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Craniopharyngiomas involving the ventricular system are rare but pose significant surgical challenges. We systematically reviewed the literature on craniopharyngiomas invading the ventricles (CP-V).PubMed, EMBASE, Scopus, Web of Science, and Cochrane were searched to include studies reporting clinical data of patients with CP-Vs. Clinico-radiological features, management, and treatment outcomes were analyzed.We included 73 studies encompassing 407 patients. Patients were mostly male (61.5%), presenting with headache (57.9%) and/or endocrine disorders (52.1%). CP-Vs mostly involved the third ventricle (96.3%), followed by the lateral ventricles (2.9%), and the fourth ventricle (1%). Tumors had cystic components in 59% of cases and were mostly adamantinomatous (70.8%). Open resection was performed in 232 cases (57%), mostly with trans-lamina terminalis (36.6%) and trans-callosal (31.9%) approaches. Endoscopic resection was performed in 169 cases (41.5%), mostly with trans-sphenoidal (74.6%) and transventricular (24.9%) approaches. Gross-total tumor resection was obtained in most cases (62.9%). Adjuvant radiotherapy was delivered in 22.8% cases. A total of 178 patients experienced persistent complications, mostly including diabetes insipidus (47.1%) and panhypopituitarism (12.7%), not significantly different after open versus endoscopic resection (p=0.117). Symptom improvement was obtained in 88% of cases. CP-Vs recurrences were reported in 94 patients (23.1%), with median progression-free survival of 13.5 months (range=0.5-252.0 months). Fifty-nine patients died (14.5%), with median overall survival of 32.0 months (range=0.5-252.0 months), significantly longer after endoscopic resection than open resection (p=0.019).CP-Vs are uncommon and challenging entities. Surgical resection is feasible, but patient-tailored selection of open/endoscopic approaches is necessary to achieve optimal outcomes and minimize complication risks.

To review the current literature on pineal region gliomas, summarizing the clinical characteristics and treatment outcomes.PubMed, Scopus, and Cochrane databases were used to identify relevant articles. Comprehensive clinical characteristic review and survival analysis were conducted.Twelve studies describing 81 patients were included. The median age was 39 years (male=54.3%). Fifty patients (61.7%) had obstructive hydrocephalus requiring cerebrospinal fluid diversion with either ventriculoperitoneal shunt (VPS) (40.0%) or endoscopic third ventriculostomy (ETV) (24.0%). Patients who underwent VPS had significant survival benefits compared to ETV (p0.05). All patients in our review underwent surgery, and gross-total resection (≥98%) was achieved in 34.6%. The supracerebellar infratentorial approach was the most employed surgical approach (62.3%). Chemotherapy was administered in 32.1% of cases, and radiotherapy in 40.7%. The median overall survival (OS) was 12 months, and the overall one-year survival rate was 60%.This study could not establish a correlation between the extent of tumor resection and positive treatment outcomes. However, among cases with hydrocephalus, patients who underwent VPS placement had better survival as compared to ETV.

Up to 50% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis (BM), yet the study of BM genomics has been limited by tissue access, incomplete clinical data, and a lack of comparison with paired extracranial specimens. Here we report a cohort of 233 patients with resected and sequenced (MSK-IMPACT) NSCLC BM and comprehensive clinical data. With matched samples (47 primary tumor, 42 extracranial metastatic), we showed CDKN2A/B deletions and cell cycle pathway alterations to be enriched in the BM samples. Meaningful clinico-genomic correlations were noted, namely EGFR alterations in leptomeningeal disease (LMD) and MYC amplifications in multifocal regional brain progression. Patients who developed early LMD frequently had uncommon, multiple, and persistently detectable EGFR driver mutations. The distinct mutational patterns identified in BM specimens compared to other tissue sites suggest specific biologic underpinnings of intracranial progression.

Thalamic gliomas are rare neoplasms that pose significant surgical challenges. The literature is limited to single-institution retrospective case series. We systematically review the literature and describe the clinical characteristics, treatment strategies, and survival outcomes of adult thalamic gliomas. Relevant articles were identified on PubMed, Scopus, and Cochrane databases. Papers containing cases of adult thalamic gliomas with clinical outcome data were included. A comprehensive review of clinical characteristics and survival analysis was conducted. We included 25 studies comprising 617 patients. The median age was 45 years (male = 58.6%). Glioblastoma was the most frequent histological type (47.2%), and 82 tumors were H3 K27M-mutant. Motor deficit was the most common presenting symptom (51.8%). Surgical resection was performed in 69.1% of cases while adjuvant chemotherapy and radiotherapy were administered in 56.3% and 72.6%, respectively. Other treatments included laser interstitial thermal therapy, which was performed in 15 patients (2.4%). The lesion laterality (P = 0.754) and the surgical approach (P = 0.111) did not correlate with overall survival. The median progression-free survival was 9 months, and the overall two-year survival rate was 19.7%. The two-year survival rates of low-grade and high-grade thalamic gliomas were 31.0% and 16.5%, respectively. H3 K27M-mutant gliomas showed worse overall survival (P = 0.017). Adult thalamic gliomas are associated with poor survival. Complete surgical resection is associated with improved survival rates but is not always feasible. H3 K27M mutation is associated with worse survival and a more aggressive approach should be considered for mutant neoplasms.

Simple Summary Orbital metastases may significantly worsen the functional status of oncological patients, leading to debilitating visual impairments. Surgical resection, orbital exenteration, and complementary therapies may result in heterogeneous clinical outcomes. In this systematic review, we aimed to comprehensively analyze the current literature on orbital metastases, describing clinical and imaging features, available management, and treatment outcomes. We found that most orbital metastases occur at later stages after primary tumors, frequently showing diffuse location within the orbit and rarely invading intracranial structures. Biopsy-only techniques were more frequently preferred in view of the less invasive approaches, but surgical resection and orbital radiotherapy were related to improved clinical outcomes. Although patients with primary breast cancer and patients undergoing resection showed superior prognoses, overall survival rates were generally poor, suggesting the need to better understand orbital metastases’ microenvironments for devising optimal systemic treatment strategies. Abstract Background: Orbital metastases often lead to severe functional impairment. The role of resection, orbital exenteration, and complementary treatments is still debated. We systematically reviewed the literature on orbital metastases. Methods: PubMed, Scopus, Web-of-Science, and Cochrane were searched upon PRISMA guidelines to identify studies on orbital metastases. Clinical characteristics, management strategies, and survival were analyzed. Results: We included 262 studies comprising 873 patients. Median age was 59 years. The most frequent primary tumors were breast (36.3%), melanoma (10.1%), and prostate (8.5%) cancers, with median time interval of 12 months (range, 0–420). The most common symptoms were proptosis (52.3%) and relative-afferent-pupillary-defect (38.7%). Most metastases showed a diffuse location within the orbit (19%), with preferential infiltration of orbital soft tissues (40.2%). In 47 cases (5.4%), tumors extended intracranially. Incisional biopsy (63.7%) was preferred over fine-needle aspiration (10.2%), with partial resection (16.6%) preferred over complete (9.5%). Orbital exenteration was pursued in 26 patients (3%). A total of 305 patients (39.4%) received chemotherapy, and 506 (58%) received orbital radiotherapy. Post-treatment symptom improvement was significantly superior after resection (p = 0.005) and orbital radiotherapy (p = 0.032). Mean follow-up was 14.3 months, and median overall survival was 6 months. Fifteen cases (1.7%) demonstrated recurrence with median local control of six months. Overall survival was statistically increased in patients with breast cancer (p < 0.001) and in patients undergoing resection (p = 0.024) but was not correlated with orbital location (p = 0.174), intracranial extension (p = 0.073), biopsy approach (p = 0.344), extent-of-resection (p = 0.429), or orbital exenteration (p = 0.153). Conclusions: Orbital metastases severely impair patient quality of life. Surgical resection safely provides symptom and survival benefit compared to biopsy, while orbital radiotherapy significantly improves symptoms compared to not receiving radiotherapy.

In the field of stimulus generalization, an old yet unresolved discussion pertains to what extent stimulus misidentifications contribute to the pattern of conditioned responding. In this article, we perform cluster analysis on six datasets (four published datasets and two unpublished datasets, included

Background: Brain metastases (BMs) carry a high morbidity and mortality burden. Neoadjuvant stereotactic radiotherapy (NaSRT) has shown promising results. We systematically reviewed the literature on NaSRT for BMs. Methods: PubMed, EMBASE, Scopus, Web-of-Science, Cochrane, and ClinicalTrial.gov were searched following the PRISMA guidelines to include studies and ongoing trials reporting NaSRT for BMs. Indications, protocols, and outcomes were analyzed using indirect random-effect meta-analyses. Results: We included 7 studies comprising 460 patients with 483 BMs, and 13 ongoing trials. Most BMs originated from non-small lung cell carcinoma (41.4%), breast cancer (18.7%) and melanoma (43.6%). Most patients had single-BM (69.8%) located supratentorial (77.8%). Patients were eligible if they had histologically-proven primary tumors and ≤4 synchronous BMs candidate for non-urgent surgery and radiation. Patients with primary tumors clinically responsive to radiotherapy, prior brain radiation, and leptomeningeal metastases were deemed non-eligible. Median planning target volume was 9.9 cm3 (range, 2.9–57.1), and NaSRT was delivered in 1-fraction (90.9%), 5-fraction (4.8%), or 3-fraction (4.3%), with a median biological effective dose of 39.6 Gy10 (range, 35.7–60). Most patients received piecemeal (76.3%) and gross-total (94%) resection after a median of 1-day (range, 1–10) post-NaSRT. Median follow-up was 19.2-months (range, 1–41.3). Actuarial post-treatment rates were 4% (95%CI: 2–6%) for symptomatic radiation necrosis, 15% (95%CI: 12–18%) and 47% (95%CI: 42–52%) for local and distant recurrences, 6% (95%CI: 3–8%) for leptomeningeal metastases, 81% (95%CI: 75–87%) and 59% (95%CI: 54–63%) for 1-year local tumor control and overall survival. Conclusion: NaSRT is effective and safe for BMs. Ongoing trials will provide high-level evidence on long-term post-treatment outcomes, further compared to adjuvant stereotactic radiotherapy.

PURPOSE: We aim to systematically review and summarize the demographics, clinical features, management strategies, and clinical outcomes of primary and radiation-induced skull-base osteosarcoma (SBO). METHODS: PubMed, Scopus, and Cochrane databases were used to identify relevant articles. Papers including SBO cases and sufficient clinical outcome data were included. A comprehensive clinical characteristic review and survival analysis were also conducted. RESULTS: Forty-one studies describing 67 patients were included. The median age was 31 years (male = 59.7%). The middle skull-base was most commonly involved (52.7%), followed by anterior (34.5%) and posterior (12.7%) skull-base. Headache (27%), exophthalmos (18%), and diplopia (10%) were common presenting symptoms. Sixty-eight percent of patients had primary SBO, while 25% had radiation-induced SBO. Surgery was the main treatment modality in 89% of cases. Chemotherapy was administered in 65.7% and radiotherapy in 50%. Median progression-free survival (PFS) was 12 months, and the overall 5-year survival was 22%. The five-year survival rates of radiation-induced SBO and primary SBO were 39% and 16%, respectively (P < 0.05). CONCLUSION: SBO is a malignant disease with poor survival outcomes. Surgical resection is the primary management modality, in conjunction with chemotherapy and radiotherapy. Complete surgical resection showed better survival rates compared to partial resection. Radiation-induced SBO has a superior survival outcome as compared to its primary counterpart.

The quality of drug products in the United States has been a matter of growing concern. Buyers and payers of pharmaceuticals have limited insight into measures of drug-product quality. Therefore, a quality-score system driven by data collection is proposed to differentiate between the qualities of drug products produced by different manufacturers. The quality scores derived using this proposed system would be based upon public regulatory data and independently-derived chemical data. A workflow for integrating the system into procurement decisions within health care organizations is also suggested. The implementation of such a quality-score system would benefit health care organizations by including the consideration of the quality of products while also considering price as a part of the drug procurement process. Such a system would also benefit the U.S. health care industry by bringing accountability and transparency into the drug supply chain and incentivizing manufacturers to place an increased emphasis on the quality and safety of their drug products.

Thin-film thermoelectric coolers are emerging as a viable option for the on-chip temperature management of electronic and photonic integrated circuits. In this work, we demonstrate the record heat flux handling capability of electrodeposited Bi2Te3 films of 720(±60) W cm–2 at room temperature, achieved by careful control of the contact interfaces to reduce contact resistance. The characteristic parameters of a single leg thin-film devices were measured in situ, giving a Seebeck coefficient of S = −121(±6) μV K–1, thermal conductivity of κ = 0.85(±0.08) W m–1 K–1, electrical conductivity of σ = 5.2(±0.32) × 104 S m–1, and electrical contact resistivity of ∼10–11 Ω m2. These thermoelectric parameters lead to a material ZT = 0.26(±0.04), which, for our device structure, allowed a net cooling of ΔTmax = 4.4(±0.12) K. A response time of τ = 20 μs was measured experimentally. This work shows that with the correct treatment of contact interfaces, electrodeposited thin-film thermoelectrics can compete with more complicated and expensive technologies such as metal organic chemical vapor deposition (MOCVD) multilayers.

Glioblastomas harbor diverse cell populations, including rare glioblastoma stem cells (GSCs) that drive tumorigenesis. To characterize functional diversity within this population, we performed single-cell RNA sequencing on >69,000 GSCs cultured from the tumors of 26 patients. We observed a high degree of inter- and intra-GSC transcriptional heterogeneity that could not be fully explained by DNA somatic alterations. Instead, we found that GSCs mapped along a transcriptional gradient spanning two cellular states reminiscent of normal neural development and inflammatory wound response. Genome-wide CRISPR–Cas9 dropout screens independently recapitulated this observation, with each state characterized by unique essential genes. Further single-cell RNA sequencing of >56,000 malignant cells from primary tumors found that the majority organize along an orthogonal astrocyte maturation gradient yet retain expression of founder GSC transcriptional programs. We propose that glioblastomas grow out of a fundamental GSC-based neural wound response transcriptional program, which is a promising target for new therapy development. Pugh and colleagues use single-cell RNA sequencing, CRISPR screens and functional assays to define a gradient of developmental and wound-response cell states in glioblastoma stem cells, revealing insights into glioblastoma origins and potential therapeutic targets.

Background: Gliomas infiltrating the corpus callosum (G-I-CC) majorly impact patient quality-of-life, but maximally safe tumor resection is challenging. We systematically reviewed the literature on G-I-CC. Methods: PubMed, EMBASE, Scopus, Web of Science, and Cochrane were searched following the PRISMA guidelines to include studies of patients with G-I-CC. Clinicopathological features, treatments, and outcomes were analyzed. Results: We included 52 studies comprising 683 patients. Most patients experienced headache (33%), cognitive decline (18.7%), and seizures (17.7%). Tumors mostly infiltrated the corpus callosum genu (44.2%) with bilateral extension (85.4%) into frontal (68.3%) or parietal (8.9%) lobes. Most G-I-CC were glioblastomas (84.5%) with IDH-wildtype (84.9%) and unmethylated MGMT promoter (53.5%). Resection (76.7%) was preferred over biopsy (23.3%), mostly gross-total (33.8%) and subtotal (32.5%). The tumor-infiltrated corpus callosum was resected in 57.8% of cases. Radiation was delivered in 65.8% of patients and temozolomide in 68.3%. Median follow-up was 12 months (range, 0.1–116). In total, 142 patients (31.8%) experienced post-surgical complications, including transient supplementary motor area syndrome (5.1%) and persistent motor deficits (4.3%) or abulia (2.5%). Post-treatment symptom improvement was reported in 42.9% of patients. No differences in rates of complications (p = 0.231) and symptom improvement (p = 0.375) were found in cases with resected versus preserved corpus callosum. Recurrences occurred in 40.9% of cases, with median progression-free survival of 9 months (0.1–72). Median overall survival was 10.7 months (range, 0.1–116), significantly longer in low-grade tumors (p = 0.013) and after resection (p < 0.001), especially gross-total (p = 0.041) in patients with high-grade tumors. Conclusions: G-I-CC show clinicopathological patterns comparable to other more frequent gliomas. Maximally safe resection significantly improves survival with low rates of persistent complications.

Background/Aim: To systematically review the patient characteristics and management approaches of adenoid cystic carcinoma (ACC) infiltrating the skull base. Materials and Methods: According to PRISMA guidelines, PubMed, Scopus, and Cochrane were searched to retrieve studies reporting management protocols and survival outcomes of patients with skull base ACCs. Patient characteristics, management strategies, and outcomes were investigated. Results: The review encompassed 17 studies involving 171 patients, with a female predominance (57.9%) and a mean age of 49±7.12 years. ACCs mostly infiltrated the paranasal sinus (22.2%), cavernous sinus (8.8%), and nasopharynx (7.1%). Perineural invasion was reported in 6.4% of cases. Facial pain, nasal obstruction, and facial paresthesia were the most common symptoms. Surgical resection (45.6%) was favored over biopsy (12.2%). Employing the free flap technique (4.7%), surgical reconstruction of the bony defect after resection was performed using abdominal and anterior thigh muscle grafts in 1.8% of patients each. As adjuvant management, 22.8% of cases had radiotherapy and 14.6% received chemotherapy. Recurrence of skull base ACCs occurred in 26.9% of cases during a mean follow up-time of 30.8±1.8 months. Conclusion: Skull base ACCs pose a surgical challenge mainly due to their proximity to critical neurovascular structures and aggressive behavior. Surgical resection and radiotherapy are shown to be safe and effective treatment modalities. The dismal prognosis and limited data on non-surgical strategies highlight the need for further evaluation of the current management paradigm and upraising innovative therapies to improve patient mortality and quality of life.

Human generalization research aims to understand the processes underlying the transfer of prior experiences to new contexts. Generalization research predominantly relies on descriptive statistics, assumes a single generalization mechanism, interprets generalization from mono-source data, and disregards individual differences. Unfortunately, such an approach fails to disentangle various mechanisms underlying generalization behavior and can readily result in biased conclusions regarding generalization tendencies. Therefore, we combined a computational model with multi-source data to mechanistically investigate human generalization. By simultaneously modeling learning, perceptual and generalization data at the individual level, we revealed meaningful variations in how different mechanisms contribute to generalization behavior. The current research suggests the need for revising the theoretical and analytic foundations in the field to shift the attention away from forecasting group-level generalization behavior and toward understanding how such phenomena emerge at the individual level. This opens the possibility of having a mechanism-specific differential diagnosis in generalization-related psychiatric disorders.

BackgroundIn recent years an increasing number of patients with cerebral metastasis (CM) have been referred to the neuro-oncology multidisciplinary team (NMDT). Our aim was to obtain a national picture of CM referrals to assess referral volume and quality and factors affecting NMDT decision making.MethodsA prospective multicenter cohort study including all adult patients referred to NMDT with 1 or more CM was conducted. Data were collected in neurosurgical units from November 2017 to February 2018. Demographics, primary disease, KPS, imaging, and treatment recommendation were entered into an online database.ResultsA total of 1048 patients were analyzed from 24 neurosurgical units. Median age was 65 years (range, 21-93 years) with a median number of 3 referrals (range, 1-17 referrals) per NMDT. The most common primary malignancies were lung (36.5%, n = 383), breast (18.4%, n = 193), and melanoma (12.0%, n = 126). A total of 51.6% (n = 541) of the referrals were for a solitary metastasis and resulted in specialist intervention being offered in 67.5% (n = 365) of cases. A total of 38.2% (n = 186) of patients being referred with multiple CMs were offered specialist treatment. NMDT decision making was associated with number of CMs, age, KPS, primary disease status, and extent of extracranial disease (univariate logistic regression, P < .001) as well as sentinel location and tumor histology (P < .05). A delay in reaching an NMDT decision was identified in 18.6% (n = 195) of cases.ConclusionsThis study demonstrates a changing landscape of metastasis management in the United Kingdom and Ireland, including a trend away from adjuvant whole-brain radiotherapy and specialist intervention being offered to a significant proportion of patients with multiple CMs. Poor quality or incomplete referrals cause delay in NMDT decision making.

Simple Summary Primary skull base chondrosarcomas (SBCs) may carry significant tumor-burden by causing severe cranial nerve neuropathies. Current treatment strategies mainly focus on surgical resection and radiotherapy protocols, with a wide range of findings in terms of efficacy and safety. The aim of our systematic review was to comprehensively analyze the current literature on primary SBCs, describing clinical and radiological characteristics, available management strategies, treatment outcomes, and prognoses. We found that most primary SBCs show benign slow-growing patterns but may cause neurological deficits by compressing critical neurovascular structures. Open surgical approaches favor maximal resection with acceptable complication rates, but only a few studies reported the use of newer endoscopic approaches. Proton-based, photon-based, and carbon-based radiotherapy protocols may also allow safe and effective local tumor control as adjuvant treatments or stand-alone strategies in patients not eligible to undergo surgery. Overall, primary SBCs’ prognoses proved to be favorable and comparable to benign skull base neoplasms. Abstract Background: Primary skull base chondrosarcomas (SBCs) can severely affect patients’ quality of life. Surgical-resection and radiotherapy are feasible but may cause debilitating complications. We systematically reviewed the literature on primary SBCs. Methods: PubMed, EMBASE, Scopus, Web-of-Science, and Cochrane were searched following the PRISMA guidelines to include studies of patients with primary SBCs. Clinical characteristics, management strategies, and treatment outcomes were analyzed. Results: We included 33 studies comprising 1307 patients. Primary SBCs mostly involved the middle-fossa (72.7%), infiltrating the cavernous-sinus in 42.4% of patients. Cranial-neuropathies were reported in 810 patients (62%). Surgical-resection (93.3%) was preferred over biopsy (6.6%). The most frequent open surgical approaches were frontotemporal-orbitozygomatic (17.6%) and pterional (11.9%), and 111 patients (21.3%) underwent endoscopic-endonasal resection. Post-surgical cerebrospinal-fluid leaks occurred in 36 patients (6.5%). Radiotherapy was delivered in 1018 patients (77.9%): photon-based (41.4%), proton-based (64.2%), and carbon-based (13.1%). Severe post-radiotherapy complications, mostly hypopituitarism (15.4%) and hearing loss (7.1%) were experienced by 251 patients (30.7%). Post-treatment symptom-improvement (46.7%) and reduced/stable tumor volumes (85.4%) showed no differences based on radiotherapy-protocols (p = 0.165; p = 0.062). Median follow-up was 67-months (range, 0.1–376). SBCs recurrences were reported in 211 cases (16.1%). The 5-year and 10-year progression-free survival rates were 84.3% and 67.4%, and overall survival rates were 94% and 84%. Conclusion: Surgical-resection and radiotherapy are effective treatments in primary SBCs, with acceptable complication rates and favorable local tumor control.

Background/aim Leptomeningeal disease (LMD) is a debilitating complication of advanced malignancies. Immune-checkpoint inhibitors (ICIs) may alter disease course. We analyzed the role and toxicity of ICIs in LMD. Materials and methods We systematically reviewed the literature reporting on outcome data of patients with LMD treated with ICIs. Results We included 14 studies encompassing 61 patients. Lung-cancer (44.3%), breast-cancer (27.9%), and melanoma (23.0%) were the most frequent primary tumors. Median duration of ICI-treatment was 7-months (range=0.5-58.0): pembrolizumab (49.2%), nivolumab (32.8%), ipilimumab (18.0%). Radiological responses included complete response (33.3%), partial response (12.5%), stable disease (33.3%), progressive disease (20.8%). Twenty-two patients developed ICI-related adverse-events, mild (100%) and/or severe (15.6%). Median progression-free and overall survival were 5.1 and 6.3 months, and 12-month survival was 32.1%. Survival correlated with ICI agents (p=0.042), but not with primary tumors (p=0.144). Patients receiving concurrent steroids showed worse survival (p=0.040). Conclusion ICI therapy is well-tolerated in patients with LMD, but concurrent steroids may worsen survival.

Background: Infratemporal fossa (ITF) tumors represent various pathologies and are seldom described in the literature, reflecting their rarity. Here we review the literature on tumors invading ITF and describe patient characteristics, treatment strategies, and clinical outcomes. Methods: Relevant articles were retrieved from PubMed, Scopus, and Cochrane. A systematic review and meta-analysis were conducted on the clinical presentation, treatment protocols, and clinical outcomes. Result: A total of 27 articles containing 106 patients with ITF tumors (median tumor size: 24.3 cm3 [interquartile range, 15.2–42 cm3]) were included (median age: 46 years [interquartile range, 32–55 years]; 59.4% were males]). Of the confirmed tumor pathology data, schwannomas (n = 24; 26.1%) and meningiomas (n = 13; 14.1%) were the most common tumors. Facial hypoesthesia (n = 22; 18.5%), auricular/preauricular pain (n = 20; 16.8%), and headaches (n = 11; 9.2%) were the most common presenting symptoms. Of patients who had surgical resection (n = 97; 95.1%), 70 (73.7%) had transcranial surgery (TCS) and 25 (26.3%) had endoscopic endonasal surgery (EES). Among available details on the extent of resection (n = 84), gross-total resection (GTR) was achieved in 62 (73.8%), and 5 (6.0%) had biopsy only. Thirty-five (33.0%) patients had postoperative complications. Among cases with available data on reconstruction techniques (n = 8), four (50%) had adipofascial antero-lateral thigh flap, three (37.5%) had latissimus dorsi free flap, and one (12.5%) had antero-lateral thigh flap. Fourteen (13.2%) patients had adjuvant chemotherapy, and sixteen (15.1%) had adjuvant radiotherapy. During a median follow-up time of 28 months (IQR, 12.25–45.75 months), 15 (14.2%) patients had recurrences, and 18 (17.0%) patients died. The median overall survival (OS) time was 36 months (95% confidence interval: 29–41 months), and the 5-year progression-free survival (PFS) rate was 61%. Conclusion: Various tumor types with different biological characteristics invade the ITF. The present study describes patient demographics, clinical presentation, management, and outcomes. Depending on the tumor type and patient condition, patient-tailored management is recommended to optimize treatment outcomes.

PURPOSE Brain metastases (BM) are common in patients with anaplastic lymphoma kinase fusion-positive NSCLC (ALK+ NSCLC). We characterized the genomics of patients with ALK+ NSCLC BM treated with alectinib with or without local therapy to identify correlations of co-mutations with CNS-specific outcomes. METHODS We retrospectively reviewed ALK+ NSCLC patients with BMs who received alectinib for the definitive treatment of BM from 1/2012 and 5/2021. Genomic characteristics of 27 specimens from 27 patients were assessed with MSK-IMPACT, a 505-gene next-generation sequencing (NGS)-based tumor sequencing assay with >700x coverage. Intracranial progression-free survival (iPFS) and overall survival (OS) from BM diagnosis were analyzed using standard statistical methods. RESULTS The median age at BM diagnosis was 57 years (range 25-83). Median iPFS was 1.94 years (95%CI: 1.58- not reached) and median OS was 6.08 years (95%CI: 1.7– not reached). All patients received alectinib for the treatment of brain metastases (78% as 1st-line TKI) and 22% received local therapy. The most frequently altered co- alterations were CDKN2A (48%), TP53 (22%), MAP2K4 (15%), SMARCA4 (11%), CREBBP (11%), and ATM (7%). CDKN2A alterations were more common in patients with intracranial progression (64% vs 31%). MAP2K4 alterations were enriched in metastatic samples (p = 0.028, q = 0.113). SMARCA4 co- alterations were associated with inferior OS (HR: 8.76, 95%CI = 1.74-44.2, p= 0.009) and trended toward association with iPFS but was insignificant (HR: 3.25, 95%CI = 0.83-12.4, p=0.089). We identified missense ALK alterations in CSF from a patient who acquired resistance to alectinib and had leptomeningeal progression (G1269A, I1171T, L1108P). CONCLUSION This study is the first analysis of CNS specific outcomes with detailed genomic annotation for ALK+ NSCLC patients who received definitive alectinib for BM. Further investigation into the role of CNS-penetrant TKIs and the genomic alterations predictive of CNS failure are needed.

Thalamic gliomas are rare neoplasms that pose significant surgical challenges. The literature is limited to single-institution retrospective case series. We systematically review the literature and describe the clinical characteristics, treatment strategies, and survival outcomes of adult thalamic gliomas.Relevant articles were identified on PubMed, Scopus, and Cochrane databases. Papers containing cases of adult thalamic gliomas with clinical outcome data were included. A comprehensive review of clinical characteristics and survival analysis was conducted.We included 25 studies comprising 617 patients. The median age was 45 years (male = 58.6%). Glioblastoma was the most frequent histological type (47.2%), and 82 tumors were H3 K27M-mutant. Motor deficit was the most common presenting symptom (51.8%). Surgical resection was performed in 69.1% of cases while adjuvant chemotherapy and radiotherapy were administered in 56.3% and 72.6%, respectively. Other treatments included laser interstitial thermal therapy, which was performed in 15 patients (2.4%). The lesion laterality (P = 0.754) and the surgical approach (P = 0.111) did not correlate with overall survival. The median progression-free survival was 9 months, and the overall two-year survival rate was 19.7%. The two-year survival rates of low-grade and high-grade thalamic gliomas were 31.0% and 16.5%, respectively. H3 K27M-mutant gliomas showed worse overall survival (P = 0.017).Adult thalamic gliomas are associated with poor survival. Complete surgical resection is associated with improved survival rates but is not always feasible. H3 K27M mutation is associated with worse survival and a more aggressive approach should be considered for mutant neoplasms.

Academic neurosurgery encompasses basic science and clinical research efforts to better understand and treat diseases of relevance to neurosurgical practice, with the overall aim of improving treatment and outcome for patients. In this article, we provide an overview of the current and future directions of British academic neurosurgery. Training pathways are considered together with personal accounts of experiences of structured integrated clinical academic training and unstructured academic training. Life as an academic consultant is also described. Funding is explored, for the specialty as a whole and at the individual level. UK academic neurosurgical organisations are highlighted. Finally, the UK’s international standing is considered.

Pineal region metastases are rare but often cause severe neurologic deficits. Surgical resection and chemoradiotherapy can provide therapeutic benefit. We investigated the literature to analyze clinical characteristics, management strategies, and survival of adult patients with pineal region metastases.PubMed, Embase, Scopus, and Cochrane were searched following the PRISMA guidelines, including studies reporting clinical outcomes of patients with pineal region metastases. Clinical presentation, management, and survival were reviewed.We included 31 studies comprising 47 patients. Lung cancer (29.8%) and carcinomas of unknown origin (14.9%) were the most frequent primary tumors. In 48.9% of patients, symptomatic pineal metastases preceded primary tumor diagnosis. Headache (67.4%) and confusion (46.5%) were the most common symptoms. Parinaud syndrome (46.5%) and hydrocephalus (87.2%) were noted. Biopsy (65.9%) was preferred over resection (34.1%), and shunting strategies used were endoscopic third ventriculostomy (43.9%) and ventriculoperitoneal (26.8%). Eleven patients (32.3%) received adjuvant chemotherapy and 32 (68%) received radiotherapy. Posttreatment improvement in symptoms (56.6%) and hydrocephalus (80.5%) were noted. In patients who received adjuvant chemotherapy/radiotherapy, significant improvement in posttreatment performance status occurred with both biopsy (P0.001) and resection (P = 0.007). No survival differences were reported between surgery and biopsy (P = 0.912) or between complete and partial resection (P = 0.220). Overall survival was neither influenced by surgical approach (P = 0.157) nor by shunting strategy (P = 0.822). Mean follow-up was 8 months and median overall survival 3 months. Only 2 cases (4.8%) of pineal metastasis showed recurrence.Pineal region metastases carry significant morbidity. Biopsy or surgical resection, combined with adjuvant chemotherapy/radiotherapy and/or shunting, may significantly improve performance status.

Brain metastases (BrM) affect up to 20% of patients with cancer and represent an increasing portion of patients with surgical brain tumors owing to improving prognoses of cancer patients in general and in many cases even of those with brain metastases. With advances in molecular biology and targeted therapy, the indications for neurosurgical sampling and specifically stereotactic biopsy are likely to change in the future. In this review the authors address some of the scientific advances in BrM biology, the clinical rationale and range of techniques currently used to perform stereotactic biopsy, and how the advent of molecular interrogation may potentially alter the way patients with BrM are managed in the future.

Purpose: The intent of this article is to evaluate a novel approach, using rapid cycle analytics and real world evidence, to optimize and improve the medication evaluation process to help the formulary decision making process, while reducing time for clinicians. Summary: The Pharmacy and Therapeutics (P&T) Committee within each health system is responsible for evaluating medication requests for formulary addition. Members of the pharmacy staff prepare the drug monograph or a medication use evaluation (MUE) and allocate precious clinical resources to review patient charts to assess efficacy and value. We explored a novel approach to evaluate the value of our intravenous acetaminophen (IV APAP) formulary admittance. This new methodology, called rapid cycle analytics, can assist hospitals in meeting and/or exceeding the minimum criteria of formulary maintenance as defined by the Joint Commission Standards. In this particular study, we assessed the effectiveness of IV APAP in total hip arthroplasty (THA) and total knee arthroplasty (TKA) procedures. We assessed the correlation to same-stay opioid utilization, average length of inpatient stay and post anesthesia care unit (PACU) time. Conclusion: We were able to explore and improve our organization’s approach in evaluating medications by partnering with an external analytics expert to help organize and normalize our data in a more robust, yet time efficient manner. Additionally, we were able to use a significantly larger external data set as a point of reference. Being able to perform this detailed analytical exercise for thousands of encounters internally and using a data warehouse of over 130 million patients as a point of reference in a short time has improved the depth of our assessment, as well as reducing valuable clinical resources allocated to MUEs to allow for more direct patient care. This clinically real-world and data-rich analytics model is the necessary foundation for using Artificial or Augmented Intelligence (AI) to make real-time formulary and drug selection decisions

Aims: Resident and peripherally derived glioma associated microglia/macrophages (GAMM) play a key role in driving tumour progression, angiogenesis, invasion and attenuating host immune responses. Differentiating these cells’ origins is challenging and current preclinical models such as irradiation-based adoptive transfer, parabiosis and transgenic mice have limitations. We aimed to develop a novel nonmyeloablative transplan- tation (NMT) mouse model that permits high levels of peripheral chimerism without blood-brain barrier (BBB) damage or brain infiltration prior to tumour implantation. Methods: NMT dosing was determined in C57BL/6J or Pep3/CD45.1 mice conditioned with concentrations of busulfan ranging from 25 mg/kg to 125 mg/kg. Donor haematopoietic cells labelled with eGFP or CD45.2 were injected via tail vein. Donor chimerism was measured in peripheral blood, bone marrow and spleen using flow cytometry. BBB integrity was assessed with anti-IgG and anti-fibrinogen antibodies. Immuno-competent chimerised animals were orthotopically implanted with murine glioma GL-261 cells. Central and peripheral cell contributions were assessed using mimmunohistochemistry and flow cytometry. GAMM subpopulation analysis of peripheral cells was performed using Ly6C/MHCII/MerTK/CD64. Results: NMT achieves >80% haematopoietic chimerism by 12 weekswithout BBB damage and normal life span. Bone marrow derived cells (BMDC) and peripheral macrophages accounted for approximately 45% of the GAMM population in GL-261 implanted tumours. Existing markers such as CD45 high/low proved inaccurate to determine central and peripheral populations while Ly6C/MHCII/MerTK/CD64 reliably differentiated GAMM subpopulations in chimerised and unchimerised mice. Conclusion: NMT is a powerful method for dissecting tumour microglia and macrophage subpopulations and can guide further investigation of BMDC subsets in glioma and neuro-inflammatory diseases.

A Monte Carlo method, implemented for quantifying confidence bounds on thermoreflectance (TR) measurements of interfacial thermal conductance G at solid-liquid interfaces modified with self-assembled monolayers (SAMs) is presented in this paper. Here we used 1-decanethiol (1DT) and 1H,1H,2H,2H-Perfluorodecanethiol (PFDT) SAMs to achieve two distinct work of adhesion. Using TR measurements in conjunction with Monte Carlo simulations, we determined G values to be 51 ± 7 MWm-2K-1, 58 ± 8 MWm-2K-1, and 72 ± 17 MWm-2K-1 for Au-PFDT-H2O, Au-1DT-H2O, and Au-H2O, respectively. Our results with the new confidence bounds position our experimental data on surfaces modified with SAMs comparable to literature. However, contrary to previous results shown in the literature, our data showed that a significant decrease in G can be seen for DI water on bare Au that was exposed in ambient for extended period. Our results indicate that G could be influenced by factors beyond a simple work of adhesion, an indication also seen from the work of Park et al.. To solidify this finding, further investigation is necessary to better understand G dependence on surface wettability.

Background Leptomeningeal disease (LMD) is a devastating complication of advanced malignancy with a poor prognosis and limited therapeutic options. Whether immune checkpoint inhibitors (ICIs) alter disease course is unknown. Methods We searched PubMed, EMBASE, Scopus, Cochrane, and clinicaltrials.gov according to PRISMA guidelines to analyze the therapeutic role and toxicity profiles of ICIs in the management of LMD. Studies reporting clinical outcome data of patients with LMD treated with ICIs were included. A comprehensive review of clinical characteristics and survival analysis was conducted. Results We included 14 studies encompassing 61 patients. The median age at LMD diagnosis was 57 years (female=63.9%). Lung cancer (44.3%), breast cancer (27.9%), and melanoma (23.0%) were the most frequent primary tumors. Parenchymal brain metastases occurred in 37 patients, mostly treated with radiotherapy (83.3%). LMD most frequently presented with headache (42.1%) and was diagnosed by MRI findings (leptomeningeal T1-contrast enhancement: 96.7%) and/or positive cerebrospinal fluid cytology (86.5%). Patients received ICIs for a median duration of 7 months (range, 0.5–58.0): pembrolizumab (49.2%), nivolumab (32.8%), and/or ipilimumab (18.0%). The most common concurrent LMD treatments were radiotherapy (54.7%) and steroids (35.7%). Radiological responses at 6-months were complete (33.3%) and partial response (12.5%), stable disease (33.3%), and progression (20.8%). 22 patients developed ICI-related adverse events, mostly mild (100%) and uncommonly severe (15.6%). Median progression-free survival was 5.1 months, median overall survival was 6.3 months, and 12-month survival was 32.1%. Survival was correlated with ICIs (P=0.042), but not with primary tumors (P=0.144). Patients concurrently receiving steroids showed worse survival (P=0.040), with a median overall survival of 1.9 months. Conclusion ICI therapy shows promise and appears to be well-tolerated in patients with LMD. Concurrent use of steroids is associated with worse survival. The role of ICIs in the multimodal management of LMD and their combination with steroids requires further analysis.

Both subthalamic nucleus (STN) and caudal zona incerta (cZI) have been implicated as the optimal locus for deep brain stimulation (DBS) in Parkinson’s disease (PD). We present a retrospective clinico-anatomical analysis of outcomes from DBS targeting both STN and cZI. Forty patients underwent bilateral DBS using an image-verified implantable guide tube/stylette technique. Contacts on the same quadripolar lead were placed in both STN and cZI. After pulse generator programming, contacts yielding the best clinical effect were selected for chronic stimulation. OFF-medication unified PD rating scale (UPDRS) part III scores pre-operatively and ON-stimulation at 1–2 year follow up were compared. Active contacts at follow-up were anatomically localised from peri-operative imaging. Overall, mean UPDRS part III score improvement was 55 ± 9% (95% confidence interval), with improvement in subscores for rigidity (59 ± 13%), bradykinesia (58 ± 13%), tremor (71 ± 24%) and axial features (36 ± 19%). Active contacts were distributed in the following locations: (1) within posterior/dorsal STN (50%); (2) dorsal to STN (24%); (3) in cZI (21%); and (4) lateral to STN (5%). When contacts were grouped by location, no significant differences between groups were seen in baseline or post-operative improvement in contralateral UPDRS part III subscores. We conclude that when both STN and cZI are targeted, active contacts are distributed most commonly within and immediately dorsal to STN. In a subgroup of cases, cZI contacts were selected for chronic stimulation in preference. Dual targeting of STN and cZI is feasible and may provide extra benefit compared with conventional STN DBS is some patients.

We present the case of a patient with Cushing's syndrome secondary to ectopic ACTH secretion. A MR of the head showed a left-sided nasal mass extending down from the cribriform plate. The patient underwent endoscopic resection with nearly complete removal of the mass. Histological examination showed an ACTH-secreting olfactory neuroblastoma (ONB). The patient's cortisol levels returned to normal range after surgery and have remained normal for over a year. ONB is a rare cause for ectopic ACTH secretion. This case highlights the diagnostic and management difficulties in patients with ectopic ACTH secretion, and provides a brief review of ONB.

Background Glioblastoma (GBM) is the most common primary brain malignancy in adults, yet survival outcomes remain poor. First line treatment is well established, however disease invariably recurs and improving prognosis is challenging. With the aim of personalizing therapy at recurrence, we have established a high content screening (HCS) platform to analyze the sensitivity profile of seven patient-derived cancer stem cell lines to 83 FDA-approved chemotherapy drugs, with and without irradiation. Methods Seven cancer stem cell lines were derived from patients with GBM and, along with the established cell line U87-MG, each patient-derived line was cultured in tandem in serum-free conditions as adherent monolayers and three-dimensional neurospheres. Chemotherapeutics were screened at multiple concentrations and cells double-stained to observe their effect on both cell death and proliferation. Sensitivity was classified using high-throughput algorithmic image analysis. Results Cell line specific drug responses were observed across the seven patient-derived cell lines. Few agents were seen to have radio-sensitizing effects, yet some drug classes showed a marked difference in efficacy between monolayers and neurospheres. In vivo validation of six drugs suggested that cell death readout in a three-dimensional culture scenario is a more physiologically relevant screening model and could be used effectively to assess the chemosensitivity of patient-derived GBM lines. Conclusion The study puts forward a number of non-standard chemotherapeutics that could be useful in the treatment of recurrent GBM, namely mitoxantrone, bortezomib and actinomycin D, whilst demonstrating the potential of HCS to be used for personalized treatment based on the chemosensitivity profile of patient tumor cells.

Glioblastoma is the most aggressive primary brain cancer with poor survival, but treatment strategies to improve prognosis have failed to materialise in over 30-years. Immune cells, in particular Tumour associated macrophages and microglia (TAMM) populate up to 40% of tumour bulk and are potential immunotherapy targets. However, functional roles of TAMM subpopulations still remain elusive and contradictory, due to limitations of existing mouse models and non-specific cell-surface markers used in human and rodent studies.

Objective To determine the interrater reliability for identification of a specific movement pattern using a Pilates Classification system. Method Videos of 5 subjects performing specific movement tasks were sent to raters trained in the DMA-CP classification system. Results Ninety-six raters completed the survey. Interrater reliability for the detection of a directional bias was excellent (Pi = 0.92, and K(free) = 0.89). Interrater reliability for classifying an individual into a specific subgroup was moderate (Pi = 0.64, K(free) = 0.55) however raters who had completed levels 1-4 of the DMA-CP training and reported using the assessment daily demonstrated excellent reliability (Pi = 0.89 and K(free) = 0.87). Conclusion The reliability of the classification system demonstrated almost perfect agreement in determining the existence of a specific movement pattern and classifying into a subgroup for experienced raters. There was a trend for greater reliability associated with increased levels of training and experience of the raters.

Glioblastoma Multiforme (GBM) is the most common primary brain tumour in adults, yet survival outcomes remain poor. First line treatment is well established but with disease recurrence almost inevitable, improving prognosis is challenging. With the aim of personalising therapy at recurrence we have established a high content screening (HCS) platform to analyse the sensitivity profile of seven patient-derived cancer stem cell lines to 82 FDA-approved chemotherapy drugs, with and without irradiation. Seven cancer stem cell lines were derived from patients with GBM, or GBM variants. Along with the established cell line U87-MG, each patient-derived line was cultured in tandem in serum-free conditions as adherent monolayers and three-dimensional neurospheres. Chemotherapeutics were screened at multiple concentrations and cells double-stained to observe their effect on both cell death and proliferation. Sensitivity was classified using high-throughput algorithmic image analysis. Cell line specific drug responses were observed across the seven patient-derived cell lines. Few agents were seen to have radio-sensitising effects, yet some drug classes showed a marked difference in efficacy between monolayers and neurospheres. In vivo validation of six drugs indicated that cell death readout in a three-dimensional culture scenario is a more physiologically relevant screening model, and can be used effectively to assess the chemosensitivity of patient-derived GBM lines. The study puts forward a number of non-standard chemotherapeutics that could be useful in the treatment of recurrent GBM, whilst demonstrating the potential of HCS to be used for personalised treatment based on the chemosensitivity profile of patient tumour cells.

Background Over the recent years an increasing number of patients with brain metastasis are being referred to the neuro-oncology multi-disciplinary team (NMDT). Our aim was to determine if referrals of this group of patients to the NMDT in the UK & Ireland comply with NICE guidelines and to assess referral volume, quality of information provided and its impact on NMDT decision-making. Methods Prospective multicentre oberservational study including all adult patients referred with ≥1 cerebral metastasis. Data was collected in neurosurgical units from 11/2017 to 02/2018. Demographics, primary disease, Karnofsky performance status (KPS), imaging and treatment recommendation were entered into an online database. Results 1049 patients were analysed from 24 neurosurgical units. Median age was 63[range 21–93] years with a median number of 3[range 1–17] referrals per NMDT. The most common primary malignancies were lung (36.5%, n=383), breast (18.5%, n=194) and melanoma (12.0%, n=126). 51.6% (n=541) of the referrals to the NMDT were within the NICE 2006 guidelines, and resulted in specialist intervention being offered in 68.8%. 41.2% (n=197) of patients being referred outside of the NICE 2006 guidelines were offered specialist treatment. NMDT decision-making was influenced by number of metastases, age, KPS, primary disease status and extent of extracranial disease (univariate logistic regression, p Conclusions This study confirmed a national change in culture of referral patterns. We identified a delay in NMDT decision-making in ~20%, contributing to increased NMDT workload. New stratification tools may be needed to reflect advancements in diagnostics and treatment modalities.

Attention modulates visual perception and is generally considered inextricably linked with conscious awareness: we become aware of stimuli as we attend to them, and we attend to stimuli as we become aware of them. Recent evidence suggests that attention can also modulate the effects of stimuli that remain invisible, and a natural explanation is that attention enhances weak perceptual representations, bringing them closer to conscious threshold even if they do not reach that threshold. However, there is also the possibility that attention may modulate neural processes that are entirely separate from those supporting conscious perception: sensorimotor mechanisms that do not create awareness however much they are enhanced. Here we provide evidence in support of this second hypothesis by showing that attentional cueing can modulate the behavioral response to invisible stimuli in a way that is distinct from enhancing their visibility. We used a masked-prime paradigm that produces a negative or positive compatibility effect depending on the perceptual strength (duration or brightness) of the prime. We found that attention enhanced the effect of both visible and invisible primes and also increased the likelihood of detecting the prime (i.e., boosted perceptual strength). Crucially, the pattern of attentional influence on priming could not be explained by attentional modulation of the prime’s perceptual strength but was predicted by a direct attentional influence on the nonconscious priming process itself. Therefore, in addition to regulating what we perceive, attention seems to influence our behavior through sensorimotor processes that are not involved in conscious awareness.

We surveyed a medical school's students' drinking habits and knowledge 12 years after a previous survey. In this current survey from two academic years, final year students drank less than second year students did. Women in their second year drank as much as men. Overall, 28% of students drank more than the safe limits; 27% of students were problem drinkers, as measured by the CAGE questionnaire, and 52%, as measured by the AUDIT questionnaire. The proportion of students not drinking any alcohol rose from 6% in the previous survey to 27% in the current survey, possibly due to context and demographic changes. In spite of this difference, there have been no statistically significant reductions in either unsafe drinking levels or CAGE scores over 12 years. A third of students overestimated the safe levels of drinking. All medical schools should write and implement an alcohol policy.

Background Glioblastoma multiforme is the most biologically aggressive brain tumour, with only 12 month survival, despite maximum treatment. Tumour-associated macrophages and microglia (TAMM) are myeloid cells populating 30–50% of glioblastoma multiforme tumours and are identified as potential immunotherapy targets. However, characterising functional roles of TAMM subpopulations remains elusive, because of flawed mouse models and inadequate cell-surface markers. In normal rodent brain, antibody markers CD11bhi and CD45hi are proposed to highlight infiltrating monocytes, whereas CD11bhi and CD45lo cells represent microglia and differentiated peripheral macrophages. This marker-set provides conflicting results in the context of the tumour microenvironment. We redressed this issue and aimed to determine whether peripheral or central TAMMs have independent roles in glioblastoma multiforme. Methods With our non-myeloablative bone-marrow transplant model, we can replace a mouse immune system using congenic donor cells marked with green fluorescence protein (GFP) without damaging the blood-brain barrier or inadvertently activating microglia; when applying this technique we subsequently distinguish between central microglial and peripheral macrophage populations. By stereotaxic intracranial implantation of murine glioblastoma multiforme (GL261), we recapitulated the normal development of a glioblastoma multiforme tumour and performed sham intracranial injections as a comparative control. Fluorescence-activated cell sorting was done to separate TAMM subpopulations for RNA sequencing. Findings Our chimeric mouse model consistently produced 70–80% peripheral blood chimerism and overcame the issue surrounding cell-surface expression markers, distinguishing peripherally infiltrating and central tissue-resident brain cells by GFP marker status. Cerebral digestion and analysis of tumour-implanted mice revealed a novel third population (FSChi/SSChi cells) on flow cytometry that stained greater than 90% CD11b/CD45+ suggestive of TAMMs; but this cell population was absent in hemispheres of both non-tumour bearing and sham-injected mice. Interpretation Our preliminary data showed that in chimeric mice implanted with glioblastoma multiforme, peripheral cells (GFP high) were the dominant infiltrating population. With RNA extraction for downstream transcriptional analysis we aim to reliably track trafficking myeloid populations and subsequently address the ambiguity surrounding TAMMs. Thereafter, we aim to develop an immunotherapy against glioblastoma multiforme using the findings from our study. Funding None.

The paper demonstrates a robust control strategy for variable air volume (VAV) air handling unit (AHU) systems which are commonly used in office buildings. Compared with traditional VAV AHU control adopting constant the setpoints of static pressure and supply air temperature, the strategy is composed of two independent modules, static pressure reset control and supply air temperature reset control. The optimization is realized by identifying optimal static pressure setpoint and supply air temperature setpoint to achieve predefined thermal comfort standards. The thermal comfort standards can be customized based on the practical operation performance through altering related parameters to tolerate unavoidable defects in real VAV AHU systems. The strategy was developed into software and applied in AHU systems of an office building located in Hong Kong. Its control performance was evaluated with respect to energy saving and indoor thermal comfort maintenance and proved to be effective.

In patients with pituitary adenomas, intra-cranial aneurysms can be an incidental finding, and are usually located outside the pituitary region. The authors describe the multi-modal management of a rare case of an aneurysm of the supraclinoid carotid that encroached into a pituitary macroadenoma.