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Study Objectives Traumatic brain injury (TBI) can result in posttraumatic epilepsy (PTE) and sleep disturbances. We hypothesized that treatment with sleep aids after TBI can ameliorate PTE. Methods CD-1 mice underwent controlled cortical impact (CCI), sham injury, or no craniotomy. Sham and CCI groups underwent a monthlong daily treatment with sleep aids including a dual orexin antagonist (DORA-22) or THIP (gaboxadol) or a respective vehicle starting on the day of CCI. We performed continuous EEG (electroencephalography) recordings at week 1 and months 1, 2, and 3 for ~1 week each time. Seizure analysis occurred at all-time points and sleep analysis occurred in week 1 and month-1/2 in all groups. Subsets of CCI and sham groups were subjected to voltageclamp experiments in hippocampal slices to evaluate GABAergic synaptic inhibition. Results DORA-22 treatment suppressed seizures in month 1–3 recordings. TBI reduced the amplitude and frequency of miniature inhibitory synaptic currents (mIPSCs) in dentate granule cells and these changes were rescued by DORA-22 treatment. Sleep analysis showed that DORA-22 increased nonrapid eye movement (NREM) sleep during lights-off whereas THIP increased REM sleep during lights-on in week 1. Both treatments displayed subtle changes in time spent in NREM or REM at month-1/2 as well. TBI not only increased normalized EEG delta power (NΔ) at week-1 and month-1 but also resulted in the loss of the homeostatic diurnal oscillation of NΔ, which was restored by DORA-22 but not THIP treatment. Conclusions Dual orexin antagonists may have a therapeutic potential in suppressing PTE potentially by enhancing GABAergic inhibition and impacting sleep homeostatic drive.

Background: The diagnosis of Parkinson’s disease (PD) is primarily clinical, but in cases of diagnostic uncertainty, evaluation of nigrostriatal dopaminergic degeneration (NSDD) by imaging of the dopamine transporter using DaTscan with single-photon emission computed tomography (SPECT) brain imaging may be helpful. Objective/Methods: In the current paper, we describe clinical scenarios for which DaTscan imaging was used in a prospective case series of 201 consecutive patients in whom a movement disorder specialist ordered DaTscan imaging to clarify NSDD. We describe the impact of DaTscan results on changing or confirming pre-DaTscan clinical diagnosis and on post-DaTscan treatment changes. Results/Conclusion: DaTscan imaging can be useful in several clinical scenarios to determine if NSDD is present. These include in patients with early subtle symptoms, suboptimal response to levodopa, prominent action tremor, drug-induced parkinsonism, and in patients with lower extremity or other less common parkinsonism clinical presentations. We also found DaTscan imaging to be useful to determine underlying NSDD in patients with PD diagnosis for 3-5 years but without apparent clinical progression or development of motor fluctuations. Overall, in 201 consecutive patients with clinically questionable NSDD, DaTscan was abnormal in 58.7% of patients, normal in 37.8%, and inconclusive in 3.5%. DaTscan imaging changed clinical diagnosis in 39.8% of patients and led to medication therapy changes in 70.1% of patients.

BackgroundTraumatic brain injury (TBI) can result in posttraumatic epilepsy (PTE) and sleep disturbances. We hypothesized that treatment with sleep aids after TBI can ameliorate PTE.MethodsCD-1 mice underwent controlled cortical impact (CCI), sham craniotomy or no craniotomy. Sham and CCI groups underwent a month-long treatment with sleep aids including a dual orexin antagonist (DORA-22) or THIP (gaboxadol). We performed week-long EEG recordings during week-1 of treatment and again at months 1, 2 and 3. Seizure analysis occurred at all-time points and sleep analysis occurred in week-1 and month-1 recordings in all groups. Subsets of animals in sleep aid-treated and untreated CCI, and sham groups were subjected to voltage clamp experiments.ResultsDORA-22 treated group had seizures at week-1 but none at months 1-3. TBI reduced amplitude and frequency of miniature inhibitory synaptic currents (mIPSCs) in dentate granule cells and these changes were rescued by DORA-22 treatment. Sleep analysis showed that DORA-22 increased non-rapid eye movement sleep (NREM) in the first 4hours of lights-off whereas THIP increased REM sleep in the first 4-hours of lights-on in week-1, At month-1 both treatments reduced time in NREM during lights-off. TBI increased NREM delta power (NΔ) along with loss of the homeostatic overnight decline of NΔ in week-1 regardless of treatment. DORA-22 and THIP treatment restored NΔ to levels similar to no craniotomy animals at month-1.ConclusionsDORA-22 treatment suppressed posttraumatic seizures possibly due to enhanced GABAergic inhibition in dentate granule cells. DORA-22 may have therapeutic potential in suppressing PTE.Summary for Social MediaTraumatic brain injury (TBI) can result is posttraumatic epilepsy and sleep disturbances. There are no treatments to prevent these complications. We tested whether treatment with sleep aids after TBI can mitigate seizures and sleep disturbances. We found that a sleep aid DORA-22 but not THIP suppressed post traumatic seizures possibly be enhancing GABAergic inhibition in the hippocampus. Sleep analysis showed that TBI disrupts the sleep homeostatic drive and DORA treatment restored it. Findings may lead to potential disease modifying therapy for posttraumatic epilepsy.

Toxic epidermal necrolysis (TEN) is a severe cutaneous reaction that can be life-threatening. In the United States, there are no established guidelines for the treatment of TEN. Supportive care including fluids and supportive therapies are the current recommendations. Research surrounding TEN involves mostly case studies or small, uncontrolled studies. Recent literature describes the use of tumor necrosis factor blockers in the treatment of TEN with positive results. These case reports describe decreased time to reepithelization, hospital length of stay, and minimal side effects. Conversely, we present three fatalities after the administration of etanercept.

Transfer RNAs (tRNAs) are the adaptor molecules required for reading the genetic code and producing proteins. Transfer RNA variants can lead to genome-wide mistranslation, the misincorporation of amino acids not specified by the standard genetic code into nascent proteins. While genome sequencing has identified putative mistranslating transfer RNA variants in human populations, little is known regarding how mistranslation affects multicellular organisms. Here, we create a multicellular model of mistranslation by integrating a serine transfer RNA variant that mistranslates serine for proline (tRNAUGG,G26ASer) into the Drosophila melanogaster genome. We confirm mistranslation via mass spectrometry and find that tRNAUGG,G26ASer misincorporates serine for proline at a frequency of ∼0.6% per codon. tRNAUGG,G26ASer extends development time and decreases the number of flies that reach adulthood. While both sexes of adult flies containing tRNAUGG,G26ASer present with morphological deformities and poor climbing performance, these effects are more pronounced in female flies and the impact on climbing performance is exacerbated by age. This model will enable studies into the synergistic effects of mistranslating transfer RNA variants and disease-causing alleles.

The MeerKAT radio telescope consists of 64 Gregorian-offset antennas located in the Karoo in the Northern Cape in South Africa. The antenna system consists of multiple subsystems working collaboratively to form a cohesive instrument capable of operating in multiple modes for defined science cases. We focus on the channelizing subsystem (F-engine), the correlation subsystem (X-engine), and the beamforming subsystem (B-engine). In the wideband instrument mode, the channelizing can produce 1024, 4096, or 32,768 channels with correlation up to 64 antennas. Narrowband mode decomposes sampled bandwidth into 32,768 channels. The F-engine also performs delay compensation, equalization, quantization, and grouping and ordering. The X-engine provides both correlation and beamforming computations (independently). This document is intended to be a stand-alone entity covering the channelizing, correlation, and beamforming processes for the MeerKAT radio telescope. This includes data reception, pre- and post-processing, and data transmission.

Burn patients have numerous risk factors for multidrug-resistant organisms (MDROs) and altered pharmacokinetics, which both independently increase the risk of treatment failure. Data on appropriate antimicrobial dosing are limited in this population and therapeutic drug monitoring (TDM) for beta-lactams is impractical at most facilities. Technology is available that can detect genetic markers of resistance, but they are not all encompassing, and often require specialized facilities that can detect less common genetic markers. Newer antimicrobials can help combat MDROs, but additional resistance patterns may evolve during treatment. Considering drug shortages and antimicrobial formularies, clinicians must remain vigilant when treating infections. This case report describes the development of resistance to ceftazidime-avibactam in a burn patient. The patient was a 54-year-old burn victim with a 58% total body surface area (TBSA) thermal burn who underwent multiple courses of antibiotics for various Pseudomonal infections. The initial Pseudomonal wound infection was sensitive to cefepime, aminoglycosides, and meropenem. A subsequent resistant pseudomonal pneumonia was treated with ceftazidime-avibactam 2.5 g every 6 hours due to the elevated MIC to cefepime (16 mcg/mL) and meropenem (>8 mcg/mL). Although the patient improved over 7 days, the patient again spiked fevers and had increased white blood counts (WBC). Repeat blood cultures demonstrated a multidrug-resistant (MDR) Pseudomonas with a minimum inhibitory concentration (MIC) to ceftazidime-avibactam of 16 mcg/mL, which is above the Clinical and Laboratory Standards Institute (CLSI) breakpoint of 8 mcg/mL. At first, resistance was thought to have occurred due to inadequate dosing, but genetic work demonstrated multiple genes encoding beta-lactamases.

Introduction In patients having emergency abdominal surgery for trauma, the presence of urologic injury tends to increase mortality and morbidity. Methods This retrospective study evaluated patients requiring emergency surgery for abdominal trauma at a Level 1 Trauma Center over 30 years (1980-2010). Special attention was given to patients with concomitant genitourinary (GU) injuries. Results Of 1105 patients requiring an emergency laparotomy for trauma, 242 (22%) had urologic injuries including kidney 178 (16%), ureter 47 (4%), and bladder 46 (4%). Of the 242 patients, 50 (20%) died early (

MeerKAT's large number of antennas, spanning 8 km with a densely packed 1 km core, create a powerful instrument for wide-area surveys, with high sensitivity over a wide range of angular scales. The MeerKAT Galaxy Cluster Legacy Survey (MGCLS) is a programme of long-track MeerKAT L-band (900-1670 MHz) observations of 115 galaxy clusters, observed for $\sim$6-10 hours each in full polarisation. The first legacy product data release (DR1), made available with this paper, includes the MeerKAT visibilities, basic image cubes at $\sim$8" resolution, and enhanced spectral and polarisation image cubes at $\sim$8" and 15" resolutions. Typical sensitivities for the full-resolution MGCLS image products are $\sim$3-5 {\mu}Jy/beam. The basic cubes are full-field and span 4 deg^2. The enhanced products consist of the inner 1.44 deg^2 field of view, corrected for the primary beam. The survey is fully sensitive to structures up to $\sim$10' scales and the wide bandwidth allows spectral and Faraday rotation mapping. HI mapping at 209 kHz resolution can be done at $0, Comment: 43 pages, 33 figures, 6 tables. Accepted for publication in Astronomy and Astrophysics

Purpose To evaluate the effectiveness of orbital radiotherapy (ORT) in the treatment of thyroid eye disease (TED)-compressive optic neuropathy. Methods A retrospective review of patients with corticosteroid-responsive compressive optic neuropathy due to TED treated with ORT. Study was conducted in compliance with Health Insurance Portability and Accountability Act. One hundred four patients (163 orbits) with a mean age of 61.7 years met inclusion criteria. Seventy-four percent (77/104) were female, and 32.7% (34/104) were current or previous smokers. A total absorbed dose of 2000 cGy fractionated in 10 treatment doses over the course of 2 weeks was administered to the retroocular tissues according to a standard protocol. The primary end point was failure of ORT, defined as persistent optic neuropathy following completion of radiotherapy that mandated urgent orbital decompression surgery. Results Ninety-eight of 104 (94%) patients or 152 of 163 (93.3%) orbits did not require orbital decompression surgery during the acute phase. Patients who responded successfully to ORT had similar improvements in visual acuity, color vision, Humphrey threshold visual field testing, and afferent pupillary defects compared with patients who failed ORT and underwent urgent decompression surgery. Only 36.7% of successfully treated patients ultimately underwent elective surgery, including orbital decompression, strabismus, or eyelid surgery, during the inactive phase of TED. Conclusions The data from this study, the largest retrospective review reported to date, supports the use of ORT in eyes with corticosteroid-responsive TED-compressive optic neuropathy. ORT may favorably alter the natural history of active-phase TED by preventing recurrent compressive optic neuropathy after withdrawal of corticosteroids.

Aim: The number of breast cancer brain metastases is a prognostic clinical variable in the modified graded prognostic assessment (GPA) Index for breast cancer. Patients & methods: We retrospectively gathered data from 127 breast cancer patients who underwent radiation therapy for brain metastasis. Patients were stratified by both breast GPA and modified breast GPA scores, and survival was determined using the Kaplan–Meier curves and Cox proportional hazards model. Results & Conclusion: The Kaplan–Meier curve for patients under the breast GPA classification were not significant, but were significant under the modified breast GPA classification. The inclusion of number of brain metastases into the modified breast GPA index improved prognosis, thus validating the use of the modified breast GPA in prognosticating patient outcome.

Gliosarcoma is a rare histopathologic variant of glioblastoma traditionally associated with a poor prognosis. While gliosarcoma may represent a distinct clinical entity given its unique histologic composition and molecular features, its relative prognostic significance remains uncertain. While treatment of gliosarcoma generally encompasses the same standardized approach used in glioblastoma, supporting evidence is limited given its rarity. Here, we characterized thirty-two cases of gliosarcoma and retrospectively evaluated survival relative to four hundred and fifty-one glioblastoma patients diagnosed during the same era within the same institution. Overall, we identified twenty-two primary gliosarcomas, representing 4.7% of WHO Grade IV primary glioblastomas, and ten secondary gliosarcomas. With median age of 62, patients were predominately Caucasian (87.5%) and male (65.6%). Tumors with available molecular profiling were primarily MGMT-unmethylated (87.5%), IDH-1-preserved (100%) and EGFR wild-type (100%). Interestingly, while no significant median survival difference between primary gliosarcoma and glioblastoma was observed across the entire cohort (11.0 vs. 14.8 months, p=0.269), median survival was worse for gliosarcoma specifically among patients who received modern temozolomide-based (TMZ) chemoradiotherapy (11.0 vs. 17.3 months, p=0.006). Matched-pair analysis also trended toward worse median survival among gliosarcomas (11.0 vs. 19.6 months, log-rank p=0.177, Breslow p=0.010). While adjuvant radiotherapy (HR 0.206, p=0.035) and TMZ-based chemotherapy (HR 0.531, p=0.000) appeared protective, gliosarcoma emerged as a significantly poor prognostic factor on multivariate analysis (HR 3.27, p=0.012). Collectively, our results suggest that gliosarcoma may still portend worse prognosis even with modern trimodality therapy.

OBJECTIVEAdvanced microsurgical techniques contribute to reduced morbidity and improved surgical management of meningiomas arising within the cerebellopontine angle (CPA). However, the goal of surgery has evolved to preserve the quality of the patient's life, even if it means leaving residual tumor. Concurrently, Gamma Knife radiosurgery (GKRS) has become an acceptable and effective treatment modality for newly diagnosed, recurrent, or progressive meningiomas of the CPA. The authors review their institutional experience with CPA meningiomas treated with GKRS, surgery, or a combination of surgery and GKRS. They specifically focus on rates of facial nerve preservation and characterize specific anatomical features of tumor location with respect to the internal auditory canal (IAC).METHODSMedical records of 76 patients with radiographic evidence or a postoperative diagnosis of CPA meningioma, treated by a single surgeon between 1992 and 2016, were retrospectively reviewed. Patients with CPA meningiomas smaller than 2.5 cm in greatest dimension were treated with GKRS, while patients with tumors 2.5 cm or larger underwent facial nerve–sparing microsurgical resection where appropriate. Various patient, clinical, and tumor data were gathered. Anatomical features of the tumor origin as seen on preoperative imaging confirmed by intraoperative investigation were evaluated for prognostic significance. Facial nerve preservation rates were evaluated.RESULTSAccording to our treatment paradigm, 51 (67.1%) patients underwent microsurgical resection and 25 (32.9%) patients underwent GKRS. Gross-total resection (GTR) was achieved in 34 (66.7%) patients, and subtotal resection (STR) in 17 (33.3%) patients. Tumors recurred in 12 (23.5%) patients initially treated surgically, requiring additional surgery and/or GKRS. Facial nerve function was unchanged or improved in 68 (89.5%) patients. Worsening facial nerve function occurred in 8 (10.5%) patients, all of whom had undergone microsurgical resection. Upfront treatment with GKRS for CPA meningiomas smaller than 2.5 cm was associated with preservation of facial nerve function in all patients over a median follow-up of 46 months, regardless of IAC invasion and tumor origin. Anatomical origin was associated with extent of resection but did not correlate with postoperative facial nerve function. Tumor size, extent of resection, and the presence of an arachnoid plane separating the tumor and the contents of the IAC were associated with postoperative facial nerve outcomes.CONCLUSIONSCPA meningiomas remain challenging lesions to treat, given their proximity to critical neurovascular structures. GKRS is a safe and effective option for managing CPA meningiomas smaller than 2.5 cm without associated mass effect or acute neurological symptoms. Maximal safe resection with preservation of neurological function can be performed for tumors 2.5 cm or larger without significant risk of facial nerve dysfunction, and, when combined with GKRS for recurrence and/or progression, provides excellent disease control. Anatomical features of the tumor origin offer critical insights for optimizing facial nerve preservation in this cohort.

Prior studies of post-operative stereotactic radiosurgery (SRS) have not distinguished between Adjuvant SRS (ARS) versus Adjuvant SRS to residual/recurrent disease (ARD). In this study, we defined ARS and ARD and investigated local control (LC), overall survival (OS), distant development of brain metastases (DBF), and leptomeningeal disease (LMD). We retrospectively identified BM patients who received surgical resection and SRS for BM from an IRB approved database between Jan 2009-Aug 2015. Patients were stratified into two groups: ARS and ARD. LC was determined by follow-up MRI studies and OS was measured from the date of surgery. LC and OS were assessed using the Kaplan-Meier method. 70 cavities underwent surgical resection of BM and received SRS to the post-operative bed. 41 cavities were classified as ARS and 29 as ARD. There was no significant difference in 12-month LC between the ARS and ARD group (71.4 vs. 80.8%, respectively; p = 0.135) from the time point of SRS. The overall 1-year survival for ARS and ARD was 79.9 and 86.1%, respectively (p = 0.339). Mean time to progression was 6.45 and 8.0 months and median follow-up was 10 and 15 months for ARS and ARD, respectively. 11.8% of ARS patients and 15.4% of ARD patients developed LMD, p = 0.72. 29.4% of ARS and 48.0% of ARD patients developed DBF, p = 0.145. Our findings suggest that observation after surgical resection, with subsequent treatment with SRS after the development of local failure, may not compromise treatment efficacy. If validated, this would spare patients who do not recur post-surgically from additional treatment.

In stratified epithelia such as the epidermis, homeostasis is maintained by the proliferation of cells in the lower epithelial layers and the concomitant loss of differentiated cells from the epithelial surface. These differentiating keratinocytes progressively stratify and form a self-regenerating multi-layered barrier that protects the underlying dermis. In such tissue, the continual loss and replacement of differentiated cells also limits the accumulation of oncogenic mutations within the tissue. Inactivating mutations in key driver genes, such as TP53 and NOTCH1, reduce the proportion of differentiating cells allowing for the long-term persistence of expanding mutant clones in the tissue. Here we show that through the expression of E6, HPV-16 prevents the early fate commitment of human keratinocytes towards differentiation and confers a strong growth advantage to human keratinocytes. When E6 is expressed either alone or with E7, it promotes keratinocyte proliferation at high cell densities, through the combined inactivation of p53 and Notch1. In organotypic raft culture, the activity of E6 is restricted to the basal layer of the epithelium and is enhanced during the progression from productive to abortive or transforming HPV-16 infection. Consistent with this, the expression of p53 and cleaved Notch1 becomes progressively more disrupted, and is associated with increased basal cell density and reduced commitment to differentiation. The expression of cleaved Notch1 is similarly disrupted also in HPV-16-positive cervical lesions, depending on neoplastic grade. When taken together, these data depict an important role of high-risk E6 in promoting the persistence of infected keratinocytes in the basal and parabasal layers through the inactivation of gene products that are commonly mutated in non-HPV-associated neoplastic squamous epithelia. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Breast cancer brain metastasis (BCBM) is associated with high morbidity and mortality. Patients with breast cancer risk factors associated with rapid development of BCBM could potentially benefit from early brain metastasis screening. We retrospectively reviewed all BCBM patients treated with brain radiotherapy at our institution from 1997 to 2015. Interval time to BCBM was defined as date of pathologic breast cancer diagnosis to date of radiographic evidence of brain metastasis. Patients were stratified by breast cancer molecular subtype and stage at diagnosis. Kaplan Meier analysis was conducted on time to development of BCBM. Breast cancer risk factors were correlated with time to BCBM on Cox proportion hazard analysis. The study cohort comprised 121 BCBM patients, with median interval time to BCBM of 46 months. Times to BCBM for Her2+/2HR+, Her2+, Her2-/HR+, and triple-negative (TNBC) subtypes were 70, 44, 42, and 28 months respectively (p = 0.002). Time to BCBM for stages I, II, III, and IV were 70, 54, 29, and 24 months, respectively (p = 0.000). BCBM patients were further stratified by both molecular subtype (TNBC vs. non-TNBC) and stage (I, II vs. III, IV). Median times to BCBM for non-TNBC/stage I-II, TNBC/stage I-II, non-TNBC stage III-IV, and TNBC/stage III-IV were 68, 47, 29, and 6 months respectively (p = 0.000). Subtype and stage were associated with shorter time to BCBM on multivariate analysis. Subtype and initial stage are independently correlated with decreased time to development of BCBM. Patients with advanced high stage and triple negative breast cancer develop brain metastases significantly earlier.

Brain metastases (BM) of pancreatic origin are extremely rare. We review the literature around BM of pancreatic origin and describe a 38-year-old woman who developed BM 10 months after pancreaticoduodenectomy for treatment of pancreatic adenocarcinoma. She underwent resection and fractionated stereotactic radiotherapy followed by re-resection and Gamma Knife radiosurgery (GKRS) when the lesion recurred. She then developed two new BM, and was treated with GKRS. The patient is alive without progression 38 months after her most recent GKRS.

Whole-brain radiation therapy (WBRT) plays an important role in patients with diffusely metastatic intracranial disease. Whether the extent of the radiation field design to C1 or C2 affects parotid dose and risk for developing xerostomia is unknown. The goal of this study is to examine the parotid dose based off of the inferior extent of WBRT field to either C1 or C2. Patients treated with WBRT with either 30 Gy or 37.5 Gy from 2011 to 2014 at a single institution were examined. Parotid dose constraints were compared with Radiation Therapy Oncology Group (RTOG) 0615 nasopharyngeal carcinoma for a 33-fraction treatment: mean

The Galactic Centre contains a supermassive black hole with a mass of 4 million suns within an environment that differs markedly from that of the Galactic disk. While the black hole is essentially quiescent in the broader context of active galactic nuclei, X-ray observations have provided evidence for energetic outbursts from its surroundings. Also, while the levels of star formation in the Galactic Centre have been approximately constant over the last few hundred Myr, there is evidence of elevated short-duration bursts, strongly influenced by interaction of the black hole with the enhanced gas density present within the ring-like Central Molecular Zone at Galactic longitude |l| < 0.7 degrees and latitude |b| < 0.2 degrees. The inner 200 pc region is characterized by large amounts of warm molecular gas, a high cosmic ray ionization rate, unusual gas chemistry, enhanced synchrotron emission, and a multitude of radio-emitting magnetised filaments, the origin of which has not been established. Here we report radio imaging that reveals bipolar bubbles spanning 1 degree x 3 degrees (140 parsecs x 430 parsecs), extending above and below the Galactic plane and apparently associated with the Galactic Centre. The structure is edge-brightened and bounded, with symmetry implying creation by an energetic event in the Galactic Centre. We estimate the age of the bubbles to be a few million years, with a total energy of 7 x 10^52 ergs. We postulate that the progenitor event was a major contributor to the increased cosmic-ray density in the Galactic Centre, and is in turn the principal source of the relativistic particles required to power the synchrotron emission of the radio filaments within and in the vicinity of the bubble cavities., 25 pages, 3 figures, 3 tables, authors' version of a Letter published in Nature on 11 September 2019

We present the confusion-limited 1.28 GHz MeerKAT DEEP2 image covering one $\approx 68'$ FWHM primary beam area with $7.6''$ FWHM resolution and $0.55 \pm 0.01$ $\mu$Jy/beam rms noise. Its J2000 center position $\alpha=04^h 13^m 26.4^s$, $\delta=-80^\circ 00' 00''$ was selected to minimize artifacts caused by bright sources. We introduce the new 64-element MeerKAT array and describe commissioning observations to measure the primary beam attenuation pattern, estimate telescope pointing errors, and pinpoint $(u,v)$ coordinate errors caused by offsets in frequency or time. We constructed a 1.4 GHz differential source count by combining a power-law count fit to the DEEP2 confusion $P(D)$ distribution from $0.25$ to $10$ $\mu$Jy with counts of individual DEEP2 sources between $10$ $\mu$Jy and $2.5$ mJy. Most sources fainter than $S \sim 100$ $\mu$Jy are distant star-forming galaxies obeying the FIR/radio correlation, and sources stronger than $0.25$ $\mu$Jy account for $\sim93\%$ of the radio background produced by star-forming galaxies. For the first time, the DEEP2 source count has reached the depth needed to reveal the majority of the star formation history of the universe. A pure luminosity evolution of the 1.4 GHz local luminosity function consistent with the Madau & Dickinson (2014) model for the evolution of star-forming galaxies based on UV and infrared data underpredicts our 1.4 GHz source count in the range $-5 \lesssim \log[S(\mathrm{Jy})] \lesssim -4$., Comment: 20 pages, 18 figures. Accepted for publication in ApJ

Background Gamma Knife radiosurgery (GKRS; Elekta AB) remains a well-established treatment modality for vestibular schwannomas. Despite highly effective tumor control, further research is needed toward optimizing long-term functional outcomes. Whereas dose-rate effects may impact post-treatment toxicities given tissue dose-response relationships, potential effects remain largely unexplored. Objective To evaluate treatment outcomes and potential dose-rate effects following definitive GKRS for vestibular schwannomas. Methods We retrospectively reviewed 419 patients treated at our institution between 1998 and 2015, characterizing baseline demographics, pretreatment symptoms, and GKRS parameters. The cohort was divided into 2 dose-rate groups based on the median value (2.675 Gy/min). Outcomes included clinical tumor control, radiographic progression-free survival, serviceable hearing preservation, hearing loss, and facial nerve dysfunction (FND). Prognostic factors were assessed using Cox regression. Results The study cohort included 227 patients with available follow-up. Following GKRS 2-yr and 4-yr clinical tumor control rates were 98% (95% CI: 95.6%-100%) and 96% (95% CI: 91.4%-99.6%), respectively. Among 177 patients with available radiographic follow-up, 2-yr and 4-yr radiographic progression-free survival rates were 97% (95% CI: 94.0%-100.0%) and 88% (95% CI: 81.2%-95.0%). The serviceable hearing preservation rate was 72.2% among patients with baseline Gardner-Robertson class I/II hearing and post-treatment audiological evaluations. Most patients experienced effective relief from prior headaches (94.7%), tinnitus (83.7%), balance issues (62.7%), FND (90.0%), and trigeminal nerve dysfunction (79.2%), but not hearing loss (1.0%). Whereas GKRS provided effective tumor control independently of dose rate, GKRS patients exposed to lower dose rates experienced significantly better freedom from post-treatment hearing loss and FND (P = .044). Conclusion Whereas GKRS provides excellent tumor control and effective symptomatic relief for vestibular schwannomas, dose-rate effects may impact post-treatment functional outcomes. Further research remains warranted.

Arrival air traffic operations in the presence of convective weather are subject to uncertainty in aircraft routing and subsequently in flight trajectory predictability. Current management of arrival operations in weather-impacted airspace results in significant flight delay and suspension of arrival metering operations. The Dynamic Routing for Arrivals in Weather (DRAW) concept provides flight route amendment advisories to Traffic Management Coordinators to mitigate the impacts of convective weather on arrival operations. DRAW provides both weather conflict and schedule information for proposed route amendments, allowing air traffic managers to simultaneously evaluate weather avoidance routing and potential schedule and delay impacts. Subject matter experts consisting of retired Traffic Management Coordinators and retired Sector Controllers with arrival metering experience participated in a simulation study of Fort Worth Air Route Traffic Control Center arrival operations. Data were collected for Traffic Management Coordinator and Sector Controller participants over three weeks of simulation activities in October, 2017. Traffic Management Coordinators reported acceptable workload levels, a positive impact on their ability to manage arrival traffic while using DRAW, and initiated weather mitigation reroutes earlier while using DRAW. Sector Controllers also reported acceptable workload levels while using DRAW.

New radio (MeerKAT and Parkes) and X-ray (XMM-Newton, Swift, Chandra, and NuSTAR) observations of PSR J1622-4950 indicate that the magnetar, in a quiescent state since at least early 2015, reactivated between 2017 March 19 and April 5. The radio flux density, while variable, is approximately 100x larger than during its dormant state. The X-ray flux one month after reactivation was at least 800x larger than during quiescence, and has been decaying exponentially on a 111+/-19 day timescale. This high-flux state, together with a radio-derived rotational ephemeris, enabled for the first time the detection of X-ray pulsations for this magnetar. At 5%, the 0.3-6 keV pulsed fraction is comparable to the smallest observed for magnetars. The overall pulsar geometry inferred from polarized radio emission appears to be broadly consistent with that determined 6-8 years earlier. However, rotating vector model fits suggest that we are now seeing radio emission from a different location in the magnetosphere than previously. This indicates a novel way in which radio emission from magnetars can differ from that of ordinary pulsars. The torque on the neutron star is varying rapidly and unsteadily, as is common for magnetars following outburst, having changed by a factor of 7 within six months of reactivation., Comment: Published in ApJ (2018 April 5); 13 pages, 4 figures

Renal cell carcinoma, sarcoma, and melanoma are considered to be "radioresistant" tumor histologies. Brain metastases (BM) from these tumors are considered unlikely to be controlled using the relatively low doses used in whole brain radiotherapy (WBRT). Our objective was to analyze the efficacy of stereotactic radiosurgery (SRS) on local control and overall survival of BM from radioresistant primary tumors. We reviewed all patients who received Gamma Knife Radiosurgery (GKRS) for BM at Columbia University Medical Center between January 2009 and April 2014. All patients were treated using the Gamma Knife Perfexion System. Dosimetric data was collected from treatment plans and metastases were categorized as radioresistant or not. Response was assessed by reviewing follow-up brain imaging studies and classified according to RECIST. Local control and median overall survival were calculated using the Kaplan-Meier method. In total, 373 tumors were analyzed from 126 patients. Of these tumors, 49 (13.1 %) originated from radioresistant cancers. The overall local control rate in the radioresistant cohort was 89.8 and 90.1 % in the non-radioresistant cohort. Univariate and multivariate analyses demonstrated that radioresistance status of the primary tumor had no statistically significant effect on local control with hazard ratios of 1.0 (p = 1.0, 95 % CI 0.388-2.576) and 0.954 (p = 0.926, 95 % CI 0.349-2.603) respectively. Median overall survival for both radioresistant and non-radioresistant cohorts was 20.0 months, with a p value of 0.926. There was no significant difference in local control of BM from radioresistant and non-radioresistant primary tumors treated with GKRS. Both cohorts showed excellent response and local control, suggesting that SRS upfront or in addition to WBRT may be an appropriate strategy in the treatment of BM from radioresistant cancers. Median overall survival for both cohorts was equal, suggesting that improved local control may be associated with an improvement in long-term survival.

BACKGROUND The energy index (EI) is a measure of dose homogeneity within a target volume calculated by the integral dose divided by the product of prescription dose and tumor volume. OBJECTIVE To assess whether a higher EI is associated with greater local control for brain metastases (BMs) treated by Gamma Knife radiosurgery (GKRS). METHODS We reviewed all patients treated with GKRS for BM at our institution between January 2009 and February 2014. Data on the prescription dose, prescription isodose line, minimum dose, mean dose, integral dose, tumor volume, and EI were collected. Tumor response was assessed by reviewing follow-up brain imaging studies and classified according to the Response Evaluation Criteria in Solid Tumors. Local control per lesion and dosimetric prognostic factors for local control were assessed by univariate and multivariate Cox proportional hazards regression analyses. RESULTS Of 213 patients treated, 126 had follow-up imaging available with a median follow-up of 6 months. Three hundred seventy-three individual tumors were analyzed. Of these, 133 showed a complete response, 157 showed a partial response, 46 remained stable, and 37 developed local failure. Tumors with EI ≥1.6 mJ·mL(-1)·Gy(-1) showed a higher rate of complete response. Local control rates at 6, 11, and 17 months were 95.4%, 86.5%, and 81.5%, respectively. On univariate analysis, the following factors were associated with higher rates of local failure: prescription doses of 16 and 18 Gy compared with a prescription dose of 20 Gy. The following factors were associated with a greater rate of local control: maximum dose and mean dose. On multivariate analysis, the only statistically significant factor associated with a greater rate of local failure was prescription dose of 16 Gy compared with 20 Gy. CONCLUSION GKRS for BM results in a high rate of local control with an 11-month rate of 86.5%. A higher EI was not significantly associated with a higher rate of local control on multivariate analysis. Prescription dose was found to be the only significant predictor of local control on multivariate analysis.

BACKGROUND We investigated effects of genetic alterations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and Kirsten rat sarcoma viral oncogene homolog (KRAS) on overall survival (OS) and local control after stereotactic radiosurgery for brain metastases in non-small cell lung cancer (NSCLC). METHODS A cohort of 89 out of 262 NSCLC patients (2003-2013) treated with gamma knife radiosurgery for brain metastases had genotyping available and were selected as our study population. RESULTS Median follow-up was 12 months. Median OS rates for the EGFR, KRAS, echinoderm microtubule-associated protein-like 4 (EML4)-ALK mutated, and wild-type cohorts were 17, 7, 27, and 12 months, respectively (P = .019), and for targeted versus nontargeted therapy 21 and 11 months, respectively (P = .071). Targeted therapy was a strong predictor of increased OS on univariate (P = .037) and multivariate (P = .022) analysis. Gender, primary tumor controlled status, recursive partitioning analysis class, and graded prognostic assessment score were associated with OS (P < .05). On multivariate analysis, positive EGFR mutational status was a highly significant predictor for decreased survival (hazard ratio: 8.2; 95% CI: 2.0-33.7; P = .003). However, when we recategorized EGFR-mutant cases based on whether they received tyrosine kinase inhibitor, OS was no longer significantly shorter (hazard ratio: 1.5; P = .471). Median OS for patients with and without local failure was 17 and 12 months, respectively (P = .577). Local failure rates for EGFR, KRAS, EML4-ALK mutated, and wild-type cohorts by lesion were 8.7%, 5.4%, 4.3%, and 5.1%, respectively. CONCLUSIONS This study suggests that EGFR tyrosine kinase mutation and ALK translocation results in improved survival to targeted therapies and that mutation status itself does not predict survival and local control in patients with brain metastases from NSCLC.

Optimal treatment of brain metastases (BMs) is debatable. However, surgery or gamma knife radiosurgery (GKRS) improves survival when combined with whole brain radiotherapy (WBRT) versus WBRT alone. We retrospectively reviewed an institutional database of patients treated with GKRS for BMs from 1998 to 2013 to explore effects of single or multi-modality therapies on survival. There were 528 patients with median age 62 years. Histologies included 257 lung, 102 breast, 62 melanoma, 40 renal cell, 29 gastrointestinal, and 38 other primary cancers. Treatments included: 206 GKRS alone, 111 GKRS plus WBRT, 109 GKRS plus neurosurgical resection (NSG), and 102 all three modalities. Median overall survival (mOS) was 16.6 months. mOS among patients with one versus multiple metastasis was 17.2 versus 16.0 months respectively (p = 0.825). For patients with one BM, mOS following GKRS alone, GKRS plus WBRT, GKRS plus NSG, and all three modalities was 9.0, 19.1, 25.5, and 25.0 months, respectively, and for patients with multiple BMs, mOS was 8.6, 20.4, 20.7, 24.5 months for the respective groups. Among all patients, multivariate analysis confirmed that tri-modality group had the longest survival (HR 0.467; 95 % CI 0.350-0.623; p < 0.001) compared to GKRS alone; however, this was not significantly different than bi-modality approaches. Uncontrolled primary extra-CNS disease, age and KPS were also independent predictors of survival. Patients treated with GKRS plus NSG, GKRS plus WBRT, or all three modalities had improved OS versus GKRS alone. In our analysis, resection and GKRS allowed avoidance of WBRT without shortening survival.

Modifiable risk factors for Alzheimer’s disease (AD) have been actively sought and identified in recent years. Despite this, it remains a challenge to encourage risk-reducing lifestyle and health behaviors in individuals at risk. The aim of this study was to investigate whether AD knowledge, beliefs, and willingness to reduce risk would be the key determinants of AD preventive behaviors.These data were drawn from Alzheimer’s Universe (www.AlzU.org), an online course and educational program developed in the USA. One hundred and forty four people (mean age=61.1; SD=9.1) who completed both baseline and follow-up (3 months after completion of the program) questionnaires were included in these analyses. Eighty three percent of participants were female, the majority (96.5%) were Caucasian and sixty eight percent had tertiary education. Linear regression suggested that changes in willingness (β=.539, p

The Collaboration for Astronomy Signal Processing and Electronics Research (CASPER) has been working for a decade to reduce the time and cost of designing, building and deploying new digital radio-astronomy instruments. Today, CASPER open-source technology powers over 45 scientific instruments worldwide, and is used by scientists and engineers at dozens of academic institutions. In this paper, we catalog the current offerings of the CASPER collaboration, and instruments past and present built by CASPER users and developers. We describe the ongoing state of software development, as CASPER looks to support a broader range of programming environments and hardware and ensure compatibility with the latest vendor tools.

We address the problem of navigating a set (fleet) of aircraft in an aerial route network so as to bring each aircraft to its destination at a specified time and with minimal distance separation assured between all aircraft at all times. The speed range, initial position, required destination, and required time of arrival at destination for each aircraft are assumed provided. Each aircraft's movement is governed by a controlled differential equation (state equation). The problem consists in choosing for each aircraft a path in the route network and a control strategy so as to meet the constraints and reach the destination at the required time. The main contribution of the paper is a model that allows to recast this problem as a decoupled collection of problems in classical optimal control and is easily generalized to the case when inertia cannot be neglected. Some qualitative insight into solution behavior is obtained using the Pontryagin Maximum Principle. Sample numerical solutions are computed using a numerical optimal control solver. The proposed model is first step toward increasing the fidelity of continuous time control models of air traffic in a terminal airspace. The Pontryagin Maximum Principle implies the polygonal shape of those portions of the state trajectories away from those states in which one or more aircraft pair are at minimal separation. The model also confirms the intuition that, the narrower the allowed speed ranges of the aircraft, the smaller the space of optimal solutions, and that an instance of the optimal control problem may not have a solution at all (i.e., no control strategy that meets the separation requirement and other constraints).

Background Studies have shown racial differences in cancer outcomes. We investigate whether survival differences existed in Hispanic patients with glioblastoma (GBM) compared with other ethnicities from our modern radiotherapy series, because no study to date has focused on outcomes in this group after radiation therapy. Methods We retrospectively evaluated 428 patients diagnosed with GBM from 1996 to 2014 at our institution, divided into 4 groups based on self-report: white, black, Hispanic, and Asian/Indian. The primary outcome was overall survival. We analyzed differences in prognostic factors among the whole cohort compared with the Hispanic cohort alone. Results Baseline characteristics of the 4 racial groups were comparable. With a median follow-up of 387 days, no survival differences were seen by Kaplan-Meier analysis. Median overall survival for Hispanic patients was 355 days versus 450 days for the entire cohort. Factors significant for patient outcomes in the entire cohort differed slightly from those specific to Hispanic patients. Low Karnofsky Performance Status was significant on multivariate analysis in the whole population, but not in Hispanic patients. Extent of resection, recursive partitioning analysis class, and radiation therapy total dose were significant on multivariate analysis in both the whole population and Hispanic patients. Conclusions We found that Hispanic patients with GBM had no difference in survival compared with other ethnicities in our cohort. Differences exist in factors associated with outcomes on single and multivariate analysis for Hispanic patients with GBM compared with the entire cohort. Additional studies focusing on Hispanic patients will aid in more personalized treatment approaches in this group.

BACKGROUND: Adjuvant hypofractionated radiotherapy (HRT) for elderly patients with newly diagnosed glioblastoma (GBM) is reasonable compared to standard fractionation radiotherapy (SRT). Comparison of HRT in the presence of temozolomide (TMZ) vs SRT with TMZ is unclear. We examined HRT for GBM with TMZ in comparison to SRT with TMZ. METHODS: Retrospective analysis of patients > 60 years-old who received SRT or HRT of newly diagnosed GBM in the post-operative setting from 1994 to 2014. Inclusion criteria included SRT (60 Gy/30 fractions or 59.4 Gy/33 fractions) vs HRT of 40 Gy/15 fractions. RESULTS: 158 patients received SRT vs 26 with HRT. Median survival receiving SRT versus HRT was 430 and 475 days (p = 0.550). 95% of the SRT patients received TMZ vs 100% with HRT. Patients receiving HRT were older (median: 72 vs 66 years). All HRT patients were treated with IMRT technique vs SRT. Multivariate Cox regression showed decreased survival in age > 70 (Hazard ratio [HR] 1.84; 95% confidence interval [CI] 1.23-2.75), lower Karnofsky performance status (HR 5.25; 95% CI 1.73-15.99), biopsy vs. surgical resection (HR 4.18; 95% CI 1.49-11.77), RT planning technique 3D- or 2D-planning vs. IMRT (HR 1.91; 95% CI 1.32-2.76 and HR 3.40; 95% CI 1.60-7.22, respectively). IMRT based planning showed no difference between HRT vs SRT. For patients receiving TMZ, there was no survival difference between HRT and SRT. CONCLUSIONS: Elderly GBM patients receiving HRT or SRT had similar overall survival. Subset analysis patients receiving concurrent TMZ showed no difference in survival between HRT and SRT.

BACKGROUND: Recent studies have suggested a difference in outcome for breast cancer patients with brain metastases based on breast cancer subtype. These subtypes are defined as ER/PR+ and HER2- (luminal A), ER/PR+ and HER2+ (luminal B), ER/PR- and HER2- (triple-negative), and ER/PR- and HER2+ (HER2). The recently published modified Graded Prognostic Analysis (GPA) score for predicting overall survival (OS) in these patients includes subtype, number of CNS metastases, age, and performance status. We investigated whether this model was predictive of outcomes in these patients treated with Gamma Knife Stereotactic Radiosurgery (GKRS) at our institution and if any additional factors were predictive. METHODS: We reviewed all patients treated by GKRS for brain metastases from breast cancer at our institution from 2000 to 2014. Characteristics included subtype, age at breast cancer diagnosis, clinical stage, chemotherapy, age at diagnosis of brain metastases, Karnofsky Performance Status, years between breast cancer diagnosis and brain metastases, number of brain metastases, extracranial metastases, controlled primary tumor, type of treatment, and GPA score. OS was calculated using the Kaplan-Meier method and Cox regression analysis was performed to identify predictors. RESULTS: 61 patients were included. The majority of patients had luminal type. These patients were more likely to present with multiple metastases (p = 0.024). The median survival after treatment for the entire cohort was 16 months. We found no significant difference in survival based on subtype. According to GPA score, patients with the highest score had the best OS (p = 0.112). Multivariate analysis showed that stage II or III breast cancer at diagnosis, more than three brain metastases, and treatment with surgery and whole brain radiation for brain metastases were predictors for worse OS. CONCLUSION: In our cohort, breast cancer subtype is not a significant predictor for survival in these patients. The breast-cancer specific GPA was a good predictor of OS.

Object The goal of this article was to show that a combination of facial nerve–sparing microsurgical resection and Gamma Knife surgery (GKS) for expansion of any residual tumor can preserve good facial nerve function in patients with recurrent vestibular schwannoma (VS). Methods Records of individuals treated by a single surgeon with a facial nerve–sparing technique for a VS between 1998 and 2009 were retrospectively analyzed for tumor recurrence. Of the 383 patients treated for VS, 151 underwent microsurgical resection, and 20 (13.2%) of these patients required postoperative retreatment for a significant expansion of residual tumor after microsurgery. These 20 patients were re-treated with GKS. Results The rate of preservation of good facial nerve function (Grade I or II on the House-Brackmann scale) in patients treated with microsurgery for VS was 97%. Both subtotal and gross-total resection had excellent facial nerve preservation rates (97% vs 96%), although subtotal resection carried a higher risk that patients would require retreatment. In patients re-treated with GKS after microsurgery, the rate of facial nerve preservation was 95%. Conclusions In patients with tumors that cannot be managed with radiosurgery alone, a facial nerve–sparing resection followed by GKS for any significant regrowth provides excellent facial nerve preservation rates.

Stereotactic radiosurgery (SRS) should be considered in the comprehensive treatment paradigm for all patients with brain metastases. This technique has proven benefits for local tumor control in individuals with as many as 4 lesions, and when combined with structured radiographic follow-up, will likely preserve a better quality of life for appropriately selected patients. Institutions and physicians treating patients with brain metastases should have the capability of safely performing SRS and individual cases should be prospectively reviewed by multidisciplinary teams to provide the best comprehensive care.

Background/Aims: In Gamma Knife radiosurgery, T1 MRI is most commonly used and is generally sufficient for targeting the trigeminal nerve. For patients whose trigeminal nerves are unclear on T1 MRI, FIESTA MRI supplements anatomical structure visualization and may improve trigeminal nerve delineation. The purpose of this study was to develop a registration strategy for T1 and FIESTA MRIs. Methods: We conducted a retrospective study on 54 trigeminal neuralgia patients. All patients were scanned with T1 and FIESTA MRIs. We evaluated 4 methods of registration: automatic image definition, superior-slice definition, middle-slice definition and inferior-slice definition. Target discrepancies were measured by deviations from an intracranial landmark on T1 and FIESTA MR images. Results: The overall range in registration error was 0.10–5.19 mm using superior-, 0.10–1.56 mm using middle- and 0.14–2.89 mm using inferior-slice definition. Registration error >2 mm was observed in 11% of the patients using superior-, 4% using middle- and 7% using inferior-slice FIESTA MRI definition. Conclusions: Among patients for whom FIESTA and T1 MRI are used, registration based on middle-slice definition reduces registration error and improves targeting of the trigeminal nerve.

The E1^E4 protein of human papillomavirus type 16 (HPV16) causes cytokeratin reorganization in the middle and upper epithelial layers and is thought to contribute to multiple facets of the virus life cycle. Although little is known as to how HPV16 E1^E4 (16E1^E4) functions are controlled following the first expression of this protein, the finding that low-risk E1^E4 proteins can be phosphorylated in vivo suggests an important role for kinases. Here, we show that 16E1^E4 is phosphorylated by cyclin-dependent kinase 1 (CDK1) and CDK2, extracellular signal-regulated kinase (ERK), protein kinase A (PKA), and PKC α, with CDK1/2 serine 32 and ERK threonine 57 phosphorylations representing the two primary events seen in cells in cycle. Interestingly, T57 phosphorylation was found to trigger a structural change in the 16E1^E4 protein that compacts the central fold region, leading to an increase in 16E1^E4 stability and overall abundance in the cell. When compared to wild-type 16E1^E4, a T57D phosphomimic was found to have greatly enhanced keratin-binding ability and an ability to modulate the binding of the unphosphorylated form, with keratin binding protecting the T57-phosphorylated form of 16E1^E4 from proteasomal degradation. In HPV16 genome-containing organotypic rafts, the T57-phosphorylated form was specifically detected in the intermediate cell layers, where productive infection occurs, suggesting that T57 phosphorylation may have a functional role at this stage of the viral life cycle. Interestingly, coexpression with 16E5 and ERK activation enhanced T57 phosphorylation, suggesting that E1^E4 and E5 may work together in vivo. Our data suggest a model in which the expression of 16E5 from the major E1^E4-E5 mRNA promotes T57 phosphorylation of E1^E4 and keratin binding, with dephosphorylation occurring following the switch to late poly(A) usage. Other forms of E1^E4, with alternative functional roles, may then increase in prevalence in the upper layers of the epithelium.

Purpose To integrate imaging performance characteristics, specifically sensitivity and specificity, of magnetic resonance angiography (MRA) and digital subtraction angiography (DSA) into arteriovenous malformation (AVM) radiosurgery planning and evaluation. Methods and Materials Images of 10 patients with AVMs located in critical brain areas were analyzed in this retrospective planning study. The image findings were first used to estimate the sensitivity and specificity of MRA and DSA. Instead of accepting the imaging observation as a binary (yes or no) mapping of AVM location, our alternative is to translate the image into an AVM probability distribution map by incorporating imagers' sensitivity and specificity, and to use this map as a basis for planning and evaluation. Three sets of radiosurgery plans, targeting the MRA and DSA positive overlap, MRA positive, and DSA positive were optimized for best conformality. The AVM obliteration rate (ORAVM) and brain complication rate served as endpoints for plan comparison. Results In our 10-patient study, the specificities and sensitivities of MRA and DSA were estimated to be (0.95, 0.74) and (0.71, 0.95), respectively. The positive overlap of MRA and DSA accounted for 67.8% ± 4.9% of the estimated true AVM volume. Compared with plans targeting MRA and DSA–positive overlap, plans targeting MRA-positive or DSA-positive improved ORAVM by 4.1% ± 1.9% and 15.7% ± 8.3%, while also increasing the complication rate by 1.0% ± 0.8% and 4.4% ± 2.3%, respectively. Conclusions The impact of imagers' quality should be quantified and incorporated in AVM radiosurgery planning and evaluation to facilitate clinical decision making.