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OBJECTIVE The authors previously evaluated risk and time course of adverse radiation effects (AREs) following stereotactic radiosurgery (SRS) for brain metastases, excluding lesions treated after prior SRS. In the present analysis they focus specifically on single-fraction salvage SRS to brain metastases previously treated with SRS or hypofractionated SRS (HFSRS), evaluating freedom from progression (FFP) and the risk and time course of AREs. METHODS Brain metastases treated from September 1998 to May 2019 with single-fraction SRS after prior SRS or HFSRS were analyzed. Serial follow-up magnetic resonance imaging (MRI) and surgical pathology reports were reviewed to score local treatment failure and AREs. The Kaplan-Meier method was used to estimate FFP and risk of ARE measured from the date of repeat SRS with censoring at the last brain MRI. RESULTS A total of 229 retreated brain metastases in 124 patients were evaluable. The most common primary cancers were breast, lung, and melanoma. The median interval from prior SRS/HFSRS to repeat SRS was 15.4 months, the median prescription dose was 18 Gy, and the median duration of follow-up imaging was 14.5 months. At 1 year after repeat SRS, FFP was 80% and the risk of symptomatic ARE was 11%. The 1-year risk of imaging changes, including asymptomatic RE and symptomatic ARE, was 30%. Among lesions that demonstrated RE, the median time to onset was 6.7 months (IQR 4.7–9.9 months) and the median time to peak imaging changes was 10.1 months (IQR 5.6–13.6 months). Lesion size by quadratic mean diameter (QMD) showed similar results for QMDs ranging from 0.75 to 2.0 cm (1-year FFP 82%, 1-year risk of symptomatic ARE 11%). For QMD < 0.75 cm, the 1-year FFP was 86% and the 1-year risk of symptomatic ARE was only 2%. Outcomes were worse for QMDs 2.01–3.0 cm (1-year FFP 65%, 1-year risk of symptomatic ARE 24%). The risk of symptomatic ARE was not increased with tyrosine kinase inhibitors or immunotherapy before or after repeat SRS. CONCLUSIONS RE on imaging was common after repeat SRS (30% at 1 year), but the risk of a symptomatic ARE was much less (11% at 1 year). The results of repeat single-fraction SRS were good for brain metastases ≤ 2 cm. The authors recommend an interval ≥ 6 months from prior SRS and a prescription dose ≥ 18 Gy. Alternatives such as HFSRS, laser interstitial thermal therapy, or resection with adjuvant radiation should be considered for recurrent brain metastases > 2 cm.

OBJECTIVE Meningiomas are the most common primary intracranial tumor, and resection is a mainstay of treatment. It is unclear what duration of imaging follow-up is reasonable for WHO grade I meningiomas undergoing complete resection. This study examined recurrence rates, timing of recurrence, and risk factors for recurrence in patients undergoing a complete resection (as defined by both postoperative MRI and intraoperative impression) of WHO grade I meningiomas. METHODS The authors conducted a retrospective, single-center study examining recurrence risk for adult patients with a single intracranial meningioma that underwent complete resection. Uni- and multivariate nominal logistic regression and Cox proportional hazards analyses were performed to identify variables associated with recurrence and time to recurrence. Two supervised machine learning algorithms were then implemented to confirm factors within the cohort that were associated with recurrence. RESULTS The cohort consisted of 823 patients who met inclusion criteria, and 56 patients (6.8%) had recurrence on imaging follow-up. The median age of the cohort was 56 years, and 77.4% of patients were female. The median duration of head imaging follow-up for the entire cohort was 2.7 years, but for the subgroup of patients who had a recurrence, the median follow-up was 10.1 years. Estimated 1-, 5-, 10-, and 15-year recurrence-free survival rates were 99.8% (95% confidence interval [CI] 98.8%–99.9%), 91.0% (95% CI 87.7%–93.6%), 83.6% (95% CI 78.6%–87.6%), and 77.3% (95% CI 69.7%–83.4%), respectively, for the entire cohort. On multivariate analysis, MIB-1 index (odds ratio [OR] per 1% increase: 1.34, 95% CI 1.13–1.58, p = 0.0003) and follow-up duration (OR per year: 1.12, 95% CI 1.03–1.21, p = 0.012) were both associated with recurrence. Gradient-boosted decision tree and random forest analyses both identified MIB-1 index as the main factor associated with recurrence, aside from length of imaging follow-up. For tumors with an MIB-1 index < 8, recurrences were documented up to 8 years after surgery. For tumors with an MIB-1 index ≥ 8, recurrences were documented up to 12 years following surgery. CONCLUSIONS Long-term imaging follow-up is important even after a complete resection of a meningioma. Higher MIB-1 labeling index is associated with greater risk of recurrence. Imaging screening for at least 8 years in patients with an MIB-1 index < 8 and at least 12 years for those with an MIB-1 index ≥ 8 may be needed to detect long-term recurrences.

OBJECTIVE Resection of brain metastases (BMs) may be associated with increased risk of leptomeningeal disease (LMD). This study examined rates and predictors of LMD, including imaging subtypes, in patients who underwent resection of a BM followed by postoperative radiation. METHODS A retrospective, single-center study was conducted examining overall LMD, classic LMD (cLMD), and nodular LMD (nLMD) risk. Logistic regression, Cox proportional hazards, and random forest analyses were performed to identify risk factors associated with LMD. RESULTS Of the 217 patients in the cohort, 47 (21.7%) developed postoperative LMD, with 19 cases (8.8%) of cLMD and 28 cases (12.9%) of nLMD. Six-, 12-, and 24-month LMD-free survival rates were 92.3%, 85.6%, and 71.4%, respectively. Patients with cLMD had worse survival outcomes from the date of LMD diagnosis compared with nLMD (median 2.4 vs 6.9 months, p = 0.02, log-rank test). Cox proportional hazards analysis identified cerebellar/insular/occipital location (hazard ratio [HR] 3.25, 95% confidence interval [CI] 1.73–6.11, p = 0.0003), absence of extracranial disease (HR 2.49, 95% CI 1.27–4.88, p = 0.008), and ventricle contact (HR 2.82, 95% CI 1.5–5.3, p = 0.001) to be associated with postoperative LMD. A predictive model using random forest analysis with an area under the receiver operating characteristic curve of 0.87 in a test cohort identified tumor location, systemic disease status, and tumor volume as the most important factors associated with LMD. CONCLUSIONS Tumor location, absence of extracranial disease at the time of surgery, ventricle contact, and increased tumor volume were associated with LMD. Further work is needed to determine whether escalating therapies in patients at risk of LMD prevents disease dissemination.

To compare functional hearing and tinnitus outcomes in treated large (~ 3 cm) vestibular schwannoma (VS) and posterior fossa meningioma cohorts, and construct willingness-to-accept profiles for an experimental brain implant to treat unilateral hearing loss.A two-way MANOVA model with two independent variables (tumor type; time from treatment) and three dependent variables (hearing effort of tumor ear; abbreviated Speech, Spatial, and Qualities of Hearing scale (SSQ12); Tinnitus Functional Index (TFI)) was used to analyze data from VS (Tumor type was statistically significant on the combined dependent variables analysis (Hearing outcome is better for posterior fossa meningioma compared to VS. Most patients with hearing loss in the tumor ear would consider a brain implant if the benefit level would be comparable to a cochlear implant.2.

OBJECTIVE The authors’ objective was to examine the safety and efficacy of salvage intracranial cesium-131 brachytherapy in combination with resection of recurrent brain tumors. METHODS The authors conducted a retrospective chart review of consecutive patients treated with intraoperative intracranial cesium-131 brachytherapy at a single institution. Permanent suture-stranded cesium-131 seeds were implanted in the resection cavity after maximal safe tumor resection. The primary outcomes of interest were local, locoregional (within 1 cm), and intracranial control, as well as rates of overall survival (OS), neurological death, symptomatic adverse radiation effects (AREs), and surgical complication rate graded according to Common Terminology Criteria for Adverse Events version 5.0. RESULTS Between 2016 and 2020, 36 patients received 40 consecutive cesium-131 implants for 42 recurrent brain tumors and received imaging follow-up for a median (interquartile range [IQR]) of 17.0 (12.7–25.9) months. Twenty patients (55.6%) with 22 implants were treated for recurrent brain metastasis, 12 patients (33.3%) with 16 implants were treated for recurrent atypical (n = 7) or anaplastic (n = 5) meningioma, and 4 patients (11.1%) were treated for other recurrent primary brain neoplasms. All except 1 tumor (97.6%) had received prior radiotherapy, including 20 (47.6%) that underwent 2 or more prior radiotherapy treatments and 23 (54.8%) that underwent prior resection. The median (IQR) tumor size was 3.0 (2.3–3.7) cm, and 17 lesions (40.5%) had radiographic evidence of ARE prior to salvage therapy. Actuarial 1-year local/locoregional/intracranial control rates for the whole cohort and patients with metastases and meningiomas were 91.6%/83.4%/47.9%, 88.8%/84.4%/45.4%, and 100%/83.9%/46.4%, respectively. No cases of local recurrence of any histology (0 of 27) occurred after gross-total resection (p = 0.012, log-rank test). The 1-year OS rates for the whole cohort and patients with metastases and meningiomas were 82.7%, 79.1%, and 91.7%, respectively, and the median (IQR) survival of all patients was 26.7 (15.6–36.4) months. Seven patients (19.4%) experienced neurological death from progressive intracranial disease (7 of 14 total deaths [50%]), 5 (13.9%) of whom died of leptomeningeal disease. Symptomatic AREs were observed in 9.5% of resection cavities (n = 4), of which 1 (2.4%) was grade 3 in severity. The surgical complication rate was 16.7% (n = 7); 4 (9.5%) of these patients had grade 3 or higher complications, including 1 patient (2.4%) who died perioperatively. CONCLUSIONS Cesium-131 brachytherapy resulted in good local control and acceptable rates of symptomatic AREs and surgical complications in this heavily pretreated cohort, and it may be a reasonable salvage adjuvant treatment for this patient population.

Interfacility transfers represent a large proportion of neurosurgical admissions to tertiary care centers each year. In this study, the authors examined the impact of the COVID-19 pandemic on the number of transfers, timing of transfers, demographic profile of transfer patients, and clinical outcomes including rates of surgical intervention.A retrospective review of neurosurgical transfer patients at a single tertiary center was performed. Patients transferred from April to November 2020 (the "COVID Era") were compared with an institutional database of transfer patients collected before the COVID-19 pandemic (the "Pre-COVID Era"). During the COVID Era, both emergent and nonemergent neurosurgical services had resumed. A comparison of demographic and clinical factors between the 2 cohorts was performed.A total of 674 patients were included in the study (331 Pre-COVID and 343 COVID-Era patients). Overall, there was no change in the average monthly number of transfers (P = 0.66) or in the catchment area of referral hospitals. However, COVID-Era patients were more likely to be uninsured (1% vs. 4%), had longer transfer times (COVID vs. Pre-COVID Era: 18 vs. 9 hours; P0.001), required higher rates of surgical intervention (63% vs. 50%, P = 0.001), had higher rates of spine pathology (17% vs. 10%), and less frequently were admitted to the intensive care unit (34% vs. 52%, P0.001). Overall, COVID-Era patients did not experience delays to surgical intervention (3.1 days vs. 3.6 days, P = 0.2). When analyzing the subgroup of COVID-Era patients, COVID infection status did not impact the time of transfer or rates of operation, although COVID-infected patients experienced a longer time to surgery after admission (14 vs. 2.9 days, P0.001).The COVID-19 pandemic did not reduce the number of monthly transfers, operation rates, or catchment area for transfer patients. Transfer rates of uninsured patients increased during the COVID Era, potentially reflecting changes in access to community neurosurgery care. Shorter time to surgery seen in COVID-Era patients possibly reflects institutional policies that improved operating room efficiency to compensate for surgical backlogs. COVID status affeted time to surgery, reflecting the preoperative care that these patients require before intervention.

Introduction. The authors present the findings of the physical modeling of the wave impact on the hydraulic structures of the construction facility known as “An offshore coal terminal at Syradasay coal deposit”. The authors have analyzed the experimental studies to provide recommendations on the most effective structural design of the connecting dam. Materials and methods. The method of physical modeling was employed to conduct the experimental studies Most of construction sciences are based on experimental research and, if the scientific support of structures, including those dealing with hydraulic engineering, is available, physical modeling is the top-priority research method in the international engineering practice. The experiments were conducted in a wave flume, which is a research and experimental facility at the Centre for Hydraulic Engineering Research and Education, NRU MGSU. The most advanced measurement equipment, produced by Wallingford (UK), was employed. The research methodology, used to verify the effectiveness of hydraulic structures, was tested on a large number of design structures that had been examined, built and are being successfully operated. Results. Given the data of experimental studies, the most effective design of a connecting dam was recommended as part of the design of an offshore coal terminal. Conclusions. The findings of this research will ensure the construction of an offshore coal terminal, which is built in difficult natural conditions typical for harsh Arctic latitudes, in the area characterized by intensive coal mining (Syradasay coal deposit), which is most relevant for the task of developing cargo port facilities along the Northern Sea Route.

Detecting biodiversity change and identifying its causes is challenging because biodiversity is multifaceted and temporal data often contain bias. Here, we model temporal change in species' abundance and biomass by using extensive data describing the population sizes and trends of native breeding birds in the United Kingdom (UK) and the European Union (EU). In addition, we explore how species’ population trends vary with species' traits. We demonstrate significant change in the bird assemblages of the UK and EU, with substantial reductions in overall bird abundance and losses concentrated in a relatively small number of abundant and smaller sized species. By contrast, rarer and larger birds had generally fared better. Simultaneously, overall avian biomass had increased very slightly in the UK and was stable in the EU, indicating a change in community structure. Abundance trends across species were positively correlated with species’ body mass and with trends in climate suitability, and varied with species' abundance, migration strategy and niche associations linked to diet. Our work highlights how changes in biodiversity cannot be captured easily by a single number; care is required when measuring and interpreting biodiversity change given that different metrics can provide very different insights. This article is part of the theme issue ‘Detecting and attributing the causes of biodiversity change: needs, gaps and solutions’.

Understanding the frequency, spatiotemporal dynamics and impacts of parasite coinfections is fundamental to developing control measures and predicting disease impacts. The European turtle dove (Streptopelia turtur) is one of Europe’s most threatened bird species. High prevalence of infection by the protozoan parasite Trichomonas gallinae has previously been identified, but the role of this and other coinfecting parasites in turtle dove declines remains unclear. Using a high-throughput sequencing approach, we identified seven strains of T. gallinae, including two novel strains, from ITS1/5.8S/ITS2 ribosomal sequences in turtle doves on breeding and wintering grounds, with further intra-strain variation and four novel sub-types revealed by the iron-hydrogenase gene. High spatiotemporal turnover was observed in T. gallinae strain composition, and infection was prevalent in all populations (89–100%). Coinfection by multiple Trichomonas strains was rarer than expected (1% observed compared to 38.6% expected), suggesting either within-host competition, or high mortality of coinfected individuals. In contrast, coinfection by multiple haemosporidians was common (43%), as was coinfection by haemosporidians and T. gallinae (90%), with positive associations between strains of T. gallinae and Leucocytozoon suggesting a mechanism such as parasite-induced immune modulation. We found no evidence for negative associations between coinfections and host body condition. We suggest that longitudinal studies involving the recapture and investigation of infection status of individuals over their lifespan are crucial to understand the epidemiology of coinfections in natural populations.

Logistical constraints concerning parasite sample storage can hinder progress with the discovery of genetic variation on a global scale. New storage methods are being developed to address this, but require testing in order to understand how widely applicable these methods are. Whatman FTA cards have been tested previously under laboratory conditions for storing low-concentration Trichomonas gallinae isolates with the conclusion that they are not suitable, but have not been tested under field conditions. Here, we conducted a field-test, comparing FTA cards with storage in ethanol for T. gallinae samples collected and cultured from wild Columbiformes in Africa using standard field methods, before transportation to the UK. After 6 months storage, both methods resulted in an overall prevalence of 100% following PCR amplification (n = 59), suggesting that FTA cards are suitable for estimation of T. gallinae prevalence. However, samples stored in ethanol produced more, and longer, sequences than those stored on FTA cards. These data suggest storage in ethanol is preferable for the acquisition of high quality genetic strain data, but that FTA cards can be used successfully to ascertain infection prevalence and identify parasite strains under field conditions.

Although overall survival (OS) has improved in patients with brain metastases (BMs), control of recurrent BMs remains a therapeutic challenge. Salvage surgery may achieve acceptable control rates in the setting of progression after previous stereotactic radiosurgery (SRS), yet it remains a question how additional adjuvant therapies may affect outcomes and how patient selection for salvage surgery may be optimized.Patients receiving salvage surgery for BM progression after previous SRS were retrospectively reviewed from a single center. Outcomes of interest included local tumor progression, leptomeningeal dissemination, and OS. Cox proportional hazard models and nominal logistic regression were applied to determine factors associated with outcomes of interest.A total of 43 patients with 50 BMs were included. After salvage surgery, local progression was observed for 17 BMs (34%), leptomeningeal dissemination was observed in 17 patients (39.5%), and censored median OS was 17.9 months. On multivariate analysis, use of brachytherapy was associated with improved local control (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04-0.6; P = 0.008). For patients treated with SRS ≥4.5 months before salvage surgery, both brachytherapy (HR, 0.07; 95% CI, 0.01-0.39; P = 0.002) and postoperative adjuvant SRS (HR, 0.14; 95% CI, 0.02-1.00; P = 0.05) were associated with improved local control compared with no adjuvant radiation therapy. Presence of extracranial malignancy (HR, 6.70; 95% CI, 2.58-17.42; P0.0001) was associated with shorter survival. Graded prognostic assessment underestimated survival in 79.1% of patients, with a mean difference of 18.9 months between graded prognostic assessment-estimated and actual OS.In properly selected patients, salvage surgery may be an appropriate therapy for BM progression after previous SRS. Adjuvant brachytherapy and repeat SRS can offer significant benefit for local control with salvage resection.

Funder: Royal Society for the Protection of Birds, Agri‐environment schemes (AES) are the primary policy mechanism for addressing farmland biodiversity declines across Europe. Despite previous studies on the impacts of AES on biodiversity, there is little empirical evidence on the scale of provision required to reverse declines. Across three regions of lowland England with contrasting farm systems (arable, pastoral, mixed), we estimated avian population growth rates (PGRs) on farmland with high AES provision (‘higher‐tier’: average bird‐friendly option cover = 7.4%), low AES provision (‘lower‐tier’: 2.3%) and no bird‐friendly AES (‘no AES’). Ten‐year PGRs were derived for 24 species and three multi‐species groups comprising farmland‐associated species (‘farmland birds’), species of conservation concern (‘priority birds’) and species restricted to farmland (‘specialist birds’). We used PGRs to simulate the proportion of the regional farmland landscape that would have to be assigned to higher‐ and lower‐tier agreements to stabilise or increase populations. In the arable and pastoral regions, 13/23 and 13/22 species, respectively, had more positive PGRs under higher‐tier AES than on no AES farmland (none had more negative PGRs), compared to 4/22 (positive) and 1/22 (negative) in the mixed region. Only two to four species per region exhibited more positive PGRs under lower‐tier AES compared to no AES farmland. Multi‐species PGRs in the arable and pastoral regions increased from no AES (strong decline), to lower‐tier (decline or stability) to higher‐tier (moderate or strong increase). There was no overall AES effect in the mixed region. To increase regional farmland bird populations by 10% over 10 years, 47% and 26% of the farmed landscape would need to be devoted to higher‐tier agreements in arable and pastoral landscapes respectively. This falls to 34% and 17% when higher‐tier is targeted at localities supporting higher abundances of target species, and to 29% and 10% when 30% of the farmed landscape is also devoted to lower‐tier. Priority and specialist birds require higher provision levels. Policy implications. Where farmland bird recovery is an AES objective, farms should prioritise higher‐tier agreement delivery over lower‐tier. Farmland bird responses to AES provision are likely to vary regionally, but careful targeting will reduce the amount needed in the landscape.

1. Supporting online figures and tables (figures S1-S4 & tables S1-S7) & Supporting online text (text S1)

BackgroundWhile genetic alterations in brain metastases (BMs) have been previously explored, there are limited data examining their association with recurrence after surgical resection. This study aimed to identify genetic alterations within BMs associated with CNS recurrence after surgery across multiple cancer types.MethodsA retrospective, single-center study was conducted with patients who underwent resection of a BM with available clinical and gene sequencing data available. Local and remote CNS recurrence were the primary study outcomes. Next-generation sequencing of the coding regions in over 500 oncogenes was performed in brain metastasis specimens. Cox proportional hazards analyses were performed to identify clinical features and genomic alterations associated with CNS recurrence.ResultsA total of 90 patients undergoing resection of 91 BMs composed the cohort. Genes most frequently mutated in the cohort included TP53 (64%), CDKN2A (37%), TERT (29%), CDKN2B (23%), NF1 (14%), KRAS (14%), and PTEN (13%), all of which occurred across multiple cancer types. CDKN2A/B co-deletion was seen in 21 (23.1%) brain metastases across multiple cancer types. In multivariate Cox proportional hazard analyses including patient, tumor, and treatment factors, CDKN2A/B co-deletion in the brain metastasis was associated with increased risk of local (HR 4.07, 95% CI 1.32-12.54, P = 0.014) and remote (HR 2.28, 95% CI 1.11-4.69, P = 0.025) CNS progression. Median survival and length of follow-up were not different based on CDKN2A/B mutation status.ConclusionsCDKN2A/B co-deletion detected in BMs is associated with increased CNS recurrence after surgical resection. Additional work is needed to determine whether more aggressive treatment in patients with this mutation may improve outcomes.

This paper considers mutual interference mitigation among automotive radars using frequency-modulated continuous wave (FMCW) signal and multiple-input multiple-output (MIMO) virtual arrays. For the first time, we derive a general interference signal model that fully accounts for not only the time-frequency incoherence, e.g., different FMCW configuration parameters and time offsets, but also the slow-time code MIMO incoherence and array configuration differences between the victim and interfering radars. Along with a standard MIMO-FMCW object signal model, we turn the interference mitigation into a spatial-domain object detection under incoherent MIMO-FMCW interference described by the explicit interference signal model, and propose a constant false alarm rate (CFAR) detector. More specifically, the proposed detector exploits the structural property of the derived interference model at both \emph{transmit} and \emph{receive} steering vector space. We also derive analytical closed-form expressions for probabilities of detection and false alarm. Performance evaluation using both synthetic-level and phased array system-level simulation confirms the effectiveness of our proposed detector over selected baseline methods., Comment: 15 pages, 10 figures

SummaryCell state evolution underlies tumor development and response to therapy1, but mechanisms specifying cancer cell states and intratumor heterogeneity are incompletely understood. Schwannomas are the most common tumors of the peripheral nervous system and are treated with surgery and ionizing radiation2–5. Schwannomas can oscillate in size for many years after radiotherapy6,7, suggesting treatment may reprogram schwannoma cells or the tumor microenvironment. Here we show epigenetic reprogramming shapes the cellular landscape of schwannomas. We find schwannomas are comprised of 2 molecular groups distinguished by reactivation of neural crest development pathways or misactivation of nerve injury mechanisms that specify cancer cell states and the architecture of the tumor immune microenvironment. Schwannoma molecular groups can arise independently, but ionizing radiation is sufficient for epigenetic reprogramming of neural crest to immune-enriched schwannoma by remodeling chromatin accessibility, gene expression, and metabolism to drive schwannoma cell state evolution and immune cell infiltration. To define functional genomic mechanisms underlying epigenetic reprograming of schwannomas, we develop a technique for simultaneous interrogation of chromatin accessibility and gene expression coupled with genetic and therapeutic perturbations in single-nuclei. Our results elucidate a framework for understanding epigenetic drivers of cancer evolution and establish a paradigm of epigenetic reprograming of cancer in response to radiotherapy.

Background/objectiveTo compare functional hearing and tinnitus outcomes in treated large (~ 3 cm) vestibular schwannoma (VS) and posterior fossa meningioma cohorts, and construct willingness-to-accept profiles for an experimental brain implant to treat unilateral hearing loss.MethodsA two-way MANOVA model with two independent variables (tumor type; time from treatment) and three dependent variables (hearing effort of tumor ear; abbreviated Speech, Spatial, and Qualities of Hearing scale (SSQ12); Tinnitus Functional Index (TFI)) was used to analyze data from VS (N=32) and meningioma (N=50) patients who were treated at a tertiary care center between 2010 and 2020. A query to probe acceptance of experimental treatment for hearing loss relative to expected benefit was used to construct willingness-to-accept profiles.ResultsTumor type was statistically significant on the combined dependent variables analysis (F[3, 76]=19.172, p 2 years) (p ≤ .017). At the 60% speech understanding level, 77% of respondents would accept an experimental brain implant.ConclusionHearing outcome is better for posterior fossa meningioma compared to VS. Most patients with hearing loss in the tumor ear would consider a brain implant if the benefit level would be comparable to a cochlear implant.Level of evidence2.

Acetyl-CoA carboxylase (ACC) regulates lipid synthesis; however, its role in inflammatory regulation in macrophages remains unclear. We generated mice that are deficient in both ACC isoforms in myeloid cells. ACC deficiency altered the lipidomic, transcriptomic, and bioenergetic profile of bone marrow–derived macrophages, resulting in a blunted response to proinflammatory stimulation. In response to lipopolysaccharide (LPS), ACC is required for the early metabolic switch to glycolysis and remodeling of the macrophage lipidome. ACC deficiency also resulted in impaired macrophage innate immune functions, including bacterial clearance. Myeloid-specific deletion or pharmacological inhibition of ACC in mice attenuated LPS-induced expression of proinflammatory cytokines interleukin-6 (IL-6) and IL-1β, while pharmacological inhibition of ACC increased susceptibility to bacterial peritonitis in wild-type mice. Together, we identify a critical role for ACC in metabolic regulation of the innate immune response in macrophages, and thus a clinically relevant, unexpected consequence of pharmacological ACC inhibition.

OBJECTIVEConvexity meningiomas are commonly managed with resection. Motor outcomes and predictors of new deficits after surgery are poorly studied. The objective of this study was to determine whether postoperative diffusion-weighted imaging (DWI) was associated with neurological deficits after convexity meningioma resection and to identify the risk factors for postoperative DWI restriction.METHODSA retrospective review of patients who had undergone convexity meningioma resection from 2014 to 2018 was performed. Univariate and multivariate logistic regressions were performed to identify variables associated with postoperative neurological deficits and a DWI signal. The amount of postoperative DWI signal was measured and was correlated with low apparent diffusion coefficient maps to confirm ischemic injury.RESULTSThe authors identified 122 patients who had undergone a total of 125 operations for convexity meningiomas. The median age at surgery was 57 years, and 70% of the patients were female. The median follow-up was 26 months. The WHO grade was I in 62% of cases, II in 36%, and III in 2%. The most common preoperative deficits were seizures (24%), extremity weakness/paralysis (16%), cognitive/language/memory impairment (16%), and focal neurological deficit (16%). Following resection, 89% of cases had no residual deficit. Postoperative DWI showed punctate or no diffusion restriction in 78% of cases and restriction > 1 cm in 22% of cases. An immediate postoperative neurological deficit was present in 14 patients (11%), but only 8 patients (7%) had a deficit at 3 months postoperatively. Univariate analysis identified DWI signal > 1 cm (p < 0.0001), tumor diameter (p < 0.0001), preoperative motor deficit (p = 0.0043), older age (p = 0.0113), and preoperative embolization (p = 0.0171) as risk factors for an immediate postoperative deficit, whereas DWI signal > 1 cm (p < 0.0001), tumor size (p < 0.0001), and older age (p = 0.0181) were risk factors for deficits lasting more than 3 months postoperatively. Multivariate analysis revealed a DWI signal > 1 cm to be the only significant risk factor for deficits at 3 months postoperatively (OR 32.42, 95% CI 3.3–320.1, p = 0.0002). Further, estimated blood loss (OR 1.4 per 100 ml increase, 95% CI 1.1–1.7, p < 0.0001), older age (OR 1.1 per year older, 95% CI 1.0–1.1, p = 0.0009), middle third location in the sagittal plane (OR 16.9, 95% CI 1.3–216.9, p = 0.0026), and preoperative peritumoral edema (OR 4.6, 95% CI 1.2–17.7, p = 0.0249) were significantly associated with a postoperative DWI signal > 1 cm.CONCLUSIONSA DWI signal > 1 cm is significantly associated with postoperative neurological deficits, both immediate and long-lasting. Greater estimated blood loss, older age, tumor location over the motor strip, and preoperative peritumoral edema increase the risk of having a postoperative DWI signal > 1 cm, reflective of perilesional ischemia. Most immediate postoperative deficits will improve over time. These data are valuable when preoperatively communicating with patients about the risks of surgery and when postoperatively discussing prognosis after a deficit occurs.

Introduction The management of recurrent craniopharyngioma is complex with limited data to guide decision-making. Some reports suggest reoperation should be avoided due to an increased complication profile, while others have demonstrated that safe reoperation can be performed. For other types of skull base lesions, maximal safe resection followed by adjuvant therapy has replaced radical gross total resection due to the favorable morbidity profiles. Methods Seventy-one patients underwent resection over a 9-year period for craniopharyngioma and were retrospectively reviewed. Patients were separated into primary resection and reoperation cohorts and stratified by surgical approach (endonasal vs. cranial) and survival analyses were performed based on cohort and surgical approach. Results Fifty patients underwent primary resection, while 21 underwent reoperation for recurrence. Fifty endonasal transsphenoidal surgeries and 21 craniotomies were performed. Surgical approaches were similarly distributed across cohorts. Subtotal resection was achieved in 83% of all cases. There were no differences in extent of resection, visual outcomes, subsequent neuroendocrine function, and complications across cohorts and surgical approaches. The median time to recurrence was 87 months overall, and there were no differences by cohort and approach. The 5-year survival rate was 81.1% after reoperation versus 93.2% after primary resection. Conclusion Compared with primary resection, reoperation for craniopharyngioma recurrence is associated with similar functional and survival outcomes in light of individualized surgical approaches. Maximal safe resection followed by adjuvant radiotherapy for residual tumor likely preserves vision and endocrine function without sacrificing overall patient survival.

Motile cilia beat with an asymmetric waveform consisting of a power stroke that generates a propulsive force and a recovery stroke that returns the cilium back to the start. Cilia are anchored to the cell cortex by basal bodies (BBs) that are directly coupled to the ciliary doublet microtubules (MTs). We find that, consistent with ciliary forces imposing on BBs, bending patterns in BB triplet MTs are responsive to ciliary beating. BB bending varies as environmental conditions change the ciliary waveform. Bending occurs where striated fibers (SFs) attach to BBs and mutants with short SFs that fail to connect to adjacent BBs exhibit abnormal BB bending, supporting a model in which SFs couple ciliary forces between BBs. Finally, loss of the BB stability protein Poc1, which helps interconnect BB triplet MTs, prevents the normal distributed BB and ciliary bending patterns. Collectively, BBs experience ciliary forces and manage mechanical coupling of these forces to their surrounding cellular architecture for normal ciliary beating.

Brain metastases occur frequently in advanced melanoma and traditionally require surgery and radiation therapy. New evidence demonstrates that systemic therapies are effective for controlling metastatic melanoma brain metastases. This study evaluated outcomes after resection of melanoma brain metastases treated with systemic therapy, with or without focal radiotherapy.All patients received immunotherapy or BRAF/MEK inhibitors preoperatively or in the immediate 3 months postoperatively. Resection cavity failure, distant central nervous system progression, and adverse radiation effects were reported in the presence and absence of focal radiotherapy using the Kaplan-Meier method.Between 2011 and 2020, 37 resection cavities in 29 patients met criteria for analysis. Of lesions, 22 (59%) were treated with focal radiotherapy, and 15 (41%) were treated with targeted therapy or immunotherapy alone. The 12- and 24-month freedom from local recurrence was 64.8% (95% confidence interval [CI] 42.1%-99.8%) and 46.3% (95% CI 24.5%-87.5%), respectively, for systemic therapy alone and 93.3% (95% CI 81.5%-100%) at both time points for focal radiotherapy (P = 0.01). On univariate analysis, focal radiotherapy was the only significant factor associated with reduction of local recurrence risk (hazard ratio 0.10, 95% CI 0.01-0.85; P = 0.04). There were no significant differences in central nervous system progression-free survival or overall survival between patients who received systemic therapy plus focal radiotherapy compared with systemic therapy alone. BRAF mutation status was reviewed for either the brain metastasis (n = 9 patients, 31%) or the primary site (n = 20 patients, 69%), and patients harboring BRAFFocal radiotherapy with systemic therapy for resected melanoma brain metastases significantly decreased resection cavity recurrence compared with systemic therapy alone. BRAF mutation status correlated with poorer outcomes.

ObjectiveInterfacility transfers represent a large proportion of neurosurgical admissions to tertiary care centers each year. In this study, the authors examined the impact of the COVID-19 pandemic on the number of transfers, timing of transfers, demographic profile of transfer patients, and clinical outcomes including rates of surgical intervention.MethodsA retrospective review of neurosurgical transfer patients at a single tertiary center was performed. Patients transferred from April to November 2020 (the "COVID Era") were compared with an institutional database of transfer patients collected before the COVID-19 pandemic (the "Pre-COVID Era"). During the COVID Era, both emergent and nonemergent neurosurgical services had resumed. A comparison of demographic and clinical factors between the 2 cohorts was performed.ResultsA total of 674 patients were included in the study (331 Pre-COVID and 343 COVID-Era patients). Overall, there was no change in the average monthly number of transfers (P= 0.66) or in the catchment area of referral hospitals. However, COVID-Era patients were more likely to be uninsured (1% vs. 4%), had longer transfer times (COVID vs. Pre-COVID Era: 18 vs. 9 hours; P < 0.001), required higher rates of surgical intervention (63% vs. 50%, P= 0.001), had higher rates of spine pathology (17% vs. 10%), and less frequently were admitted to the intensive care unit (34% vs. 52%, P < 0.001). Overall, COVID-Era patients did not experience delays to surgical intervention (3.1 days vs. 3.6 days, P= 0.2). When analyzing the subgroup of COVID-Era patients, COVID infection status did not impact the time of transfer or rates of operation, although COVID-infected patients experienced a longer time to surgery after admission (14 vs. 2.9 days, P < 0.001).ConclusionThe COVID-19 pandemic did not reduce the number of monthly transfers, operation rates, or catchment area for transfer patients. Transfer rates of uninsured patients increased during the COVID Era, potentially reflecting changes in access to community neurosurgery care. Shorter time to surgery seen in COVID-Era patients possibly reflects institutional policies that improved operating room efficiency to compensate for surgical backlogs. COVID status affeted time to surgery, reflecting the preoperative care that these patients require before intervention.

Computational head models are promising tools for understanding and predicting traumatic brain injuries. Most available head models are developed using inputs (i.e. head geometry, material properties and boundary conditions) from experiments on cadavers or animals and employ hereditary integral-based constitutive models that assume linear viscoelasticity in part of the rate-sensitive material response. This leads to high uncertainty and poor accuracy in capturing the nonlinear brain tissue response. To resolve these issues, a framework for the development of subject-specific three-dimensional head models is proposed, in which all inputs are derived in vivo from the same living human subject: head geometry via magnetic resonance imaging (MRI), brain tissue properties via magnetic resonance elastography (MRE), and full-field strain-response of the brain under rapid head rotation via tagged MRI. A nonlinear, viscous dissipation-based visco-hyperelastic constitutive model is employed to capture brain tissue response. Head models are validated using quantitative metrics that compare spatial strain distribution, temporal strain evolution, and the magnitude of strain maxima, with the corresponding experimental observations from tagged MRI. Results show that our head models accurately capture the strain-response of the brain. Further, employment of the nonlinear visco-hyperelastic constitutive framework provides improvements in the prediction of peak strains and temporal strain evolution over hereditary integral-based models.

Risk factors for a postoperative cerebrospinal fluid leak (CSF) after surgery include an intraoperative high flow of CSF, elevated body mass index, defect size, and defect site. In our prior series, a high postoperative CSF leak rate for tumors of the central skull base (planum, sella, and clivus) appeared to be due to graft migration. We changed our closure technique from a single layer of collagen +/- fat graft to a novel graft, termed a "Bow tie" (a tri-layer fat graft with two pieces of collagen matrix), and report our results in this study.Retrospective temporal epoch study of a single otolaryngologist's experience of closing skull base defects in our skull base center from 2005 to 2017.One hundred and forty-nine patients met inclusion criteria in two time periods, pre- and post-introduction of the Bow tie technique. In epoch I, from 2005 to 2013, 79 patients had reconstruction with a single layer of dural graft (25 had additional free fat graft). In epoch II, from 2014 to 2017, 70 patients had reconstruction with the Bow tie.CSF leak rates were 8.7% overall: 15.2% in epoch I and 1.4% in epoch II (p = 0.01). After controlling the procedure, defects with a size greater than 2 cm had a 5.7 greater likelihood of failure. Epoch II had a lower incidence of major complications.Using a single surgeon's experience, the multilayer Bow tie has a significant reduction in postoperative CSF leak and associated major complications for defects of the central skull base.III Laryngoscope, 2022.

Disease activity in rheumatoid arthritis (RA) is influenced by activation of circulating and synovial immune cells. Regulatory T cells (Tregs) and monocytes are key cells that drive inflammation in RA. This study investigated if a relationship exists between disease activity in RA and circulating Treg and monocyte numbers and phenotypes. A potential sialic acid (Sia) mediated link between Tregs and monocytes was also probed in vitro. Peripheral blood mononuclear cells (PBMCs) were isolated from RA patient (n = 62) and healthy control (n = 21) blood using density gradient separation. Flow cytometry was used to count and phenotype Treg and monocyte subsets, and to sort healthy control Tregs for Sia cell culture experiments. The effects of Sia on activated Treg FoxP3 and NFκB expression was assessed by flow cytometry and concentrations of secreted TNFα, IL-10 and IFNγ determined by ELISA. High disease activity RA patients who were unresponsive to disease modifying anti-rheumatic drugs (n = 31), have significantly lower relative numbers (percentages) of CD4+CD25+CD127- Tregs (p < 0.01) and memory CD45RA-FoxP3+ Tregs (p < 0.01), compared to low disease activity responders (n = 24). Relative numbers of non-classical CD169+ monocytes are associated with disease activity in RA (p = 0.012). Sia reduced Treg expression of FoxP3, NFκB and cytokines in vitro. A strong association has been identified between non-classical CD169+ monocytes and post-treatment disease activity in RA. This study also indicates that Sia can reduce Treg activation and cytokine release. We postulate that such a reduction could be mediated by interaction with sialyted proteins captured by CD169+ monocytes.

Primary cilia are specialized cell-surface organelles that mediate sensory perception and, in contrast to motile cilia and flagella, are thought to lack motility function. Here, we show that primary cilia in human and mouse pancreatic islets exhibit movement that is required for glucose-dependent insulin secretion. Islet primary cilia contain motor proteins conserved from those found in classic motile cilia, and their three-dimensional motion is dynein-driven and dependent on adenosine 5′-triphosphate and glucose metabolism. Inhibition of cilia motion blocks beta cell calcium influx and insulin secretion. Human beta cells have enriched ciliary gene expression, and motile cilia genes are altered in type 2 diabetes. Our findings redefine primary cilia as dynamic structures having both sensory and motile function and establish that pancreatic islet cilia movement plays a regulatory role in insulin secretion.

In this paper, we present the results of a systematic statistical analysis of the fungal glycome in comparison with the prokaryotic and protistal glycomes as described in the scientific literature and presented in the Carbohydrate Structure Database (CSDB). The monomeric and dimeric compositions of glycans, their non-carbohydrate modifications, glycosidic linkages, sizes of structures, branching degree and net charge are assessed. The obtained information can help elucidating carbohydrate molecular markers for various fungal classes which, in its turn, can be demanded for the development of diagnostic tools and carbohydrate-based vaccines against pathogenic fungi. It can also be useful for revealing specific glycosyltransferases active in a particular fungal species.

Aims To evaluate the effect of an intimate partner violence intervention education component on nurses' attitudes in addressing intimate partner violence; complementary aims included understanding nurses' perceptions of the education and how it influenced their attitudes and confidence to address intimate partner violence in practice. Design An explanatory sequential mixed methods design embedded within a 15-site cluster randomized clinical trial that evaluated an intimate partner violence intervention within the Nurse-Family Partnership programme. Methods Data were collected between February 2011 and September 2016. Quantitative assessment of nurses' attitudes about addressing intimate partner violence was completed by nurses in the intervention (n = 77) and control groups (n = 101) at baseline, 12 months and at study closure using the Public Health Nurses' Responses to Women Who Are Abused Scale. Qualitative data were collected from nurses in the intervention group at two timepoints (n = 14 focus groups) and focused on their perceptions of the education component. Data were analysed using content analysis. Results Nurses in the intervention group reported large improvements in their thoughts, feelings and perceived behaviours related to addressing intimate partner violence; a strong effect of the education was found from baseline to 12 months and baseline to study closure timepoints. Nurses reported that the education component was acceptable and increased their confidence to address intimate partner violence. Conclusion Nurses reported improved attitudes about and confidence in addressing intimate partner violence after receiving the education component. However, these findings need to be considered together with trial results showing no main effects for clients, and a low level of intervention fidelity. Impact These evaluation findings underscore that improvement in nurses' self-reported educational outcomes about addressing intimate partner violence cannot be assumed to result in adherence to intervention implementation or improvement in client outcomes. These are important considerations for developing nurse education on intimate partner violence.

Computational models of the brain and its biomechanical response to skull accelerations are important tools for understanding and predicting traumatic brain injuries (TBIs). However, most models have been developed using experimental data collected on animal models and cadaveric specimens, both of which differ from the living human brain. Here we describe efforts to noninvasively measure the biomechanical response of the human brain with MRI—at non-injurious strain levels—and generate data that can be used to develop, calibrate, and evaluate computational brain biomechanics models. Specifically, this paper reports on a project supported by the National Institute of Neurological Disorders and Stroke to comprehensively image brain anatomy and geometry, mechanical properties, and brain deformations that arise from impulsive and harmonic skull loadings. The outcome of this work will be a publicly available dataset ( http://www.nitrc.org/projects/bbir ) that includes measurements on both males and females across an age range from adolescence to older adulthood. This article describes the rationale and approach for this study, the data available, and how these data may be used to develop new computational models and augment existing approaches; it will serve as a reference to researchers interested in using these data.

Objective Meningioma incidence increases with age, yet limited data exist on how comorbidities impact complication rates in elderly patients undergoing meningioma resection. The objective of this study was to report surgical outcomes and identify risk factors for perioperative complications. Methods We performed a retrospective study of patients 75 years and older undergoing meningioma resection. Outcomes included survival and complications. Major complications were those requiring surgical intervention or causing permanent neurological deficit. Recursive partitioning, Kaplan-Meier survival, univariate and multi-variate (MVA) analyses were performed. Results From 1996 to 2014, 103 patients with a median age of 79 years (IQR 77–83 years) underwent cranial meningioma resection. Median follow-up was 5.8 years (IQR 1.7–8.7 years). Median actuarial survival was 10.5 years. Complications occurred in 32 patients (31.1%), and 13 patients (12.6%) had multiple complications. Major complications occurred in 16 patients (15.5%). Increasing age was not a significant predictor of any (p = 0.6408) or major complication (p = 0.8081). On univariate analysis, male sex, Charlson Comorbidity Index greater than 8, and cardiovascular comorbidities were significantly associated with major complications. On MVA only cardiovascular comorbidities (OR 3.94, 95% CI 1.05–14.76, p = 0.0238) were significantly associated with any complication. All patients with major complications had cardiovascular comorbidities, and on MVA male gender (OR 3.78, 95%CI 1.20–11.93, p = 0.0212) was associated with major complications. Conclusions Cardiovascular comorbidities and male gender are significant risk factors for complications after meningioma resection in patients aged 75 years and older. While there is morbidity associated with meningioma resection in this cohort, there is also excellent long-term survival.

Background Prior single-site evaluations of Child Adult Relationship Enhancement in Primary Care (PriCARE), a 6-session group parent training, demonstrated reductions in child behavioral problems and improvements in positive parenting attitudes. Objective To measure the impact of PriCARE on disruptive child behaviors, parenting stress, and parenting attitudes in a multisite study. Methods Caregivers of children 2- to 6-year-old with behavior concerns recruited from 4 pediatric primary care practices were randomized 2:1 to PriCARE intervention (n = 119) or waitlist control (n = 55). Seventy-nine percent of caregivers identified as Black and 59% had annual household incomes under $22,000. Child behavior, parenting stress, and parenting attitudes were measured at baseline and 2 to 3 months after intervention using the Eyberg Child Behavior Inventory, Parenting Stress Index, and Adult-Adolescent Parenting Inventory-2. Marginal standardization implemented in a linear regression compared mean change scores from baseline to follow-up by treatment arm while accounting for clustering by site. Results Mean change scores from baseline to follow-up demonstrated greater improvements (decreases) in Eyberg Child Behavior Inventory problem scores but not intensity scores in the PriCARE arm compared to control, (problem: −4.4 [−7.5, −1.2] vs −1.8 [−4.1, 0.4], P= .004; intensity: −17.6 [−28.3, −6.9] vs −10.4 [−18.1, −2.6], P= .255). Decreases in parenting stress were greater in the PriCARE arm compared to control (−3.3 [−4.3, −2.3] vs 0 [−2.5, 2.5], P= .025). Parenting attitudes showed no significant changes (all P> .10). Conclusions PriCARE showed promise in improving parental perceptions of the severity of child behaviors and decreasing parenting stress but did not have an observed impact on parenting attitudes.

Vestibular schwannomas are WHO grade I tumors of the eighth cranial nerve that lead to hearing loss, tinnitus, vestibular dysfunction, and facial nerve compromise. The management of vestibular schwannomas consists of observation, radiosurgery, or microsurgical resection. In this review, we discuss the various treatment modalities specifically targeting large vestibular schwannomas in addition to their treatment risk profiles. Although there has been a trend towards treatment with radiosurgery for smaller lesions, consensus reports still advocate for surgical debulking in patients with large vestibular schwannomas. There has been a shift in management philosophy towards functional preservation at the cost of more extensive resection, yet subtotal resection of vestibular schwannomas is associated with higher rates of recurrence on follow-up. Some groups have demonstrated new promise for the management of large vestibular schwannomas with stereotactic radiosurgery alone and multimodality therapy involving subtotal surgical resection with planned postoperative radiosurgery to residual tumor. Although most groups would still advocate for microsurgical debulking of large vestibular schwannomas with evidence of brainstem compression, hybrid treatment strategies have become preferable. More work is required to determine which patients are at risk of progression after a subtotal resection to stratify those who should or should not receive postoperative stereotactic radiosurgery.

OBJECTIVEHyperostosing sphenoid wing meningiomas cause bony hyperostosis that may extend into the orbit, resulting in proptosis, restriction of extraocular movements, and/or compressive optic neuropathy. The extent of bony removal necessary and the optimal reconstruction strategy to prevent enophthalmos is debated. Herein, the authors present their surgical outcomes and reconstruction results.METHODSThis is a retrospective review of 54 consecutive patients undergoing resection of sphenoid wing meningiomas associated with bony hyperostosis. The majority of cases were operated on by the senior author. Extent of tumor resection, volumetric bone resection, radiographic exophthalmos index, complications, and recurrence were analyzed.RESULTSThe median age of the cohort was 52.1 years, with women comprising 83% of patients. Proptosis was a presenting symptom in 74%, and 52% had decreased visual acuity. The WHO grade was I (85%) or II (15%). The median follow-up was 2.6 years. On volumetric analysis, a median 86% of hyperostotic bone was resected. Gross-total resection of the intracranial tumor was achieved in 43% and the orbital tumor in 27%, and of all intracranial and orbital components in 20%. Orbital reconstruction was performed in 96% of patients. Postoperative vision was stable or improved in 98% of patients and diplopia improved in 89%. Postoperative complications occurred in 44% of patients, and 26% of patients underwent additional surgery for complication management. The most frequent complications were medical complications and extraocular movement deficits. The median preoperative exophthalmos index was 1.26, which improved to 1.12 immediately postoperatively and to 1.09 at the 6-month follow-up (p < 0.001). Postoperatively, 18 patients (33%) underwent adjuvant radiotherapy after subtotal resection. Tumors recurred/progressed in 12 patients (22%).CONCLUSIONSResection of hyperostosing sphenoid wing meningiomas, particularly achieving gross-total resection of hyperostotic bone with a good aesthetic result, is challenging and associated with notable medical and ocular morbidity. Recurrence rates in this series are higher than previously reported. Nevertheless, the authors were able to attain improvement in proptosis and visual symptoms in the majority of patients by using a multidisciplinary approach.