bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling Relations between Compacted and Uncompacted Crown Ratio for the Northern United States
Authors: Westfall James A , Westfall Megan B E , Randolph KaDonna C
Published: August 2019

Tree crown ratio is useful in various applications such as prediction of tree mortality probabilities, growth potential, and fire behavior. Crown ratio is commonly assessed in two ways: (1) compacted crown ratio (CCR—lower branches visually moved upwards to fill missing foliage gaps) and (2) uncompacted crown ratio (UNCR—no missing foliage adjustment). The national forest inventory of the United States measures CCR on all trees, whereas only a subset of trees also are assessed for UNCR. Models for 27 species groups are presented to predict UNCR for the northern United States. The model formulation is consistent with those developed for other US regions while also accounting for the presence of repeated measurements and heterogeneous variance in a mixed-model framework. Ignoring random-effects parameters, the fit index values ranged from 0.43 to 0.78, and root mean squared error spanned 0.08–0.15; considerable improvements in both goodness-of-fit statistics were realized via inclusion of the random effects. Comparison of UNCR predictions with models developed for the southern United States exhibited close agreement, whereas comparisons with models used in Forest Vegetation Simulator variants indicated poor association. The models provide additional analytical flexibility for using the breadth of northern region data in applications where UNCR is the appropriate crown characteristic.
Relative moment tensors and deep Yakutat seismicity
Authors: Plourde Alexandre P , Bostock Michael G
Published: August 2019

We introduce a new relative moment tensor (MT) inversion method for clusters of nearby earthquakes. The method extends previous work by introducing constraints from S-waves that do not require modal decomposition and by employing principal component analysis to produce robust estimates of excitation. At each receiver, P and S waves from each event are independently aligned and decomposed into principal components. P-wave constraints on MTs are obtained from a ratio of coefficients corresponding to the first principal component, equivalent to a relative amplitude. For S waves we produce constraints on MTs involving three events, where one event is described as a linear combination of the other two, and coefficients are derived from the first two principal components. Nonlinear optimization is applied to efficiently find best-fitting tensile-earthquake and double-couple solutions for relative MT systems. Using synthetic data, we demonstrate the effectiveness of the P and S constraints both individually and in combination. We then apply the relative MT inversion to a set of 16 earthquakes from southern Alaska, at ∼125 km depth within the subducted Yakutat terrane. Most events are compatible with a stress tensor dominated by downdip tension, however, we observe several pairs of earthquakes with nearly antiparallel slip implying that the stress regime is heterogeneous and/or faults are extremely weak. The location of these events near the abrupt downdip termination of seismicity and the low-velocity zone suggest that they are caused by weakening via grain-size and volume reduction associated with eclogitization of the lower crustal gabbro layer.
Petrov–Galerkin space-time hp-approximation of parabolic equations in H1/2
Authors: Devaud Denis
Published: August 2019

We analyse a class of variational space-time discretizations for a broad class of initial boundary value problems for linear, parabolic evolution equations. The space-time variational formulation is based on fractional Sobolev spaces of order $1/2$ and the Riemann–Liouville derivative of order $1/2$ with respect to the temporal variable. It accommodates general, conforming space discretizations and naturally accommodates discretization of infinite horizon evolution problems. We prove an inf-sup condition for $hp$-time semidiscretizations with an explicit expression of stable test functions given in terms of Hilbert transforms of the corresponding trial functions; inf-sup constants are independent of temporal order and the time-step sequences, allowing quasi-optimal, high-order discretizations on graded time-step sequences, and also $hp$-time discretizations. For solutions exhibiting Gevrey regularity in time and taking values in certain weighted Bochner spaces, we establish novel exponential convergence estimates in terms of $N_t$, the number of (elliptic) spatial problems to be solved. The space-time variational setting allows general space discretizations and, in particular, for spatial $hp$-FEM discretizations. We report numerical tests of the method for model problems in one space dimension with typical singular solutions in the spatial and temporal variable. $hp$-discretizations in both spatial and temporal variables are used without any loss of stability, resulting in overall exponential convergence of the space-time discretization.
Sulphur systems biology—making sense of omics data
Authors: Watanabe Mutsumi , Hoefgen Rainer
Published: August 2019

Systems biology approaches have been applied over the last two decades to study plant sulphur metabolism. These ‘sulphur-omics’ approaches have been developed in parallel with the advancing field of systems biology, which is characterized by permanent improvements of high-throughput methods to obtain system-wide data. The aim is to obtain a holistic view of sulphur metabolism and to generate models that allow predictions of metabolic and physiological responses. Besides known sulphur-responsive genes derived from previous studies, numerous genes have been identified in transcriptomics studies. This has not only increased our knowledge of sulphur metabolism but has also revealed links between metabolic processes, thus indicating a previously unexpected complex interconnectivity. The identification of response and control networks has been supported through metabolomics and proteomics studies. Due to the complex interlacing nature of biological processes, experimental validation using targeted or systems approaches is ongoing. There is still room for improvement in integrating the findings from studies of metabolomes, proteomes, and metabolic fluxes into a single unifying concept and to generate consistent models. We therefore suggest a joint effort of the sulphur research community to standardize data acquisition. Furthermore, focusing on a few different model plant systems would help overcome the problem of fragmented data, and would allow us to provide a standard data set against which future experiments can be designed and compared.
A 21 cm pilot survey for pulsars and transients using the Focal L-Band Array for the Green Bank Telescope
Authors: Rajwade K M , Agarwal D , Lorimer D R , Pingel N M , Pisano D J , Ruzindana M , Jeffs B , Warnick K F , Roshi D A , McLaughlin M A
Published: August 2019

Phased array feed (PAF) receivers are at the forefront of modern day radio astronomy. PAFs are currently being developed for spectral line and radio continuum surveys and to search for pulsars and fast radio bursts. Here, we present results of the pilot survey for pulsars and fast radio bursts using the Focal plane L-band Array for the Green Bank Telescope (FLAG) receiver operating in the frequency range of 1.3–1.5 GHz. With a system temperature of ∼18 K, the receiver provided unprecedented sensitivity to the survey over an instantaneous field of view (FoV) of 0.1 deg2. For the survey, we implemented both time and frequency domain search pipelines designed to find pulsars and fast radio bursts that were validated by test pulsar observations. Although no new sources were found, we were able to demonstrate the capability of this instrument from observations of known pulsars. We report an upper limit on the rate of fast radio bursts above a fluence of 0.36 Jy ms to be 1.3 × 106 events per day per sky. Using population simulations, we show that the FLAG will find a factor of 2–3 more pulsars in same survey duration compared to its single pixel counterpart at the Green Bank Telescope. We also demonstrate that the new phased array receiver, ALPACA for the Arecibo telescope, will be a superior survey instrument and will find pulsars at a higher rate than most contemporary receivers by a factor of 2–10.
Exploring the M-dwarf Luminosity–Temperature–Radius relationships using Gaia DR2
Authors: Morrell Sam , Naylor Tim
Published: August 2019

There is growing evidence that M-dwarf stars suffer radius inflation when compared to theoretical models, suggesting that models are missing some key physics required to completely describe stars at effective temperatures less than about 4000 K. The advent of Gaia DR2 distances finally makes available large data sets to determine the nature and extent of this effect. We employ an all-sky sample, comprising of >15 000 stars, to determine empirical relationships between luminosity, temperature, and radius. This is accomplished using only geometric distances and multiwave-band photometry, by utilizing a modified spectral energy distribution fitting method. The radii we measure show an inflation of $3\!-\!7{{\ \rm per\ cent}}$ compared to models, but no more than a $1\!-\!2{{\ \rm per\ cent}}$ intrinsic spread in the inflated sequence. We show that we are currently able to determine M-dwarf radii to an accuracy of $2.4{{\ \rm per\ cent}}$ using our method. However, we determine that this is limited by the precision of metallicity measurements, which contribute $1.7{{\ \rm per\ cent}}$ to the measured radius scatter. We also present evidence that stellar magnetism is currently unable to explain radius inflation in M-dwarfs.
The potassium absorption on HD189733b and HD209458b
Authors: Keles Engin , Mallonn Matthias , von Essen Carolina , Carroll Thorsten A , Alexoudi Xanthippi , Pino Lorenzo , Ilyin Ilya , Poppenhäger Katja , Kitzmann Daniel , Nascimbeni Valerio , Turner Jake D , Strassmeier Klaus G
Published: August 2019

In this work, we investigate the potassium excess absorption around 7699 Å of the exoplanets HD189733b and HD209458b. For this purpose, we used high-spectral resolution transit observations acquired with the 2 × 8.4 m Large Binocular Telescope (LBT) and the Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI). For a bandwidth of 0.8 Å, we present a detection >7σ with an absorption level of 0.18 per cent for HD189733b. Applying the same analysis to HD209458b, we can set 3σ upper limit of 0.09 per cent, even though we do not detect a K-excess absorption. The investigation suggests that the K feature is less present in the atmosphere of HD209458b than in the one of HD189733b. This comparison confirms previous claims that the atmospheres of these two planets must have fundamentally different properties.
Diversification of Retinoblastoma Protein Function Associated with Cis and Trans Adaptations
Authors: Mouawad Rima , Prasad Jaideep , Thorley Dominic , Himadewi Pamela , Kadiyala Dhruva , Wilson Nathan , Kapranov Philipp , Arnosti David N
Published: August 2019

Retinoblastoma proteins are eukaryotic transcriptional corepressors that play central roles in cell cycle control, among other functions. Although most metazoan genomes encode a single retinoblastoma protein, gene duplications have occurred at least twice: in the vertebrate lineage, leading to Rb, p107, and p130, and in Drosophila, an ancestral Rbf1 gene and a derived Rbf2 gene. Structurally, Rbf1 resembles p107 and p130, and mutation of the gene is lethal. Rbf2 is more divergent and mutation does not lead to lethality. However, the retention of Rbf2 >60 My in Drosophila points to essential functions, which prior cell-based assays have been unable to elucidate. Here, using genomic approaches, we provide new insights on the function of Rbf2. Strikingly, we show that Rbf2 regulates a set of cell growth-related genes and can antagonize Rbf1 on specific genes. These unique properties have important implications for the fly; Rbf2 mutants show reduced egg laying, and lifespan is reduced in females and males. Structural alterations in conserved regions of Rbf2 gene suggest that it was sub- or neofunctionalized to develop specific regulatory specificity and activity. We define cis-regulatory features of Rbf2 target genes that allow preferential repression by this protein, indicating that it is not a weaker version of Rbf1 as previously thought. The specialization of retinoblastoma function in Drosophila may reflect a parallel evolution found in vertebrates, and raises the possibility that cell growth control is equally important to cell cycle function for this conserved family of transcriptional corepressors.
Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Closure of Myelomeningocele Within 48 Hours to Decrease Infection Risk
Authors: Beier Alexandra D , Nikas Dimitrios C , Assassi Nadege , Bauer David F , Blount Jeffrey P , Durham Susan R , Flannery Ann Marie , Klimo Paul , McClung-Smith Catherine , Rehring Patricia , Tamber Mandeep S , Tyagi Rachana , Mazzola Catherine A
Published: August 2019

BACKGROUND

Appropriate timing for closure of myelomeningocele (MM) varies in the literature. Older studies present 48 h as the timeframe after which infection complication rates rise.

OBJECTIVE

The objective of this guideline is to determine if closing the MM within 48 h decreases the risk of wound infection or ventriculitis.

METHODS

The Guidelines Task Force developed search terms and strategies used to search PubMed and Embase for relevant literature published between 1966 and September 2016. Strict inclusion/exclusion criteria were used to screen abstracts and to develop a list of relevant articles for full-text review. Full text articles were then reviewed and when appropriate, included in the evidentiary table. The class of evidence was evaluated, discussed, and assigned to each study that met inclusion criteria.

RESULTS

A total of 148 abstracts were identified and reviewed. A total of 31 articles were selected for full text analysis. Only 4 of these studies met inclusion criteria.

CONCLUSION

There is insufficient evidence that operating within 48 h decreases risk of wound infection or ventriculitis in 1 Class III study. There is 1 Class III study that provides evidence of global increase in postoperative infection after 48 h, but is not specific to wound infection or ventriculitis. There is 1 Class III study that provides evidence if surgery is going to be delayed greater than 48 h, antibiotics should be given.

The full guideline can be found at https://www.cns.org/guidelines/guidelines-spina-bifida-chapter-4.
BSCI-05. HOW MICROGLIA, BRAIN RESIDENT MYELOID CELLS, RESPOND TO BREAST CANCER METASTASIS INTO THE BRAIN?
Authors: Wojnicki Kamil , Kochalska Agata , Gieryng Anna , Czernicki Tomasz , Matyja Ewa , Kaminska Bozena
Published: August 2019

Brain metastasis from different cancers, including lung, breast, melanoma, colorectal or renal cell carcinoma is relatively common and its frequency increases with a prolonged survival of cancer patients. New anti-cancer therapies frequently fail to reduce metastatic burden. While the important role of tumor-associated macrophages as pro-tumorigenic cells facilitating tissue remodeling, invasion and metastasis is well documented, much less is known about the immune microenvironment of brain metastases and potential mechanisms that mediate interactions of cancer cells with brain immune cells - microglia. Triple-negative breast cancer metastases to the brain were discovered in 46% of patients. We evaluated the abundance and morphology of microglia on sections from breast cancer metastases using immunohistochemistry. We found that microglia cells are activated, surround the breast tumor cells and do not infiltrate the solid tumor. Searching for a potential attractant of microglia, we determined osteopontin levels in six human breast cancer cell lines and found upregulation of osteopontin in transformed cells, with the highest level in the triple-negative MDA-MB-231 cells. MDA-MB-231 cells activated primary murine microglia cultures when co-cultured. Invasion of MDA-MB-231 cells in co-cultures with murine immortalized BV2 microglial cells and human SV40 immortalized microglia was increased, as demonstrated using Matrigel Invasion Assay. Using immunofluorescence we detected osteopontin in cancer cells in human breast cancer metastases. Moreover, we found that minocycline, a clinically used antibiotic, reduces the osteopontin production in human breast cancer cells and the most sensitive cells were MDA-MB-231 cells. Our study shows that metastatic cancer cells may employ microglia to facilitate extravasation and colonization of brain parenchyma. We postulate that osteopontin mediates interactions between microglia and metastatic cancer cells and minocycline may interfere with those interactions. Funding: TEAM TECH CORE FACILITY FNP: Development of comprehensive diagnostics and personalized therapy in neuro-oncology
LPTO-09. INTRATHECAL TOPOTECAN FOR LEPTOMENINGEAL METASTASIS IN SOLID TUMORS: THE MD ANDERSON EXPERIENCE
Authors: Sinicrope Kaylyn D , Barata Pedro , Walker Julie , Tremont-Lukats Ivo W , Groves Morris , Loghin Monica , Seligman Christa , Ferguson Sherise , Weathers Shiao-Pei , Penas-Prado Marta , Kamiya-Matsuoka Carlos , Harrison Rebecca , Tummala Sudhakar , Trevino Christopher R , Peinado Shanta , Murthy Rashmi K , Seyedeh Dibaj , de Groot John , O’Brien Barbara
Published: August 2019

BACKGROUND: Leptomeningeal metastasis (LM) is a devastating complication of cancer resulting in progressive neurologic decline. Although intrathecal (IT) methotrexate and cytarabine are commonly used for solid tumor LM, we routinely use IT topotecan due to previously demonstrated similar efficacy and modest side effect profile. We report updated data on our experience. METHODS: We reviewed clinical records of patients with solid tumor LM treated with IT topotecan at MD Anderson Cancer Center from 2008–2018. Patient characteristics and course were summarized by descriptive statistics. Overall survival (OS) was estimated with Kaplan-Meier, and the association of KPS with OS evaluated with log-rank test. RESULTS: 138 patients were treated with IT topotecan. The median age was 54 years (range, 22–76), 81% were female. Breast cancer (62%) was the most common primary, then lung (21%), melanoma (4%). Median time from primary diagnosis to LM was 3.4 (range, 0.07–25.2) years. LM was diagnosed by CSF cytology alone in 8 (6%), MRI alone in 21 (15%), CSF+MRI in 108 (78%). Patients most commonly presented with headache (39%) or sensory changes (18%), and had a median KPS of 80 (range, 60–100). 66% had prior/concurrent brain metastasis. 71 patients (52%) received WBRT following LM diagnosis. 41% had adverse effects, most commonly nausea/vomiting (22%) and headache (20%). The majority were grade 1 (63%); 7 were grade 4 (2 Ommaya malfunctions and 5 infections). Patients received a median of 9 (range, 1–79) doses, most stopped due to CNS progression (42%). Median OS was 6.5 months (95% CI 4.7, 7.8). OS was 3.8 mos with KPS ≤70, vs. 7.5 mos with KPS >70 (p< 0.001). CONCLUSIONS: IT topotecan has a modest side effect profile. Patients with higher functional status at diagnosis had significantly better survival. This study supports the continued use of IT topotecan as a well-tolerated option for LM.
TRLS-07. BRAINSTORM: OUTCOMES FROM A MULTI-INSTITUTIONAL PHASE I/II STUDY OF RRx-001 IN COMBINATION WITH WHOLE BRAIN RADIATION THERAPY FOR PATIENTS WITH BRAIN METASTASES
Authors: Kim Michelle , Parmar Hemant , Schipper Matthew , Devasia Theresa , Aryal Madhava , Kesari Santosh , O’Day Steven , Morikawa Aki , Spratt Daniel , Junck Larry , Mammoser Aaron , Hayman James , Lawrence Theodore , Tsien Christina , Aiken Robert , Goyal Sharad , Abrouk Nacer , Trimble Malcolm , Cao Yue , Lao Christopher
Published: August 2019

INTRODUCTION: To determine the recommended Phase II dose of RRx-001, a radiosensitizer with vascular normalizing properties, when used with whole-brain radiation therapy (WBRT) for brain metastases, and to assess whether quantitative changes in perfusion MRI after RRx-001 correlate with response. METHODS AND MATERIALS: Five centers participated in this phase I/II trial of RRx-001 given once pre-WBRT then twice weekly during WBRT (30 Gy/10 fractions). Four dose levels were planned (5 mg/m2, 8.4 mg/m2, 16.5 mg/m2, 27.5 mg/m2). Dose-escalation was managed by the Time-to-Event Continual Reassessment Model (TITE-CRM). Correlative DCE-MRI was performed in a subset of patients and linear mixed models used to correlate change in 24-hour T1, Ktrans (capillary permeability) and Vp (plasma volume) with change in tumor volume. RESULTS: Between 2015–2017, 31 patients were enrolled. Two patients dropped out prior to any therapy and 7 were treated with concurrent temozolomide following a study amendment. Median age was 60 years (range, 30–76) and 17 were male. The most common tumor types were melanoma (58%) and non-small cell lung cancer (20%). No dose-limiting toxicities were observed. The most common severe adverse event was grade 3 asthenia in 6.9% (2/29). The median intracranial response rate was 46% (95%CI 24–68) and median overall survival was 5.2 months (95%CI 4.5–9.4). No neurologic deaths occurred. Among 10 evaluable patients undergoing DCE-MRI, a reduction in Vp 24 hours after RRx-001 was associated with reduced tumor volume at 1 month and 4 months (p≤0.01). CONCLUSION: The addition of RRx-001 to WBRT is safe and well-tolerated with favorable intracranial response rates. Because activity was observed across all dose levels, and in the absence of a dose response, the recommended Phase 2 dose is 10 mg administered twice weekly. A reduction in Vp by DCE-MRI 24 hours after RRx-001 suggests anti-angiogenic activity that is associated with longer-term tumor response.
OTHR-14. TREATMENT MONITORING OF IMMUNOTHERAPY AND TARGETED THERAPY USING FET PET IN PATIENTS WITH MELANOMA AND LUNG CANCER BRAIN METASTASES: INITIAL EXPERIENCES
Authors: Galldiks Norbert , Abdulla Diana , Scheffler Matthias , Schweinsberg Viola , Schlaak Max , Kreuzberg Nicole , Landsberg Jenny , Lohmann Philipp , Ceccon Garry , Werner Jan-Michael , Celik Eren , Ruge Maximilian , Kocher Martin , Marnitz Simone , Fink Gereon , Langen Karl-Josef , Wolf Juergen , Mauch Cornelia
Published: August 2019

BACKGROUND: Due to the lack of specificity of contrast-enhanced (CE) MRI, both the response assessment and differentiation of progression from pseudoprogression (PsP) following immunotherapy using checkpoint inhibitors (ICI) or targeted therapy (TT) may be challenging, especially when ICI or TT is applied in combination with radiotherapy (RT). Here, we evaluated the value of amino acid PET using O-(2-[18F]fluoroethyl)-L-tyrosine (FET) as a problem-solving tool in comparison to CE-MRI in patients with brain metastases (BM) secondary to malignant melanoma (MM) and NSCLC. METHODS: We retrospectively identified 31 patients with 74 BM secondary to MM (n=20 with 42 BM) and NSCLC (n=11 with 32 BM) who underwent 52 FET-PET scans during the course of disease. All patients had RT prior to ICI or TT initiation (61%) or RT concurrent to ICI or TT (39%). In 13 patients, FET-PET was performed for treatment response assessment of ICI or TT using baseline and follow-up scans (median time between scans, 4.2 months). In the remaining 18 patients, FET-PET was used for the differentiation of progression from PsP related to RT plus ICI or TT. In all BM, metabolic activity on FET-PET was evaluated by calculation of tumor/brain ratios. FET-PET imaging findings were compared to CE-MRI and correlated to the clinical follow-up or neuropathological findings after neuroimaging. RESULTS: In 4 of 13 patients (31%), FET-PET provided additional information for treatment response evaluation beyond the information provided by CE-MRI alone. Furthermore, responding patients on FET-PET had a median stable clinical follow-up of 10 months. In 10 of 18 patients (56%) with CE-MRI findings suggesting progression, FET-PET detected PsP. In 9 of these 10 patients, PsP was confirmed by a median stable clinical follow-up of 11 months. CONCLUSIONS: FET-PET may add valuable information for treatment monitoring in individual BM patients undergoing RT in combination with ICI or TT.
RADI-23. CLINICAL RISK ASSESSMENT SCORE TO ESTIMATE THE LIKELIHOOD OF PSEUDOPROGRESSION VERSUS TUMOR RECURRENCE FOLLOWING STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES
Authors: Skeie Bente Sandvei , Enger Per Øyvind , Pedersen Paal-Henning , Skeie Geir Olve
Published: August 2019

OBJECTIVE: A major challenge in the follow-up of patients managed with stereotactic radiosurgery (SRS) for brain metastases (BM) is to differentiate pseudoprogression (PP) from tumor recurrence (TR). A clinical score based on tumor and treatment related factors would be valuable when selecting appropriate treatment. MATERIAL AND METHODS: Follow-up images of 97 consecutive patients treated with SRS for 406 BM were analyzed. Of these 100 (24.6 %) BM in 48 (49.5 %) patients responded either with TR (delayed growth; 53 (13.1 %) BM) or PP (temporary volume increase; 47 (11.6 %) BM). Differences between the 2 groups were analyzed and used to develop a PP risk assessment score (PP-RAS). RESULTS: Significant factors associated with a higher incidence of PP versus TR were: primary lung cancer vs. other primaries, BM volume ≤ 2cc (or BM ≤ 1.5 cm in diameter), Target cover ratio > 98 % and prior radiation SRS or WBRT. Based on the presence (0) or not (1) of these 5 parameters, a risk assessment score for PP versus TR was established. A PP-RAS score of 0 corresponds with high likelihood of PP vs. TR, whereas a score of 5 corresponds with a high risk of TR. A score of ≤ 1 point was associated with 100 % PP, 2 points with 57 % PP and 43 % TR, 3 points with 57 % TR and 43 % PP, whereas ≥ 4 points were associated with 84 % TR and 16 % PP, π=24.57, df =4, p < 0.001). CONCLUSION: Based on these 5 parameters at the time of SRS our risk assessment score could robustly differentiate between PP versus growth following SRS. The score is user-friendly and may be a useful tool to guide the decision making whether to retreat or observe at appropriate follow-up intervals.
RADI-24. VENTRICULOMEGALY AFTER STEREOTACTIC RADIOSURGERY (SRS) FOR BRAIN METASTASES (BM): A PILOT ANALYSIS OF TWO INSTITUTIONAL EXPERIENCES
Authors: Alattar Ali , Bartek Jiri , HIrshman Brian , Chen Clark
Published: August 2019

INTRODUCTION: Ventriculomegaly, or dilatation of the cerebrospinal fluid (CSF) space, occurs after whole-brain radiation (WBRT) of brain metastasis (BM) patients due to either 1) hydrocephalus or 2) cerebral atrophy from radiation-induced white matter injury. In this study, we examined whether cumulative radiation from repeat stereotactic radiosurgery (SRS) increases the risk of ventriculomegaly. METHODS: Patients were included if they underwent SRS of BM from 2007–2017 and had imaging follow-up. We examined a cohort of 214 patients treated at the University of California San Diego (1,106 BM) and a second cohort of 148 patients (1,760 BM) treated at Karolinska Institutet. Ventriculomegaly was defined according to established morphometric criteria. Patients were grouped according to the development of new ventriculomegaly at last follow-up. Demographic, clinical, and dosimetric factors were compared between groups using univariable and multivariable logistic regressions. RESULTS: In the UCSD cohort, 63 patients (29%) presented with ventriculomegaly before SRS. Of 151 remaining patients with normal ventricular size before first SRS, 30 (20%) developed new ventriculomegaly. The odds of developing ventriculomegaly increased with history of WBRT (OR 5.247, p< 0.001) and trended toward significance with a greater number of SRS treatments (OR 1.296, p=0.075). In the Karolinska cohort, the odds of developing new ventriculomegaly trended towards significance with a greater number of SRS treatments (OR 1.605, p=0.26). To test whether this trend would achieve significance in a larger sample, we repeated the analysis in the combined cohort of 362 patients. The association between number of SRS treatments and developing ventriculomegaly reached significance (OR 1.254, p=0.049). CONCLUSIONS: These pilot findings suggest that cumulative radiation from repeat stereotactic radiosurgery (SRS) potentially increases the risk of ventriculomegaly. Based on our study, a prospective study of >350 patients will be needed to further test this hypothesis.
RADI-27. ROLE OF STEREOTACTIC RADIOSURGERY IN THE CARE OF PATIENTS WITH >/= 25 CUMULATIVE BRAIN METASTASES
Authors: Benjamin Carolina , Mureb Monica , Donahue Bernadine , Sulman Erik , Silverman Joshua , Bernstein Kenneth , Kondziolka Douglas
Published: August 2019

INTRODUCTION: Stereotactic radiosurgery (SRS) is an accepted treatment for multiple brain metastases. However, the upper limit of the number of brain metastases over the course of care suitable for this approach is controversial. METHODS: From a review of our prospective registry, 48 patients treated with SRS for ≥ 25 brain metastases in either single or multiple sessions between 2013 and 2019 were identified. Patient, tumor, and treatments characteristics were evaluated. Clinical outcomes and overall survival (OS) were analyzed. RESULTS: Thirty-one females (64.6%) and 17 males (35.4%) with a median age of 56 years (25–91) were included. Primary diagnoses included lung (n=23, 47.9%), breast (n=13, 27.1%), melanoma (n=8, 16.7%), and other (n=4, 8.33%). Initial median GPA index was 2 (0.5–3). Nine patients (18.8%) had received whole brain radiation therapy (WBRT) prior to first SRS treatment, with a median dose of 35Gy (30–40.5Gy). Ten patients (20.8%) received WBRT after initial SRS, with a median dose of 30Gy (20-30Gy). Thus, only 19 patients (40%) ever received WBRT. Median number of radiosurgeries per patient was 3 (1–12). Median number of cumulative tumors irradiated was 31 (25–110). Median number of tumors irradiated at first SRS was 10 (1–35). Median marginal dose for the largest tumor per session was 16Gy (10-21Gy). Median SRS total tumor volume was 6.8cc (0.8–23.4). Median follow-up since initial SRS was 16 months (1–71). At present, 21 (43.7%) are alive. Median OS from the diagnosis of brain metastases was 31 months (2–97), and OS from the time of first SRS, 22 months (1–70). Median KPS at first SRS and last follow-up was the same (90). Sixty-three percent did not require a corticosteroid course. CONCLUSION: In selected patients with a large number of cumulative brain metastases (≥ 25), SRS is effective and safe. Therefore, WBRT may not be required in this population.
RADI-30. TREATMENT OF MULTIPLE BRAIN METASTASES WITH CYBERKNIFE® (CK) INITIAL EXPERIENCE AT THE RADIONCOLOGY DEPARTMENT JÚLIO TEIXEIRA SA – PORTO – PORTUGAL
Authors: Costa Maria Adelina , Vale Joana , Silva Catarina , Campos Guilherme , Fonseca Graça , Cavaco Ana , Guedes Ricardo , Genésio Paula , Rodrigues Fátima , Conde João , Calçada Cármen , Fardilha Carlos , Ponte Fernanda , Costa Paulo
Published: August 2019

Brain metastases (BM) represent an important cause of morbidity and mortality being the most common intracranial tumors in adults. Their incidence is rising for several reasons: an aging population, better systemic treatment and better diagnostic imaging techniques allowing the detection of smaller metastases in asymptomatic patients. Traditionally, the most widely used treatment for patients with multiple BM is whole brain radiation therapy (WBRT), which remains a source of debate because, although distant brain control rates have been shown to be greater with WBRT, it has no impact on overall survival and the negative effects on cognition and quality of life are higher. Radiosurgery plays a significant role in the modern management of BM. We analyzed 38 patients with multiple BM (13 with more than one treatment, totalizing 61 cases) treated with CyberKnife® (CK) in the Radioncology Department Júlio Teixeira SA, from August 2016 to February 2019, for a total of 178 lesions. The average volume was 9,2cc (0,01-73,2). Total dose ranged 18-30Gy delivered in 1–5 fractions. The average nCI was 1,23 (0,19-1,69). Tumor coverage of at least 95% was obtained by prescribing the therapeutic dose to isodose lines ranging from 69–90%. Whole brain tissue was outlined as a critical structure. The average volume of 14Gy (single fraction) and 23Gy (multiple fractions) for normal brain tissue was 6,35cc and 12,4cc, respectively. The treatment was well tolerated, with improvement or resolution of the initial neurological symptoms. Among all radiosurgical platforms the CK offers the advantage of delivering with stereotactic precision high doses of radiation without the invasive attachment of a localizing frame. As a result, in many cases, became the method of choice for treating multiple brain metastases. The attractive therapeutic profile of CK radiosurgery is reflected by a high tumor control and low toxicity allowing retreatment for recurrent metastases.
The Impact of E-liquid Propylene Glycol and Vegetable Glycerin Ratio on Ratings of Subjective Effects, Reinforcement Value, and Use in Current Smokers
Authors: Smith Tracy T , Heckman Bryan W , Wahlquist Amy E , Cummings K Michael , Carpenter Matthew J
Published: August 2019

Introduction

Electronic nicotine delivery systems (ENDS) vary on a wide range of characteristics that may affect reinforcement value and use. One characteristic is the ratio of two solvents commonly used in most e-liquids: propylene glycol (PG) and vegetable glycerin (VG). The goal of this study was to understand how PG/VG ratio affects subjective effects, reinforcement value, and tobacco use patterns among current smokers who try using ENDS.

Aims and Methods

Current smokers with minimal ENDS use history (n = 30) sampled, in a double-blind fashion, three different e-liquids that varied in PG/VG ratio (70/30, 50/50, 0/100) while holding constant other aspects of the e-liquid and ENDS. Participants tried each e-liquid before rating the subjective effects on a modified version of the Cigarette Evaluation Questionnaire. Reinforcement value was assessed using a preference task where participants chose between the three e-liquids. The impact of each e-liquid on cigarette reinforcement was assessed using a modified version of the Cigarette Purchase Task. Participants were randomly assigned to receive one e-liquid to take home for 1 week.

Results

PG/VG ratio had minimal impact on most of the tested outcomes. Participants rated the highest PG concentration as having a stronger “throat hit” than the other two. There was no significant difference between the number of participants who preferred each of the PG/VG ratios in the preference assessment. PG/VG ratio did not affect cigarette or ENDS use during the sampling week.

Conclusions

These data suggest that PG/VG ratio has minimal impact on subjective effects and reinforcement value in ENDS naive current smokers.

Implications

These data suggest that PG/VG ratio, within the range that is commonly used, has minimal impact on subjective effects, reinforcement value, or uptake in current smokers with minimal ENDS experience.
High Rates of Menthol Cigarette Use Among Pregnant Smokers: Preliminary Findings and Call for Future Research
Authors: Stroud Laura R , Vergara-Lopez Chrystal , McCallum Meaghan , Gaffey Allison E , Corey Alana , Niaura Raymond
Published: August 2019

Introduction

Smoking during pregnancy remains widespread and is causally associated with infant morbidity and mortality. Despite links between menthol cigarette use and decreased smoking cessation, little is known regarding rates or characteristics of pregnant menthol cigarette smokers.

Methods

Participants were drawn from two low-income, racially/ethnically diverse cohorts of pregnant smokers recruited from 2006 to 2015 (N = 166, Mage = 25 ± 5). Demographics, menthol cigarette use, daily cigarette use, quit status, and consecutive weeks quit were assessed by prospective interviews. Nicotine dependence was assessed using the Fagerström Test of Nicotine Dependence. Nicotine levels were assessed via saliva cotinine.

Results

High rates of menthol use were found in both cohorts (85% and 87%). Across both cohorts, menthol smokers were more likely to identify as racial/ethnic minorities, were less educated, and reported lower income than non-menthol smokers (ps < .03). Menthol smokers also reported fewer continuous weeks quit (8.4 vs. 14.5 weeks quit; p < .03) and a tendency toward decreased likelihood of quitting smoking over pregnancy (29% vs. 48%; p < .08) in unadjusted but not in covariate-adjusted analyses. No differences emerged in cigarettes per day, nicotine dependence or nicotine exposure.

Conclusions

We found very high rates of menthol cigarette use in pregnant smokers—particularly among racial/ethnic minority and low socioeconomic status smokers—and some evidence for associations with reduced smoking cessation in pregnancy. Consideration of pregnant smokers as a uniquely vulnerable population is warranted in evaluating regulation of menthol in cigarettes. Further research is needed regarding the impact of menthol on smoking persistence in pregnancy and on maternal and infant health outcomes.

Implications

This study highlights high rates of menthol cigarette use in pregnant women in the Northeast, United States, with evidence for higher rates of menthol use among racial/ethnic minority, less educated and low-income pregnant smokers, and preliminary evidence for associations between menthol cigarette use and reduced smoking cessation. Consideration of the effects of menthol on smoking persistence in pregnant women and on the health of their offspring is warranted in the development of regulations regarding menthol in cigarettes.
Sofosbuvir Add-on to Ribavirin Treatment for Chronic Hepatitis E Virus Infection in Solid Organ Transplant Recipients Does Not Result in Sustained Virological Response
Authors: van Wezel E M , de Bruijne J , Damman K , Bijmolen M , van den Berg A P , Verschuuren E A M , Ruigrok G A , Riezebos-Brilman A , Knoester M
Published: August 2019

Ribavirin is effective for treating immunocompromised patients with chronic hepatitis E virus infection. However, ribavirin treatment is not always successful. We describe 3 solid organ transplant recipients treated with sofosbuvir and ribavirin after failing ribavirin monotherapy. Complete elimination of hepatitis E virus could not be achieved.
Global Health Politics
Authors: McInnes Colin , Lee Kelley , Youde Jeremy
Published: August 2019

Global health politics has emerged over the last two decades as a distinct interdisciplinary field of study which, although its boundaries are not set, is beginning to demonstrate signs of maturity. It is concerned with the actions, practices, and policies that govern the sphere of global health. Its emergence then is intimately linked with the reconceptualisation of health as global. The field addresses not only the processes of decision-making, but also the structures of power that shape what is possible and the requirement for collective action to address global problems. Politics is unavoidable, necessary and integral to effectively addressing global health challenges. The study of global health politics therefore is not about how to minimise interference in rational decision-making, but rather about explaining and improving the quality of political institutions and processes that will in turn improve global health actions and ultimately outcomes. Fundamental to this is an understanding of the nature of politics and the workings of power. But the field also requires knowledge and techniques from a variety of disciplines, which intersect to produce a more complete understanding than any one discipline can provide. The result is inherently both multi- and interdisciplinary, characterised by methodological pluralism and varied theoretical perspectives.
Shifting Metaphors in the Conceptualization of Musical Knowledge and Learning
Authors: Dyndahl Petter
Published: August 2019

In a chapter that takes its point of departure in a prophetic citation concerning sound and music by Francis Bacon, Petter Dyndahl examines how different epistemological positions and metaphors can contribute to the imagination and understanding of musical knowledge and learning. Dyndahl’s main focus is on discourses regarding these subjects, and he considers how knowledge in music both consists of, and is expressed by and communicated via, musical imagination. In doing so, Dyndahl discusses how different kinds of metaphors and tools are central to learning in general and how the presented approaches and perspectives, in terms of music and music education, are relevant to learning communities and to educational and professional fields of music.
Noise and Tranquility at Stonehenge
Authors: Berkaak Odd Are
Published: August 2019

By tracing archaeological, poetic, artistic, literary, legal, and political factors, Odd Are Berkaak investigates and discusses a number of controversies surrounding the sound environment at the world-famous prehistoric monument Stonehenge. Berkaak pieces together an understanding of how imagination—as built on subjective impressions, on the one side, and on collectively constructed cognitive schema, on the other—links the sensory experience of tranquility and the cultural category of dignity. In his quest, Berkaak touches on a number of aspects ranging from the promotion of cultural heritage to painting and literature.
Embodied Listening
Authors: Huvenne Martine
Published: August 2019

Martine Huvenne discusses how imagined worlds in film originate in human bodily resonance in correspondence with movements in the sounds themselves and not solely in the interaction between the audio and the visual. In addition to her own research, Huvenne bases her chapter on a case study of the work and practice of the sound designer Nicolas Becker, in this way using informed knowledge and insight from the producer’s perspective. She argues that sounds can reveal invisible aspects of characters, relationships, and inner worlds, allowing an audience to experience a lived world, thereby providing perceptual elements that enables it to create an imagined world.
Presence, Environment, and Sound and the Role of Imagination
Authors: Grimshaw-Aagaard Mark
Published: August 2019

Mark Grimshaw-Aagaard addresses the role of sound in the creation of presence in virtual and actual worlds. He argues that imagination is a central part of the generation and selection of perceptual hypotheses—models of the world in which we can act—that emerge from what Grimshaw-Aagaard calls the “exo-environment” (the sensory input) and the “endo-environment” (the cognitive input). Grimshaw-Aagaard further divides the exo-environment into a primarily auditory and a primarily visual dimension and he deals with the actual world of his own apartment and the virtual world of first-person-shooter computer games in order to exemplify how we perceptually construct an environment that allows for the creation of presence.
Auditory Mirrors
Authors: Sanio Sabine
Published: August 2019

With the general goal of describing “how music understands itself socially and politically,” Sabine Sanio starts out by focusing on the musical neo-avant-garde, and especially on John Cage, and continues by discussing aspects of the musical idea of space. Although her chapter draws on several threads reaching back to the beginning of the twentieth century, the central topics of the chapter are current issues dealing with musical explorations of the sound itself, modern data technologies, and public spaces. Using a number of examples, Sanio discusses how the relationship between composers and audiences is both socially and aesthetically challenged by redefinitions of the concept of space and character of the musical live event—or live-like event.
Introduction
Authors: Grimshaw-Aagaard Mark , Walther-Hansen Mads , Knakkergaard Martin
Published: August 2019

The Oxford Handbook of Sound and Imagination is a two-volume anthology that covers the topic of imagination in the context of sound and music. There are seventy chapters in ten parts across two volumes that present thinking and research on the topic from a broad multidisciplinary perspective, and the fields of study represented include (but are not limited to): music (composition, improvisation, philosophy, therapy, and so forth); sound studies; acoustics and bioacoustics; cognition and neurology; psychology; literature, poetry, and comics; heritage studies; anthropology; branding and advertising; audio technology; film studies; computer games and virtual reality; and aesthetics. Volume 1 of the handbook contains thirty-nine chapters organized across five parts (“Foundations,” “Society and Identity,” “Language,” “Image,” and “Space and Place”).
Imagination, Multimodality, and Sound
Authors: Braga Joaquim
Published: August 2019

Joaquim Braga deals with the role of sound in multimodal environments and multimodal surfaces. He argues that imagination not only bridges sensory dimensions that are absent from perception but also is central to “the relationship of presence,” that is, the connection between presently perceived sensory input. This involves assessing both the individuating dimension and the relational disposition of sound, which allows sound—through the activation of imagination—to develop sensory relations. Central to his discussion of the function and contribution of sound in different media is the process of “sonic individuation”—a process of individuation of different modalities—that is presented as a precondition for the creation of relations between these modalities.
Music Analysis and Data Compression
Authors: Meredith David
Published: August 2019

David Meredith focuses on how the musical knowledge that underpins both music perception and musical imagery can be acquired by compressing musical information. He works from the notion that the goal of music analysis is to find the best possible explanations for the structures of musical “objects,” such as individual works or movements as well as extracts from works or collections of works. In opposition to what Meredith considers to be the subjectively grounded evaluation of different analyses of the same music that is carried out by music analysts adopting a humanistic approach, he proposes that the relative quality of two analyses of the same object can be measured in terms of how well they allow us to carry out objectively evaluable tasks, such as recognizing composers or genres, or finding errors in musical data.
A Different Way of Imagining Sound
Authors: Ockelford Adam
Published: August 2019

Adam Ockelford draws attention to that section of the population that tends not to engage in everyday listening in the usual way; those for whom the acoustic properties of sound are prioritized over its function. In particular, Ockelford points to the listening of autistic children for whom the perceptual qualities of sound exert an especial fascination at the expense of the meaning that everyday listening normally offers. Through research that supports his contention that the development of musical abilities in children precedes that of language skills, Ockelford makes the claim that the aural imagination of some of those on the autism spectrum is one that processes all sounds, even speech, for their music-structural properties and thus it is music that is the autistic person’s gateway to communication and empathy.
The Aesthetics of Improvisation
Authors: Hamilton Andy
Published: August 2019

In his chapter on musical improvisation, Andy Hamilton deals with the cultural aspects and historical practices of the subject. Hamilton sets out to explore the artistic status of improvised music, and this involves a discussion of the connection between imagination and art and the differences between composition and improvisation. These discussions provide a theoretical framework to outline and defend an aesthetics of imperfection as a contrast to an aesthetics of perfection. Finally, the artistic value of jazz as an improvised art form is discussed and Hamilton ponders whether jazz music should be described as art music or as a form of classical music.