Corneal perforation in ocular graft-versus-host disease

PURPOSE: Corneal perforation is a rare, vision-threatening complication of ocular graft-versus-host disease (GVHD) and is not well understood. Our objective was to examine the clinical disease course and histopathologic correlation in patients who progressed to this outcome. METHODS: This study is a retrospective case series from four academic centers in the United States. All patients received a hematopoietic stem cell transplant (HSCT) prior to developing ocular GVHD. Variables of interest included patient demographics, time interval between HSCT and ocular events, visual acuity throughout clinical course, corticosteroid and infection prophylaxis regimens at time of corneal perforation, medical/surgical interventions, and histopathology. RESULTS: Fourteen eyes from 14 patients were analyzed. Most patients were male (86%) and Caucasian (86%), and average age at time of hematopoietic stem cell transplant was 47 years. The mean interval between hematopoietic stem cell transplant and diagnosis of ocular graft-versus-host disease was 9.5 months, and between hematopoietic stem cell transplant and corneal perforation was 37 months. Initial best-corrected visual acuity was 20/40 or better in 9 eyes, and all eyes had moderate or poor visual outcomes despite aggressive management, including corneal gluing in all patients followed by keratoplasty in 8 patients. The mean follow-up after perforation was 34 months (range 2-140 months). Oral prednisone was used prior to perforation in 11 patients (79%). On histopathology, representative specimens in the acute phase demonstrated ulcerative keratitis with perforation but minimal inflammatory cells and no microorganisms, consistent with sterile corneal melt in the setting of immunosuppression; and in the healed phase, filling in of the perforation site with fibrous scar. CONCLUSIONS: In these patients, an extended time interval was identified between the diagnosis of ocular graft-versus-host disease and corneal perforation. This represents a critical window to potentially prevent this devastating outcome. Further study is required to identify those patients at greatest risk as well as to optimize prevention strategies

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Maria Cosway’s Hours: Cosmopolitan and Classical Visual Culture in Thomas Macklin’s Poets Gallery

Thomas Macklin’s Gallery of Poets opened at the Mitre Tavern in Fleet Street in 1788 with the aim to ‘display British Genius’ through ‘Prints Illustrative of the Most Celebrated British Poets’. Early newspaper coverage promised ‘a monument of the powers of the pencil in England, as the Vatican is at Rome’. The incongruous juxtaposition between Fleet Street and the Vatican spells out the cosmopolitan ambition of the literary gallery phenomenon through its real and imagined geographies of display. Through the format of the paper gallery of prints, Macklin’s Poets offered the inventions of British Poets as a repository of painting. This chapter examines how the cosmopolitan idiom of the paper gallery is negotiated in the first number of Macklin’s Poets. This essay examines the extent to which this ambition was achieved in the first Number of Macklin’s Poets which carried an engraving of Maria Cosway’s The Hours, originally a painting with an impressively European iconographic heritage. The painting was first exhibited at the Royal Academy in 1783, and was retroactively associated by Macklin with Thomas Gray’s ‘Ode on the Spring’. The trope of the Hours brought with it a weighty provenance derived from classical marble bas-relief, through the antiquarian pages of Pietro Santi Bartoli and Bernard de Montfaucon to Flaxman’s designs for Wedgwood plaques and vases. Cosway’s name also imported into Gray’s poem her reputation as a cosmopolitan, cultured woman who had completed the Grand Tour and who moved in elite circles including those of the Prince of Wales in London and the Duke of Orleans, Pierre d’Hancarville and Thomas Jefferson in Paris. The iconographies of the painting, the print, and the poem articulate a European cosmopolitan tradition for British Art

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe

Prefrontal cortex activation during dual task conditions in older and younger adults

Mobility limitations in the elderly are associated with morbidities and premature death. Although the effects of age-related changes in brain structure on gait are well described, little is known about age related functional changes. The prefrontal cortex (PFC) contributes to attention, planning and complex gait tasks. We compared the PFC activation while performing simultaneous tasks (dual tasks) in young and old adults. We hypothesized that older adults have greater activation of the PFC under dual-task conditions. Healthy younger (n=15, 18-41 years) and older (n=15, 65-76 years) adults were matched on education and gender. Participants walked on an instrumented treadmill at a self-selected pace with a 0% slope while subtracting from predetermined three digit numbers by seven (Serial7). PFC activation was measured by near infrared spectroscopy and estimated by general linear models. T-tests compared Serial7 scores and PFC activation between groups. Analyses showed that older adults did not walk slower (p=0.13), and performed as well on the serial7 task (p=0.15) as the younger adults. There was a greater activation (for HbO2 t=4.1,

Influence of Recent Standing, Moving, or Sitting on Daytime Ambulatory Blood Pressure

Background There are no recommendations for being seated versus nonseated during ambulatory blood pressure (BP) monitoring (ABPM). The authors examined how recent standing or moving versus sitting affect average daytime BP on ABPM. Methods and Results This analysis used baseline assessments from a clinical trial in desk workers with office systolic BP (SBP) 120 to 159 mm Hg or diastolic BP (DBP) 80 to 99 mm Hg. ABPM was measured every 30 minutes with a SunTech Medical Oscar 2 monitor. Concurrent posture (standing or seated) and moving (steps) were measured via a thigh‐worn accelerometer. Linear regression determined within‐person BP variability explained (R2) by standing and steps before ABPM readings. Mean daytime BP and the prevalence of mean daytime BP >135/85 mm Hg from readings after sitting (seated) or after recent standing or moving (nonseated) were compared with all readings. Participants (n=266, 59% women; age, 45.2±11.6 years) provided 32.5±3.9 daytime BP readings. Time standing and steps before readings explained variability up to 17% for daytime SBP and 14% for daytime DBP. Using the 5‐minute prior interval, seated SBP/DBP was lower (130.8/79.7 mm Hg, P<0.001) and nonseated SBP/DBP was higher (137.8/84.3 mm Hg, P<0.001) than mean daytime SBP/DBP from all readings (133.9/81.6 mm Hg). The prevalence of mean daytime SBP/DBP ≥135/85 mm Hg also differed: 38.7% from seated readings, 70.3% from nonseated readings, and 52.6% from all readings (P<0.05). Conclusions Daytime BP was systematically higher after standing and moving compared with being seated. Individual variation in activity patterns could influence the diagnosis of high BP using daytime BP readings on ABPM

Femoral Deformity Correction in Children and Young Adults Using Taylor Spatial Frame

The Taylor spatial frame (TSF) has been used commonly in children and young adults. Its use in the tibia is more extensively studied and applied than in the femur. We asked whether normal alignment can be achieved with accuracy during correction of femoral deformities while avoiding major complications in children and young adults. We retrospectively reviewed the clinical and radiographic records of 20 patients (22 limbs), ages 5.9 to 24.6 years, who underwent a TSF for femoral deformity. Etiology included a number of diagnoses of the pediatric age. Minimum followup was 4.5 months (mean, 15.7 months; range, 4.5–35 months). The mean time in frame was 6.2 months (range, 2.6–19 months). Frontal and sagittal plane deformities were corrected to within normal values. A mean limb lengthening of 4.9 cm (range, 1.5–9 cm) was performed in eight femora in seven of which the limb length discrepancy was a secondary concern. External fixation index in the lengthening subgroup was 2.2 months/cm. The 15 complications in 13 limbs included pin tract infection, knee stiffness, delayed union, skin irritation, and posterior knee subluxation. No complications occurred in nine limbs. Computer-assisted femoral deformity correction with six-axis deformity analysis and the TSF is an accurate and safe technique in children and young adults

Global warming impairs stock-recruitment dynamics of corals

Changes in disturbance regimes due to climate change are increasingly challenging the capacity of ecosystems to absorb recurrent shocks and reassemble afterwards, escalating the risk of widespread ecological collapse of current ecosystems and the emergence of novel assemblages(1-3). In marine systems, the production of larvae and recruitment of functionally important species are fundamental processes for rebuilding depleted adult populations, maintaining resilience and avoiding regime shifts in the face of rising environmental pressures(4,5). Here we document a regional-scale shift in stock-recruitment relationships of corals along the Great Barrier Reef-the world's largest coral reef system-following unprecedented back-to-back mass bleaching events caused by global warming. As a consequence of mass mortality of adult brood stock in 2016 and 2017 owing to heat stress(6), the amount of larval recruitment declined in 2018 by 89% compared to historical levels. For the first time, brooding pocilloporids replaced spawning acroporids as the dominant taxon in the depleted recruitment pool. The collapse in stock-recruitment relationships indicates that the low resistance of adult brood stocks to repeated episodes of coral bleaching is inexorably tied to an impaired capacity for recovery, which highlights the multifaceted processes that underlie the global decline of coral reefs. The extent to which the Great Barrier Reef will be able to recover from the collapse in stock-recruitment relationships remains uncertain, given the projected increased frequency of extreme climate events over the next two decades(7)

Outcomes of Nonagenarians with Acute Ischemic Stroke Treated with Intravenous Thrombolytics

BackgroundNonagenarians are under-represented in thrombolytic trials for acute ischemic stroke (AIS). The effectiveness of intravenous thrombolytics in nonagenarians in terms of safety and outcome is not well established.Materials and MethodsWe used a multinational registry to identify patients aged 90 years or older with good baseline functional status who presented with AIS. Differences in outcomes—disability level at 90 days, frequency of symptomatic intracerebral hemorrhage (sICH), and mortality—between patients who did and did not receive thrombolytics were assessed using multivariable logistic regression, adjusted for prespecified prognostic factors. Coarsened exact matching (CEM) was utilized before evaluating outcome by balancing both groups in the sensitivity analysis.ResultsWe identified 227 previously independent nonagenarians with AIS; 122 received intravenous thrombolytics and 105 did not. In the unmatched cohort, ordinal analysis showed a significant treatment effect (adjusted common odds ratio [OR]: .61, 95% confidence interval [CI]: .39-.96). There was an absolute difference of 8.1% in the rate of excellent outcome in favor of thrombolysis (17.4% versus 9.3%; adjusted ratio: .30, 95% CI: .12-.77). Rates of sICH and in-hospital mortality were not different. Similarly, in the matched cohort, CEM analysis showed a shift in the primary outcome distribution in favor of thrombolysis (adjusted common OR: .45, 95% CI: .26-.76).ConclusionsNonagenarians treated with thrombolytics showed lower stroke-related disability at 90 days than those not treated, without significant difference in sICH and in-hospital mortality rates. These observations cannot exclude a residual confounding effect, but provide evidence that thrombolytics should not be withheld from nonagenarians because of age alone