bluuebunny/crossref_metadata_2025 huggingface dataset:
RADI-18. STEREOTACTIC RADIOSURGERY OR FRACTIONATED STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES FROM SMALL CELL LUNG CANCER
Authors: Thomas Evan , Travis Roman , Boggs D Hunter , Marcrom Sam , Markert James , Spencer Sharon , Riley Kristen , Strickler Scott , Bredel Markus , Willey Christopher , Guthrie Bart , Fiveash John
Published: August 2019

BACKGROUND: Current standard of care (SOC) management of the brain differs between non-small cell lung cancer (NSCLC) & small cell lung cancer (SCLC). For SCLC, WBRT is considered SOC, even for solitary metastasis. In the setting of no-known metastases, prophylactic cranial irradiation (PCI) is considered SOC. SRS is occasionally utilized in SCLC, e.g. in setting of limited metastasis after WBRT/PCI, or limited metastasis after excellent systemic response to extracranial therapy, or if patient declines WBRT. In this study, we sought to understand more about the nature and outcomes of patients with SCLC who received intracranial SRS at our institution. METHODS: We reviewed radiosurgery treatments from 2005 thru 2019 for patients with SCLC who received SRS. Variables included were: time interval between diagnosis/SRS and death, prior WBRT/ PCI, number of targets, performance status, modality (GK or linac), prior surgery, and available follow-up. RESULTS: We identified 92 SRS treatments among 74 patients. 30 received upfront SRS, the remainder as post-WBRT/PCI salvage. Median survival after initial diagnosis was 22.0 months (min = 6.6, max 55.4). Median survival after first SRS was 6.1 months (min = 0.5, max = 40.4). Median recorded KPS was 75.6. Mean number of mets treated was 3.4 (min = 1, max = 12). Prescription dose range was 12 to 20Gy in single fraction, and 25 to 30Gy in five fraction treatment. 53 treatments were performed on Gamma Knife, 37 with linear accelerator. Four patients were treated post-operatively, one patient was treated pre-operatively. CONCLUSIONS: Survival in our cohort of SCLC patients receiving intracranial SRS compared favorably with historical SCLC controls (8-13mo after dx). Future work will seek to clarify whether there is a difference in brain metastasis velocity between patients treated with upfront PCI/WBRT or SRS, and also seek to address the minimum necessary dose to control SCLC metastases.
RADI-26. DOSIMETRIC EVALUATION OF 6 MV VERSUS 10 MV PHOTONS FOR HIPPOCAMPAL AVOIDANCE WHOLE BRAIN RADIOTHERAPY
Authors: Julie Diana , Mahase Sean , No Diana , Salah Khaled , Knisely Jonathan
Published: August 2019

OBJECTIVE: Whole brain radiotherapy (WBRT) causes neurocognitive decline. Hippocampal avoidance WBRT (HA-WBRT) reduces hippocampal irradiation, potentially mitigating neurocognitive sequelae. We compared hippocampal and brain dosimetry with HA-WBRT with 6 megavoltage (MV) versus 10 MV photon energies. METHODS: Twenty consecutive patients treated with WBRT were retrospectively replanned with HA-WBRT techniques using 6 MV and 10 MV photons. Coplanar volumetric modulated arc therapy was employed, with a prescription dose of 3000 cGy in 10 fractions. Planning was done with Eclipse version 13.6 or 15.6. Nine patients were planned with 2.5 mm multileaf collimator leaves, with the remainder planned with 5 mm leaves. The hippocampi were contoured and a HA structure was generated using a uniform 5 mm expansion. A planning target volume (PTV) was defined as the brain parenchyma minus the HA structure. NRG-CC001 dose constraints were used. For each variable, descriptive statistics were calculated. Comparisons were made using two-tailed Wilcoxon signed rank tests or paired t-tests. RESULTS: The minimum hippocampal dose (D100%) was improved with 6 MV plans, 841 cGy compared to 914 cGy with 10 MV (p< 0.005). The maximum hippocampal dose (D0.03cc) was reduced with 6 MV planning, 1614 cGy versus 1676 cGy for 10 MV (p< 0.0001). With 6 MV photons, a greater number of plans met NRG-CC001 constraints without deviations. 6 MV photons improved PTV coverage by the 95% isodose line, 96.6% compared to 95.9% for 10 MV (p=0.021). 6 MV photon plans decreased the volume of PTV receiving ≥105% of the prescription, 84.2% versus 87.9% for 10 MV (p=0.006). The mean dose, hot spots, and cold spots did not differ by photon energy. PTV dose constraints were always met. CONCLUSION: 6 MV photon HA-WBRT plans are dosimetrically superior to 10 MV, reducing hippocampal radiation dose, without compromise in brain coverage and improved target dose homogeneity.
RADI-41. CLINICAL OUTCOMES FOLLOWING RAPID DELIVERY SINGLE ISOCENTER RADIOSURGERY FOR FIVE OR MORE BRAIN METASTASES: VOLUMETRIC MODULATED ARC THERAPY VS. DYNAMIC CONFORMAL ARC
Authors: Vaslow Zachary , Manning Matthew , Sintay Benjamin , Wiant David , Boyles Susan , Stern Joseph
Published: August 2019

BACKGROUND: Recent advances in the delivery of stereotactic radiosurgery (SRS) has led to wider availability and use of this technology. The ability to rapidly delivery radiosurgery to multiple targets utilizing single-isocenter techniques represents an additional step forward for these otherwise time-consuming therapies. The current retrospective study measures and compares clinical outcomes in patients with 5 or more brain metastases treated using a single-isocenter RapidArc (RA) volumetric-modulated arc therapy (VMAT) approach, with those treated using a single-isocenter dynamic conformal arc (DCA) approach. METHODS: We queried retrospectively a radiosurgery database registry of 680 patients from 11/2012- 3/2019. We included patients with 5 or more brain metastases who had documented SRS treatment plans utilizing a single-isocenter approach, either VMAT or DCA. Radiosurgery was delivered using a linac-based platform capable of delivering radiotherapy to multiple simultaneous targets. We obtained information on patient gender, age, number of lesions, primary cancer histology. Patients were separated by collimation plan (VMAT vs DCA); overall survival (OS) was estimated using Kaplan-Meier method. RESULTS: We found 49 patients that met our criteria for inclusion. Median age was 57 yrs. with a majority being females (n=28, 57.2%). Number of targets was between 5 and 20; median number of targets was 7. Most common primary site histology was non-small cell lung (51.0%), followed by breast (14.2%). For DCA collimation group, median OS was 20.5 weeks (95% CI: 12.4, 34.5), with a 6 month OS of 36.0% (95% CI: 19.2%, 54.9%). For VMAT collimation group, median OS was 20.0 weeks (95% CI: 10.8, 46.1), with a 6 month OS of 39.1% (95% CI: 11.3%, N/A). CONCLUSIONS: For patients with 5 or more brain metastases treated with rapid delivery single-isocenter radiosurgery, no significant difference in survival outcomes were demonstrated between DCA and VMAT collimation techniques.
RADI-44. MANAGEMENT OF MULTIPLE BRAIN METASTASES BY STAGED SRS FOCUSING ON UTMOST RISK LESIONS
Authors: Zhen Junjie , Li Shaoqun , Lai Mingyao , Wen Lei , Zhou Cheng , Cai Linbo
Published: August 2019

BACKGROUND: Patients with multiple large brain metastases (LBMs) are subject to cause intracranial hypertension, which remains a clinical difficulty so far. The present study is to investigate whether staged stereotactic radiosurgery (SRS) is a feasible solution to improve clinical symptoms and life quality in palliative management. METHODS: Patients with brain metastases treated between 1 January 2016 and 30 March 2019 were retrospectively studied. The patients inclusion criteria included were: 1) metastatic lesions ≥ 3; 2) tumor lesions with a supratentorial invasion ≥ 3 cm or a subtentorial invasion ≥ 2 cm; 3) with neurological impairment or with a high risk for intracranial hypertension. The first stage of SRS dose regimens for utmost risk supratentorial lesions were 20-24Gy within 2-fractions (fx); whereas 24Gy/3-fx for subtentorial lesions. For the 2nd stage, the rest metastatic lesions with relatively lower risk were treated with 16-18Gy/1-fx one week after that. RESULTS: A total of 30 patients were enrolled included in this study. The neurological symptoms were significantly relieved following 1st stage of SRS, with a median period of 3 days (2–14 days). 13 out of 30 patients were randomly selected for MR imaging two weeks after SRS. It suggested that 84.6% (11/13) of the patients were observed with a clear reduction of tumor volume. The median reduced diameter was 0.38 (0.17–0.83) cm and a median volume reduction was 3.22 (0.01–9.08) mm3. According to RANO-BM, the objective remission rate of utmost risk lesions was 100%, whereas the less critical lesions was 95.16% (59/62). One patient (3.33%) was identified with acute adverse reaction (> grade 3). CONCLUSIONS: Staged SRS with a priority for utmost risk lesions was indicated to be an effective approach for multiple large brain metastases. Further prospective study is highly warranted.
SURG-03. SPATIAL COORDINATES FROM GAMMA KNIFE RADIOSURGERY REVEAL PRIMARY CANCERS HAVE REGIONAL CNS TOPOGRAPHICAL DISTRIBUTION FOR BRAIN METASTASES
Authors: Neman Josh , Franklin Meredith , Madaj Zachary , Triche Tim , Sadlik Gal , Deshpande Krutika , Zada Gabriel
Published: August 2019

Brain metastases arise in the central nervous system (CNS) following spread of circulating mesenchymal-type cells from primary tumors. While accumulating evidence underlines the importance of the neural niche in the establishment and progression of metastases, there still remains ambiguity over CNS anatomical spatial distribution from primary cancers. We evaluated 973 patients with brain metastases (breast, colorectal, lung, melanoma, renal) totaling 2,106 lesions treated from 1994–2015 with gamma knife radiosurgery at the University of Southern California Keck Medical Center for topographical distribution analysis. MRI images of the brain were taken and used in conjunction with the frame to precisely localize tumors and measure their size. Each tumor was given an x, y, and z-coordinate derived from the head frame that corresponded to its volumetric center within a 3-dimensional Cartesian field. Topographical analyses were conducted using logistic and multinomial spatial generalized additive models (GAM). For each cancer origin type we compared the observed brain metastases to set of randomly generated spatial observations to determine whether there were statistically significant localization patterns. Spatial pattern results show: 1) melanoma has highest probability to metastasize to the right frontal (74.5%, 95% confidence interval [Cl] = 63.6%- 85.4%) and to occipital lobe (72.4%, 95% Cl = 65.8%-78.9%), 2) while breast cancers have highest proclivity to metastasize to left cerebellar hemisphere (25%, 95% Cl=16.0%-34.1%) and brainstem (16.6%, 95% Cl= 10.8%-22.4%), 3) with lung tumors metastasizing to the left (23.7%, 95% Cl= 16.0–31.3%) and right parietal (24.7%, 95% Cl=16.7–32.8%), left temporal lobe (25.2%, 95% Cl=21.4%-29.1%). Colon and renal metastases show weak spatial patterns across the CNS. We conclude there is evidence of non-uniform spatial distribution of metastasis in the brain. These tumor-specific CNS topography patterns may underlie the ability of cancer cells to adapt to the regional neural microenvironments in order to facilitate colonization and establishment of metastasis.
SURG-05. LASER INTERSTITIAL THERMAL THERAPY FOR MELANOMA BRAIN METASTASIS: A CASE SERIES
Authors: Palejwala Ali , O’Connor Kyle , Glenn Chad , Sughrue Michael
Published: August 2019

Stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) have been established as non-invasive treatment modalities for intracranial metastasis from malignant melanoma, with SRS emerging as a safe and effective stand along therapy. However, either due to tumor regrowth or radiation necrosis, these radiation modalities can fail. MR-guided laser interstitial thermal therapy (LITT) has emerged as an option for these tumors. Clinical data for five patients at our institution was retrospectively reviewed. These were all the patients that had undergone LITT for intracranial metastatic melanoma after prior treatment failure that included a radiation modality. Demographics, prior treatments, surgical data, perioperative complications, adjuvant treatments, and follow imaging data were gathered. Of the five patients, one patient had received WBRT, three patients had received prior SRS to the area that underwent LITT, and one patient had a prior craniotomy with adjuvant SRS. Two of the tumors were located in the premotor area (frontal lobe), two tumors were located in the motor strip, and one tumor was located in the cerebellum. The average tumor volume was 4.32 cc (range 1.86 - 7.84 cc). Median time of hospital stay was 2 days (with a 2.6 day average). No perioperative complications were encountered. Three of the patients had received adjuvant therapy at our institution; these patients were not delayed in receiving adjuvant therapy. Of these three patients, only one patient had a BRAF mutation detected. Four patients received follow up imaging at our institution, with no patients demonstrating tumor regrowth in the site of LITT. Regrowth of intracranial metastasis of malignant melanoma is a known possibility of traditional radiation therapies. LITT should be considered as a safe, effective option for those that fail these traditional therapies, especially those located in areas difficult to access. The low complication rate allows patients to restart adjuvant therapies.
SURG-07. CORRELATION BETWEEN VOLUMETRIC ANALYSIS AND CLINICAL OUTCOMES OF BRAIN METASTASES TREATED WITH LASER INTERSTITIAL THERMAL THERAPY (LITT)
Authors: Bastos Dhiego , Loree Jonathan , Kumar Vinodh , Shah Komal , Rao Ganesh , Weinberg Jeffrey S , Prabhu Sujit
Published: August 2019

PURPOSE: Describe and analyze the volumetric responses of metastatic brain tumors treated with LITT and how changes correlate with local recurrence (LR). MATERIALS AND METHODS: Retrospective study with consecutive patients with progressive disease after SRS for brain metastasis. Spider and scatter plots and Locally Weighed Scatterplot Smoothing (LOWESS) for tumor and edema volume were created to analyze volume changes. Patients were compared using Chi-square tests and odds ratios (OR). RESULTS: 61 consecutive patients with 82 lesions (5 newly diagnosed, 46 recurrence and 31 radiation necrosis). Mean tumor volume was 4.84cm3, mean edema volume was 43.86cm3 and the mean ablation volume was 8.09cm3. LOWESS showed an initial increase in the first month, followed by steady decrease in the following months. Tumor edema shows a plateau or a slight increase in the first month, followed by a steady decrease in the subsequent months. Patients with LR showed an increase in the edema in the first 60 days, whereas tumor volume tended to remain stable, increasing in size after the third/fourth month. After 60 days, if edema volume is above baseline or increasing in size from nadir, there is an increased risk of LR (OR 4.22; 95% CI 1.5011.89,P=0.0053). Tumor volume above baseline ablation volume or increasing from a nadir on the first scan after day 60 had an increased risk of recurrence (OR 3.46; 95% CI 1.239.71,P=0.0016). If both edema and tumor volume are above baseline or increasing after day 60, there is also an increased risk of LR (OR 4.00; 95% CI 1.4111.36,P=0.0077). CONCLUSIONS: If either edema or tumor volume fail to fall below baseline or show an increasing trend on the first scan after day 60 post LITT, patients have an increased risk of LR. Qualitatively edema was the first feature observed in LR followed by increase in tumor volume.
SURG-09. SURGICAL AND PERI-OPERATIVE CONSIDERATIONS FOR BRAIN METASTASES: A NATIONWIDE ANALYSIS
Authors: Gupta Saksham , Larsen Alexandra Giantini , Dawood Hassan , Fandino Luis , Knelson Erik , Smith Timothy , Lee Eudocia , Aizer Ayal , Bi Wenya
Published: August 2019

BACKGROUND: Brain metastases are the most frequent brain tumors in adults, whose management remains nuanced. We aim to improve risk stratification for brain metastases patients who might be candidates for surgical resection. METHODS: We conducted a nationwide, retrospective cohort analysis of adult patients who received craniotomy for resection of brain metastasis using the 2012–2015 American College of Surgeons National Surgical Quality Improvement Project databases. Our primary outcomes of interest were post-operative medical complications, reoperation, readmission, and mortality. RESULTS: 3500 cases were included, of which 17% were considered frail and 24% were infratentorial. The most common 30-day medical complications were pneumonia (4%), venous thromboembolism (VTE;3%), and urinary tract infections (2%). Cardiac events and cerebrovascular accidents tended to occur in the early post-operative period, while VTEs and infections occurred in a more delayed fashion. Reoperation and unplanned readmission occurred in 5% and 12% of patients, respectively. Infratentorial approach and frailty were associated with reoperation before discharge (OR 2.0 for both; p=0.01 and p=0.03 respectively), but not after discharge. Frail patients were especially at risk for surgical evacuation of hematoma (OR 3.6). Infratentorial approaches conferred heightened risk for readmission for hydrocephalus (OR 5.1, p=0.02) and reoperation for cerebrospinal fluid diversion (OR 7.1, p< 0.001). Overall 30-day mortality was 4%, with nearly three-quarters occurring after discharge. Pre-frailty and frailty were associated with increased odds for post-discharge mortality (OR 1.7 and 2.7, p< 0.05), but not pre-discharge mortality. We developed a model to predictors of death, which identified frailty, thrombocytopenia, and high American Society of Anesthesiologists score as the strongest predictors of 30-day mortality (AUROC 0.75). CONCLUSION: Optimization of metrics contributing to patient frailty and heightened surveillance in patients with infratentorial metastases may be considered in the peri-operative period.
SURG-11. THE ROLE OF MAGNETIC RESONANCE-GUIDED LASER ABLATION FOR INTRACRANIAL METASTATIC TUMORS
Authors: Semonche Alexa , Eichberg Daniel , Theodotou Christian , Shah Ashish , Banerjee Christopher , Berger Michael , Wallo Amanda , Komotar Ricardo , Ivan Michael
Published: August 2019

INTRODUCTION: Laser interstitial thermal therapy (LITT) is a novel, minimally-invasive adjuvant therapy that is well-suited for intracranial tumors in deep or critical areas, recurrences failing standard therapy, and poor open-surgical candidates. To better characterize safety and clinical outcomes, we present the largest single-institutional experience with LITT for recurrent brain metastases. METHODS: All patients undergoing LITT for single recurrent brain metastases from 2013–2018 at the University of Miami were included in this study. Primary outcomes included extent of ablation (EOA), time-to-recurrence (TTR), and overall survival (OS). Secondary endpoints include neurologic status and complication rate. Kaplan-Meier survival analysis was performed to quantify TTR and OS, compare outcomes by primary tumor of origin, and identify potential predictors of TTR and OS. RESULTS: Thirty-six patients underwent 44 LITT procedures; all had undergone prior treatment with stereotactic radiosurgery (SRS). Mean age was 56.8 years and 83.3% were female. Average pretreatment tumor volume was 6.6cm3. Patients were treated with a mean ablation dose of 12.4W (9.8-14W), achieving a median EOA of 100% (range 55–100%). At median follow-up of 11.6 months (IQR 4.6–19.1 months), 34 of 44 (87.3%) cases had tumor control on radiographic imaging and 22 of 36 (61.1%) of patients remain alive. Median TTR was 55.9 months; median OS was 25.5 months. Neither TTR nor OR differed significantly by primary tumor of origin (P >.05). EOA >88% predicted longer TTR (P=.01) Neurologic status was stable or improved in all surviving patients. No major complications occurred (0% rate). CONCLUSIONS: Our institutional experience demonstrates LITT is safe for intracranial metastases resistant to SRS and offers several advantages over open surgical treatment. TTR and OS were not associated with primary tumor of origin. A threshold EOA >88% predicted longer TTR. Randomized studies are needed to evaluate the role of LITT as a treatment adjunct.
Affordances in Real, Virtual, and Imaginary Musical Performance
Authors: Duby Marc
Published: August 2019

Marc Duby bases his exploration of sound and imagination on James J. Gibson’s affordance concept. In this chapter, Duby shows how musicians benefit from real and imagined actions in their interaction with real (such as pianos), virtual (such as MIDI controllers), and air instruments (such as air guitars [imaginary instruments]). In each case, Duby explores the connection between gesture and sound and how the various instruments afford creativity. This leads to discussions of the range of imaginary possibilities the instruments afford musicians in the act of performing, composing, and listening, and how the special case of the air guitar challenges existing theories of embodied cognition.
Art and Iconography
Authors: Gubel Eric
Published: August 2019

Rooted in Late Bronze Age Levantine traditions, Phoenician art emerges in the early first millennium bce, spiced with new elements adopted and adapted from contemporary Egyptian models, while also permeable to influence from artistic trends popular with neighboring cultures and overseas recipients of Phoenician luxurious exports. During its acme between the late ninth and early seventh centuries bce, the art shared a common repertoire of motifs among sculptors, metalsmiths, ivory carvers, and seal cutters in a predominantly Egyptianizing style. Mass-produced terracotta plaques, figurines, and the minor arts displayed a more diversified array of autochthonous characteristics. In line with the evolution of sculpture, the Cypriot component was definitely replaced by Greek idioms from the later sixth century bce onward. If Punic art cannot possibly be defined as a mere perpetuation of the Phoenician production, and was impacted by more complex patterns of cultural interaction (e.g. North Africa, Iberia), the latter’s heritage is undeniable in many artistic media.
Achievement Goals
Authors: Murayama Kou , Elliot Andrew J.
Published: August 2019

This chapter describes the achievement goal construct’s origins and highlights noteworthy developments in the literature. Specifically it describes how the original dichotomous model of achievement goals developed into the modern trichotomous, 2 × 2, and 3 × 2 models of achievement goals. This historical overview is then used to provide the context for the key theoretical and conceptual issues surrounding the current achievement goal approach and a discussion of how these issues have an impact on empirical studies on achievement goals, especially focusing on the measurement of achievement goals. Finally, the text highlights several emerging lines of research in the literature. This includes achievement goal complexes, expansion of the competence-based model of achievement goals (e.g., potential-based achievement goals), and possible methodological improvement in assessing achievement goals.
The Temporal Elements of Psychological Resilience to Potential Trauma
Authors: Long Kan , Bonanno George
Published: August 2019

Potential trauma is common across the life span. Responses to these highly aversive events vary significantly, yet many individuals will demonstrate psychological resilience and a clear pattern of psychological health and adaptive functioning in the wake of extreme adversity. Amid expanding conceptual diversity and a proliferation of research, we present a novel, unified framework for resilience that consists of four constituent, temporally related elements: baseline or preadversity functioning, the actual aversive circumstances, postadversity resilient outcomes, and predictors of resilient outcomes. The temporal framework integrates and extends several existing lines of research by conceptualizing resilience as a process that unfolds over time with each temporal element playing an essential role.
Chevetogne, Taizé, and the Groupe des Dombes
Authors: Famerée Joseph
Published: August 2019

Since the mid-twentieth century, three institutions in the French-speaking world have been playing unquestionably important roles in ecumenism. The institutions here presented are, in chronological order of foundation, the Benedictine monastery of Chevetogne (Belgium), the Groupe des Dombes, and the Taizé community (France). The monks of Chevetogne, founded by Lambert Beauduin, celebrate the liturgy, simultaneously in two chapels, in the Latin and Byzantine rites, in order to anticipate spiritually Christian unity in diversity. The Groupe des Dombes, founded by Paul Couturier, consists of French-speaking theologians, twenty Protestants and twenty Catholics. Theological reflection and common prayer are the two pillars of their work, emphasizing the conversion of the churches. Taizé, founded by Roger Schutz, is an ecumenical community, which seeks to be a ‘parable of communion’, inspiring a ‘pilgrimage of trust on earth’, especially among young people.
Promotions and the Peter Principle*
Authors: Benson Alan , Li Danielle , Shue Kelly
Published: August 2019

The best worker is not always the best candidate for manager. In these cases, do firms promote the best potential manager or the best worker in their current job? Using microdata on the performance of sales workers at 131 firms, we find evidence consistent with the Peter Principle, which proposes that firms prioritize current job performance in promotion decisions at the expense of other observable characteristics that better predict managerial performance. We estimate that the costs of promoting workers with lower managerial potential are high, suggesting either that firms are making inefficient promotion decisions or that the benefits of promotion-based incentives are great enough to justify the costs of managerial mismatch. We find that firms manage the costs of the Peter Principle by placing less weight on sales performance in promotion decisions when managerial roles entail greater responsibility and when frontline workers are incentivized by strong pay for performance.
A DOUBLE-MASKED, RANDOMIZED, SHAM-CONTROLLED, SINGLE-CENTER STUDY WITH PHOTOBIOMODULATION FOR THE TREATMENT OF DRY AGE-RELATED MACULAR DEGENERATION
Authors: Markowitz Samuel N. , Devenyi Robert G. , Munk Marion R. , Croissant Cindy L. , Tedford Stephanie E. , Rückert Rene , Walker Michael G. , Patino Beatriz E. , Chen Lina , Nido Monica , Tedford Clark E.
Published: August 2019

Purpose:

The LIGHTSITE I study investigated the efficacy and safety of photobiomodulation (PBM) treatment in subjects with dry age-related macular degeneration.

Methods:

Thirty subjects (46 eyes) were treated with the Valeda Light Delivery System, wherein subjects underwent two series of treatments (3× per week for 3–4 weeks) over 1 year. Outcome measures included best-corrected visual acuity, contrast sensitivity, microperimetry, central drusen volume and drusen thickness, and quality of life assessments.

Results:

Photobiomodulation-treated subjects showed a best-corrected visual acuity mean letter score gain of 4 letters immediately after each treatment series at Month 1 (M1) and Month 7 (M7). Approximately 50% of PBM-treated subjects showed improvement of ≥5 letters versus 13.6% in sham-treated subjects at M1. High responding subjects (≥5-letter improvement) in the PBM-treated group showed a gain of 8 letters after initial treatment (P < 0.01) and exhibited earlier stages of age-related macular degeneration disease. Statistically significant improvements in contrast sensitivity, central drusen volume, central drusen thickness, and quality of life were observed (P < 0.05). No device-related adverse events were reported.

Conclusion:

Photobiomodulation treatment statistically improved clinical and anatomical outcomes with more robust benefits observed in subjects with earlier stages of dry age-related macular degeneration. Repeated PBM treatments are necessary to maintain benefits. These pilot findings support previous reports and suggest the utility of PBM as a safe and effective therapy in subjects with dry age-related macular degeneration.
Complementary and Integrative Health Treatments for Migraine
Authors: Patel Palak S. , Minen Mia T.
Published: August 2019

Background:

Migraine is a chronic disabling neurologic condition that can be treated with a combination of both pharmacologic and complementary and integrative health options.

Evidence Acquisition:

With the growing interest in the US population in the use of nonpharmacologic treatments, we reviewed the evidence for supplements and behavioral interventions used for migraine prevention.

Results:

Supplements reviewed included vitamins, minerals, and certain herbal preparations. Behavioral interventions reviewed included cognitive behavioral therapy, biofeedback, relaxation, the third-wave therapies, acupuncture, hypnosis, and aerobic exercise.

Conclusions:

This article should provide an appreciation for the wide range of nonpharmacologic therapies that might be offered to patients in place of or in addition to migraine-preventive medications.
Network-Based Matching of Patients and Targeted Therapies for Precision Oncology*
Authors: Liu Qingzhi , Ha Min Jin , Bhattacharyya Rupam , Garmire Lana , Baladandayuthapani Veerabhadran
Published: August 2019

The extensive acquisition of high-throughput molecular profiling data across model systems (human tumors and cancer cell lines) and drug sensitivity data, makes precision oncology possible – allowing clinicians to match the right drug to the right patient. Current supervised models for drug sensitivity prediction, often use cell lines as exemplars of patient tumors and for model training. However, these models are limited in their ability to accurately predict drug sensitivity of individual cancer patients to a large set of drugs, given the paucity of patient drug sensitivity data used for testing and high variability across different drugs. To address these challenges, we developed a multilayer network-based approach to impute individual patients’ responses to a large set of drugs. This approach considers the triplet of patients, cell lines and drugs as one inter-connected holistic system. We first use the omics profiles to construct a patient-cell line network and determine best matching cell lines for patient tumors based on robust measures of network similarity. Subsequently, these results are used to impute the “missing link” between each individual patient and each drug, calledPersonalized Imputed Drug Sensitivity Score(PIDS-Score), which can be construed as a measure of the therapeutic potential of a drug or therapy. We applied our method to two subtypes of lung cancer patients, matched these patients with cancer cell lines derived from 19 tissue types based on their functional proteomics profiles, and computed their PIDS-Scores to 251 drugs and experimental compounds. We identified the best representative cell lines that conserve lung cancer biology and molecular targets. The PIDS-Score based top sensitive drugs for the entire patient cohort as well as individual patients are highly related to lung cancer in terms of their targets, and their PIDS-Scores are significantly associated with patient clinical outcomes. These findings provide evidence that our method is useful to narrow the scope of possible effective patient-drug matchings for implementing evidence-based personalized medicine strategies.

Data and code availability

https://github.com/bayesrx/bayesrx.github.io/tree/master/authors/liu-q./Shiny app (data and results visualization tool):https://qingzliu.shinyapps.io/psb-app/
Analysis of Practices to Promote Reproducibility and Transparency in Anaesthesiology Research: Are Important Aspects “Hidden Behind the Drapes?”
Authors: Okonya Ochije , Rorah Drayton , Tritz Daniel , Umberham Blake A. , Wiley Matt , Vassar Matt
Published: August 2019

Introduction

Reliable, high-quality research is essential to the field of anaesthesiology. Reproducibility and transparency has been investigated in the biomedical domain and in the social sciences, with both lacking to provide necessary information to reproduce the study findings. In this study, we investigated 14 indicators of reproducibility in anaesthesiology research.

Methods

We used the National Library of Medicine (NLM) catalogue to search for all anaesthesiology journals that are MEDLINE indexed and provided English texts. PubMed was searched with the list of journals to identify all publications from January 1, 2014 to December 31, 2018. We randomly sampled 300 publications that fit the inclusion criteria for our analysis. Data extraction was then conducted in a blinded, duplicate fashion using a pilot-tested Google form.

Results

The PubMed search of these journals identified 171,441 publications, with 28,310 being within the time frame. From the 300 publications sampled, 296 full-text publications were accessible. Most of the studies did not include materials or protocol availability statements. The majority of publications did not provide a data analysis script statement (121/122, 99% [98% to 100%]) or a preregistration statement (94/122, 77% [72% to 81%]).

Conclusion

Anaesthesiology research needs to drastically improve indicators of reproducibility and transparency. By making research publically available and improving accessibility to detailed study components, primary research can be reproduced in subsequent studies and help contribute to the development of new practice guidelines.
Kirkpatrick–Baez active optics system at FERMI: system performance analysis
Authors: Raimondi Lorenzo , Manfredda Michele , Mahne Nicola , Cocco Daniele , Capotondi Flavio , Pedersoli Emanuele , Kiskinova Maya , Zangrando Marco
Published: August 2019

FERMI is the first and only seeded EUV-SXR free-electron laser (FEL) facility available to users; it operates at Elettra – Sincrotrone Trieste (Italy) and it presents five operating endstations. Three of them, namely LDM (Low Density Matter), DiProI (Diffraction and Projection Imaging) and MagneDyn (Magneto-Dynamical studies), use a Kirkpatrick–Baez (KB) active X-ray optics system to focus the FEL pulses into the experimental chambers. The present work reports on the final results of the upgraded KB Active Optics Systems (KAOS), which have been mechanically modified in order to improve stability and repeatability with respect to the original design. The results have been obtained on both the FERMI FEL lines, FEL1 and FEL2, and are particularly relevant for the latter as it is the low-wavelength line recently opened to users. After a thorough description of the new mechanical layout of the system and the aspects that have been improved after the refurbishment, a set of simulations of the optical performances are presented. The code used to simulate the behavior of KAOS is WISEr, a physical-optics-based tool, which is freely accessible, and integrated into the Oasys platform, that takes into account the specific surface metrology characterization of the beamline mirrors, including figure errors and microroughness power spectral density. The results of WISEr are then used as a reference for the actual optimization of the optical system. This procedure relies heavily on a wavefront sensor (WFS) mounted out of focus to optimize the refocusing mirrors alignment as well as their curvature bending (by minimization of the coefficients of the Zernike wavefront expansion). Moreover, the WFS data are used to reconstruct the focal spot parameters by means of a back-propagation of the electric field. Finally, these results are compared with those obtained after the FEL ablation of a PMMA layer positioned on the focal plane, and analyzed ex situ in a post-mortem fashion. The mechanically refurbished optical system and the multi-technique alignment approach, aimed at optimizing the mirrors' curvature, pitch and roll angles, allowed a focal spot of 1.8 µm × 2.4 µm at 4.14 nm wavelength (FEL2) to be inferred, confirmed by the PMMA ablation imprints.
Uber SA: disruption of the local taxi industry?
Authors: Bick Geoff
Published: August 2019

Learning outcomes

Learning outcomes are as follows: to understand the repercussions of a disruptive technology, in addition to its perceived benefits; to incorporate the human element into the technology benefits; to appreciate alternate sides of an argument regarding an issue; and to analyse the cross-functional implications of an innovation that changes the “rules of the game” for doing business.

Case overview/synopsis

Uber, a US-based multinational, provides a real-time technology platform to enable users to utilise ride-sharing with Uber drivers. This is an example of a “shared economy” or “collaborative consumption” business model, which has disrupted the status quo of the taxi industry around the world. Uber was launched in South Africa in 2013, creating many job opportunities but causing much reaction from the taxi industry and the authorities.

Complexity academic level

This is a short case which can be used across a number of programmes, as most students will have had some experience or exposure to the Uber model, and is very useful as an “ice-breaker” case to introduce students to the case study method of analysis and teaching. This case can be used for undergraduate and postgraduate students in business schools or other institutions or on executive education programmes as part of a strategy, marketing, business model innovation or entrepreneurship module.

Supplementary materials

Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

CSS 11: Strategy
Design and characterization of a T-shaped two-axis force sensor
Authors: Zhong Liang , Li Feifei , Peng Yuxin , Yang Qiang , Zhang Mingming , Wang Jian
Published: August 2019

Purpose

This paper aims to propose a type of T-shaped two-axis force sensor for measuring the forces in x- and z-axes. The developed sensor has a simple structure and can be effectively assembled into compact devices.

Design/methodology/approach

A T-shaped plate, with both ends fixed on a base, is used as the substrate of the sensor. Eight strain gauges are placed in the root of the plate or near the sensor head, which can construct two full Wheatstone bridges on the upper and lower surfaces of the plate. When the x- or z-axes forces are applied to the sensor head, different deformation can be generated to the strain gauges. Therefore, the two Wheatstone bridges can be constructed with a different configuration for measuring the forces in x- or z-axes, respectively.

Findings

A prototype was designed and constructed and experiments were carried out to test the basic performance of the sensor. It has been verified that the developed sensor could measure the x- and z-axes forces independently with a high resolution of 2.5 and 5 mN, respectively.

Originality/value

Only one thin plate was used in the design, the forces in x- and z-axes could be measured independently and simultaneously, which made the sensor with a simple structure and compact size. Experiments were also verified that there was no crosstalk error occurred in one axis when the force was applied to the other axis.
Transnational queer sociological analysis of sexual identity and civic‐political activism in Hong Kong, Taiwan and mainland China
Authors: Kong Travis S.K.
Published: August 2019

The sociology of homosexuality lacks engagement with queer theory and postcolonialism and focuses primarily on the global metropoles, thus failing to provide a plausible account of non‐Western non‐normative sexual identities. This research adopts the author’s newly proposed transnational queer sociology to address these deficiencies. First, it critiques the Western model of sexual identity predominantly employed to elucidate non‐Western, non‐normative sexualities. It does so by examining not only the queer flows between West and non‐West but also those among and within non‐Western contexts to produce translocally shared and mutually referenced experiences. Second, the proposed approach combines sociology with queer theory by emphasizing the significant role of material, as well as discursive, analyses in shaping queer identities, desires and practices. This article employs the approach to examine young gay male identities, as revealed in 90 in‐depth interviews conducted in Hong Kong (n = 30), Taiwan (Taipei, n = 30) and mainland China (Shanghai, n = 30) between 2017 and 2019. More specifically, it highlights the interplay between the state and identity by investigating the intersection and intertwining effects of these young men’s sexual and cultural/national identities, revealing three different forms of civic‐political activism. The article both demonstrates the way in which sexuality and the state are mutually constituted and provides nuanced analysis of the heterogeneity of contemporary homosexualities in Hong Kong, Taiwan and mainland China. In applying a new sociological approach to understanding sexuality, this research joins the growing body of scholarship within sociology that is decentring the Western formation of universal knowledge.
Transition from mesenchymal to bleb‐based motility is predominantly exhibited by CD133‐positive subpopulation of fibrosarcoma cells
Authors: Chikina Aleksandra S. , Rubtsova Svetlana N. , Lomakina Maria E. , Potashnikova Daria M. , Vorobjev Ivan A. , Alexandrova Antonina Y.
Published: August 2019

Background Information

Metastatic disease is caused by the ability of cancer cells to reach distant organs and form secondary lesions at new locations. Dissemination of cancer cells depends on their migration plasticity – an ability to switch between motility modes driven by distinct molecular machineries. One of such switches is mesenchymal‐to‐amoeboid transition. Although mesenchymal migration of individual cells requires Arp2/3‐dependent actin polymerisation, amoeboid migration is characterised by a high level of actomyosin contractility and often involves the formation of membrane blebs. The acquisition of amoeboid motility by mesenchymal cells is often associated with enhanced metastasis.

Results

We studied the ability of mesenchymal HT1080 fibrosarcoma cells to switch to amoeboid motility. We induced the transition from lamellipodium‐rich to blebbing phenotype either by down‐regulating the Arp2/3 complex, pharmacologically or by RNAi, or by decreasing substrate adhesiveness. Each of these treatments induced blebbing in a subset of fibrosarcoma cells, but not in normal subcutaneous fibroblasts. A significant fraction of HT1080 cells that switched to blebbing behaviour exhibited stem cell‐like features, such as expression of the stem cell marker CD133, an increased efflux of Hoechst‐33342 and positive staining for Oct4, Sox2 and Nanog. Furthermore, the isolated CD133+ cells demonstrated an increased ability to switch to bleb‐rich amoeboid phenotype both under inhibitor's treatment and in 3D collagen gels.

Conclusions

Together, our data show a significant correlation between the increased ability of cells to switch between migration modes and their stem‐like features, suggesting that migration plasticity is an additional property of stem‐like population of fibrosarcoma cells. This combination of features could facilitate both dissemination of these cells to distant locations, and their establishment self‐renewal in a new microenvironment, as required for metastasis formation.

Significance

These data suggest that migration plasticity is a new feature of cancer stem‐like cells that can significantly facilitate their dissemination to a secondary location by allowing them to adapt quickly to challenging microenvironments. Moreover, it complements their resistance to apoptosis and self‐renewal potential, thus enabling them not only to disseminate efficiently, but also to survive and colonise new niches.
Sex‐limited penetrance of lymphedema to females with CELSR1 haploinsufficiency: A second family
Authors: Erickson Robert P. , Lai Li‐Wen , Mustacich Debbie J. , Bernas Michael J. , Kuo Phillip H. , Witte Marlys H.
Published: August 2019

A second multigeneration family with hereditary lymphedema (LE) secondary to a variant in the planar polarity gene, CELSR1, is described. Dominant inheritance of the variant was discovered using whole‐exome sequencing and confirmed by Sanger sequencing. In contrast to heterozygous males, all heterozygous females showed LE during physical examination albeit variable in severity and age of onset. Lymphscintigraphy in affected females showed previously undescribed lymphatic abnormalities consistent with lymphangiectasia, valve dysfunction, and thoracic duct reflux.
Disaggregated determinants of aid: Development aid projects in the Philippines
Authors: Lio Rosvold Elisabeth
Published: August 2019

Motivation

Across the world, rapid‐onset disasters caused by natural hazards such as storms and floods return with seemingly greater force every year. Many disaster hot spots are particularly vulnerable because of already fragile humanitarian and political situations, some having been affected by armed conflict for decades. These phenomena augment the need for long‐term aid, but do they influence the distribution of aid projects?

Purpose

This article revisits the long‐standing debate over whether donor interests or recipient needs best predict the distribution of development aid. It disaggregates the analysis down to province level in the Philippines, and includes local hazards when assessing an area’s need for aid.

Approach and methods

Making use of geocoded data on aid projects, rapid‐onset disasters caused by natural hazards and armed conflict in Philippine provinces between 1996 and 2012, this article provides an exhaustive assessment of the within‐country determinants of World Bank development aid projects.

Findings

The article finds that need to some extent influences the distribution of aid projects across Philippine provinces but that, in general, domestic political alliances bias projects in favour of the politically dominant group. Previous exposure to conflict is associated with increased likelihood of new projects, but only in dominant group‐majority provinces. While previous disaster exposure is a weak predictor of aid in all provinces, low Human Development Index (HDI) levels significantly predict aid inflow in excluded group‐majority provinces.

Policy implications

In sum, the article challenges the idea that (international) donors’ priorities override the interests of the recipient/local governmesnt in the distribution of aid projects. It also shows that even if the donor’s explicit policy is disaster mitigation and relief, there is still some way to go before these considerations are effectively incorporated into development aid efforts.
Pathogenic B‐cell receptor signaling in lymphoid malignancies: New insights to improve treatment
Authors: Young Ryan M. , Phelan James D. , Wilson Wyndham H. , Staudt Louis M.
Published: August 2019

Signals emanating from the B‐cell receptor (BCR) promote proliferation and survival in diverse forms of B‐cell lymphoma. Precision medicine strategies targeting the BCR pathway have been generally effective in treating lymphoma, but often fail to produce durable responses in diffuse large B‐cell lymphoma (DLBCL), a common and aggressive cancer. New insights into DLBCL biology garnered from genomic analyses and functional proteogenomic studies have identified novel modes of BCR signaling in this disease. Herein, we describe the distinct roles of antigen‐dependent and antigen‐independent BCR signaling in different subtypes of DLBCL. We highlight mechanisms by which the BCR cooperates with TLR9 and mutant isoforms of MYD88 to drive sustained NF‐κB activity in the activated B‐cell‐like (ABC) subtype of DLBCL. Finally, we discuss progress in detecting and targeting oncogenic BCR signaling to improve the survival of patients with lymphoma.