Broad anti-SARS-CoV-2 antibody immunity induced by heterologous ChAdOx1/mRNA-1273 vaccination.

Heterologous prime-boost immunization strategies have the potential to augment COVID-19 vaccine efficacy. We longitudinally profiled severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S)-specific serological and memory B cell (MBC) responses in individuals who received either homologous (ChAdOx1:ChAdOx1) or heterologous (ChAdOx1:mRNA-1273) prime-boost vaccination. Heterologous messenger RNA (mRNA) booster immunization induced higher serum neutralizing antibody and MBC responses against SARS-CoV-2 variants of concern (VOCs) compared with that of homologous ChAdOx1 boosting. Specificity mapping of circulating B cells revealed that mRNA-1273 boost immunofocused ChAdOx1-primed responses onto epitopes expressed on prefusion-stabilized S. Monoclonal antibodies isolated from mRNA-1273-boosted participants displayed overall higher binding affinities and increased breadth of reactivity against VOCs relative to those isolated from ChAdOx1-boosted individuals. Overall, the results provide molecular insight into the enhanced quality of the B cell response induced after heterologous mRNA booster vaccination.

Surveillance after resection of vestibular schwannoma: measurement techniques and predictors of growth.

OBJECTIVES: To compare different methods of measuring tumor growth after resection of vestibular schwannoma and to identify predictors of growth. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center, inpatient surgery with ambulatory follow-up. PATIENTS: All patients who underwent vestibular schwannoma resection by the senior author from September 1991 to April 2012 and had two or more postoperative MRI scans. INTERVENTIONS: Vestibular schwannoma resection. Measurement of tumor size and enhancement pattern on postoperative magnetic resonance imaging scans. MAIN OUTCOME MEASURES: Tumor size as measured in one (linear), two (planar), and three (volumetric) dimensions using standard radiology workstation tools versus time elapsed since surgical resection. RESULTS: Eighty-eight patients were included with mean follow-up of 3.9 years. Linear measurement of tumor size was found to have modest correlation with planar and volumetric measurements. Excellent correlation was found between the planar and volumetric methods. Nodular enhancement increased risk for tumor growth (OR 6.25, p = 0.03 on planar analysis). If there was growth, tumors with nodular enhancement typically showed increase in size beginning 2 years postoperatively, whereas those with linear or no enhancement were typically stable in size through 5 years. Younger age and larger preoperative tumor size were also risk factors for growth (OR 0.9/p = 0.01 and OR 1.09/p = 0.02). CONCLUSION: Simple planar measurement is an efficient method that correlates well with the more time-consuming volumetric method. The major risk factor for tumor growth is nodular enhancement on a baseline scan, a finding that warrants annual MRI beginning 2 years postoperatively. Younger age and larger preoperative size minimally increased risk of growth.

Comparative emissions of random orbital sanding between conventional and self-generated vacuum systems.

Conventional abrasive sanding generates high concentrations of particles. Depending on the substrate being abraded and exposure duration, overexposure to the particles can cause negative health effects ranging from respiratory irritation to cancer. The goal of this study was to understand the differences in particle emissions between a conventional random orbital sanding system and a self-generated vacuum random orbital sanding system with attached particle filtration bag. Particle concentrations were sampled for each system in a controlled test chamber for oak wood, chromate painted (hexavalent chromium) steel panels, and gel-coated (titanium dioxide) fiberglass panels using a Gesamtstaub-Probenahmesystem (GSP) sampler at three different locations adjacent to the sanding. Elevated concentrations were reported for all particles in the samples collected during conventional sanding. The geometric mean concentration ratios for the three substrates ranged from 320 to 4640 times greater for the conventional sanding system than the self-generated vacuum sanding system. The differences in the particle concentration generated by the two sanding systems were statistically significant with the two sample t-test (P < 0.0001) for all three substances. The data suggest that workers using conventional sanding systems could utilize the self-generated vacuum sanding system technology to potentially reduce exposure to particles and mitigate negative health effects.

Neuroimaging of cerebrovascular disease in the aging brain.

Cerebrovascular disease remains a significant public health burden with its greatest impact on the elderly population. Advances in neuroimaging techniques allow detailed and sophisticated evaluation of many manifestations of cerebrovascular disease in the brain parenchyma as well as in the intracranial and extracranial vasculature. These tools continue to contribute to our understanding of the multifactorial processes that occur in the age-dependent development of cerebrovascular disease. Structural abnormalities related to vascular disease in the brain and vessels have been well characterized with CT and MRI based techniques. We review some of the pathophysiologic mechanisms in the aging brain and cerebral vasculature and the related structural abnormalities detectable on neuroimaging, including evaluation of age-related white matter changes, atherosclerosis of the cerebral vasculature, and cerebral infarction. In addition, newer neuroimaging techniques, such as diffusion tensor imaging, perfusion techniques, and assessment of cerebrovascular reserve, are also reviewed, as these techniques can detect physiologic alterations which complement the morphologic changes that cause cerebrovascular disease in the aging brain.Further investigation of these advanced imaging techniques has potential application to the understanding and diagnosis of cerebrovascular disease in the elderly.

Fungal infections of the central nervous system.

Fungal infections of the central nervous system (CNS) frequently occur in the immunocompromised or debilitated host. Imaging findings are non-specific but may be organized into extra-axial, parenchymal, and vascular categories. Furthermore, knowledge of fungal morphology may predict the imaging manifestations with large, hyphal species having a predilection for brain parenchymal involvement, while small, unicellular organisms typically result in meningitis. Advanced imaging techniques such as diffusion-weighted imaging, MR perfusion and MR spectroscopy, when combined with clinical findings, may help in differentiating fungal disease from other mimckers such as pyogenic infection or cystic metastases.

Comparison of CT perfusion and digital subtraction angiography in the evaluation of delayed cerebral ischemia.

RATIONALE AND OBJECTIVES: Delayed cerebral ischemia (DCI) is a devastating condition that occurs secondary to aneurysmal subarachnoid hemorrhage (A-SAH). The purpose is to compare computed tomography perfusion (CTP) and digital subtraction angiography (DSA) for determining DCI in A-SAH. MATERIALS AND METHODS: A retrospective study of A-SAH patients admitted at our institution between December 2004 and December 2008 was performed. CTP and DSA were obtained at days 6-8 after aneurysm rupture. Both qualitative and quantitative analyses of CT perfusion deficits were performed. DSA was categorized as presence or absence of vasospasm. The reference standard for determining DCI was based on clinical deterioration or infarction on CT or MRI. The test characteristics of CTP and DSA were calculated and their graphs of conditional probabilities were constructed using Bayesian analysis. RESULTS: Fifty-seven patients were included; 79% (45/57) had DCI. Seventy percent (40/57) had CTP perfusion deficits; 80% (36/45) of the DCI and 33% (4/12) of no DCI patients. Sixty-three percent (36/57) had DSA demonstrating vasospasm; 73% (33/45) of the DCI and 25% (3/12) of no DCI patients. Quantitative analysis of the CTP data revealed a significant difference in cerebral blood flow values for the DCI (29.4 mL/100 g/minute) and no DCI groups (40.5 mL/100 g/minute, P = .0213). The sensitivity, specificity, and positive and negative predictive values for CTP were 0.80 (95% CI 0.68-0.92), 0.67 (95% CI 0.40-0.93), 0.90 (95% CI 0.82-0.96), 0.47 (95% CI 0.27-0.62), and for DSA were 0.73 (95% CI 0.60-0.86), 0.75 (95% CI 0.50-0.99), 0.92 (95% CI 0.82-0.98), and 0.43 (95% CI 0.26-0.53), respectively. CONCLUSION: CTP and DSA have similar test characteristics and Bayesian analysis for determining DCI in A-SAH patients.

Role of CT perfusion imaging in the diagnosis and treatment of vasospasm.

The current role of CT perfusion (CTP) imaging in the diagnosis and treatment of vasospasm in the setting of aneurysmal subarachnoid hemorrhage is discussed in this article, with specific attention directed towards defining the terminology of vasospasm and delayed cerebral ischemia. A commonly used CTP technique in clinical practice is described. A review of the literature regarding the usefulness of CTP for the diagnosis of vasospasm and its role in guiding treatment are discussed. Recent research advances in the utilization of CTP and associated ongoing challenges are also presented.

Developing a new reference standard: is validation necessary?

RATIONALE AND OBJECTIVES: A gold standard is often an imperfect diagnostic test, falling short of achieving 100% accuracy in clinical practice. Using an imperfect gold standard without fully comprehending its limitations and biases can lead to erroneous classification of patients with and without disease. This will ultimately affect treatment decisions and patient outcomes. Therefore, validation is essential before implementing a reference standard into practice. Performing a comprehensive validation process is discussed, along with its advantages and challenges. The different types of validation methods are reviewed. An example from our work in developing a new reference standard for vasospasm diagnosis in aneurysmal subarachnoid hemorrhage patients is provided. CONCLUSION: Employing a new reference standard may result in a definitional shift of the disease and classification scheme of patients; therefore, it is important to also assess the impact of a new reference standard on patient outcomes and its clinical effectiveness.

The synthesis and characterization of [IMesH](+)[(eta(3)-C(5)H(5))V(N)Cl(2)](-): An anionic vanadium(v) complex with a terminal nitrido ligand.

A series of new half-sandwich vanadium complexes have been prepared. The structures of two new anionic vanadium half-sandwich complexes, [CpVCl(3)](-) and [CpV(N)Cl(2)](-) are presented. (15)N isotopic labelling studies have been conducted to unambiguously assign the V[triple bond, length as m-dash]N infra red stretching frequencies of both a neutral and an anionic (cyclopentadienyl)vanadium nitrido complex. The influence of strongly pi-basic coligands on the hapticity of the cyclopentadienyl ligands in half-sandwich complexes of vanadium is discussed.

Structural dissociation of attentional control and memory in adults with and without mild traumatic brain injury.

Memory and attentional control impairments are the two most common forms of dysfunction following mild traumatic brain injury (TBI) and lead to significant morbidity in patients, yet these functions are thought to be supported by different brain networks. This 3 T magnetic resonance diffusion tensor imaging (DTI) study investigates whether microstructural integrity of white matter, as measured by fractional anisotropy (FA) within a small set of individually localized regions of interest (ROIs), is associated with these cognitive domains in normal adults and adults with mild TBI. Results in a sample of 23 normal controls reveal a significant correlation between attentional control and FA within a ROI in the left hemisphere anterior corona radiata. Furthermore, the controls demonstrate a correlation between memory performance and FA in a ROI placed in the uncinate fasciculus. Next, to examine whether these relationships are found in the pathological ranges of attention, memory and microstructural white matter integrity associated with mild TBI, these analyses were applied to a group of 43 mild TBI patients. Results, which generally demonstrated a wider range of attention, memory and FA scores, replicated the correlation between attentional control and FA in left hemisphere anterior corona radiata, as well as the correlation between memory performance and FA in the uncinate fasciculus. These two sets of brain-behaviour relationships were highly specific, as shown by a lack of correlation between attention and uncinate fasciculus FA and the lack of correlation between memory performance and anterior corona radiata FA. Furthermore, a 'correlational double dissociation' was demonstrated to exist between two distinct frontal structures independently associated with attention and memory, respectively, via a series of multiple regression analyses in both normal controls and adults with mild TBI. The results of the multiple regression analyses provide direct evidence that tract-specific variation in microstructural white matter integrity among normal controls and among mild TBI patients can account for much of the variation in performance in specific cognitive domains. More generally, such findings suggest that diffusion anisotropy measurement can be used as a quantitative biomarker for neurocognitive function and dysfunction.