A Quantitative Method to Measure the Kinetics of Elemental Mercury Emissions From Black Shale (Nova Scotia, Canada).

A controlled chamber method using continuous gold trap atomic fluorescence spectroscopy (AFS) (Tekran 2537X) for the analysis of Hg(0) emissions from moderate mass rock samples was developed and tested. A series of black shale and other bedrock samples from Nova Scotia, Canada, were used to test the method and its reproducibility. Hg(0) emissions at 170°C were measured to quantify both free surficial Hg(0) and Hg(0) that had penetrated the rock structure. High volumes of chamber air (45 L) were sampled using 30 min collection times to achieve detectable elemental mercury (Hg(0)) emissions. We found higher percentage masses of Hg(0) were released (1.1%-4.1% of total Hg mass present) in black shale samples as compared to granite and basalt samples from the same region (0.0%-0.3% released) over 350 h of continuous analysis time. The pseudo first order emission rate constants ranged from 0.015-0.245 h-1 (mean 0.063 h-1, standard deviation (SD) 0.102) for the black shale samples analyzed and was 0.004 h-1 for the granite sample. The 24-h zero-order emission rate constants ranged between 0.41 and 3.54 ng h-1 (mean 1.4 ng h-1, SD 1.3) for the black shale samples analyzed and were ~ 0.01 ng h-1 for the granite and basalt samples. This technique has useful implications for examining rock properties and Hg(0) emission rates.

Role of immune mediators in predicting hospitalization of SARS-CoV-2 positive patients.

BACKGROUND: Several immune mediators (IM) including cytokines, chemokines, and their receptors have been suggested to play a role in COVID-19 pathophysiology and severity. AIM: To determine if early IM profiles are predictive of clinical outcome and which of the IMs tested possess the most clinical utility. METHODS: A custom bead-based multiplex assay was used to measure IM concentrations in a cohort of SARS-CoV-2 PCR positive patients (n = 326) with varying disease severities as determined by hospitalization status, length of hospital stay, and survival. Patient groups were compared, and clinical utility was assessed. Correlation plots were constructed to determine if significant relationships exist between the IMs in the setting of COVID-19. RESULTS: In PCR positive SARS-CoV-2 patients, IL-6 was the best predictor of the need for hospitalization and length of stay. Additionally, MCP-1 and sIL-2Rα were moderate predictors of the need for hospitalization. Hospitalized PCR positive SARS-CoV-2 patients displayed a notable correlation between sIL-2Rα and IL-18 (Spearman's ρ = 0.48, P=<0.0001). CONCLUSIONS: IM profiles between non-hospitalized and hospitalized patients were distinct. IL-6 was the best predictor of COVID-19 severity among all the IMs tested.

Quantification of hematoma and perihematomal edema volumes in intracerebral hemorrhage study: Design considerations in an artificial intelligence validation (QUANTUM) study.

BACKGROUND: Hematoma and perihematomal edema volumes are important radiographic markers in spontaneous intracerebral hemorrhage. Accurate, reliable, and efficient quantification of these volumes will be paramount to their utility as measures of treatment effect in future clinical studies. Both manual and semi-automated quantification methods of hematoma and perihematomal edema volumetry are time-consuming and susceptible to inter-rater variability. Efforts are now underway to develop a fully automated algorithm that can replace them. A (QUANTUM) study to establish inter-quantification method measurement equivalency, which deviates from the traditional use of measures of agreement and a comparison hypothesis testing paradigm to indirectly infer quantification method measurement equivalence, is described in this article. The Quantification of Hematoma and Perihematomal Edema Volumes in Intracerebral Hemorrhage study aims to determine whether a fully automated quantification method and a semi-automated quantification method for quantification of hematoma and perihematomal edema volumes are equivalent to the hematoma and perihematomal edema volumes of the manual quantification method. METHODS/DESIGN: Hematoma and perihematomal edema volumes of supratentorial intracerebral hemorrhage on 252 computed tomography scans will be prospectively quantified in random order by six raters using the fully automated, semi-automated, and manual quantification methods. Primary outcome measures for hematoma and perihematomal edema volumes will be quantified via computed tomography scan on admission (<24 h from symptom onset) and on day 3 (72 ± 12 h from symptom onset), respectively. Equivalence hypothesis testing will be conducted to determine if the hematoma and perihematomal edema volume measurements of the fully automated and semi-automated quantification methods are within 7.5% of the hematoma and perihematomal edema volume measurements of the manual quantification reference method. DISCUSSION: By allowing direct equivalence hypothesis testing, the Quantification of Hematoma and Perihematomal Edema Volumes in Intracerebral Hemorrhage study offers advantages over radiology validation studies which utilize measures of agreement to indirectly infer measurement equivalence and studies which mistakenly try to infer measurement equivalence based on the failure of a comparison two-sided null hypothesis test to reach the significance level for rejection. The equivalence hypothesis testing paradigm applied to artificial intelligence application validation is relatively uncharted and warrants further investigation. The challenges encountered in the design of this study may influence future studies seeking to translate artificial intelligence medical technology into clinical practice.

Characterizing Determinants of Near-Road Ambient Air Quality for an Urban Intersection and a Freeway Site.

INTRODUCTION: Near-road ambient air pollution concentrations that are affected by vehicle emissions are typically characterized by substantial spatial variability with respect to distance from the roadway and temporal variability based on the time of day, day of week, and season. The goal of this work is to identify variables that explain either temporal or spatial variability based on case studies for a freeway site and an urban intersection site. The key hypothesis is that dispersion modeling of near-road pollutant concentrations could be improved by adding estimates or indices for site-specific explanatory variables, particularly related to traffic. Based on case studies for a freeway site and an urban intersection site, the specific aims of this project are to (1) develop and test regression models that explain variability in traffic-related air pollutant (TRAP) ambient concentration at two near-roadway locations; (2) develop and test refined proxies for land use, traffic, emissions and dispersion; and (3) prioritize inputs according to their ability to explain variability in ambient concentrations to help focus efforts for future data collection and model development.The key pollutants that are the key focus of this work include nitrogen oxides (NOx), carbon monoxide (CO), black carbon (BC), fine particulate matter (PM2.5; PM ≤ 2.5 µm in aerodynamic diameter), ultrafine particles (UFPs; PM ≤ 0.1 µm in aerodynamic diameter), and ozone (O3). NOx, CO, and BC are tracers of vehicle emissions and dispersion. PM2.5 is influenced by vehicle table emissions and regional sources. UFPs are sensitive to primary vehicle emissions. Secondary particles can form near roadways and on regional scales, influencing both PM2.5 and UFP concentrations. O3 concentrations are influenced by interaction with NOx near the roadway. Nitrogen dioxide (NO2), CO, PM2.5, and O3 are regulated under the National Ambient Air Quality Standards (NAAQS) because of demonstrated health effects. BC and UFPs are of concern for their potential health effects. Therefore, these pollutants are the focus of this work. METHODS: The methodological approach includes case studies for which variables are identified and assesses their ability to explain either temporal or spatial variability in pollutant ambient concentrations. The case studies include one freeway location and one urban intersection. The case studies address (1) temporal variability at a fixed monitor 10 meters from a freeway; (2) downwind concentrations perpendicular to the same location; (3) variability in 24-hour average pollutant concentrations at five sites near an urban intersection; and (4) spatiotemporal variability along a walking path near that same intersection.The study boundary encompasses key factors in the continuum from vehicle emissions to near-road exposure concentrations. These factors include land use, transportation infrastructure and traffic control, vehicle mix, vehicle (traffic) flow, on-road emissions, meteorology, transport and evolution (transformation) of primary emissions, and production of secondary pollutants, and their resulting impact on measured concentrations in the near-road environment. We conducted field measurements of land use, traffic, vehicle emissions, and near-road ambient concentrations in the vicinity of two newly installed fixed-site monitors. One is a monitoring station jointly operated by the U.S. Environmental Protection Agency (U.S. EPA) and the North Carolina Department of Environmental Quality (NC DEQ) on I-40 between Airport Boulevard and I-540 in Wake County, North Carolina. The other is a fixed-site monitor for measuring PM2.5 at the North Carolina Central University (NCCU) campus on E. Lawson Street in Durham, North Carolina. We refer to these two locations as the freeway site and the urban site, respectively. We developed statistical models for the freeway and urban sites. RESULTS: We quantified land use metrics at each site, such as distances to the nearest bus stop. For the freeway site, we quantified lane-by-lane total vehicle count, heavy vehicle (HV) count, and several vehicle-activity indices that account for distance from each lane to the roadside monitor. For the urban site, we quantified vehicle counts for all 12 turning movements through the intersection. At each site, we measured microscale vehicle tailpipe emissions using a portable emission measurement system.At the freeway site, we measured the spatial gradient of NOx, BC, UFPs, and PM, quantified particle size distributions at selected distances from the roadway and assessed partitioning of particles as a function of evolving volatility. We also quantified fleet-average emission factors for several pollutants.At the urban site, we measured daily average concentrations of nitric oxide (NO), NOx, O3, and PM2.5 at five sites surrounding the intersection of interest; we also measured high resolution (1-second to 10-second averages) concentrations of O3, PM2.5, and UFPs along a pedestrian transect. At both sites, the Research LINE-source (R-LINE) dispersion model was applied to predict concentration gradients based on the physical dispersion of pollution.Statistical models were developed for each site for selected pollutants. With variables for local wind direction, heavy-vehicle index, temperature, and day type, the multiple coefficient of determination (R2) was 0.61 for hourly NOx concentrations at the freeway site. An interaction effect of the dispersion model and a real-time traffic index contributed only 24% of the response variance for NOx at the freeway site. Local wind direction, measured near the road, was typically more important than wind direction measured some distance away, and vehicle-activity metrics directly related to actual real-time traffic were important. At the urban site, variability in pollutant concentrations measured for a pedestrian walk-along route was explained primarily by real-time traffic metrics, meteorology, time of day, season, and real-world vehicle tailpipe emissions, depending on the pollutant. The regression models explained most of the variance in measured concentrations for BC, PM, UFPs, NO, and NOx at the freeway site and for UFPs and O3 at the urban site pedestrian transect. CONCLUSIONS: Among the set of candidate explanatory variables, typically only a few were needed to explain most of the variability in observed ambient concentrations. At the freeway site, the concentration gradients perpendicular to the road were influenced by dilution, season, time of day, and whether the pollutant underwent chemical or physical transformations. The explanatory variables that were useful in explaining temporal variability in measured ambient concentrations, as well as spatial variability at the urban site, were typically localized real-time traffic-volume indices and local wind direction. However, the specific set of useful explanatory variables was site, context (e.g., next to road, quadrants around an intersection, pedestrian transects), and pollutant specific. Among the most novel of the indicators, variability in real-time measured tailpipe exhaust emissions was found to help explain variability in pedestrian transect UFP concentrations. UFP particle counts were very sensitive to real-time traffic indicators at both the freeway and urban sites. Localized site-specific data on traffic and meteorology contributed to explaining variability in ambient concentrations. HV traffic influenced near-road air quality at the freeway site more so than at the urban site. The statistical models typically explained most of the observed variability but were relatively simple. The results here are site-specific and not generalizable, but they are illustrative that near-road air quality can be highly sensitive to localized real-time indicators of traffic and meteorology.

Clinical characteristics and long-term outcomes for patients who undergo cytoreductive surgery for thoracic meningiomas: a retrospective analysis.

OBJECTIVE: Primary spinal meningiomas represent a rare indolent neoplasm usually situated in the intradural-extramedullary compartment. They have a predilection for afflicting the thoracic spine and most frequently present with sensory and/or motor symptoms. Resection is the first-line treatment for symptomatic tumors, whereas other clinical factors will determine the need for adjuvant therapy. In this study, the authors aimed to elucidate clinical presentation, functional outcomes, and long-term outcomes in this population in order to better equip clinicians with the tools to counsel their patients. METHODS: This is a retrospective analysis of patients treated at the authors' institution between 1998 and 2018. All patients with thoracic meningiomas who underwent resection and completed at least one follow-up appointment were included. Multiple preoperative clinical variables, hospitalization details, and long-term outcomes were collected for the cohort. RESULTS: Forty-six patients who underwent resection for thoracic meningiomas were included. The average age of the cohort was 59 years, and the median follow-up was 53 months. Persistent sensory and motor symptoms were present in 29 patients (63%). Fifteen lesions were ventrally positioned. There were 43 WHO grade I tumors, 2 WHO grade II tumors, and 1 WHO grade III tumor; the grade III tumor was the only case of recurrence. The median length of hospitalization was 4 days. Seventeen patients (37%) were discharged to rehabilitation facilities. Thirty patients (65.2%) experienced resolution or improvement of symptoms, and there were no deaths within 30 days of surgery. Only 1 patient developed painful kyphosis and was managed medically. Ventral tumor position, new postoperative deficits, and length of stay did not correlate with disposition to a facility. Age, ventral position, blood loss, and increasing WHO grade did not correlate with length of stay. CONCLUSIONS: Outcomes are overall favorable for patients who undergo resection of thoracic meningiomas. Symptomatic patients often experience improvement, and patients generally do not require significant future operations. Tumors located ventrally, while anatomically challenging, do not necessarily herald a significantly worse prognosis or limit the extent of resection.

Plasmodium falciparum Cyclic GMP-Dependent Protein Kinase Interacts with a Subunit of the Parasite Proteasome.

Malaria is caused by the protozoan parasite Plasmodium, which undergoes a complex life cycle in a human host and a mosquito vector. The parasite's cyclic GMP (cGMP)-dependent protein kinase (PKG) is essential at multiple steps of the life cycle. Phosphoproteomic studies in Plasmodium falciparum erythrocytic stages and Plasmodium berghei ookinetes have identified proteolysis as a major biological pathway dependent on PKG activity. To further understand PKG's mechanism of action, we screened a yeast two-hybrid library for P. falciparum proteins that interact with P. falciparum PKG (PfPKG) and tested peptide libraries to identify its phosphorylation site preferences. Our data suggest that PfPKG has a distinct phosphorylation site and that PfPKG directly phosphorylates parasite RPT1, one of six AAA+ ATPases present in the 19S regulatory particle of the proteasome. PfPKG and RPT1 interact in vitro, and the interacting fragment of RPT1 carries a PfPKG consensus phosphorylation site; a peptide carrying this consensus site competes with the RPT1 fragment for binding to PfPKG and is efficiently phosphorylated by PfPKG. These data suggest that PfPKG's phosphorylation of RPT1 could contribute to its regulation of parasite proteolysis. We demonstrate that proteolysis plays an important role in a biological process known to require Plasmodium PKG: invasion by sporozoites of hepatocytes. A small-molecule inhibitor of proteasomal activity blocks sporozoite invasion in an additive manner when combined with a Plasmodium PKG-specific inhibitor. Mining the previously described parasite PKG-dependent phosphoproteomes using the consensus phosphorylation motif identified additional proteins that are likely to be direct substrates of the enzyme.

Factors associated with NO2 and NOX concentration gradients near a highway.

The objective of this research is to learn how the near-road gradient, in which NO2 and NOX (NO + NO2) concentrations are elevated, varies with changes in meteorological and traffic variables. Measurements of NO2 and NOX were obtained east of I-15 in Las Vegas and fit to functions whose slopes (dCNO2 /dx and dCNOX /dx, respectively) characterize the size of the near-road zone where NO2 and NOX concentrations from mobile sources on the highway are elevated. These metrics were used to learn about the near-road gradient by modeling dCNO2 /dx and dCNOX /dx as functions of meteorological variables (e.g., wind direction, wind speed), traffic (vehicle count), NOX concentration upwind of the road, and O3 concentration at two fixed-site ambient monitors. Generalized additive models (GAM) were used to model dCNO2 /dx and dCNOX /dx versus the independent variables because they allowed for nonlinearity of the variables being compared. When data from all wind directions were included in the analysis, variability in O3 concentration comprised the largest proportion of variability in dCNO2 /dx, followed by variability in wind direction. In a second analysis constrained to winds from the west, variability in O3 concentration remained the largest contributor to variability in dCNO2 /dx, but the relative contribution of variability in wind speed to variability in dCNO2 /dx increased relative to its contribution for the all-wind analysis. When data from all wind directions were analyzed, variability in wind direction was by far the largest contributor to variability in dCNOX /dx, with smaller contributions from hour of day and upwind NOX concentration. When only winds from the west were analyzed, variability in upwind NOX concentration, wind speed, hour of day, and traffic count all were associated with variability in dCNOX /dx. Increases in O3 concentration were associated with increased magnitude near-road dCNO2 /dx, possibly shrinking the zone of elevated concentrations occurring near roads. Wind direction parallel to the highway was also related to an increased magnitude of both dCNO2 /dx and dCNOX /dx, again likely shrinking the zone of elevated concentrations occurring near roads. Wind direction perpendicular to the road decreased the magnitude of dCNO2 /dx and dCNOX /dx and likely contributed to growth of the zone of elevated concentrations occurring near roads. Thus, variability in near-road concentrations is influenced by local meteorology and ambient O3 concentration.

Quantitation of circulating wild-type alpha-1-antitrypsin in heterozygous carriers of the S and Z deficiency alleles.

BACKGROUND: Alpha-1-antitrypsin (A1AT) deficiency disease results from mutations in the A1AT gene. Controversy exists in regards to treatment of heterozygous carriers of the S and Z deficiency alleles. Quantitation of allelic expression has not been possible with standard laboratory methods. Here we show that the recently described method for liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of A1AT tryptic peptides can differentiate between mutated (S and Z) and wild-type (non-S and non-Z) proteins allowing for quantitation of circulating allelic expression in heterozygous patients. METHODS: Serum (244 M/M, 61 M/Z, and 63 M/S) was combined with isotopically labeled peptide standards, digested with trypsin, and quantitated by LC-MS/MS. Total and allele-specific A1AT quantitation was performed by comparison of peptide peak height ratios to a standard curve for each peptide. Linear regression was used to compare results and central 95(th) percentile intervals were calculated using parametric analysis. RESULTS: Quantitation of circulating wild-type A1AT based on the proteotypic and allelic (non-S and non-Z) peptides was validated in M/M patients. Proteotypic peptide concentrations correlated linearly with quantitation by non-Z and non-S peptides [slopes (Spearman correlation coefficient) of 1.09 (0.89) and 0.98 (0.80), respectively]. Allele-specific quantitation showed significant differences in wild-type protein expression in M/Z and M/S patients. Although average total A1AT concentration was lower for M/Z patients, the percentage of wild-type protein in M/Z patients was significantly higher at 82 % (55- > 95 %) compared to 63 % (43-83 %) for M/S heterozygotes. In a cohort of M/Z patients with sufficient total A1AT (≥80 mg/dL), half had insufficient wild-type protein that could have clinical implications for pulmonary dysfunction. CONCLUSIONS: For the first time, a method to quantitate A1AT allele protein expression is described. Given the wide range of circulating wild-type protein observed in heterozygous patients, this method has the potential to reveal correlations between allele concentration and development and/or severity of clinical symptoms.

The argon beam coagulator: a more effective and expeditious way to address presacral bleeding.

Presacral bleeding is a dreaded complication of pelvic surgery. Rapid and effective control of such bleeding is important to avoid potentially life-threatening outcomes. Various methods for controlling presacral bleeding, all with only limited success, have been described in the literature. We report the alternative technique of using the argon beam coagulator (ABC) to control presacral bleeding. We demonstrate its efficacious use in both open surgery and a laparoscopic case. Our approach involved applying an argon beam at bone setting directly to the bleeders and using a "point and shoot" technique. We found that ABC is a simpler, equally effective and expeditious way of addressing presacral bleeding. To the best of our knowledge, there has been only one previously reported case in the literature of the use of ABC to control presacral bleeding.

Survey of patient satisfaction after Doppler-guided transanal hemorrhoidal dearterialization performed in ambulatory settings.

BACKGROUND: Transanal hemorrhoidal dearterialization (THD) is a recently developed procedure to minimize postoperative pain from hemorrhoidectomy. This technique utilizes Doppler signals to aid ligation of hemorrhoidal arteries followed by mucopexy of redundant mucosa if needed. The aim of the present study was to assess patient satisfaction after THD. METHODS: This is a retrospective cohort study of patients who underwent THD at three different sites from April 2007 through October 2010. All procedures were performed in ambulatory settings according to protocol. Telephone surveys were conducted after a minimum of 1-month follow-up to assess patients' satisfaction on a scale of 1-10. Patients were asked whether the procedure had alleviated their symptoms. Patients were asked to recall duration of pain and time from surgery to return to work. RESULTS: Between April 2007 and October 2010, 216 patients with grade III-IV hemorrhoids underwent THD. There were 165 males and 61 females. Average age was 52.2 ± 14.2 years. All patients were discharged the same day after meeting ambulatory surgery center discharge criteria. Postoperative difficulty urinating occurred in 37 (17 %) patients, and six of them required temporary urinary catheterization. Transitory postoperative bleeding was reported by 38 (18 %) patients. Transitory incontinence to stool and flatus occurred in 18 (9 %) and 16 patients (8 %), respectively. Pelvic muscle spasms occurred in 21 (10 %) patients. Median follow-up was 23 months (range 1-42 months) with 143 (66 %) having at least 9 months between procedure and interview. Mean patient satisfaction was 8.5 ± 0.7 (on a scale of 1-10 with 10 being the best), and 91.5 % of patients felt the procedure had "helped" them. Average number of days with discomfort was 6.7 ± 2.1. Patients returned to work after an average of 10.3 ± 3.2 days. Our study is limited by lack of long-term follow-up and by retrospective complication assessment. CONCLUSIONS: Patient satisfaction with THD performed in ambulatory settings is high. Our data support performance of this procedure in an ambulatory setting.

Extracranial arteriovenous malformation mimicking a peripheral nerve tumor: illustrative case.

BACKGROUND: Arteriovenous malformations (AVMs) are vascular malformations that are more commonly found intracranially, followed by the head, neck, limbs, and trunk. Extracranially, AVMs can mimic peripheral nerve tumors, leading to misdiagnosis. OBSERVATIONS: A 19-year-old female, who presented with left lateral lower leg pain, was preoperatively thought to have a peripheral nerve tumor; at surgery, however, she was found to have an extracranial AVM. The distinct margins of the tumor on preoperative magnetic resonance imaging suggested that the patient might have a peripheral nerve tumor; however, the clinical symptoms of focal pain at rest and the absence of Tinel's sign should have raised questions about this diagnosis. LESSONS: This case highlights the difficulty in differentiating a peripheral nerve tumor from an extracranial AVM in certain clinical scenarios. It is important to use a multifaceted diagnostic approach to get a correct preoperative diagnosis and plan treatment appropriately.

Automated Preoperative and Postoperative Volume Estimates Risk of Retreatment in Chronic Subdural Hematoma: A Retrospective, Multicenter Study.

BACKGROUND AND OBJECTIVES: Several neurosurgical pathologies, ranging from glioblastoma to hemorrhagic stroke, use volume thresholds to guide treatment decisions. For chronic subdural hematoma (cSDH), with a risk of retreatment of 10%-30%, the relationship between preoperative and postoperative cSDH volume and retreatment is not well understood. We investigated the potential link between preoperative and postoperative cSDH volumes and retreatment. METHODS: We performed a retrospective chart review of patients operated for unilateral cSDH from 4 level 1 trauma centers, February 2009-August 2021. We used a 3-dimensional deep learning, automated segmentation pipeline to calculate preoperative and postoperative cSDH volumes. To identify volume thresholds, we constructed a receiver operating curve with preoperative and postoperative volumes to predict cSDH retreatment rates and selected the threshold with the highest Youden index. Then, we developed a light gradient boosting machine to predict the risk of cSDH recurrence. RESULTS: We identified 538 patients with unilateral cSDH, of whom 62 (12%) underwent surgical retreatment within 6 months of the index surgery. cSDH retreatment was associated with higher preoperative (122 vs 103 mL; P < .001) and postoperative (62 vs 35 mL; P < .001) volumes. Patients with >140 mL preoperative volume had nearly triple the risk of cSDH recurrence compared with those below 140 mL, while a postoperative volume >46 mL led to an increased risk for retreatment (22% vs 6%; P < .001). On multivariate modeling, our model had an area under the receiver operating curve of 0.76 (95% CI: 0.60-0.93) for predicting retreatment. The most important features were preoperative and postoperative volume, platelet count, and age. CONCLUSION: Larger preoperative and postoperative cSDH volumes increase the risk of retreatment. Volume thresholds may allow identification of patients at high risk of cSDH retreatment who would benefit from adjunct treatments. Machine learning algorithm can quickly provide accurate estimates of preoperative and postoperative volumes.

Clinical and Imaging Outcomes After Trigeminal Schwannoma Radiosurgery: Results From a Multicenter, International Cohort Study.

BACKGROUND AND OBJECTIVES: An international, multicenter, retrospective study was conducted to evaluate the long-term clinical outcomes and tumor control rates after stereotactic radiosurgery (SRS) for trigeminal schwannoma. METHODS: Patient data (N = 309) were collected from 14 international radiosurgery centers. The median patient age was 50 years (range 11-87 years). Sixty patients (19%) had prior resections. Abnormal facial sensation was the commonest complaint (49%). The anatomic locations were root (N = 40), ganglion (N = 141), or dumbbell type (N = 128). The median tumor volume was 4 cc (range, 0.2-30.1 cc), and median margin dose was 13 Gy (range, 10-20 Gy). Factors associated with tumor control, symptom improvement, and adverse radiation events were assessed. RESULTS: The median and mean time to last follow-up was 49 and 65 months (range 6-242 months). Greater than 5-year follow-up was available for 139 patients (45%), and 50 patients (16%) had longer than 10-year follow-up. The overall tumor control rate was 94.5%. Tumors regressed in 146 patients (47.2%), remained unchanged in 128 patients (41.4%), and stabilized after initial expansion in 20 patients (6.5%). Progression-free survival rates at 3 years, 5 years, and 10 years were 91%, 86%, and 80 %. Smaller tumor volume (less than 8 cc) was associated with significantly better progression-free survival ( P = .02). Seventeen patients with sustained growth underwent further intervention at a median of 27 months (3-144 months). Symptom improvement was noted in 140 patients (45%) at a median of 7 months. In multivariate analysis primary, SRS ( P = .003) and smaller tumor volume ( P = .01) were associated with better symptom improvement. Adverse radiation events were documented in 29 patients (9%). CONCLUSION: SRS was associated with long-term freedom (10 year) from additional management in 80% of patients. SRS proved to be a valuable salvage option after resection. When used as a primary management for smaller volume tumors, both clinical improvement and prevention of new deficits were optimized.

Analysis of yeast protein kinases using protein chips.

We have developed a novel protein chip technology that allows the high-throughput analysis of biochemical activities, and used this approach to analyse nearly all of the protein kinases from Saccharomyces cerevisiae. Protein chips are disposable arrays of microwells in silicone elastomer sheets placed on top of microscope slides. The high density and small size of the wells allows for high-throughput batch processing and simultaneous analysis of many individual samples. Only small amounts of protein are required. Of 122 known and predicted yeast protein kinases, 119 were overexpressed and analysed using 17 different substrates and protein chips. We found many novel activities and that a large number of protein kinases are capable of phosphorylating tyrosine. The tyrosine phosphorylating enzymes often share common amino acid residues that lie near the catalytic region. Thus, our study identified a number of novel features of protein kinases and demonstrates that protein chip technology is useful for high-throughput screening of protein biochemical activity.

Establishment of Age- and Sex-Specific Reference Cerebral Ventricle Volumes.

BACKGROUND: The diagnosis of hydrocephalus is dependent on clinical symptoms and radiographic findings including ventriculomegaly. Our goal was to generate a data set of ventricular volume utilizing non-pathologic computed tomography (CT) scans for adults to help define reference ventricle size. METHODS: We performed a retrospective analysis of non-contrast head CTs for adults at a single institution to identify patients who had undergone imaging and did not have a diagnosis of hydrocephalus, history of ventriculoperitoneal shunting, or treatments for hydrocephalus. A convolutional neural network was trained on hand-segmented scans from a variety of age ranges and then utilized to automate the segmentation of the entire data set. RESULTS: Ventricles on 866 CT scans were segmented to generate a reference range of volumes for both male and female individuals ranging in age from 18-99 years. The generated data were binned by age ranges. CONCLUSIONS: We have developed a convolutional neural network that can segment the ventricles on CT scans of adult patients over a range of ages. This network was used to measure the ventricular volume of non-pathologic head CTs to produce reference ranges for several age bins. This data set could be utilized to aid in the diagnosis of hydrocephalus by comparing potentially pathologic scans to reference ventricular volumes.

Flow Diverter Devices for Treatment of Intracranial Aneurysms in Small Parent Vessels-A Systematic Review of Literature.

BACKGROUND: The overall safety and efficacy of flow diverting stents (FDSs) deployed in small caliber parent arteries (≤2.5 mm) for the treatment of intracranial aneurysms remains unclear. Recent studies have provided additional outcomes data to assess the use of FDSs for such arteries. In the present review, we have summarized the reported clinical and angiographic outcomes of FDS-treated brain aneurysms in small parent arteries. METHODS: A systematic literature review was performed for outcomes data related to FDS-treated intracranial aneurysms using PubMed, Ovid Medline, and Web of Science. Procedural data, angiographic outcomes, and clinical outcomes at various time points were collected and summarized. RESULTS: The 19 studies included 580 patients with 604 aneurysms, of which 6.1% had been acutely ruptured and 28.3% had been previously treated. The procedural complication rate and symptomatic stroke rate was 9.8% and 7.5%. The complete occlusion rate at the last radiographic follow-up (mean, 12.1 months) was 73.6%. At the last clinical follow-up (mean, 10.6 months), the FDS-associated mortality was 2.5%. CONCLUSIONS: FDSs for the treatment of intracranial aneurysms located in small caliber arteries was associated with rates of long-term complete aneurysm occlusion, mortality, and permanent neurologic deficit comparable to the rates with FDS-treated aneurysms in larger parent arteries. However, the relatively increased risk of symptomatic stroke of these FDS-treated aneurysms should not be ignored. Direct comparisons with alternative endovascular approaches are necessary to further define the optimal use of FDS for these aneurysms.

Routine postoperative fluid restriction to prevent syndrome of inappropriate antidiuretic hormone secretion after transsphenoidal resection of pituitary adenoma.

OBJECTIVE: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common problem during the postoperative course after pituitary surgery. Although treatment of this condition is well characterized, prevention strategies are less studied and reported. The authors sought to characterize outcomes and predictive factors of SIADH after implementation of routine postoperative fluid restriction for patients undergoing endoscopic transsphenoidal surgery for pituitary adenoma. METHODS: In March 2018, routine postoperative fluid restriction to 1000 ml/day for 7 days was instituted for all patients who underwent surgery for pituitary adenoma. These patients were compared with patients who underwent surgery for pituitary adenoma between March 2016 and March 2018, prior to implementation of routine fluid restriction. Patients with preoperative history of diabetes insipidus (DI) or concern for postsurgical DI were excluded. Patients were followed by neuroendocrinologists and neurosurgeons, and sodium levels were checked between 7 and 10 days postoperatively. SIADH was defined by a serum sodium level less than 136 mmol/L, with or without symptoms within 10 days after surgery. Thirty-day readmission was recorded and reviewed to determine underlying reasons. RESULTS: In total, 82 patients in the fluid-unrestricted cohort and 135 patients in the fluid-restricted cohort were analyzed. The patients in the fluid-restricted cohort had a significantly lower rate of postoperative SIADH than patients in the fluid-unrestricted cohort (5% vs 15%, adjusted OR [95% CI] 0.1 [0.0-0.6], p = 0.01). Higher BMI was associated with lower rate of postoperative SIADH (adjusted OR [95%] 0.9 [0.9-1.0], p = 0.03), whereas female sex was associated with higher rate of SIADH (adjusted OR [95% CI] 3.1 [1.1-9.8], p = 0.03). There was no difference in the 30-day readmission rates between patients in the fluid-unrestricted and fluid-restricted cohorts (4% vs 7%, adjusted OR [95% CI] 0.5 [0-5.1], p = 0.56). Thirty-day readmission was more likely for patients with history of hypertension (adjusted OR [95% CI] 5.7 [1.3-26.3], p = 0.02) and less likely for White patients (adjusted OR [95% CI] 0.3 [0.1-0.9], p = 0.04). CONCLUSIONS: Routine fluid restriction reduced the rate of SIADH in patients who underwent surgery for pituitary adenoma but was not associated with reduction in 30-day readmission rate.

Optimizing the residency application process: insights from neurological surgery during the pandemic virtual application cycle.

OBJECTIVE: In this article, the authors describe the impact of the COVID-19 virtual match cycle and discuss approaches to optimize future cycles through applicant and neurosurgical education leadership insights. METHODS: Anonymous surveys of neurosurgery program leaders (program directors and program chairs), program administrators (PAs), and 2020-2021 neurosurgery residency match applicants were distributed by the SNS, in conjunction with the Association of Resident Administrators in Neurological Surgery and AANS Young Neurosurgeons Committee. RESULTS: Responses were received from 77 (67.0%) of 115 PAs, 119 (51.7%) of 230 program leaders, and 124 (44.3%) of 280 applicants representing geographically diverse regions. During the virtual application cycle relative to the previous year, programs received more Electronic Residency Application Service applications (mean 314.8 vs 285.3, p < 0.0001) and conducted more applicant interviews (mean 45.2 vs 39.9, p = 0.0003). More than 50% of applicants applied to > 80 programs; 60.3% received ≤ 20 interview invitations, and 9% received > 40 invitations. Overall, 65% of applicants completed ≤ 20 interviews, whereas 34.7% completed > 20 interviews. Program leaders described one 4-week home subinternship (93.3%) and two 4-week external subinternships (68.9%) as optimal neurosurgical exposure; 62.8% of program leaders found the standardized letter of recommendation template to be somewhat (47.5%) or significantly (15.3%) helpful. Applicants, PAs, and program leaders all strongly preferred a hybrid model of in-person and virtual interview options for future application cycles over all in-person or all virtual options. Ninety-three percent of applicants reported matching within their top 10-ranked programs, and 52.9% of programs matched residents within the same decile ranking as in previous years. CONCLUSIONS: Optimizing a national strategy for the neurosurgery application process that prioritizes equity and reduces costs, while ensuring adequate exposure for applicants to gain educational opportunities and evaluate programs, is critical to maintain a successful training system.

Comparison and evolution of transcranial versus endoscopic endonasal approaches for suprasellar Meningiomas: A systematic review.

BACKGROUND: Meningiomas of the tuberculum sellae (TS) and planum sphenoidale (PS) are challenging to treat surgically. Transcranial approaches (TCAs) were the mainstay before endoscopic endonasal approaches (EEA) were developed, however the efficacy and safety of EEA approaches relative to TCA approaches remains unclear. METHODS: The authors conducted a PRISMA-compliant systematic review of existing literature detailing the outcomes of both approaches. PubMed, Embase, Cochrane Library, and Clinicaltrials.gov were searched. Studies were included if they analyzed TS and/or PS meningiomas, included ≥ 5 patients, and reported at least one outcome of interest. RESULTS: Overall, 44 retrospective studies met inclusion criteria, the majority being from single centers, between 2004 and 2020. In studies directly comparing postoperative outcomes among TCA and EEA approaches, EEA had significantly higher odds of visual improvement (OR = 3.24, p = 0.0053) and significantly higher odds of CSF leak (OR = 3.71, p = 0.0098) relative to TCA. Further, there were no significant differences between visual worsening (p = 0.17), complications (p = 0.51), and GTR rates (p = 0.30) for the two approaches. Meta-analysis demonstrated no significant association between nasoseptal flap (NSF) use and postoperative outcomes among EEA patients. There was also no significant association between study publication year and postoperative EEA outcomes. CONCLUSION: The present study demonstrates that EEA offers a viable alternative to TCA in the treatment of suprasellar meningiomas. In particular, EEA shows promise for superior visual outcomes, though postoperative CSF leaks are an important consideration among patients undergoing this approach.