A Case Report of Thalamic Infarction after Lumbar Drain: A Unique Cause of Perioperative Stroke?

In the case presented, a patient has an unexplained episode of hypertension during aneurysm clipping. Following the procedure, the patient was discovered to have bilateral thalamic infarctions unrelated to the vascular location of the aneurysm. After a review of the case, it becomes apparent that intracranial hypotension caused by lumbar over drainage of cerebrospinal fluid (CSF) is the likely cause of both the episode of intraoperative hypertension and the thalamic infarcts. It is often presumed that having an open dura protects against intracranial hypotension and subsequent herniation. We present this case to suggest that opening the dura might not be protective in all cases and anesthesiologists must pay particular attention to the rate of CSF drainage. Lumbar CSF drainage is a technique frequently employed during neurological surgery and it is important for anesthesiologists to understand the signs, symptoms, and potential consequences of intracranial hypotension from rapid drainage

XUV Frequency Combs via Femtosecond Enhancement Cavities

We review the current state of tabletop extreme ultraviolet (XUV) sources based on high harmonic generation (HHG) in femtosecond enhancement cavities (fsEC). Recent developments have enabled generation of high photon flux (1014 photons/sec) in the XUV, at high repetition rates (>50 MHz) and spanning the spectral region from 40 nm - 120 nm. This level of performance has enabled precision spectroscopy with XUV frequency combs and promises further applications in XUV spectroscopic and photoemission studies. We discuss the theory of operation and experimental details of the fsEC and XUV generation based on HHG, including current technical challenges to increasing the photon flux and maximum photon energy produced by this type of system. Current and future applications for these sources are also discussed.Comment: invited review article, 38 page

Paradoxical Emboli Secondary to Hepatic Pathology: Common or Coincidental?

Paradoxical cerebral emboli from cardiac and pulmonary sources are well described in the peer-reviewed literature. We outline a case with a hepatic etiology and describe diagnostic and management options. Though this paper represents the first documentation of such, we believe that transpulmonary shunting with concurrent paradoxical cerebral microemboli is more prevalent than recognized. We introduce this case report to compel practitioners to consider paradoxical emboli in selected cirrhotic patients since it can often be difficult to elicit subtle neurologic changes on clinical examination of patients with end stage liver disease

Quantitative 166Ho-microspheres SPECT derived from a dual-isotope acquisition with 99mTc-colloid is clinically feasible

Purpose: Accurate dosimetry is essential in radioembolization. To this purpose, an automatic protocol for healthy liver dosimetry based on dual isotope (DI) SPECT imaging, combining holmium-166 ( 166Ho)-microspheres, and technetium-99 m ( 99mTc)-colloid was developed: 166Ho-microspheres used as scout and therapeutic particles, and 99mTc-colloid to identify the healthy liver. DI SPECT allows for an automatic and accurate estimation of absorbed doses, introducing true personalized dosimetry. However, photon crosstalk between isotopes can compromise image quality. This study investigates the effect of 99mTc downscatter on 166Ho dosimetry, by comparing 166Ho-SPECT reconstructions of patient scans acquired before ( 166Ho-only) and after additional administration of 99mTc-colloid ( 166Ho-DI). Methods: The 166Ho-only and 166Ho-DI scans were performed in short succession by injecting 99mTc-colloid on the scanner table. To compensate for 99mTc downscatter, its influence was accounted for in the DI image reconstruction using energy window-based scatter correction methods. The qualitative assessment was performed by independent blinded comparison by two nuclear medicine physicians assessing 65 pairs of SPECT/CT. Inter-observer agreement was tested by Cohen’s kappa coefficient. For the quantitative analysis, two volumes of interest within the liver, VOI TUMOR, and VOI HEALTHY were manually delineated on the 166Ho-only reconstruction and transferred to the co-registered 166Ho-DI reconstruction. Absorbed dose within the resulting VOIs, and in the lungs (VOI LUNGS), was calculated based on the administered therapeutic activity. Results: The qualitative assessment showed no distinct clinical preference for either 166Ho-only or 166Ho-DI SPECT (kappa = 0.093). Quantitative analysis indicated that the mean absorbed dose difference between 166Ho-DI and 166Ho-only was − 2.00 ± 2.84 Gy (median 27 Gy; p value < 0.00001), − 5.27 ± 8.99 Gy (median 116 Gy; p value = 0.00035), and 0.80 ± 1.08 Gy (median 3 Gy; p value < 0.00001) for VOI HEALTHY, VOI TUMOR, and VOI LUNGS, respectively. The corresponding Pearson’s correlation coefficient between 166Ho-only and 166Ho-DI for absorbed dose was 0.97, 0.99, and 0.82, respectively. Conclusion: The DI protocol enables automatic dosimetry with undiminished image quality and accuracy. Clinical trials: The clinical study mentioned is registered with Clinicaltrials.gov (NCT02067988) on 20 February 2014

166Holmium–99mTechnetium dual‑isotope imaging: scatter compensation and automatic healthy‑liver segmentation for 166Holmium radioembolization dosimetry

Background Partition modeling allows personalized activity calculation for holmium-166 (166Ho) radioembolization. However, it requires the definition of tumor and non-tumorous liver, by segmentation and registration of a separately acquired CT, which is time-consuming and prone to error. A protocol including 166Ho-scout, for treatment simulation, and technetium-99m (99mTc) stannous phytate for healthy-liver delineation was proposed. This study assessed the accuracy of automatic healthy-liver segmentation using 99mTc images derived from a phantom experiment. In addition, together with data from a patient study, the effect of different 99mTc activities on the 166Ho-scout images was investigated. To reproduce a typical scout procedure, the liver compartment, including two tumors, of an anthropomorphic phantom was filled with 250 MBq of 166Ho-chloride, with a tumor to non-tumorous liver activity concentration ratio of 10. Eight SPECT/CT scans were acquired, with varying levels of 99mTc added to the non-tumorous liver compartment (ranging from 25 to 126 MBq). For comparison, forty-two scans were performed in presence of only 99mTc from 8 to 240 MBq. 99mTc image quality was assessed by cold-sphere (tumor) contrast recovery coefficients. Automatic healthy-liver segmentation, obtained by thresholding 99mTc images, was evaluated by recovered volume and Sørensen–Dice index. The impact of 99mTc on 166Ho images and the role of the downscatter correction were evaluated on phantom scans and twenty-six patients’ scans by considering the reconstructed 166Ho count density in the healthy-liver. Results All 99mTc image reconstructions were found to be independent of the 166Ho activity present during the acquisition. In addition, cold-sphere contrast recovery coefficients were independent of 99mTc activity. The segmented healthy-liver volume was recovered fully, independent of 99mTc activity as well. The reconstructed 166Ho count density was not influenced by 99mTc activity, as long as an adequate downscatter correction was applied. Conclusion The 99mTc image reconstructions of the phantom scans all performed equally well for the purpose of automatic healthy-liver segmentation, for activities down to 8 MBq. Furthermore, 99mTc could be injected up to at least 126 MBq without compromising 166Ho image quality. Clinical trials The clinical study mentioned is registered with Clinicaltrials.gov (NCT02067988) on February 20, 2014

Holmium-166 Radioembolization: Current Status and Future Prospective

Since its first suggestion as possible option for liver radioembolization treatment, the therapeutic isotope holmium-166 (166Ho) caught the experts’ attention due to its imaging possibilities. Being not only a beta, but also a gamma emitter and a lanthanide, 166Ho can be imaged using single-photon emission computed tomography and magnetic resonance imaging, respectively. Another advantage of 166Ho is the possibility to perform the scout and treatment procedure with the same particle. This prospect paves the way to an individualized treatment procedure, gaining more control over dosimetry-based patient selection and treatment planning. In this review, an overview on 166Ho liver radioembolization will be presented. The current clinical workflow, together with the most relevant clinical findings and the future prospective will be provided

Gamma camera characterization at high holmium-166 activity in liver radioembolization

Background High activities of holmium-166 (166Ho)–labeled microspheres are used for therapeutic radioembolization, ideally directly followed by SPECT imaging for dosimetry purposes. The resulting high-count rate potentially impacts dead time, affecting the image quality and dosimetric accuracy. This study assesses gamma camera performance and SPECT image quality at high 166Ho activities of several GBq. To this purpose, the liver compartment, including two tumors, of an anthropomorphic phantom was filled with 166Ho-chloride, with a tumor to non-tumorous liver activity concentration ratio of 10:1. Multiple SPECT/CT scans were acquired over a range of activities up to 2.7 GBq. Images were reconstructed using a commercially available protocol incorporating attenuation and scatter correction. Dead time effects were assessed from the observed count rate in the photopeak (81 keV, 15% width) and upper scatter (118 keV, 12% width) window. Post reconstruction, each image was scaled with an individual conversion factor to match the known total activity in the phantom at scanning time. The resulting activity concentration was measured in the tumors and non-tumorous liver. The image quality as a function of activity was assessed by a visual check of the absence of artifacts by a nuclear medicine physician. The apparent lung shunt fraction (nonzero due to scatter) was estimated on planar and SPECT images. Results A 20% count loss due to dead time was observed around 0.7 GBq in the photopeak window. Independent of the count losses, the measured activity concentration was up to 100% of the real value for non-tumorous liver, when reconstructions were normalized to the known activity at scanning time. However, for tumor spheres, activity concentration recovery was ~80% at the lowest activity, decreasing with increasing activity in the phantom. Measured lung shunt fractions were relatively constant over the considered activity range. Conclusions At high 166Ho count rate, all images, visually assessed, presented no artifacts, even at considerable dead time losses. A quantitative evaluation revealed the possibility of reliable dosimetry within the healthy liver, as long as a post-reconstruction scaling to scanning activity is applied. Reliable tumor dosimetry, instead, remained hampered by the dead time

Would transcranial direct current stimulation (tDCS) enhance the effects of working memory training in older adults with mild neurocognitive disorder due to Alzheimer’s disease: study protocol for a randomized controlled trial

© 2015 Cheng et al. Background: There has been longstanding interesting in cognitive training for older adults with cognitive impairment. In this study, we will investigate the effects of working memory training, and explore augmentation strategies that could possibly consolidate the effects in older adults with mild neurocognitive disorder. Transcranial direct current stimulation (tDCS) has been demonstrated to affect the neuronal excitability and reported to enhance memory performance. As tDCS may also modulate cognitive function through changes in neuroplastic response, it would be adopted as an augmentation strategy for working memory training in the present study. Methods/Design: This is a 4-week intervention double-blind randomized controlled trial (RCT) of tDCS. Chinese older adults (aged 60 to 90 years) with mild neurocognitive disorder due to Alzheimer 's disease (DSM-5 criteria) would be randomized into a 4-week intervention of either tDCS-working memory (DCS-WM), tDCS-control cognitive training (DCS-CC), and sham tDCS-working memory (WM-CD) groups. The primary outcome would be working memory test - the n-back task performance and the Chinese version of the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog). Secondary outcomes would be test performance of specific cognitive domains and mood. Intention-to-treat analysis would be carried out. Changes of efficacy indicators with time and intervention would be tested with mixed effect models. Discussion: This study adopts the theory of neuroplasticity to evaluate the potential cognitive benefits of non-invasive electrical brain stimulation, working memory training and dual stimulation in older adults at risk of cognitive decline. It would also examine the tolerability, program adherence and adverse effects of this novel intervention. Information would be helpful for further research of dementia prevention studies. Trial registration: ChiCTR-TRC- 14005036Date of registration: 31 July 2014.published_or_final_versio

Functional Genomic and Proteomic Analysis Reveals Disruption of Myelin-Related Genes and Translation in a Mouse Model of Early Life Neglect

Early life neglect is an important public health problem which can lead to lasting psychological dysfunction. Good animal models are necessary to understand the mechanisms responsible for the behavioral and anatomical pathology that results. We recently described a novel model of early life neglect, maternal separation with early weaning (MSEW), that produces behavioral changes in the mouse that persist into adulthood. To begin to understand the mechanism by which MSEW leads to these changes we applied cDNA microarray, next-generation RNA-sequencing (RNA-seq), label-free proteomics, multiple reaction monitoring (MRM) proteomics, and methylation analysis to tissue samples obtained from medial prefrontal cortex to determine the molecular changes induced by MSEW that persist into adulthood. The results show that MSEW leads to dysregulation of markers of mature oligodendrocytes and genes involved in protein translation and other categories, an apparent downward biasing of translation, and methylation changes in the promoter regions of selected dysregulated genes. These findings are likely to prove useful in understanding the mechanism by which early life neglect affects brain structure, cognition, and behavior

‘Content to be sad’ or ‘runaway apprentice’? The psychological contract and career agency of young scientists in the entrepreneurial university

This article examines employee agency in psychological contracts by exploring how young scientists proactively shape their careers in response to unmet expectations induced by academic entrepreneurialism. It uses the lens of social exchange to examine their relationships with the professors engaged in two types of activities: collaborative research characterized by diffuse/reciprocal exchange, and commercial ventures, by restricted/negotiated exchange. These two categories show how career agency varies in orientation, form and behavioural outcome depending on the relational context within which their psychological contracts evolve. Those involved in collaborative research experienced a relational psychological contract and responded to unfulfilled career promises by ‘extended investment’ in their current jobs. They use ‘proxy agency’ by enlisting the support of their professors. However, some become ‘trapped’ in perennial temporary employment and are ‘content to be sad’. By contrast, those involved in research commercialization experienced a transactional contract and assert ‘personal agency’ by crafting their own entrepreneurial careers. They are ‘runaways’ who seek autonomy. The evidence is based on interviews with 24 doctoral/postdoctoral researchers and 16 professors from three leading UK universities. The study extends psychological contract theory by incorporating career agency and sheds new light on changing academic careers