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Despite extensive paleoenvironmental research on the postglacial history of the Kenai Peninsula, Alaska, uncertainties remain regarding the region's deglaciation, vegetation development, and past hydroclimate. To elucidate this complex environmental history, we present new proxy datasets from Hidden and Kelly lakes, located in the eastern Kenai lowlands at the foot of the Kenai Mountains, including sedimentological properties (magnetic susceptibility, organic matter, grain size, and biogenic silica), pollen and macrofossils, diatom assemblages, and diatom oxygen isotopes. We use a simple hydrologic and isotope mass balance model to constrain interpretations of the diatom oxygen isotope data. Results reveal that glacier ice retreated from Hidden Lake's headwaters by ca. 13.1 cal ka BP, and that groundwater was an important component of Kelly Lake's hydrologic budget in the Early Holocene. As the forest developed and the climate became wetter in the Middle to Late Holocene, Kelly Lake reached or exceeded its modern level. In the last ca. 75 years, rising temperature caused rapid changes in biogenic silica content and diatom oxygen isotope values. Our findings demonstrate the utility of mass balance modeling to constrain interpretations of paleolimnologic oxygen isotope data, and that groundwater can exert a strong influence on lake water isotopes, potentially confounding interpretations of regional climate.
Alzheimer’s disease (AD) cerebrospinal fluid (CSF) biomarkers are promising tools to help identify the underlying pathology of neurocognitive disorders. In this manuscript, we report our experience with AD CSF biomarkers in 262 consecutive patients in a tertiary care memory clinic.
We retrospectively reviewed 262 consecutive patients who underwent lumbar puncture (LP) and CSF measurement of AD biomarkers (Aβ1–42, total tau or t-tau, and p-tau181). We studied the safety of the procedure and its impact on patient’s diagnosis and management.
The LP allowed to identify underlying AD pathology in 72 of the 121 patients (59%) with early onset amnestic mild cognitive impairment (aMCI) with a high probability of progression to AD; to distinguish the behavioral/dysexecutive variant of AD from the behavioral variant of frontotemporal dementia (bvFTD) in 25 of the 45 patients (55%) with an atypical neurobehavioral profile; to identify AD as the underlying pathology in 15 of the 27 patients (55%) with atypical or unclassifiable primary progressive aphasia (PPA); and to distinguish AD from other disorders in 9 of the 29 patients (31%) with psychiatric differential diagnoses and 19 of the 40 patients (47%) with lesional differential diagnoses (normal pressure hydrocephalus, encephalitis, prion disease, etc.). No major complications occurred following the LP.
Our results suggest that CSF analysis is a safe and effective diagnostic tool in select patients with neurocognitive disorders. We advocate for a wider use of this biomarker in tertiary care memory clinics in Canada.
Dysgeusia is a frequent, yet underreported side effect of chemotherapy for cancer. We report here the first use of gabapentin in two glioblastoma patients who developed dysgeusia following intra-arterial administration of carboplatin or oral administration of lomustine, respectively. Treatment initiation was followed by resolution of taste alteration within weeks. Both patients reported significant improvement in their quality of life and regained weight, allowing further chemotherapy cycles. We hypothesized that in these two cases, chemotherapy impeded gustatory cells turnover and function, resulting in a gustatory “deafferentation-like” syndrome which was successfully addressed by the medication.
Sediments that accumulate in high-latitude lakes serve as valuable environmental archives of changing conditions in a region currently undergoing rapid change. A previously unexplored sedimentary sequence reaching back 16,000 years from Lakes Peters and Schrader (Neruokpuk Lakes) in the northeastern Brooks Range (69°N), Alaska, shows distinct changes in accumulation rates and biophysical properties including bulk density (BD), organic matter (OM) content, and grain-size distribution at five widely distributed core sites. The oldest sediments contain little OM and accumulated rapidly as glaciers retreated around 15 ka. OM peaked between 12 and 10 ka along with Northern Hemisphere summer insolation. BD increased and OM decreased until around 5 ka, possibly reflecting a decrease in river-transported terrestrial OM. From 5–2 ka, OM consistently increased, suggesting a rise in river discharge, or a rise in summer temperatures, which led to higher productivity, or both. After 2 ka, sediments increased in BD and decreased in OM, suggesting glacier growth. Evidence for glacier expansion late during the Little Ice Age is weak, but increased sedimentation rates may reflect glacier retreat during the last century. This study provides a framework for future paleoenvironmental research of a rare archive in a relatively pristine Arctic setting.
Background: Neurosurgical residents face a unique combination of challenges, including long duty hours, technically challenging cases, and uncertain employment prospects. We sought to assess the demographics, interests, career goals, self-rated happiness, and overall well-being of Canadian neurosurgery residents. Methods: A cross-sectional survey was developed and sent through the Canadian Neurosurgery Research Collaborative to every resident enrolled in a Canadian neurosurgery program as of April 1, 2016. Results: We analyzed 76 completed surveys of 146 eligible residents (52% response rate). The median age was 29 years, with 76% of respondents being males. The most popular subspecialties of interest for fellowship were spine, oncology, and open vascular neurosurgery. The most frequent self-reported number of worked hours per week was the 80- to 89-hour range. The majority of respondents reported a high level of happiness as well as stress. Sense of accomplishment and fatigue were reported as average to high and overall quality of life was low for 19%, average for 49%, and high for 32%. Satisfaction with work-life balance was average for 44% of respondents and was the only tested domain in which significant dissatisfaction was identified (18%). Overall, respondents were highly satisfied with their choice of specialty, choice of program, surgical exposure, and work environment; however, intimidation was reported in 36% of respondents and depression by 17%. Conclusions: Despite a challenging residency and high workload, the majority of Canadian neurosurgery residents are happy and satisfied with their choice of specialty and program. However, work-life balance, employability, resident intimidation, and depression were identified as areas of active concern.
We propose a simple modification to an established blood-brain barrier disruption (BBBD) animal model that allows us to use ketamine/xylazine as the anaesthetic agent, therefore decreasing the complexity and the cost of the model, while maintaining similar efficiency.
Sixty-two Long Evans rats were anaesthetized by intraperitoneal injection of ketamine/ xylazine. Osmotic BBBD was performed by administering 25% mannitol into the internal carotid artery in a retrograde fashion from the external carotid. The infusion rate of mannitol, as well as the duration was adjusted in a stepwise fashion to identify optimal parameters for BBBD and minimize complications. As a supplementary step to previously reported models, a vascular clip was applied to the common carotid artery prior to the infusion of mannitol, therefore isolating our model system from the depressant hemodynamic effects of ketamine/xylazine. Evans blue dye was used to control for BBBD intensity.
Using this model at an initial infusion rate of 0.15 ml/sec, a significant incidence of brain hemorrhage (75%) and a death rate of 62.5% were observed. Decreasing the infusion rate in a stepwise fashion, 0.08 ml/sec was found to produce optimal BBBD, as demonstrated by Evans blue staining. At this rate, 6/7 animals depicted grade II staining, whereas one animal depicted grade IV.
The application of a clip to the common carotid artery prior to mannitol infusion allowed us to isolate the cerebral circulation from the depressant hemodynamic effects of ketamine/xylazine. This supplementary step produced consistent and efficient BBBD in our animal model.
We report survival and pretreatment prognostic factors for survival and chemosensitivity in 53 oligodendrogliomas treated with PCV (procarbazine, lomustine and vincristine) chemotherapy.
A total of 53 patients with histologically proven oligodendroglioma, anaplastic oligodendroglioma or oligo-astrocytoma and treated with PCVwere extracted from the London Regional Cancer Center database. A retrospective review was conducted to evaluate overall survival and pretreatment prognostic factors for survival and chemosensitivity.
The median survival time from diagnosis was 123.6 months. The overall five- and ten-year survival rates were 72.7% and 52.7% respectively. Age <40, seizure as an initial symptom, absence of cognitive deficit and presence of a homogeneous hypodense lesion without contrast enhancement on the initial pretreatment CT scan were all factors independently associated with favorable outcome. The presence of increased cellularity, pleomorphism, mitosis, vascular proliferation and grading as an anaplastic lesion using these surrogates on pathological assessment, were all associated with an unfavorable outcome in univariable analysis. In multivariable analysis, only the anaplastic grading and presence of increased cellularity were significant determinants of unfavorable survival. The only factor adversely associated with chemosensitivity was the presence of a focal symptom at presentation.
Overall survival is significantly longer in oligodendroglial lesions than in fibrillary astrocytic tumors. A two tier grading system using standard morphological features seems accurate in predicting outcome in these patients. The presence of a neoplastic astrocytic component does not seem to impact the outcome. No clinical, radiological or pathological factor could be identified to reliably predict chemotherapy response.
The purpose of this study was to develop and validate a self-administered questionnaire to measure the health-related quality of life (QOL) of patients with brain cancer. We wanted to assess both core and disease-specific concerns in a single, easy-to-use instrument, thus promoting concision and clinical utility. The questionnaire departs from its predecessors in that it was designed for- and validated among French speaking Canadians.
A focus group of health professionals was used to develop items for the questionnaire, which was later validated with 105 patients suffering from brain cancer. The underlying structure of the questionnaire was investigated using principal component analysis and confirmed using a principal factor analysis.
The final version of the questionnaire contains 30 items. Seven multi-item scales, tapping into distinct dimensions of QOL, were uncovered (i.e., functional well-being, symptom severity/fear of death, social support/acceptance of disease, autonomy in personal care, digestive symptomatology, neurocognitive function, and pain). Assessment of reliability revealed elevated internal consistency for each of the seven scales (Cronbach coefficient alpha ≥≥.65), whereas known-groups validity (anchor-based approach) revealed that the different dimensions uniquely discriminated between patients with different functional levels (Karnofsky Performance Scores) and clinical status (exposure to neurosurgery, radiotherapy, and use of chemotherapy and anticonvulsants).
Our QOL questionnaire, the Sherbrooke Neuro-Oncology Assessment Scale, or SNAS, taps into both core and disease-specific issues relevant to neuro-oncology patients. It has good validity and reliability, and clearly reflects the multidimensional nature of QOL. Depending on the research focus, it may be used in clinical trials to track the impact of disease and/or treatment on satisfaction, functional status, and general well-being.
The brain functions as an integrated multi-networked organ. Complex neurocognitive functions are not attributed to a single brain area but depend on the dynamic interactions of distributed brain areas operating in large-scale networks. This is especially important in the field of neurosurgery where intervention within a spatially localized area may indirectly lead to unwanted effects on distant areas. As part of a preliminary integrated work on functional connectivity, we present our initial work on diffusion tensor imaging tractography to produce in vivo white matter tracts dissection.
Diffusion weighted data and high-resolution T1-weighted images were acquired from a healthy right-handed volunteer (25 years old) on a whole-body 3 T scanner. Two approaches were used to dissect the tractography results: 1) a standard region of interest technique and 2) the use of Brodmann's area as seeding points, which represents an innovation in terms of seeds initiation.
Results are presented as tri-dimensional tractography images. The uncinate fasciculus, the inferior longitudinal fasciculus, the inferior fronto-occipital fasiculus, the corticospinal tract, the corpus callosum, the cingulum, and the optic radiations where studied by conventional seeding approach, while Broca's and Wernicke's areas, the primary motor as well as the primary visual cortices were used as seeding areas in the second approach.
We report state-of-the-art tractography results of some of the major white matter bundles in a normal subject using DTI. Moreover, we used Brodmann's area as seeding areas for fiber tracts to study the connectivity of known major functional cortical areas.
Adequate animal glioma models are mandatory for the pursuit of preclinical research in neuro-oncology. Many implantation models have been described, but none perfectly emulate human malignant gliomas. This work reports our experience in standardizing, optimizing and characterizing the Fischer/F98 glioma model on the clinical, pathological, radiological and metabolic aspects.
Materials and methods:
F98 cells were implanted in 70 Fischer rats, varying the quantity of cells and volume of implantation solution, and using a micro-infusion pump to minimize implantation trauma, after adequate coordinates were established. Pathological analysis consisted in hematoxylin and eosin (H&E) staining and immunohistochemistry for GFAP, vimentin, albumin, TGF-b1, TGF-b2, CD3 and CD45. Twelve animals were used for MR imaging at 5, 10, 15 and 20 days. Corresponding MR images were compared with pathological slides. Two animals underwent 18F-FDG and 11C-acetate PET studies for metabolic characterization of the tumors.
Implantation with 1x104 cells produced a median survival of 26 days and a tumor take of 100%. Large infiltrative neoplasms with a necrotic core were seen on H&E. Numerous mitosis, peritumoral infiltrative behavior, and neovascular proliferation were also obvious. GFAP and vimentin staining was positive inside the tumor cells. Albumin staining was observed in the extracellular space around the tumors. CD3 staining was negligible. The MR images correlated the pathologic findings. 18F-FDG uptake was strong in the tumors.
The standardized model described in this study behaves in a predictable and reproducible fashion, and could be considered for future pre-clinical studies. It adequately mimics the behavior of human malignant astrocytomas.
This study reports our findings in assessing in vivo tumour growth with magnetic resonance imaging using a commercial magnet and antenna in F98 implanted Fischer rats. A comparison of T1 gadolinium-enhanced coronal MR scans and pathology specimens in corresponding animals was accomplished.
One rat was used in serial experiments to establish adequate imaging parameters. Afterward, 12 animals implanted with F98 cells underwent a MR study following intervals spanning five, ten, 15 and 20 days on a 1.5T human Siemens. Using a small loop antenna, a coronal T1 weighted MRI scan with Gadolinium was performed. Images were analyzed and volumes of enhancing tumour were calculated. The animals were sacrificed after the imaging procedure and brain were harvested and processed in pathology. Pathology specimens and MR images were analyzed using image processing software. One hematoxylin + eosin (H&E) slide per specimen was compared to the corresponding MR slice depicting the largest area of enhancement.
The MR enhancement areas obtained were 2.18mm2, 8.25mm2, 21.6mm2 and 23.17mm2 at five, ten, 15 and 20 days. Tumour margin measurements on pathologic samples produced areas of 0.29mm2, 4.43 mm2, 8.3mm2, and 12.9mm2 at five, ten, 15 and 20 days respectively.
The T1-enhancing images constantly overestimated the tumour bulk on H&E. This phenomenon is explained by enhancement of the brain around tumour, the extra-axial tumour growth, and a shrinking factor of 17% related to the fixation process. Nonetheless, the radiological tumour growth paralleled the histological samples. This technology is thus suitable to follow tumour growth in F98 implanted rats.
The impact of malignant glioma resection on survival is still a matter of controversy. The lack of well-designed prospective studies as well as control of all factors in retrospective studies plays an important role in this debate. Amongst some of these uncontrolled factors, are the inclusion of different histological grades, the lack of objective methods to estimate the extent of resection and unspecified delays in post-operative imaging.
We retrospectively reviewed 126 consecutive patients with glioblastoma, operated on by the senior authors at the Centre Hospitalier Universitaire de Sherbrooke, who met the following criteria: >18 years of age, newly diagnosed glioblastoma, pre-operative magnetic resonance imaging (MRI) within 2 weeks prior to surgery, and a post-operative MRI within 72 hours after surgery. Extent of tumour resection was calculated using pre and post-operative tumour delimitation on gadolinium-enhanced T1 MRI in a volumetric analysis.
Applying stringent specific inclusion criteria, 126 patients were retained in the analysis. The median overall survival was 271 days and the median extent of resection was 65%. Patients with more than 90% of tumour resection had a significantly better outcome, improving median survival from 225 to 519 days (P=0.006). Other factors that significantly improved survival were the use of radiotherapy, the number of regimens and type of chemotherapy used.
A more aggressive approach combining maximal safe resection and use of salvage chemotherapy seems to confer a survival advantage for glioblastoma patients.
Malignant astrocytomas are aggressive neoplasms with a dismal prognosis despite optimal treatment. Maximal resective surgery is traditionally complemented by radiation therapy. Chemotherapy is now used on patients as initial therapy when their functional status is congruent with further treatment. The classic agents used are nitrosoureas, but temozolomide has taken the front seat recently, with recent data demonstrating increased survival when this agent is used concurrently with radiation therapy in newly diagnosed glioblastoma patients. A new class of agents, refered to as biological modifiers, are increasingly used in clinical trials in an effort to affect the intrinsic biologic aberrations harboured by tumor cells. These drugs comprise differentiation agents, anti-angiogenic agents, matrix-metalloproteinase inhibitors and signal transduction inhibitors, among others. This article reviews the standard cytotoxic agents that have been used to treat malignant astrocytomas, and the different combination regimens offering promise. In addition, recent advances with biological modifiers are also discussed.
Basal cell carcinomas are common lesions that can have a locally invasive behavior. The authors present a case of a scalp lesion with skull and dura-mater invasion that was unrecognized prior to surgical undertaking.
A 66-year-old female presented with an extensive ulcerating lesion on the frontal scalp, deemed to be a basal cell carcinoma. The plastic surgery team brought her to the operating room for resection but subsequently backed off after the discovery of bony invasion. Imaging revealed extensive bony and epidural extension.
Resection of the invaded frontal scalp, bone, dura-mater and proximal part of the superior sagittal sinus was performed. This was followed by a reconstructive procedure consisting of a duraplasty, a cranioplasty, and a skin rotation flap and partial-thickness skin grafting.
Radiological evaluation of scalp basal cell carcinomas should be done prior to surgery to rule out any bony or intracranial invasion.
Matching the broad-band emission of active galaxies with the predictions of theoretical models can be used to derive constraints on the properties of the emitting region and to probe the physical processes involved. AP Librae is the third low frequency peaked BL Lac (LBL) detected at very high energy (VHE, E>100GeV) by an Atmospheric Cherenkov Telescope; most VHE BL Lacs (34 out of 39) belong to the high-frequency and intermediate-frequency BL Lac classes (HBL and IBL). LBL objects tend to have a higher luminosity with lower peak frequencies than HBLs or IBLs. The characterization of their time-averaged spectral energy distribution is challenging for emission models such as synchrotron self-Compton (SSC) models.
The debate about which media metric efficiently measures the
effectiveness of a web-based advertisement, such as banners, is still
alive and well. Nonetheless, the most widely used measure of
effectiveness for banner advertisements is still the click-through
rate. The purpose of this article is to review the measures currently
used to measure effectiveness in web advertising and to empirically
determine the factors that might contribute to observed variations in
click-through rates based on an actual sample of advertising campaigns.
The study examined the complete set of all advertising insertions of 77
customers of a large advertising agency over a one-year period. A
resulting sample of 1,258 placements was used to study the effect of
banner formats and exposure levels on click-through rates using
analysis of variance. Results suggest that the strongest effect on
click-through rates comes from the use of trick banners
(η2 = 0.25) and that other factors such as size of the
advertisement, motion, use of “click here,” and “online
only” type of announcers all have a significant impact of
click-through rates. Implications of these findings as well as limitations
of the current study are discussed and directions for future research
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