato expression was also detected in the inner segment of rod photoreceptors. (<b>F</b>) tdTomato expression continues to be detected in Müller cells and rod photoreceptors following complete maturation of retinal cell types at P13. Interestingly, tdTomato-labeled cells were enriched in the peripheral region and relatively sparser in the central region of the retina. (<b>G</b>) Ki67 immunolabeling of P0 <i>Prss56</i>^<i>Cre/+</i>; <i>R26</i>^{<i>tdTomato/+</i>} eyes demonstrate Ki67 expression in tdTomato positive retinal cells. E, embryonic day; GCL, ganglionic cell layer; INL, inner nuclear layer; ONBL, outer neuroblastic layer; ONL, outer nuclear layer; P, postnatal day. Scale bars: 100μm (<b>B</b>-<b>F</b>) and 50μm (<b>G</b>).</p

Conditional RAX-Cre-mediated ablation of <i>Prss56</i> from fully differentiated Müller glia leads to ocular size reduction.

<p><i>Prss56</i> was conditionally ablated from Müller cells in a time-specific manner by crossing <i>Prss56</i>^<i>F/F</i> to the inducible RAX-Cre mouse strain (<i>Rax-Cre</i>^<i>ERT2</i>). CRE expression was induced by tamoxifen injection at P8, a time point preceding complete Müller glia differentiation. (<b>A</b>) Representative images of slit lamp examination by broad-beam illumination following tamoxifen injection at P8. <i>Prss56</i>^<i>F/F</i><i>; Rax-Cre</i>^<i>ERT2</i> eyes were indistinguishable from control <i>Prss56</i>^<i>F/+</i><i>; Rax-Cre</i>^<i>ERT2</i> eyes at 2 months of age. (<b>B</b>, <b>C</b>) Following tamoxifen injection (TAM +; horizontal axis) at P8, <i>Prss56</i>^<i>F/F</i><i>Rax-Cre</i>^<i>ERT2</i> mice display a significant decrease in ocular axial length (<b>B</b>) and increase in retinal thickness (<b>C</b>) compared to control eyes (<i>Prss56</i>^<i>F/+</i><i>; Rax-Cre</i>^<i>ERT2</i> or <i>Prss56</i>^<i>F/F</i> mice without <i>Rax-Cre</i>^<i>ERT2</i>), N = 6 to 8 per group. (<b>D</b>) Following tamoxifen injection at P8, a significant reduction in VCD was detected in <i>Prss56</i>^<i>F/F</i><i>; Rax-Cre</i>^<i>ERT2</i> eyes compared to control <i>Prss56</i>^<i>F/+</i><i>; Rax-Cre</i>^<i>ERT2</i> eyes, N = 6 per group. Ocular axial length, retinal thickness, and VCD in uninjected <i>Prss56</i>^<i>F/F</i><i>; Rax-Cre</i>^<i>ERT2</i> and <i>Prss56</i>^<i>F/+</i><i>; Rax-Cre</i>^<i>ERT2</i> mice were indistinguishable. (<b>E</b>) Representative OCT images showing reduced axial length and VCD in <i>Prss56</i>^<i>F/F</i><i>; Rax-Cre</i>^<i>ERT2</i> eyes compared to the control <i>Prss56</i>^<i>F/+</i><i>; Rax-Cre</i>^<i>ERT2</i> or <i>Prss56</i>^<i>F/F</i> mice. (<b>F</b>) qPCR analysis following tamoxifen injection at P8 revealed that <i>Prss56</i> mRNA was significantly upregulated in <i>Prss56</i>^<i>F/F</i> <i>; Rax-Cre</i>^<i>ERT2</i> retina compared to their <i>Prss56</i>^<i>F/+</i> <i>; Rax-Cre</i>^<i>ERT2</i> counterparts or uninjected controls, N≥ 6 per group. Values are presented as mean ±SD; * p<0.05, ** p<0.01, *** p<0.001, t-test. (<b>G-I</b>) Müller glia endfeet organization of <i>Prss56</i>^<i>Cre</i>; <i>R26</i>^{<i>tdTomato</i>} reporter mice during retinal development. Representative images of retinal section (<b>G, I</b>) or whole mount (<b>H</b>) showing Müller glia endfeet from control and <i>Prss56</i> mutant mice at P6. (<b>I</b>) Magnified images of the retinal endfeet are shown. The ILM of <i>Prss56</i> mutant mice (<i>Prss56</i>^{<i>Cre/gclr4</i>}; <i>R26</i>^{<i>tdTomato</i>}) at P6 is marked by regions of increased endfeet complexity (arrow head) compared to the ILM of control mice (<i>Prss56</i>^<i>Cre/+</i>; <i>R26</i>^{<i>tdTomato</i>}). A substantial proportion of endfeet appear more spread out, occupying a larger area in the mutant compared to control retinal whole mounts (occupying smaller area). Red boxes highlight individual endfoot. N = 4 per genotype and scale bars = 17μm in <b>G</b> and <b>I</b>, and 50μm in <b>H</b>. ACD, anterior chamber depth; AL, axial length; VCD, vitreous chamber depth.</p

PRSS56 activity is required during both the vision-independent and dependent stages of ocular growth.

<p>To determine the temporal window critical for the PRSS56-mediated effect on ocular axial growth, <i>Prss56</i> conditional mutant mice (<i>Prss56</i>^<i>F/F</i>) were crossed to mice expressing the ubiquitous inducible Ubc-Cre recombinase (<i>Ubc-Cre</i>^<i>ERT2</i>). (<b>A</b>) Schematic of tamoxifen treatment at distinct developmental stages preceding and following the opening of the eyes. Tamoxifen injection at two different time points, P6 and P8, was performed to ablate <i>Prss56</i> after the earliest detectable effect of mutant <i>Prss56</i> on ocular axial length. (<b>B</b>-<b>D</b>) OCT-based ocular biometry demonstrates that following tamoxifen injection, <i>Prss56</i>^<i>F/F</i><i>; Ubc-Cre</i>^<i>ERT2</i> mice display a significantly reduced ocular axial length (<b>B</b>) and increased retinal thickness (<b>C</b>) and a significant decrease in VCD (<b>D</b>) compared to the control <i>Prss56</i>^<i>F/+</i>; Ubc-Cre^<i>ERT2</i> mice (measured at P17). The ocular axial length, retinal thickness, and VCD of uninjected <i>Prss56</i>^<i>F/F</i><i>; Ubc-Cre</i>^<i>ERT2</i> <i>and Prss56</i>^<i>F/+</i><i>; Ubc-Cre</i>^<i>ERT2</i> mice were indistinguishable. Administration of tamoxifen at P6 caused a greater decrease in ocular axial length compared to administration at P8 suggesting a requirement for continuous PRSS56 activity during ocular development to sustain normal ocular growth, N = 6 to 8 per group for <b>A</b> and <b>B</b>. (<b>E</b>-<b>G</b>) OCT measurements demonstrate that following tamoxifen injection at P13 (a time point when the eyes are open), <i>Prss56</i>^<i>F/F</i><i>; Ubc-Cre</i>^<i>ERT2</i> mice display a slight but significant decrease in ocular axial length (<b>E</b>) and increase in retinal thickness (<b>F</b>) at P30 and P45. Reduced ocular axial length was associated with a significant decrease in VCD in <i>Prss56</i>^<i>F/F</i><i>; Ubc-Cre</i>^<i>ERT2</i> mice compared to <i>Prss56</i>^<i>F/+</i><i>; Ubc-Cre</i>^<i>ERT2</i> and uninjected controls at P30 and P45, N = 5 to 10 per group (<b>G</b>). <b>(H</b>-<b>J)</b> Ocular biometry following tamoxifen injection at the beginning of a critical emmetropization period (P18) shows that the ocular axial length is not significantly different between the <i>Prss56</i>^<i>F/F</i><i>; Ubc-Cre</i>^<i>ERT2</i> and control mice at any of the three ages examined (P30, P45, and P60). However, <i>Prss56</i>^<i>F/F</i><i>; Ubc-Cre</i>^<i>ERT2</i> mice display a slightly thicker retina and significantly reduced VCD compared to the control groups. (<b>K</b>) Following <i>Prss56</i> ablation at P13 and P18, the eyes display a decrease in the combined value of retinal thickness and VCD. (<b>L</b>) qPCR analysis revealed elevated <i>Prss56</i> mRNA levels in <i>Prss56</i>^<i>F/F</i><i>; Ubc-Cre</i>^<i>ERT2</i> retina compared to <i>Prss56</i>^<i>F/+</i><i>; Ubc-Cre</i>^<i>ERT2</i> retina following tamoxifen injection at P8, P13, or P18 (shown are data from mice harvested at P17 and P60, respectively). (<b>M</b>) Following <i>Prss56</i> ablation at P18, the eyes display a hyperopic shift in refraction compared to control eyes at 3 months (N = 6 per group). Values are presented as mean ± SD (or mean ± SEM in <b>L</b>); * p<0.05, ** p<0.01, *** p<0.001, t-test.</p