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Segmental neurofibromatosis (SNF) is a rare subtype of neurofibromatosis (NF). The disease is characterized by features circumscribed to one or more body cutaneous and/or subcutaneous segments. This is a classic example of somatic mosaicism which occurs by postzygotic mutation of the NF1 gene late in the course of embryonic development affecting localized neural crest lines in the fetus. Our case series reported three novel patients who had segmental spinal expression of the disease classified as true mosaic/segmental NF1, along with their management plan treated at one of the largest NF1 center.

Horizontal Axis Wind Turbines (HAWT’s) has losses due to the axial free stream wind velocityconverting into radial and tangential velocity as it moves through the rotating rotor. By fitting aguide ring to the hub some of these losses could be recovered. Computational Fluid Dynamics(CFD) simulations were carried out on a conventional HAWT rotor, and a similar rotor fitted witha guide ring. The purpose of the guide ring is to direct the axial free stream velocity onto the rotor. Simulations were conducted at 0.5 m/s and 1 m/s free stream velocities. Water was used as thefluid for simulation as future experimental verification will be conducted in a water tunnel. Guiderings were placed at 15 % and 20 % of the rotor radius, to investigate the effect on rotorefficiency. Investigative CFD results showed that a guide ring placed at 15 % increased the rotorefficiency with 24 % at peak power coefficient rotor Tip Speed Ratio (TSR) for 1 m/s free streamvelocity. A guide ring placed at 20 % increase the efficiency with 1 % at peak power coefficientrotor TSR for 1 m/s free stream velocity. This implies, that precise positioning of a guide ring tothe hub can produce a significant increase in the efficiency. These investigative results justifyfurther research for HAWT’s fitted with guide rings and their placement. &nbsp

Biogeochemical properties of soils play a crucial role in soil and stream chemistry throughout a watershed. How water interacts with soils during subsurface flow can have impacts on water quality, thus, it is fundamental to understand where and how certain soil water chemical processes occur within a catchment. In this study, ~200 soil samples were evaluated throughout a small catchment in the Front Range of Colorado, USA to examine spatial and vertical patterns in major soil solutes among different landscape units: riparian areas, alluvial/colluvial fans, and steep hillslopes. Solutes were extracted from the soil samples in the laboratory and analyzed for major cation (Li, K, Mg, Br, and Ca) and anion (F, Cl, NO2, NO3, PO4, and SO4) concentrations using ion chromatography. Concentrations of most solutes were greater in near surface soils (10 cm) than in deeper soils (100 cm) across all landscape units, except for F which increased with depth, suggestive of surface accumulation processes such as dust deposition or enrichment due to biotic cycling. Potassium had the highest variation between depths, ranging from 1.04 mg/l (100 cm) to 3.13 mg/l (10 cm) sampled from riparian landscape units. Nearly every solute was found to be enriched in riparian areas where vegetation was visibly denser, with higher mean concentrations than the hillslopes and fans, except for NO3 which had higher concentrations in the fans. Br, NO2, and PO4 concentrations were often below the detectable limit, and Li and Na were not variable between depths or landscape units. Ratioed stream water concentrations (K:Na, Ca:Mg, and NO3:Cl) vs. discharge relationships compared to the soil solute ratios indicated a hydraulic disconnection between the shallow soils (3 solutes may serve as valuable tracers to identify subsurface flowpaths as they are distinct among landscape units and depth within this catchment. However, interflow and/or shallow groundwater flow likely have little direct connection to streamflow generation.

Given the prevalence of dementia and the development of pathology-specific disease modifying therapies, high-value biomarker strategies to inform medical decision making are critical. In-vivo tau positron emission tomography (PET) is an ideal target as a biomarker for Alzheimer’s disease diagnosis and treatment outcome measure. However, tau PET is not currently widely accessible to patients compared to other neuroimaging methods. In this study, we present a convolutional neural network (CNN) model that impute tau PET images from more widely-available cross-modality imaging inputs. Participants (n=1,192) with brain MRI, fluorodeoxyglucose (FDG) PET, amyloid PET, and tau PET were included. We found that a CNN model can impute tau PET images with high accuracy, the highest being for the FDG-based model followed by amyloid PET and MRI. In testing implications of AI-imputed tau PET, only the FDG-based model showed a significant improvement of performance in classifying tau positivity and diagnostic groups compared to the original input data, suggesting that application of the model could enhance the utility of the metabolic images. The interpretability experiment revealed that the FDG- and MRI-based models utilized the non-local input from physically remote ROIs to estimate the tau PET, but this was not the case for the PiB-based model. This implies that the model can learn the distinct biological relationship between FDG PET, MRI, and tau PET from the relationship between amyloid PET and tau PET. Our study suggests that extending neuroimaging’s use with artificial intelligence to predict protein specific pathologies has great potential to inform emerging care models.

The standard tapping machine used for the ASTM test standards on impact noise insulation does not have any provision to measure input force. A modified tapping machine with a force transducer was used for eight different residential floors, revealing that the force injected into the structure varies by approximately 37 dB. This variation is due to the combination of the tapping machine and the floor compliance. On one of the floors for the same test, the force injected due to the tapping machine varies by 2.6 dB for a single hammer. The floor impedance was also measured using accelerometers and the lightweight floor impedance is about 40 dB lower than heavyweight floors. The impedance varies by 20 - 30 dB throughout the frequency spectra for the four light-weight joist-framed floors. The authors propose that this injected force be measured, and an injected-to-radiated energy ratio be used to compare various floor-ceiling assemblies.

Mutations in the rhodopsin gene may cause photoreceptor degeneration in autosomal dominant retinitis pigmentosa (ADRP) by dominant negative or toxic gain-of-function mechanisms. Controversy exists as to the mechanism by which the widely studied P23H mutation induces rod cell dysfunction and death. Inherited disease caused by dominant negative mutations may be amenable to treatment using wild-type gene augmentation. Indeed, prior studies in the RHOP23H, Rho+/- transgenic mouse model of ADRP have suggested that a therapeutic benefit may be achieved when wild-type rhodopsin is overexpressed following subretinal delivery of a recombinant adeno-associated viral (AAV) vector. In this study, we investigated the effect of wild-type rhodopsin supplementation on the rate of retinal degeneration in the more clinically relevant RhoP23H/+ knock-in mouse model of ADRP. Four AAVs carrying the human rhodopsin coding sequence were first designed and compared for efficacy in the rhodopsin knockout mouse. All four vectors were capable of driving expression of the human transgene in the knockout retina with the protein being appropriately trafficked to de novo rod outer segments. The most efficient of these vectors was injected at one of two doses into the subretinal space of RhoP23H/+ mice and the effect on retinal structure and function determined longitudinally by spectral-domain optical coherence tomography and electroretinography, respectively, over a 3-month period. Although significant overexpression of rhodopsin protein was achieved in this model, no beneficial effect on retinal structure or function was observed at either dose. Lack of therapeutic efficacy in this model may be attributable to the relative rapidity of degeneration in the RhoP23H/+ mouse relative to the human disease, over- or under dosing at the level of individual photoreceptors, late timing of the intervention, or a possible predominant toxic gain-of-function mechanism of degeneration.

Purpose: Age-related macular degeneration leads to retinal pigment epithelium (RPE) cell death and loss of central vision. In vivo studies have shown that the RPE layer has an innate, but limited, ability to repopulate atrophic areas. We aimed to establish a semiautomated, in vitro, wound healing assay workflow for targeted screening of compounds able to influence RPE wound healing. Methods: The ARPE-19 phenotype was evaluated using bright-field microscopy, immunocytochemistry, and quantitative real-time polymerase chain reaction. ARPE-19 monolayers were simultaneously scratched in a 96-well format and treated with Hoechst-33342 and an array of compounds. Initial wound dimensions and wound healing were subsequently evaluated using the EVOS FL Auto 2.0 imaging platform combined with automated image analyses. Results: Long-term cultured ARPE-19 cells displayed a more in vivo RPE-like phenotype compared with recently seeded or short-term cultured cells. No statistical difference of initial scratch width was observed between short-term and long-term cultured cells, but more wells were excluded from analyses in total in the latter case due to scratch width, scratch smoothness, and imaging errors. Furthermore, the previous time spent in continuous culture had an effect on the observation of an altered wound healing response to different treatment conditions. Conclusions: We have established a semiautomated, 96-well format, in vitro wound healing assay with a reproducible workflow. This would enable screening of a significant number of compounds and greatly advances the potential of identifying novel therapeutics that may enhance the innate ability of RPE cells to repopulate atrophic areas.

Automotive mufflers are heavy, large, and loud at low frequencies. Carbon nanotube (CNT) speakers are solid-state, lightweight, flexible, and capable of handling high temperatures. This makes them suitable as loudspeakers in active exhaust noise cancellation applications. A coaxial CNT speaker designed for active noise control in an exhaust system is developed. Test results for resistance, in-pipe axial sound pressure level, and efficiency are presented. The maximum in-pipe sound pressure level was above 120 dB (re 20 μPa) using 105 W of electrical power. The maximum power efficiency was 0.008%. The weight, dimensions, and sound pressure level of the speaker show promise for active exhaust noise cancellation applications.

The authors describe retinal reconstruction and restoration of visual function in heritably blind mice missing the rhodopsin gene using a novel method of ex vivo gene therapy and cell transplantation. Photoreceptor precursors with the same chromosomal genetic mutation were treated ex vivo using minicircle DNA, a non-viral technique that does not present the packaging limitations of adeno-associated virus (AAV) vectors. Following transplantation, genetically modified cells reconstructed a functional retina and supported vision in blind mice harboring the same founder gene mutation. Gene delivery by minicircles showed comparable long-term efficiency to AAV in delivering the missing gene, representing the first non-viral system for robust treatment of photoreceptors. This important proof-of-concept finding provides an innovative convergence of cell and gene therapies for the treatment of hereditary neurodegenerative disease and may be applied in future studies toward ex vivo correction of patient-specific cells to provide an autologous source of tissue to replace lost photoreceptors in inherited retinal blindness. This is the first report using minicircles in photoreceptor progenitors and the first to transplant corrected photoreceptor precursors to restore vision in blind animals.

Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) is widely used to quantify viral RNA genomes for diagnostics and research, yet conventional RT-qPCR protocols are unable to accurately distinguish between the different viral RNA species that exist during infection. Here we show that false-priming and self-priming occur during reverse transcription with several published Zika virus (ZIKV) primer sets. We developed a RT-qPCR assay using tagged primers and thermostable reverse transcriptase, which greatly reduced the occurrence of nonspecific cDNA products. Furthermore, we optimized the assay for use in multiplex qPCR which allows for simultaneous quantitative detection of positive-strand and negative-strand ZIKV RNA along with an internal control from both human and mosquito cells. Importantly, this assay is sensitive enough to study early stages of virus infection in vitro. Strikingly, using this assay, we detected ZIKV negative-strand RNA as early as 3 h post-infection in mammalian cell culture, at a time point prior to the onset of positive-strand RNA synthesis. Overall, the strand-specific RT-qPCR assay developed herein is a valuable tool to quantify ZIKV RNA and to study viral replication dynamics during infection. The application of these findings has the potential to increase accuracy of RNA detection methods for a variety of viral pathogens.HighlightsSelf-primed cDNA is amplified by widely-used ZIKV qPCR primer setsUse of tagged primers and thermostable RT increases strand-specificity for RT-qPCRMultiplexed qPCR allows for simultaneous quantitation of (+) and (-) strand viral RNAs, and an internal controlStrand-specific RT-qPCR can detect fewer than one copy of viral RNA per cell in human and mosquito cells

Moyamoya disease (MMD) is a pathophysiologically complex disorder characterized by progressive stenosis of the internal carotid arteries at the skull base and formation of circuitous and expanded collaterals angiographically “puff of smoke” at the base of brain. However, these collateral blood vessels are fragile and prone to ischemic or hemorrhagic events during the peri and intra-operative period. Direct and indirect bypass techniques have been devised with the goal of promoting angiogenesis, inducing formation of collateral vessels, and restoring perfusion to the oxygen deprived area of the brain. Mayfield skull clamp can cause blood pressure instability. This technical note highlights the surgical management of MMD without the use of Mayfield skull clamp with the goal of minimizing risk of perioperative blood pressure volatility.

A simulation and experimental study of multilayered chiral metamaterial stacks, optically active in the important mid-IR region of the spectrum. We demonstrate the ability to tune the spectral response based on layer configuration.

Background: In the current era of modern neurosurgery, the treatment strategies have been shifted to “nerve-preservation approaches” for achieving a higher facial and hearing function preservation rate following facial nerve tumors.Objective: We have conducted this novel report on determining the outcome of patients with facial nerve schwannomas (FNS) treated with hypo fractionated stereotactic radiosurgery (hfSRS).Methods: Retrospective chart review of a prospectively maintained database search was conducted. Patients who underwent hfSRS CyberKnife (Accuray Inc, Sunnyvale, California., USA) for FNS were included. Outcomes consisted of tumor control, facial and hearing nerve function as graded by House-Brackmann (HB) and Gardner-Robertson scale, and adverse radiation effects. SPSS 23 was used to perform statistical analysis.Results: With an institutional board review approval, we retrospectively identified 5 patients with FNS [4 intracranial (80%) and 1 extracranial (20%)] treated with hfSRS (2011-2019). Patients received definitive SRS in 3 patients (60.0%) wile adjuvant to surgical resection in 2 patients (40.0%). A median tumor volume of 7.5 cm3 (range, 1.5-19.6 cm3) received a median prescription dose of 23.2 Gy (range, 21-25 Gy) administered in median of 3 fractions (range, 3-5 session). With a median radiographic follow-up of 31.4 months (range, 13.0-71.0 months) and clinical follow-up of 32.6 months (range, 15.1-72.0 months), the local tumor control was 100.0%. At last clinical follow-up, the facial nerve function improved or remained unchanged HB I-II in 80.0% of the patients, while the hearing nerve function improved or remained stable in 100.0% (Gardner-Robertson I-II) of the patients. Temporary clinical toxicity was seen in 3 patients (60.0%) which resolved. None of the patient developed adverse radiation effect.Conclusion: From our case series, hfSRS in FNS seems to be safe and efficacious in terms of local tumor control, and improved facial and hearing nerve function.

Segmental neurofibromatosis (SNF) is a rare subtype of neurofibromatosis (NF). The disease is characterized by features circumscribed to one or more body cutaneous and/or subcutaneous segments. This is a classic example of somatic mosaicism which occurs by postzygotic mut ation of the NF1 gene late in the course of embryonic development affecting localized neural crest lines in the fetus. Spinal neurofibromatosis, on the other hand, is characterized by histologically proven bilateral neurofibromas of the spinal roots.Hereby we describe a novel manifestation of spinal SNF.Our case report demonstrated one patient who had segmental spinal expression of the disease classified as true mosaic/segmental NF1 along with its management plan treated at one of the largest NF1 centers to exist.This will aid in understanding the rare clinical presentation and treatment options for this novel phenotype.

Cerebellopontine angle (CPA) meningiomas can affect hearing function and require expeditious treatment to prevent permanent hearing loss. The authors sought to determine the factors associated with functional hearing outcome in CPA meningioma patients treated with surgery and/or radiation therapy in the form of either stereotactic radiosurgery or stereotactic radiation therapy.Consecutive patients with CPA meningiomas who had presented at our hospital from 2008 to 2018 were identified through retrospective chart review. Hearing function (as defined by pure tone average (PTA) and speech discrimination score (SDS) on Audiogram) was assessed before and after surgery for CPA meningioma. Audiograms with PTA 50 dB and SDS 69% were defined as poor hearing functional outcome. Multivariable Cox Proportional Hazards Regression Model was used to assess the associations between pre-operative hearing functional assessment and post-operative hearing functional outcomes.The study cohort included 31 patients (80.6% females, with a mean age of 61.3 ± 15.2 years) with a median clinical follow-up of 5 months (range: 1 week-98 months). The mean pre-operative PTA and SDS were 23.8 ± 11.2 dB and 64.4 ± 22.2% respectively. At the last visit, there was significant hearing recovery, with an improvement of 29.7 ± 18.0 dB (p 0.001) and 87.6 ± 17.8% (p 0.001) in PTA and SDS respectively. After adjusting for age, gender, tumor volume, location, and tumor classification, Multivariable Cox Proportional Hazards Regression Model was conducted which revealed that patients undergoing surgery through retro sigmoid approach [Hazards Ratio (HR): 32.1, 95% Confidence Interval (CI): 2.11-491.0, p = 0.01] and gross total resection (GTR) (HR: 2.99, 95% CI: 1.09-9.32, p = 0.05) had significantly higher risk of poor hearing functional outcome compared to petrosal approach and near/subtotal resection. Moreover, patients with poor preoperative hearing had 85% higher chance of poor hearing functional outcome postoperatively (HR: 0.15, 95%CI: 0.03-0.59, p = 0.007).Postoperative improvement in hearing is a reasonable expectation following surgery for CPA meningioma. Preoperative hearing, surgical approach and extent of surgical resection are predictive factors of postoperative hearing function outcome and can therefore aid in identification of patients at higher risk of hearing loss.

BACKGROUND Intracranial solitary fibrous tumors (ISFTs) are rare mesenchymal tumors originating in the meninges and constitute a heterogeneous group of clinical and biological behavior. Benign histotypes, such as hemangiopericytomas are now considered as a cellular phenotypic variant of this heterogenous group of rare spindle-cell tumors. IFSTs are poorly recognized and remain a diagnostic challenge due to rarity and resemblance to other brain tumors. Previously, IFSTs were thought to pursue a slow, indolent, and nonaggressive course, however, a growing body of literature based on longer follow-up demonstrates an unpredictable clinical course and an uncertain diagnosis. OBSERVATIONS A rare case report of malignant transformation of IFST following radiation therapy is reported. In this case a 60-year-old female who underwent gross total resection of the cerebellopontine angle tumor with histopathology consistent with solitary fibrous tumor followed by salvage stereotactic radiosurgery, presented with another recurrence after 2 years of surgery. The authors performed complete removal of the tumor with pathology now consistent with malignant solitary fibrous tumor. A recent follow-up magnetic resonance imaging did not show any recurrence or residual tumor, and the patient reports a generalized well-being. LESSONS This report will help to understand the natural history and unusual clinical behavior of these intracranial tumors.

Rhodopsin (RHO) gene mutations are a common cause of autosomal dominant retinitis pigmentosa (ADRP). The need to suppress toxic protein expression together with mutational heterogeneity pose challenges for treatment development. Mirtrons are atypical RNA interference effectors that are spliced from transcripts as short introns. Here, we develop a novel mirtron-based knockdown/replacement gene therapy for the mutation-independent treatment of RHO-related ADRP, and demonstrate efficacy in a relevant mammalian model. Splicing and potency of rhodopsin-targeting candidate mirtrons are initially determined, and a mirtron-resistant codon-modified version of the rhodopsin coding sequence is validated in vitro. These elements are then combined within a single adeno-associated virus (AAV) and delivered subretinally in a RhoP23H knock-in mouse model of ADRP. This results in significant mouse-to-human rhodopsin RNA replacement and is associated with a slowing of retinal degeneration. This provides proof of principle that synthetic mirtrons delivered by AAV are capable of reducing disease severity in vivo., Rhodopsin-related dominant retinitis pigmentosa is a degenerative disease of the retina of the eye for which there is no current treatment. In this study, the authors use a novel form of RNA-interference- artificial mirtrons- to slow retinal degeneration in a mouse model of the disease.

Climate projections suggest that snowfall-dominated areas will decline substantially in the coming decades. Such climate impacts are already being observed in Colorado where the dominant source of ...

Purpose In the current era of modern neurosurgery, the treatment strategies have been shifted to “nerve-preservation approaches” for achieving a higher facial and hearing function preservation rate following facial nerve tumors. We have conducted this novel report on determining the outcome of patients with facial nerve schwannomas (FNS) treated with hypo fractionated stereotactic radiosurgery (hfSRS). Methods Retrospective chart review of a prospectively maintained database search was conducted. Patients who underwent hfSRS CyberKnife (Accuray Inc, Sunnyvale, California., USA) for FNS were included. Outcomes consisted of tumor control, facial and hearing nerve function as graded by House-Brackmann (HB) and Gardner-Robertson scale, and adverse radiation effects. SPSS 23 was used to perform statistical analysis. Results With an institutional board review approval, we retrospectively identified 5 patients with FNS [4 intracranial (80%) and 1 extracranial (20%)] treated with hfSRS (2011–2019). Patients received definitive SRS in 3 patients (60.0%) wile adjuvant to surgical resection in 2 patients (40.0%). A median tumor volume of 7.5 cm3 (range, 1.5–19.6 cm3) received a median prescription dose of 23.2 Gy (range, 21–25 Gy) administered in median of 3 fractions (range, 3–5 session). With a median radiographic follow-up of 31.4 months (range, 13.0–71.0 months) and clinical follow-up of 32.6 months (range, 15.1–72.0 months), the local tumor control was 100.0%. At last clinical follow-up, the facial nerve function improved or remained unchanged HB I-II in 80.0% of the patients, while the hearing nerve function improved or remained stable in 100.0% (Gardner-Robertson I-II) of the patients. Temporary clinical toxicity was seen in 3 patients (60.0%) which resolved. None of the patient developed adverse radiation effect. Conclusion hfSRS in FNS is safe and efficacious in terms of local tumor control, improved facial and hearing nerve function, and very low incidence of complications.

Introduction: This Wingspan Stent is a self-expanding, laser-cut, nitinol stent designed for the treatment of severe symptomatic intracranial artery stenosis to be used in conjunction with the Gateway angioplasty balloon. This review will describe the technical features of the stent, its composition, design, and functional characteristics, as well as an overview of its safety and efficacy.Areas covered: The engineering and manufacturing specifications are described for the stent. A systematic review of the literature from 2005 to 2019 is performed to define the safety profile of the stent as an implant for cerebral artery revascularization, stroke prophylaxis, and acute stroke treatment. These reports are compared to the published reports of patients with similar characteristics treated with medical therapy alone.Expert opinion: Although prior off-label studies have shown variable results, recent on-label studies have shown that the Wingspan stent itself is very safe, with low complication rates, and that it may confer long-term benefits in stroke prevention compared to medical therapy alone. Provided that established guidelines are followed, the Wingspan stent is effective in cerebral artery revascularization, and improves clinical outcomes in acute large vessel occlusive stroke with underlying intracranial atherosclerotic stenosis.

In multistory buildings, the isolation of sound from floor to ceiling is a major concern. The building codes use an impact insulation class (IIC) rating defined by ASTM to characterize the acoustical performance of floor–ceiling assemblies due to impacts. The measurement process defined in this standard has repeatability and reproducibility limitations due to low-frequency, non-diffuse sound fields in receiving rooms. A comparison method is proposed in this article that uses a reference sample with known sound power to calculate the room or path contribution to the measured sound pressure level, which is then used to calculate the sound power of the floor–ceiling assembly. The proposed method is tested for a small-scale hardboard plate, and the test results are within 1 to 2 dB of baseline sound power values. A simply supported plate used as the reference plate showed MAC values higher than 0.9 for analytical and experimental mode shapes. The analytical natural frequencies are within 1% to 2% of experimental frequencies and analytical sound power values are within 1-2 dB of experimental data. This study showed that for a small-scale assembly, the new method was able to characterize the room contribution within 1 to 2 dB. © 2020 Institute of Noise Control Engineering