Levetiracetam-loaded biodegradable polymer implants in the tetanus toxin model of temporal lobe epilepsy in rats

Approximately one-third of people with epilepsy receive insufficient benefit from currently available anticonvulsant medication, and some evidence suggests that this may be due to a lack of effective penetration into brain parenchyma. The current study investigated the ability of biodegradable polymer implants loaded with levetiracetam to ameliorate seizures following implantation above the motor cortex in the tetanus toxin model of temporal lobe epilepsy in rats. The implants led to significantly shorter seizures and a trend towards fewer seizures for up to 1 week. The results of this study indicate that drug-eluting polymer implants represent a promising evolving treatment option for intractable epilepsy. Future research is warranted to investigate issues of device longevity and implantation site

Introduction: Historical thinking, historical consciousness

In September, 2014, the University of Ottawa Education Research Unit, Making History / Faire l’histoire, hosted Canadian History at the Crossroads, a SSHRC-funded symposium in collaboration with the Canadian Museum of History in Gatineau, Québec. The symposium brought together multiple stakeholders, historians, history and museum educators, classroom teachers—including Governor General’s award winners as well as teacher education and graduate students—to stimulate further public dialogue on pedagogies of history and the politics of remembrance. Building on some of the symposium’s original contributions as well as other submissions, this Canadian Journal of Education Special Capsule advances current debates in history education, historical thinking, and historical consciousness, and forges new directions for collective understandings of the past, by connecting with everyday lived experiences in the present. The contributions range from discussions of how young people themselves understand their past to the link- ages between forms of remembering and conceptions of the nation itself.

Development and Screening of Contrast Agents for In Vivo Imaging of Parkinson’s Disease

Purpose: The goal was to identify molecular imaging probes that would enter the brain, selectively bind to Parkinson’s disease (PD) pathology, and be detectable with one or more imaging modalities. Procedure: A library of organic compounds was screened for the ability to bind hallmark pathology in human Parkinson’s and Alzheimer’s disease tissue, alpha-synuclein oligomers and inclusions in two cell culture models, and alpha-synuclein aggregates in cortical neurons of a transgenic mouse model. Finally, compounds were tested for blood–brain barrier permeability using intravital microscopy. Results: Several lead compounds were identified that bound the human PD pathology, and some showed selectivity over Alzheimer’s pathology. The cell culture models and transgenic mouse models that exhibit alpha-synuclein aggregation did not prove predictive for ligand binding. The compounds had favorable physicochemical properties, and several were brain permeable. Conclusions: Future experiments will focus on more extensive evaluation of the lead compounds as PET ligands for clinical imaging of PD pathology

Multimodal MRI can identify perfusion and metabolic changes in the invasive margin of glioblastomas.

PURPOSE: To use perfusion and magnetic resonance (MR) spectroscopy to compare the diffusion tensor imaging (DTI)-defined invasive and noninvasive regions. Invasion of normal brain is a cardinal feature of glioblastomas (GBM) and a major cause of treatment failure. DTI can identify invasive regions. MATERIALS AND METHODS: In all, 50 GBM patients were imaged preoperatively at 3T with anatomic sequences, DTI, dynamic susceptibility perfusion MR (DSCI), and multivoxel spectroscopy. The DTI and DSCI data were coregistered to the spectroscopy data and regions of interest (ROIs) were made in the invasive (determined by DTI), noninvasive regions, and normal brain. Values of relative cerebral blood volume (rCBV), N-acetyl aspartate (NAA), myoinositol (mI), total choline (Cho), and glutamate + glutamine (Glx) normalized to creatine (Cr) and Cho/NAA were measured at each ROI. RESULTS: Invasive regions showed significant increases in rCBV, suggesting angiogenesis (invasive rCBV 1.64 [95% confidence interval, CI: 1.5-1.76] vs. noninvasive 1.14 [1.09-1.18]; P < 0.001), Cho/Cr (invasive 0.42 [0.38-0.46] vs. noninvasive 0.35 [0.31-0.38]; P = 0.02) and Cho/NAA (invasive 0.54 [0.41-0.68] vs. noninvasive 0.37 [0.29-0.45]; P = < 0.03), suggesting proliferation, and Glx/Cr (invasive 1.54 [1.27-1.82] vs. noninvasive 1.3 [1.13-1.47]; P = 0.028), suggesting glutamate release; and a significantly reduced NAA/Cr (invasive 0.95 [0.85-1.05] vs. noninvasive 1.19 [1.06-1.31]; P = 0.008). The mI/Cr was not different between the three ROIs (invasive 1.2 [0.99-1.41] vs. noninvasive 1.3 [1.14-1.46]; P = 0.68). In the noninvasive regions, the values were not different from normal brain. CONCLUSION: Combining DTI to identify the invasive region with perfusion and spectroscopy, we can identify changes in invasive regions not seen in noninvasive regions.This study was funded from a National Institutes of Health Research Clinician Scientist FellowshipThis is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/jmri.2499

Speckle-pattern visibility of light transmitted through a multimode optical fiber

We show that the reduction in visibility of the speckle pattern obtained from laser light that has been passed through a step-index light guide can be found from a knowledge of the model dispersion of the guide, and the bandwidth of the laser beam

A Study of the Diverse T Dwarf Population Revealed by WISE

We report the discovery of 87 new T dwarfs uncovered with the Wide-field Infrared Survey Explorer (WISE) and three brown dwarfs with extremely red near-infrared colors that exhibit characteristics of both L and T dwarfs. Two of the new T dwarfs are likely binaries with L7+/-1 primaries and mid-type T secondaries. In addition, our follow-up program has confirmed 10 previously identified T dwarfs and four photometrically-selected L and T dwarf candidates in the literature. This sample, along with the previous WISE discoveries, triples the number of known brown dwarfs with spectral types later than T5. Using the WISE All-Sky Source Catalog we present updated color-color and color-type diagrams for all the WISE-discovered T and Y dwarfs. Near-infrared spectra of the new discoveries are presented, along with spectral classifications. To accommodate later T dwarfs we have modified the integrated flux method of determining spectral indices to instead use the median flux. Furthermore, a newly defined J-narrow index differentiates the early-type Y dwarfs from late-type T dwarfs based on the J-band continuum slope. The K/J indices for this expanded sample show that 32% of late-type T dwarfs have suppressed K-band flux and are blue relative to the spectral standards, while only 11% are redder than the standards. Comparison of the Y/J and K/J index to models suggests diverse atmospheric conditions and supports the possible re-emergence of clouds after the L/T transition. We also discuss peculiar brown dwarfs and candidates that were found not to be substellar, including two Young Stellar Objects and two Active Galactic Nuclei. The coolest WISE-discovered brown dwarfs are the closest of their type and will remain the only sample of their kind for many years to come.Comment: Accepted to ApJS on 15 January 2013; 99 pages in preprint format, 30 figures, 12 table

Biomechanical Measures of Neuromuscular Control and Valgus Loading of the Knee Predict Anterior Cruciate Ligament Injury Risk in Female Athletes

Background: Female athletes participating in high-risk sports suffer anterior cruciate ligament injury at a 4- to 6-fold greater rate than do male athletes. Hypothesis: Prescreened female athletes with subsequent anterior cruciate ligament injury will demonstrate decreased neuromuscular control and increased valgus joint loading, predicting anterior cruciate ligament injury risk. Study Design: Cohort study; Level of evidence, 2. Methods: There were 205 female athletes in the high-risk sports of soccer, basketball, and volleyball prospectively measured for neuromuscular control using 3-dimensional kinematics (joint angles) and joint loads using kinetics (joint moments) during a jump-landing task. Analysis of variance as well as linear and logistic regression were used to isolate predictors of risk in athletes who subsequently ruptured the anterior cruciate ligament. Results: Nine athletes had a confirmed anterior cruciate ligament rupture; these 9 had significantly different knee posture and loading compared to the 196 who did not have anterior cruciate ligament rupture. Knee abduction angle (P \u3c .05) at landing was 8° greater in anterior cruciate ligament–injured than in uninjured athletes. Anterior cruciate ligament–injured athletes had a 2.5 times greater knee abduction moment (P \u3c .001) and 20% higher ground reaction force (P \u3c .05), whereas stance time was 16% shorter; hence, increased motion, force, and moments occurred more quickly. Knee abduction moment predicted anterior cruciate ligament injury status with 73% specificity and 78% sensitivity; dynamic valgus measures showed a predictive r 2 of 0.88. Conclusion: Knee motion and knee loading during a landing task are predictors of anterior cruciate ligament injury risk in female athletes. Clinical Relevance: Female athletes with increased dynamic valgus and high abduction loads are at increased risk of anterior cruciate ligament injury. The methods developed may be used to monitor neuromuscular control of the knee joint and may help develop simpler measures of neuromuscular control that can be used to direct female athletes to more effective, targeted interventions

Biomechanical Measures of Neuromuscular Control and Valgus Loading of the Knee Predict Anterior Cruciate Ligament Injury Risk in Female Athletes

Background: Female athletes participating in high-risk sports suffer anterior cruciate ligament injury at a 4- to 6-fold greater rate than do male athletes. Hypothesis: Prescreened female athletes with subsequent anterior cruciate ligament injury will demonstrate decreased neuromuscular control and increased valgus joint loading, predicting anterior cruciate ligament injury risk. Study Design: Cohort study; Level of evidence, 2. Methods: There were 205 female athletes in the high-risk sports of soccer, basketball, and volleyball prospectively measured for neuromuscular control using 3-dimensional kinematics (joint angles) and joint loads using kinetics (joint moments) during a jump-landing task. Analysis of variance as well as linear and logistic regression were used to isolate predictors of risk in athletes who subsequently ruptured the anterior cruciate ligament. Results: Nine athletes had a confirmed anterior cruciate ligament rupture; these 9 had significantly different knee posture and loading compared to the 196 who did not have anterior cruciate ligament rupture. Knee abduction angle (P \u3c .05) at landing was 8° greater in anterior cruciate ligament–injured than in uninjured athletes. Anterior cruciate ligament–injured athletes had a 2.5 times greater knee abduction moment (P \u3c .001) and 20% higher ground reaction force (P \u3c .05), whereas stance time was 16% shorter; hence, increased motion, force, and moments occurred more quickly. Knee abduction moment predicted anterior cruciate ligament injury status with 73% specificity and 78% sensitivity; dynamic valgus measures showed a predictive r 2 of 0.88. Conclusion: Knee motion and knee loading during a landing task are predictors of anterior cruciate ligament injury risk in female athletes. Clinical Relevance: Female athletes with increased dynamic valgus and high abduction loads are at increased risk of anterior cruciate ligament injury. The methods developed may be used to monitor neuromuscular control of the knee joint and may help develop simpler measures of neuromuscular control that can be used to direct female athletes to more effective, targeted interventions

Management of Acute and Recurrent Gout: A Clinical Practice Guideline From the American College of Physicians

Description: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the management of gout. Methods: Using the ACP grading system, the committee based these recommendations on a systematic review of randomized, controlled trials; systematic reviews; and large observational studies published between January 2010 and March 2016. Clinical outcomes evaluated included pain, joint swelling and tenderness, activities of daily living, patient global assessment, recurrence, intermediate outcomes of serum urate levels, and harms. Target Audience and Patient Population: The target audience for this guideline includes all clinicians, and the target patient population includes adults with acute or recurrent gout. Recommendation 1: ACP recommends that clinicians choose corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or colchicine to treat patients with acute gout. (Grade: strong recommendation, high-quality evidence). Recommendation 2: ACP recommends that clinicians use low-dose colchicine when using colchicine to treat acute gout. (Grade: strong recommendation, moderate-quality evidence). Recommendation 3: ACP recommends against initiating long-term urate-lowering therapy in most patients after a first gout attack or in patients with infrequent attacks. (Grade: strong recommendation, moderate-quality evidence). Recommendation 4: ACP recommends that clinicians discuss benefits, harms, costs, and individual preferences with patients before initiating urate-lowering therapy, including concomitant prophylaxis, in patients with recurrent gout attacks. (Grade: strong recommendation, moderate-quality evidence)