An interdisciplinary consensus on the management of brain metastases in patients with renal cell carcinoma.

Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery. Nonetheless, the optimal approach for the management of brain metastases from renal cell carcinoma remains unclear. To improve patient care, the authors sought to standardize practical management strategies. They performed an unstructured literature review and elaborated on the current management strategies through an international group of experts from different disciplines assembled via the network of the International Kidney Cancer Coalition. Experts from different disciplines were administered a survey to answer questions related to current challenges and unmet patient needs. On the basis of the integrated approach of literature review and survey study results, the authors built algorithms for the management of single and multiple brain metastases in patients with renal cell carcinoma. The literature review, consensus statements, and algorithms presented in this report can serve as a framework guiding treatment decisions for patients. CA Cancer J Clin. 2022;72:454-489.

Structural and biochemical characterization of the mitomycin C repair exonuclease MrfB.

Mitomycin C (MMC) repair factor A (mrfA) and factor B (mrfB), encode a conserved helicase and exonuclease that repair DNA damage in the soil-dwelling bacterium Bacillus subtilis. Here we have focused on the characterization of MrfB, a DEDDh exonuclease in the DnaQ superfamily. We solved the structure of the exonuclease core of MrfB to a resolution of 2.1 Å, in what appears to be an inactive state. In this conformation, a predicted α-helix containing the catalytic DEDDh residue Asp172 adopts a random coil, which moves Asp172 away from the active site and results in the occupancy of only one of the two catalytic Mg2+ ions. We propose that MrfB resides in this inactive state until it interacts with DNA to become activated. By comparing our structure to an AlphaFold prediction as well as other DnaQ-family structures, we located residues hypothesized to be important for exonuclease function. Using exonuclease assays we show that MrfB is a Mg2+-dependent 3'-5' DNA exonuclease. We show that Leu113 aids in coordinating the 3' end of the DNA substrate, and that a basic loop is important for substrate binding. This work provides insight into the function of a recently discovered bacterial exonuclease important for the repair of MMC-induced DNA adducts.

DAXX promotes centromeric stability independently of ATRX by preventing the accumulation of R-loop-induced DNA double-stranded breaks.

Maintaining chromatin integrity at the repetitive non-coding DNA sequences underlying centromeres is crucial to prevent replicative stress, DNA breaks and genomic instability. The concerted action of transcriptional repressors, chromatin remodelling complexes and epigenetic factors controls transcription and chromatin structure in these regions. The histone chaperone complex ATRX/DAXX is involved in the establishment and maintenance of centromeric chromatin through the deposition of the histone variant H3.3. ATRX and DAXX have also evolved mutually-independent functions in transcription and chromatin dynamics. Here, using paediatric glioma and pancreatic neuroendocrine tumor cell lines, we identify a novel ATRX-independent function for DAXX in promoting genome stability by preventing transcription-associated R-loop accumulation and DNA double-strand break formation at centromeres. This function of DAXX required its interaction with histone H3.3 but was independent of H3.3 deposition and did not reflect a role in the repression of centromeric transcription. DAXX depletion mobilized BRCA1 at centromeres, in line with BRCA1 role in counteracting centromeric R-loop accumulation. Our results provide novel insights into the mechanisms protecting the human genome from chromosomal instability, as well as potential perspectives in the treatment of cancers with DAXX alterations.

Rituximab and lenalidomide for the treatment of relapsed or refractory indolent non-Hodgkin lymphoma: real-life experience.

The combination of rituximab and lenalidomide (R-len) stands as an established treatment for relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). However, the reproducibility of clinical trial results in routine clinical practice is unknown. To address this gap in knowledge, we reviewed our experience with patients diagnosed with R/R follicular lymphoma (FL) or marginal zone lymphoma (MZL) treated with this combination. Eighty-four patients underwent treatment with R-len, 69 (82%) affected by FL and 15 (18%) by MZL. The median age at the time of treatment initiation was 65 years (range, 39-94), 38 patients (45%) had a pre-treatment FLIPI score of 3-5, 19 (23%) had a bulky disease, 29 (37%) had a lymphoma refractory to the last treatment line, while in 20 (24%) cases the disease was refractory to rituximab. The best overall response rate (ORR) was 82%, and 52% achieved a complete response (CR). The best CR rates for FL and MZL patients were 55% and 40%, respectively. With a median follow-up of 22 months, the median progression-free survival (mPFS) was 22 months (95% CI 19-36) and the 2-year overall survival (OS) was 83% (95% CI 74-93). The median duration of CR (DoCR) was 46 months (95% CI 22-NR). Factors associated with shorter PFS in multivariate analysis were bulky disease and rituximab refractoriness. The most common adverse events (AE) included hematologic toxicity, fatigue and gastrointestinal disorders, such as diarrhea and constipation. Neutropenia and thrombocytopenia were the most common severe toxicities (grade ≥3 in 25% and 4%, respectively). No new safety signals were reported. Real-life results of R-len in patients with R/R iNHL appear consistent with those reported in prospective studies, and further support its use as comparator arm in controlled clinical trials.

Craniospinal irradiation for CNS leukemia: rates of response and durability of CNS control.

PURPOSE: Management of CNS involvement in leukemia may include craniospinal irradiation (CSI), though data on CSI efficacy are limited. METHODS: We retrospectively reviewed leukemia patients who underwent CSI at our institution between 2009 and 2021 for CNS involvement. CNS local recurrence (CNS-LR), any recurrence, progression-free survival (PFS), CNS PFS, and overall survival (OS) were estimated. RESULTS: Of thirty-nine eligible patients treated with CSI, most were male (59%) and treated as young adults (median 31 years). The median dose was 18 Gy to the brain and 12 Gy to the spine. Twenty-five (64%) patients received CSI immediately prior to allogeneic hematopoietic cell transplant, of which 21 (84%) underwent total body irradiation conditioning (median 12 Gy). Among 15 patients with CSF-positive disease immediately prior to CSI, all 14 assessed patients had pathologic clearance of blasts (CNS-response rate 100%) at a median of 23 days from CSI start. With a median follow-up of 48 months among survivors, 2-year PFS and OS were 32% (95% CI 18-48%) and 43% (95% CI 27-58%), respectively. Only 5 CNS relapses were noted (2-year CNS-LR 14% (95% CI 5-28%)), which occurred either concurrently or after a systemic relapse. Only systemic relapse after CSI was associated with higher risk of CNS-LR on univariate analysis. No grade 3 or higher acute toxicity was seen during CSI. CONCLUSION: CSI is a well-tolerated and effective treatment option for patients with CNS leukemia. Control of systemic disease after CSI may be important for CNS local control. CNS recurrence may reflect reseeding from the systemic space.

Prognostic value of cerebrospinal fluid tumor cell count in leptomeningeal disease from solid tumors.

PURPOSE: Treatment decisions for leptomeningeal disease (LMD) rely on patient risk stratification, since clinicians lack objective prognostic tools. The introduction of rare cell capture technology for identification of cerebrospinal fluid tumor cells (CSF-TCs), such as CNSide assay, improved the sensitivity of LMD diagnosis, but prognostic value is unknown. This study assesses the prognostic value of CSF-TC density in patients with LMD from solid tumors. METHODS: We conducted a retrospective cohort study of patients with newly diagnosed or previously treated LMD from a single institution who had CNSide assay testing for CSF-TCs from 2020 to 2023. Univariable and multivariable survival analyses were conducted with Cox proportional-hazards modeling. Maximally-selected rank statistics were used to determine an optimal cutpoint for CSF-TC density and survival. RESULTS: Of 31 patients, 29 had CSF-TCs detected on CNSide. Median (interquartile range [IQR]) CSF-TC density was 67.8 (4.7-639) TCs/mL. CSF cytology was positive in 16 of 29 patients with positive CNSide (CNSide diagnostic sensitivity = 93.5%, negative predictive value = 85.7%). Median (IQR) survival from time of CSF-TC detection was 176 (89-481) days. On univariable and multivariable analysis, CSF-TC density was significantly associated with survival. An optimal cutpoint for dichotomizing survival by CSF-TC density was 19.34 TCs/mL. The time-dependent sensitivity and specificity for survival using this stratification were 76% and 67% at 6 months and 65% and 67% at 1 year, respectively. CONCLUSIONS: CSF-TC density may carry prognostic value in patients with LMD from solid tumors. Integrating CSF-TC density into LMD patient risk-stratification may help guide treatment decisions.

Metabolic, behavioural, and psychosocial risk factors and cardiovascular disease in women compared with men in 21 high-income, middle-income, and low-income countries: an analysis of the PURE study.

BACKGROUND: There is a paucity of data on the prevalence of risk factors and their associations with incident cardiovascular disease in women compared with men, especially from low-income and middle-income countries. METHODS: In the Prospective Urban Rural Epidemiological (PURE) study, we enrolled participants from the general population from 21 high-income, middle-income, and low-income countries and followed them up for approximately 10 years. We recorded information on participants' metabolic, behavioural, and psychosocial risk factors. For this analysis, we included participants aged 35-70 years at baseline without a history of cardiovascular disease, with at least one follow-up visit. The primary outcome was a composite of major cardiovascular events (cardiovascular disease deaths, myocardial infarction, stroke, and heart failure). We report the prevalence of each risk factor in women and men, their hazard ratios (HRs), and population-attributable fractions (PAFs) associated with major cardiovascular disease. The PURE study is registered with ClinicalTrials.gov, NCT03225586. FINDINGS: In this analysis, we included 155 724 participants enrolled and followed-up between Jan 5, 2005, and Sept 13, 2021, (90 934 [58·4%] women and 64 790 [41·6%] men), with a median follow-up of 10·1 years (IQR 8·5-12·0). At study entry, the mean age of women was 49·8 years (SD 9·7) compared with 50·8 years (9·8) in men. As of data cutoff (Sept 13, 2021), 4280 major cardiovascular disease events had occurred in women (age-standardised incidence rate of 5·0 events [95% CI 4·9-5·2] per 1000 person-years) and 4911 in men (8·2 [8·0-8·4] per 1000 person-years). Compared with men, women presented with a more favourable cardiovascular risk profile, especially at younger ages. The HRs for metabolic risk factors were similar in women and men, except for non-HDL cholesterol, for which high non-HDL cholesterol was associated with an HR for major cardiovascular disease of 1·11 (95% CI 1·01-1·21) in women and 1·28 (1·19-1·39) in men, with a consistent pattern for higher risk among men than among women with other lipid markers. Symptoms of depression had a HR of 1·09 (0·98-1·21) in women and 1·42 (1·25-1·60) in men. By contrast, consumption of a diet with a PURE score of 4 or lower (score ranges from 0 to 8), was more strongly associated with major cardiovascular disease in women (1·17 [1·08-1·26]) than in men (1·07 [0·99-1·15]). The total PAFs associated with behavioural and psychosocial risk factors were greater in men (15·7%) than in women (8·4%) predominantly due to the larger contribution of smoking to PAFs in men (ie, 1·3% [95% CI 0·5-2·1] in women vs 10·7% [8·8-12·6] in men). INTERPRETATION: Lipid markers and depression are more strongly associated with the risk of cardiovascular disease in men than in women, whereas diet is more strongly associated with the risk of cardiovascular disease in women than in men. The similar associations of other risk factors with cardiovascular disease in women and men emphasise the importance of a similar strategy for the prevention of cardiovascular disease in men and women. FUNDING: Funding sources are listed at the end of the Article.

The Impact of Autonomous and Controlled Sexting Motivations on Subjective Well-being and Relationship Quality.

Although many studies have examined reasons for sexting among young people, few have taken into account the underlying motivations associated with different reasons and how that may be associated with divergent positive or negative outcomes. This study addressed this gap by employing Self-determination Theory to assess how autonomous and controlled motivations for sexting were related to subjective well-being and relationship quality among emerging adults. Online survey data from 267 emerging adults (72 men, 195 women) ages 18-25 who had sent sexually explicit images or videos of themselves through electronic means to a committed partner were analyzed using Structural Equation Modeling. Autonomous and controlled motivations for sexting were significantly related to pleasant affect, with autonomous motivation predicting more pleasant affect and controlled motivation predicting less pleasant affect. Autonomous motivations for sexting were related to enhanced relationship quality, whereas controlled motivations for sexting were related to decreased relationship quality. Neither form of motivation had a statistically significant relationship with unpleasant affect or life satisfaction. These results demonstrate that the quality of motivations for sexting among emerging adults in committed relationships may contribute to different outcomes, particularly in terms of relationship quality. Implications for counselors, educators, and practitioners working with emerging adults who sext are discussed.

Prevalence and predictors of prolonged length of stay among patients admitted under general internal medicine in a tertiary government hospital in Manila, Philippines: a retrospective cross-sectional study.

BACKGROUND: Prolonged hospitalization leads to poorer health outcomes and consumes limited hospital resources. This study identified factors associated with prolonged length of stay (PLOS) among internal medicine patients admitted in a tertiary government hospital. METHODS: We reviewed the medical records of 386 adult patients admitted under the primary service of General Internal Medicine at the Philippine General Hospital from January 1 to December 31, 2019. PLOS was defined as at least 14 days for emergency admissions or 3 days for elective admissions. Sociodemographics, clinical characteristics, admission- and hospital system-related factors, disease-specific factors, outcome on the last day of hospitalization, and hospitalization costs were obtained. We determined the proportion with PLOS and reviewed reasons for discharge delays. We conducted multiple logistic regression analyses to assess associations between various factors and PLOS. RESULTS: The prevalence of PLOS is 19.17% (95% CI 15.54, 23.42). Positive predictors include being partially dependent on admission (aOR 2.61, 95% CI 0.99, 6.86), more co-managing services (aOR 1.26, 95% CI 1.06, 1.50), and longer duration of intravenous antibiotics (aOR 1.36, 95% CI 1.22, 1.51). The only negative predictor is the need for intravenous antibiotics (aOR 0.14, 95% CI 0.04, 0.54). The most common reason for discharge delays was prolonged treatment. The median hospitalization cost of patients with PLOS was PHP 77,427.20 (IQR 102,596). CONCLUSIONS: Almost a fifth of emergency admissions and a quarter of elective admissions had PLOS. Addressing factors related to predictors such as functional status on admission, number of co-managing services, and use of intravenous antibiotics can guide clinical and administrative decisions, including careful attention to vulnerable patients and judicious use of resources.

Online Learning is a Rollercoaster: Postsecondary Students With Learning Disabilities Navigate the COVID-19 Pandemic.

Most of what researchers know about the challenges students with learning disabilities (LDs) experience during postsecondary education is based on experiences during face-to-face learning on campus. Less is known about challenges students with LD face during learning online-the mode of instruction students had to navigate during the COVID-19 pandemic. Therefore, the purpose of our research was to examine the lived experience of undergraduate students with LD during their first full semester of online instruction as a result of the pandemic. We interviewed six students in Western Canada and used a phenomenological approach to analyze their experiences. Overall, we extracted six main themes from their interviews. Two of these themes, (a) the broad impact of having LD and (b) accommodations during COVID-19, were specific to being a student with LD. The remaining four themes were more generally related to their overall student experience: (c) online learning is different, (d) the role of others, (e) emotional impact, and (f) resilience and perseverance. We discuss these results in terms of recommendations for future research and teaching in online learning environments.

Disparities in Access to Radiation Therapy by Race and Ethnicity in the United States With Focus on American Indian/Alaska Native People.

OBJECTIVES: Striking disparities in access to radiation therapy (RT) exist, especially among racial and ethnic-minority patients. We analyzed census block group data to evaluate differences in travel distance to RT as a function of race and ethnicity, socioeconomic status, and rurality. METHODS: The Directory of Radiotherapy Centers provided the addresses of facilities containing linear accelerators for RT. We classified block groups as majority (≥ 50%) American Indian/Alaska Native (AI/AN), black, white, Asian, no single racial majority, or Hispanic regardless of race. We used the Area Deprivation Index to classify deprivation and Rural-Urban Commuting Area codes to classify rurality. Generalized linear mixed models tested associations between these factors and distance to nearest RT facility. RESULTS: Median distance to nearest RT facility was 72 miles in AI/AN-majority block groups, but 4 to 7 miles in block groups with non-AI/AN majorities. Multivariable models estimated that travel distances in AI/AN-majority block groups were 39 to 41 miles longer than in areas with non-AI/AN majorities. Travel distance was 1.3 miles longer in the more deprived areas versus less deprived areas and 16 to 32 miles longer in micropolitan, small town, and rural areas versus metropolitan areas. CONCLUSIONS: Cancer patients in block groups with AI/AN-majority populations, nonmetropolitan location, and low socioeconomic status experience substantial travel disparities in access to RT. Future research with more granular community- and individual-level data should explore the many other known barriers to access to cancer care and their relationship to the barriers posed by distance to RT care.

'Doing' hypertension: Experiential knowledge and practice in the self-management of 'high blood' in the Philippines.

Patients' embodied experiences do not always correspond to the biomedical concepts of particular diseases. Drawing from year-long fieldwork in the Philippines that involved semi-structured interviews, focus group discussions and digital diaries, we examine how individuals 'do' hypertension through their embodied experiences and the knowledge and practice that emerge from them. Drawing inspiration from Annemarie Mol's work on the notion of 'multiplicity' of disease, our analysis was informed by a commitment to privileging patients' embodied experiences and the multiple ontologies of hypertension. We find that for patients diagnosed with hypertension in the Philippines, symptoms enact illness; patients rely on their own embodied knowledge to define their illness' nature (e.g., diagnosis), experience (e.g., frequency of symptoms and non-chronicity) and praxis (e.g., self-care practices). We show how this knowledge gained from having embodied experiences of living with the disease interacts in various ways with biomedical knowledge, other diagnostic labels and clinical practices, to shape how hypertension manifests and is managed by patients. Beyond interrogating the relationship between what counts as a 'disease' and what is considered a 'symptom', our findings underscore the need to pay attention instead to the mutually co-constitutive processes of embodied experiences and disease categories in co-producing patient knowledge.

The Impact of COVID-19 on US Radiation Oncology Residents.

The purpose of our study is to assess the impact of COVID-19 on the clinical responsibilities, training, and wellness of US radiation oncology residents. An anonymous cross-sectional survey was sent to all 91 radiation oncology residency programs in the USA. The survey included questions related to demographics, changes in clinical duties and training, job prospects, and wellness indicators. Univariate and multivariate logistic regression analyses were used to evaluate factors associated with residents endorsing high satisfaction with their departments' response to COVID-19. A total of 96 residents completed the survey from 67 US radiation oncology programs. In the multivariate logistic regression model, remote contouring (OR: 3.91 (95% CI: 1.11, 13.80), p = 0.03) and belief that one will be adequately trained to independently practice after completing residency (OR: 4.68 (1.12, 19.47), p = 0.03) were significantly associated with high resident satisfaction with their department's response to COVID-19. Most residents indicated that hypofractionation was encouraged to a greater extent (n = 79, 82.3%), patients were triaged by disease risk (n = 67, 69.8%), and most agreed/strongly agreed that they have been provided with adequate personal protective equipment (PPE) (n = 85, 88.5%). The COVID-19 pandemic has affected the training and wellness of radiation oncology residents. Our analysis suggests that radiation oncology programs might increase resident satisfaction with their department's response to COVID-19 by enabling remote contouring and working with residents to identity and remedy possible concerns regarding their ability to independently practice post residency.

Clinical Features of de novo Pure 16q21q24.1 Chromosome Duplication.

Pure partial duplications of the long arm of chromosome 16 are rare and few cases are described with delineation by chromosomal microarray. Data about clinical abnormalities of pure partial 16q duplications are incomplete because many individuals die during the perinatal period. We describe the clinical features of a 47-month-old Brazilian girl with 16q21q24.1 duplication. To the best of our knowledge, she is the first person with this specific chromosome segment duplication, and we compare her phenotype with the only reported individual alive with intermediate-distal pure 16q duplication.

Post-hoc physiological waveform extraction from motion estimation in simultaneous multislice (SMS) functional MRI using separate stack processing.

PURPOSE: Motion estimation is an essential step in functional MRI (fMRI) preprocessing. Usually, fMRI processing software packages (eg, FSL and AFNI) automatically estimate motion parameters in order to counteract the effects of motion. However, the time courses of the motion estimation for fMRI data also contain information about physiological processes. Here, we show that respiration and cardiac signals can be extracted from motion estimation at significantly higher bandwidth than is possible with current methods. METHOD: To detect motion at high effective temporal resolution (HighRes), the motion parameters of stacks of simultaneously acquired slices were estimated separately, then combined. This method was validated by extracting physiological motion signals from resting state fMRI (rsfMRI) data (Enhanced Nathan Kline Institute-Rockland Sample) and comparing them to respiration belt and pulse oximeter signals. RESULTS: HighRes motion time-courses with an effective sampling rate of 15.5 and 11.4 Hz were extracted from repetition time (TR) = 0.645 and 1.4 s data, respectively. Respiration waveforms were extracted with significantly higher accuracy than the original motion parameters. Even cardiac waveforms could be extracted, despite the fact that the sampling time or TR values were too long to sample cardiac frequencies. CONCLUSION: HighRes motion traces provide insight into the subjects' motion at higher frequencies than can be estimated using standard techniques. In its simplest form, this technique can recover accurate respiration signals and may reveal additional complexity in brain motion.

Effect of 'pH' on the Rate of Pyroglutamate Formation in Solution and Lyophilized Solids.

N-terminal glutamate can cyclize to form pyroglutamate (pGlu) in pharmaceutically relevant peptides and proteins. The reaction occurs nonenzymatically during storage for monoclonal antibodies and shows a strong 'pH' dependence in solution, but the solid-state reaction has not been studied in detail. This work investigates the effect of 'pH' and buffer species on pGlu formation for a model peptide (EVQLVESGGGLVQPGGSLR) in lyophilized solids and in solution. The model peptide was formulated from 'pH' 4 to 'pH' 9 in citrate, citrate-phosphate, phosphate, and carbonate buffers and stored at 50 °C for at least 10 weeks. pGlu formation and loss of the parent peptide were monitored by reversed-phase high-performance liquid chromatography. The apparent 'pH' dependence of the reaction rate in the solid state differed markedly from that in solution. Interestingly, in the 'pH' range often used to formulate mAbs ('pH' 5.5-6), the rate of pGlu formation in the solid state was greater than that in solution. The results have implications for the rational design of stable formulations of peptides and proteins, and for the transition from solid to solution formulations during development.

Distinct imaging patterns of pseudoprogression in glioma patients following proton versus photon radiation therapy.

PURPOSE: Criteria by the Radiologic Assessment in Neuro-Oncology (RANO) group outline the diagnosis of pseudoprogression (Ps) after photon therapy for gliomas based on timing and location. We noted that patients receiving proton therapy manifested radiographic changes that appear different than Ps after photon therapy, which could be interpreted as tumor progression. In this study, we retrospectively reviewed MR imaging after proton or photon radiation for gliomas. We propose criteria to characterize proton pseudoprogression (ProPs) as distinct from Ps seen after photons. METHODS: Post-treatment MR imaging, clinical and pathological data of low grade glioma patients were reviewed. Overall, 57 patients receiving protons were reviewed for the presence of ProPs, and 43 patients receiving photons were reviewed for any equivalent imaging changes. Data collected included the location and timing of the new enhancement, tumor grade, molecular subtype, chemotherapy received, and clinical symptoms. RESULTS: Fourteen patients (24.6%) had new enhancement following radiation therapy that was unique to treatment with protons. The mean time to development of the ProPs was 15.4 months (7-27 months). We established the following criteria to characterize ProPs: located at the distal end of the proton beam; resolves without tumor-directed therapy; and subjectively multifocal, patchy, and small (< 1 cm). In the group receiving photons, none had changes that met our criteria for ProPs. CONCLUSION: Patients who receive protons have unique imaging changes after radiation therapy. ProPs could be mistaken for tumor progression, but typically resolves on follow up. Further studies are needed to understand the radiobiology and pathophysiology underlying these imaging changes.

Radiation-induced brain injury in patients with meningioma treated with proton or photon therapy.

INTRODUCTION: Radiation therapy is often used to treat meningioma with adverse features or when unresectable. Proton therapy has advantages over photon therapy in reducing integral dose to the brain. This study compared the incidence of radiological and clinical adverse events after photon versus proton therapy in the treatment of meningioma. METHODS: A retrospective review was conducted on patients with meningioma treated with proton or photon therapy at two high-volume tertiary cancer centers. Patients with a history of prior radiation therapy (RT) or less than 3 months of follow-up were excluded. Post-RT imaging changes were categorized into abnormal T2 signal intensities (T2 changes) or abnormal T1 post-contrast and T2 signal intensities (T1c+T2 changes) on magnetic resonance imaging (MRI). Clinical outcomes of adverse events and survival were compared between the proton and photon therapies. RESULTS: Among the total of 77 patients, 38 patients received proton therapy and 39 patients received photon therapy. The median age at diagnosis was 55 years and median follow-up was 2.2 years. No significant differences in symptomatic adverse events were observed between the two groups: grade ≥ 2 adverse events were seen in 4 (10.5%) patients in the proton group and 3 (7.7%) patients in the photon group (p = 0.67). The 2-year cumulative incidences of T2 changes were 38.3% after proton therapy and 47.7% after photon therapy (p = 0.53) and the 2-year cumulative incidences of T1c+T2 changes were 26.8% after proton therapy and 5.3% after photon therapy (p = 0.02). One patient experienced grade ≥ 4 adverse event in each group (p = 0.99). Estimated 2-year progression-free survival was 79.5% (proton therapy 76.0% vs. photon therapy 81.3%, p = 0.66) and 2-year overall survival was 89.7% (proton therapy 86.6% vs. photon therapy 89.3%, p = 0.65). CONCLUSIONS: Following RT, high rates of T2 changes were seen in meningioma patients regardless of treatment modality. Proton therapy was associated with significantly higher rates of T1c+T2 changes compared with photon therapy, but severe adverse events were uncommon in both groups and survival outcomes were comparable between the two groups. Future studies will aim at correlating the MRI changes with models that can be incorporated into RT planning to avoid toxicity.

Encapsulation of Graphene in the Hydrophobic Core of a Lipid Bilayer.

Theoretical simulations have predicted that a lipid bilayer forms a stable superstructure when a sheet of graphene is inserted in its hydrophobic core. We experimentally produced for the first time a lipid-graphene-lipid assembly by combining the Langmuir-Blodgett and the Langmuir-Schaefer methods. Graphene is sandwiched and remains flat within the hydrophobic core of the lipid bilayer. Using infrared spectroscopy, ellipsometry, and neutron reflectometry, we characterized the superstructure at every fabrication step. The hybrid superstructure is mechanically stable and graphene does not disturb the natural lipid bilayer structure.

Nonspatial Features Reduce the Reliance on Sustained Spatial Auditory Attention.

OBJECTIVE: Top-down spatial attention is effective at selecting a target sound from a mixture. However, nonspatial features often distinguish sources in addition to location. This study explores whether redundant nonspatial features are used to maintain selective auditory attention for a spatially defined target. DESIGN: We recorded electroencephalography while subjects focused attention on one of three simultaneous melodies. In one experiment, subjects (n = 17) were given an auditory cue indicating both the location and pitch of the target melody. In a second experiment (n = 17 subjects), the cue only indicated target location, and we compared two conditions: one in which the pitch separation of competing melodies was large, and one in which this separation was small. RESULTS: In both experiments, responses evoked by onsets of events in sound streams were modulated by attention, and we found no significant difference in this modulation between small and large pitch separation conditions. Therefore, the evoked response reflected that target stimuli were the focus of attention, and distractors were suppressed successfully for all experimental conditions. In all cases, parietal alpha was lateralized following the cue, but before melody onset, indicating that subjects initially focused attention in space. During the stimulus presentation, this lateralization disappeared when pitch cues were strong but remained significant when pitch cues were weak, suggesting that strong pitch cues reduced reliance on sustained spatial attention. CONCLUSIONS: These results demonstrate that once a well-defined target stream at a known location is selected, top-down spatial attention plays a weak role in filtering out a segregated competing stream.