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Improving standardized in vitro digestion protocols for phytosterols (PSs) is critical for understanding their bioaccessibility (BA) in food products and supplements. In this study, in vitro BA of phytosterol esters (PSEs) and free cholesterol (Ch) was compared under modified digestion conditions. The addition of Ch esterase (CE) to the INFOGEST model containing bovine bile resulted in a 70% increase in PS BA and an 18.5% reduction in Ch micellarization. Relative to the standardized INFOGEST model, substitution of pure bile salts (PBSs) did not significantly change PS BA or Ch micellarization. In the presence of CE, the substitution resulted in a 49.9% reduction in PS BA and a 13% increase in Ch micellarization. The differing results may be due to inhibitory effects of PBSs on the activity of intestinal enzymes, including CE. These results suggest that the INFOGEST model should include Ch esterase and the continued use of bile extract to evaluate PS BA.

Cultural geography has a long tradition of embracing video as both an observational method and a form of public engagement with research findings. In this article, we describe the making of Posthuman Landscapes, a silent film composed of moving panoramic images depicting the landscapes of three regional Australian towns (Griffith, Port Hedland, and Port Lincoln), along with creative writing that responded to the material qualities of those places in the form of ‘tweets’. Created as part of Boyd’s 3-year project called ‘Engaging Youth in Regional Australia’, the film formed part of a touring exhibition designed to disseminate research findings to communities within these towns. As artist-geographers, we approached the making of the video from a posthuman perspective in which the human and non-human are entangled. Our conceptual guide for working creatively with the landscapes was the posthuman concept of enchantment, which considers how the extraordinary can appear within the everyday to shake and disrupt ordinary affects. The concept of enchantment inspired us to juxtapose the inevitable familiarity and unfamiliarity that the audiences in these three towns would encounter through the film as it traveled from place to place. Here, we discuss how this juxtaposition of the familiar and unfamiliar was layered through both our film-making and writing practices, how this juxtaposition attempted to promote a posthuman orientation to landscape, and how such creative engagements contribute to knowledge translation in cultural geographical research.

After considering the nature and role of creative co-production in research contexts, Boyd describes the processes involved in producing artworks for the ‘Finding Home’ exhibition based on research findings from the Engaging Youth in Regional Australia (EYRA) Study. Commencing with work produced by some of the study’s participants, Boyd moves on to discuss the commissioning of a set of textile works and a contemporary Aboriginal artwork for the exhibition. The chapter is interwoven with a description of Boyd’s own artworks as an artist-geographer, produced in response but also in sympathy with the rest of the exhibition as it emerged. The chapter concludes with some first-hand reflections on curating a research exhibition.

In this final chapter, Boyd considers the strengths and limitations of the methods used to evaluate the ‘Finding Home’ exhibition, including what can or can’t be measured about the visitor experience. This is further elaborated by pointing out that part of what visitors experience in response to an art exhibition is ineffable, and in making this point, Boyd returns to the concept of affective knowledge translation introduced in Chap. 1. Boyd goes on to emphasise the importance of establishing rapport in working with multiple actors during the production of an art exhibition, as well as raising some caveats about research exhibitions as a ‘technique’ of knowledge translation. Boyd suggests how universities can better support art-based knowledge translation efforts and concludes with some thoughts about transdisciplinarity.

In this chapter, Boyd summarises the Engaging Youth in Regional Australia (EYRA) Study whose findings formed the basis of the touring art exhibition called ‘Finding Home’. Rooted in placed-based understandings of youth belonging and well-being, the study sought to challenge some of the long-standing assumptions about young people’s internal migration decisions in regional Australia. Specifically, the study’s findings support an enhanced understanding of regional youth engagement that takes into account the affective and material dimensions of young people’s relationships with regional places.

Beginning with the discipline of geography and its intersections with the humanities, Boyd explores how art has made its way across the academy to the social sciences and health and into science itself. Maintaining a focus on how art has become a vehicle for knowledge translation and exchange, the chapter builds a case for art as geography, especially in the realm of affective knowledge translation.

PURPOSE: The objective of this work was to evaluate phantom dosimetry of a novel kilovoltage (kV) x-ray source, which employs a stationary tungsten anode and a linearly swept scanning electron-beam. The source utilizes converging x-ray collimation along with orthogonal mechanical rotation to distribute surface flux over large area. In this study, this was investigated as a potential solution to fast-falloff limitations expected with kV radiotherapy. This was done with the aim of future clinical development of a lower-cost radiotherapy alternative to megavoltage (MV) linac systems. METHODS: Radiochromic film was employed for dosimetry on the kV x-ray source of the Linear-Converging Radiotherapy System (LCRS). The source utilizes charge particle optics to magnetically deflect and focus an electron beam along a stationary, reflection tungsten target in an ultra-high-vacuum stainless-steel chamber. Resulting x-rays were collimated into converging beamlets that span a large planar angle and converge at the system isocenter. In this study, radiochromic film dosimetry was done at 140 and 145 kVp for a designated planning treatment volume (PTV) of 4-cm diameter. An acrylic phantom was employed for dose distribution measurements of stationary and rotational delivery. Film dosimetry was evaluated in planes parallel to the source x-ray window at various depths, as well as in the plane of gantry rotation. RESULTS: At 140 and 145 kVp and using a collimated 4-cm square field at depth, lesion-to-skin dose ratio was shown to improve with additional beams from different relative source positions, where the different beams are focused at the same isocenter and do not overlap at the phantom surface. It was only possible to achieve a 1:1 D(max)-to-surface ratio with four delivery beams, but the ratio improved to 4:1 with 12 beams, focused at the same isocenter depth of 7.8 cm in an acrylic phantom. For the tests conducted, the following D(max)-to-surface ratios were obtained: 0.4:1 lesion-to-skin ratio for stationary delivery from one entry beam, 0.71:1 lesion-to-skin ratio was obtained for two beams, 1.07:1 ratio for four beams, and 4:1 for 12 beams. Dose-depth profiles were evaluated for stationary and rotational dosimetry. Additionally, rotational dosimetry was measured for a case more analogous to a clinical scenario, where the isocenter was located at an off-center simulated lesion. CONCLUSIONS: The results demonstrate potential dose-depth improvements with kV arc therapy by distributing the surface flux with a wide converging beam along with perpendicular mechanical source rotation of the LCRS. The system delivered tolerable dose to a large surface area when a threshold of multiple, separated beams was reached. The radiochromic film data supports the feasibility of the construct of the LCRS kV radiotherapy system design.

Background Transthyretin amyloidosis, also called ATTR amyloidosis, is a life-threatening disease characterized by progressive accumulation of misfolded transthyretin (TTR) protein in tiss...

The ability of computed tomography (CT) to distinguish between benign congenital lung malformations and malignant cystic pleuropulmonary blastomas (PPBs) is unclear.To assess whether chest CT can detect malignant tumors among postnatally detected lung lesions in children.This retrospective multicenter case-control study used a consortium database of 521 pathologically confirmed primary lung lesions from January 1, 2009, through December 31, 2015, to assess diagnostic accuracy. Preoperative CT scans of children with cystic PPB (cases) were selected and age-matched with CT scans from patients with postnatally detected congenital lung malformations (controls). Statistical analysis was performed from January 18 to September 6, 2020. Preoperative CT scans were interpreted independently by 9 experienced pediatric radiologists in a blinded fashion and analyzed from January 24, 2019, to September 6, 2020.Accuracy, sensitivity, and specificity of CT in correctly identifying children with malignant tumors.Among 477 CT scans identified (282 boys [59%]; median age at CT, 3.6 months [IQR, 1.2-7.2 months]; median age at resection, 6.9 months [IQR, 4.2-12.8 months]), 40 cases were extensively reviewed; 9 cases (23%) had pathologically confirmed cystic PPB. The median age at CT was 7.3 months (IQR, 2.9-22.4 months), and median age at resection was 8.7 months (IQR, 5.0-24.4 months). The sensitivity of CT for detecting PPB was 58%, and the specificity was 83%. High suspicion for malignancy correlated with PPB pathology (odds ratio, 13.5; 95% CI, 2.7-67.3; P = .002). There was poor interrater reliability (κ = 0.36 [range, 0.06-0.64]; P .001) and no significant difference in specific imaging characteristics between PPB and benign cystic lesions. The overall accuracy rate for distinguishing benign vs malignant lesions was 81%.This study suggests that chest CT, the current criterion standard imaging modality to assess the lung parenchyma, may not accurately and reliably distinguish PPB from benign congenital lung malformations in children. In any cystic lung lesion without a prenatal diagnosis, operative management to confirm pathologic diagnosis is warranted.

Goosegrass control options in bermudagrass are limited. Topramezone is one option that offers excellent control of mature goosegrass, but application to bermudagrass results in unacceptable symptoms of bleaching and necrosis typical of hydroxyphenylpyruvate dioxygenase inhibitors. Previous research has shown that adding chelated iron reduced the phytotoxicity of topramezone without reducing the efficacy of the herbicide, resulting in safening when applied to bermudagrass. Our objective was to examine additional iron sources to determine whether similar safening effects occur with other sources. Field trials were conducted in the summers of 2016 to 2018 (Auburn University). Mixtures of topramezone and methylated seed oil were combined with six different commercial iron sources, including sodium ferric ethylenediamine di-o-hydroxyphenyl-acetate (FeEDDHA), ferrous diethylenetriamine pentaacetic acid (FeDTPA), iron citrate, FeSO4, and a combination of iron oxide/sucrate/sulfate, some of which contained nitrogen. Bermudagrass necrosis and bleaching symptoms were visually rated on a 0% to 100% scale. Reflectance (normalized difference vegetation index) and clipping yield measurements were also collected. Application of FeDTPA and FeSO4 reduced symptoms of bleaching and necrosis when applied with topramezone. Other treatments that contained nitrogen did not reduce injury but did reduce bermudagrass recovery time following the appearance of necrosis. Inclusion of small amounts of nitrogen often negated the safening effects of FeSO4. The iron oxide/sucrate/sulfate product had no effect on bleaching or necrosis. Data suggest that the iron source had a differential effect on bleaching and necrosis reduction when applied in combination with topramezone to bermudagrass. Overall, FeSO4 and FeDTPA safened topramezone the most on bermudagrass.

POST goosegrass and other grassy weed control in bermudagrass is problematic. Fewer herbicides that can control goosegrass are available due to regulatory pressure and herbicide resistance. Alternative herbicide options that offer effective control are needed. Previous research demonstrates that topramezone controls goosegrass, crabgrass, and other weed species; however, injury to bermudagrass may be unacceptable. The objective of this research was to evaluate the safening potential of topramezone combinations with different additives on bermudagrass. Field trials were conducted at Auburn University during summer and fall from 2015 to 2018 and 2017 to 2018, respectively. Treatments included topramezone mixtures and methylated seed oil applied in combination with five different additives: triclopyr, green turf pigment, green turf paint, ammonium sulfate, and chelated iron. Bermudagrass bleaching and necrosis symptoms were visually rated. Normalized-difference vegetative index measurements and clipping yield data were also collected. Topramezone plus chelated iron, as well as topramezone plus triclopyr, reduced bleaching potential the best; however, the combination of topramezone plus triclopyr resulted in necrosis that outweighed reductions in bleaching. Masking agents such as green turf paint and green turf pigment were ineffective in reducing injury when applied with topramezone. The combination of topramezone plus ammonium sulfate should be avoided because of the high level of necrosis. Topramezone-associated bleaching symptoms were transient and lasted 7 to 14 d on average. Findings from this research suggest that chelated iron added to topramezone and methylated seed oil mixtures acted as a safener on bermudagrass.

Desmoplastic small round cell tumor is a rare sarcoma with 5-year overall survival of 15%. An 8-year-old female presented with diffuse abdominal/pelvic desmoplastic small round cell tumor including numerous liver metastasis. She underwent neoadjuvant chemotherapy followed by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Residual disease was found shortly after CRS/HIPEC which was resected, followed by whole abdomen/pelvic radiation and autologous hematopoietic cell transplant. Previous papers have reported dismal survival in patients with liver metastasis and residual disease arguing against CRS/HIPEC. Our patient remains disease-free over 6 years after completing therapy indicating long-term survival is achievable with aggressive multimodal therapy.

Cosmic microwave background (CMB) measurements are fundamentally limited by photon statistics. Therefore, ground-based CMB observatories have been increasing the number of detectors that are simultaneously observing the sky. Thanks to the advent of monolithically fabricated transition edge sensor (TES) arrays, the number of on-sky detectors has been increasing exponentially for over a decade. The next-generation experiment CMB-S4 will increase this detector count by more than an order of magnitude from the current state-of-the-art to ~500,000. The readout of such a huge number of exquisitely precise sub-Kelvin sensors is feasible using an existing technology: frequency-domain multiplexing (fMux). To further optimize this system and reduce complexity and cost, we have recently made significant advances including the elimination of 4 K electronics, a massive decrease of parasitic in-series impedances, and a significant increase in multiplexing factor., Comment: 7 pages, 6 figures, Submitted to the JLTP for LTD-18

We report a new measurement of the 60 keV transition from 241Am. It uses a metallic magnetic calorimeter gamma-ray detector calibrated in the region around 60 keV by four accurately known X-rays and gamma rays from the decay of 169Yb. We determine an energy of 59,539.3 ± 0.3 (stat) ± 0.3 (syst) eV, which is 1.6 ± 0.4 eV lower than the current literature value of 59,540.9 ± 0.1 eV. We discuss the sources of this uncertainty and approaches to address them.

Metallic magnetic calorimeters (MMCs) combine the excellent energy resolution of cryogenic gamma ray detectors with a very small nonlinearity and a reproducible response, owing to their magnetization-based sensor and their metallic heat flow path. These attributes make MMCs well suited for photon and particle spectroscopy applications requiring the highest accuracy. We are developing high-resolution MMC gamma ray detectors with the goal of improving the quality of key nuclear decay data for nuclear safeguards and fundamental science. Our exploratory “integrated” (SQUIDs and sensors on the same chip) 14-pixel MMC designs recently demonstrated energy resolution of 37.5 eV at 60 keV. Here, we describe the design and optimization for a new generation of MMC detectors using both “integrated” and “split” designs (SQUIDs and sensors on separate chips). The new designs are expected to have an energy resolution

Decision making algorithms are used in a multitude of different applications. Conventional approaches for designing decision algorithms employ principled and simplified modelling, based on which one can determine decisions via tractable optimization. More recently, deep learning approaches that use highly parametric architectures tuned from data without relying on mathematical models, are becoming increasingly popular. Model-based optimization and data-centric deep learning are often considered to be distinct disciplines. Here, we characterize them as edges of a continuous spectrum varying in specificity and parameterization, and provide a tutorial-style presentation to the methodologies lying in the middle ground of this spectrum, referred to as model-based deep learning. We accompany our presentation with running examples in super-resolution and stochastic control, and show how they are expressed using the provided characterization and specialized in each of the detailed methodologies. The gains of combining model-based optimization and deep learning are demonstrated using experimental results in various applications, ranging from biomedical imaging to digital communications.

Clinical genetic testing enables the detection of specific gene mutations and variants that predispose individuals and their family members to disease. In recent years, tremendous strides have been made in the variety of clinically useful tests. Targeted testing for specific mutations that cause well-known syndromes enables the efficient diagnosis of genetic diseases with cutaneous manifestations. Testing for specific genes, however, may not always reveal a diagnosis. Expanded options are available. This review outlines the major types of available technology with a focus on those tests most useful for pediatric dermatologists.

This paper defines the notion of dialogic local space and highlights its importance to teaching and learning. A dialogic local space values multiple local realities as it invites us to listen to, t...

There is a long history of collaboration between artists and geographers, with creative forms of research and dissemination of findings taking shape as artworks. In addition, there has been significant push from academia for researchers to maximise their research in ways that cater to, and engage with, broader public audiences. Art and creative practices tap into this through formats such as exhibitions, performances and participatory workshops which draw upon arts-based research methodologies with which geographers are becoming increasingly engaged. However, with this enthusiasm to adopt art practices for research dissemination purposes, tensions can arise in determining the levels of collaboration and authorship between artists and geographers, especially when the artist is employed as a research assistant on the project. In this ‘In Practice’ article, we explore the tensions and challenges that creative collaborations produce with respect to copyright and authorship, specialist skills and the delicate balance of doing creative research as part of a research team. We argue that geographers and artists need to address these issues from the outset and revisit them throughout the research process, and we offer some suggestions for how art–geography research collaborations might best be negotiated.

In an age of billion dollar particle accelerators and Mars rovers, it is surprising that solitary waves were first discovered by a man on horseback with no tools but his own eyes. A century and a h...

Chebyshev polynomial spectral methods are very accurate, but are plagued by the cost and ill-conditioning of dense discretization matrices. Modified schemes, collectively known as “integration sparsification”, have mollified these problems by discretizing the highest derivative as a diagonal matrix. Here, we examine five case studies where the highest derivative diagonalization fails. Nevertheless, we show that Galerkin discretizations do yield banded matrices that retain most of the advantages of “integration sparsification”. Symbolic computer algebra greatly extends the reach of spectral methods. When spectral methods are implemented using exact rational arithmetic, as is possible for small truncation N in Maple, Mathematica and their ilk, roundoff error is irrelevant, and sparsification failure is not worrisome. When the discretization contains a parameter L , symbolic algebra spectral methods return, as answer to an eigenproblem, not discrete numbers but rather a plane algebraic curve defined as the zero set of a bivariate polynomial P ( λ , L ) ; the optimal approximations to the eigenvalues λ j are in the middle of the straight portions of the zero contours of P ( λ ; L ) where the isolines are parallel to the L axis.

This study of whole class minilesson talk adds to the literature on how teacher talk shapes student involvement with learning. Minilesson talk is commonly associated with monologic, authoritative t...

When members of a classroom community routinely listen to one another and build on one another's ideas, not only do students learn and improve their cognitive and communication skills, but teacher and students develop a disposition to listen, think and talk together. However, such dialogic, classroom talk is rare. In this study we show how a teacher's epistemological commitment (that student ideas matter) combined with oracy practices (safe space for student talk; student ideas drive classroom talk; support multiple perspectives) realized through speculation and reasoning (S&R) words foster dialogic talk. We examined S&R words (think, would, might/maybe, if, so, but, how, why) in 1299 turns of talk in two lessons in one classroom of six 4–5th grade English Language Learners. Statistical discourse analysis showed that S&R words occurred more often during what we refer to as connect episodes (students made personal connections to the content), not after particular types of turns. Close discourse analysis showed how S&R word use cultivated a language of possibility and how management of classroom discourse modality promoted dialogic talk.

Objective To assess the nocioceptive input of habitual nocturnal jaw clenching that acts as a contributing factor in migraine pathogenesis. Background Habitual nocturnal jaw clenching has been implicated as a trigger, particularly in those whose headaches are present upon waking or shortly thereafter. Nocturnal EMG studies of patients diagnosed with migraine show nearly twice the temporalis clenching EMG levels and double the bite force as matched asymptomatic controls, leading to the speculation that parafunctional clenching activity may have some role in headache pathogenesis. The NTI (Nociceptive Trigeminal Inhibition) oral device is a dental splint designed to reduce nocturnal jaw clenching intensity and is FDA approved for the prevention of medically diagnosed migraine pain based on open label studies. There are no prior placebo-controlled trials to assess the migraine prevention efficacy of the NTI splint. This is the first placebo-controlled cross-over study to assess the efficacy of the NTI splint in patients with Chronic Migraine. Method A placebo controlled, single-blinded cross-over study was done with IRB oversight assessing the efficacy of the NTI splint compared to placebo using the change in the HIT-6 score as the outcome measure. Results 68% of refractory chronic migraine sufferers using the NTI as measured by sequential HIT 6 scores had at least a one-category improvement (severe to substantial, or substantial to some, or some to none) compared to 12% when using a placebo device. 36% of subjects using the NTI device reported a two-category improvement in their HIT-6 score, compared to 0% when using placebo. Conclusion The improvement in HIT-6 scores produced by the NTI device, suggests that patients with Chronic Migraine may have intense nocturnal jaw clenching as a contributing factor to their headache related disability. An NTI device is one method of assessing whether jaw-clenching is a contributing factor to ongoing migraine. Trial registration Current Controlled Trials NCT04871581. 04/05/2021. Retrospectively registered.

BACKGROUND: Pediatric lung lesions are a group of mostly benign pulmonary anomalies with a broad spectrum of clinical disease and histopathology. Our objective was to evaluate the characteristics of children undergoing resection of a primary lung lesion and to identify preoperative risk factors for malignancy. METHODS: A retrospective cohort study was conducted by using an operative database of 521 primary lung lesions managed at 11 children’s hospitals in the United States. Multivariable logistic regression was used to examine the relationship between preoperative characteristics and risk of malignancy, including pleuropulmonary blastoma (PPB). RESULTS: None of the 344 prenatally diagnosed lesions had malignant pathology (P < .0001). Among 177 children without a history of prenatal detection, 15 (8.7%) were classified as having a malignant tumor (type 1 PPB, n = 11; other PPB, n = 3; adenocarcinoma, n = 1) at a median age of 20.7 months (interquartile range, 7.9–58.1). Malignancy was associated with the DICER1 mutation in 8 (57%) PPB cases. No malignant lesion had a systemic feeding vessel (P = .0427). The sensitivity of preoperative chest computed tomography (CT) for detecting malignant pathology was 33.3% (95% confidence interval [CI]: 15.2–58.3). Multivariable logistic regression revealed that increased suspicion of malignancy by CT and bilateral disease were significant predictors of malignant pathology (odds ratios of 42.15 [95% CI, 7.43–340.3; P < .0001] and 42.03 [95% CI, 3.51–995.6; P = .0041], respectively). CONCLUSIONS: In pediatric lung masses initially diagnosed after birth, the risk of PPB approached 10%. These results strongly caution against routine nonoperative management in this patient population. DICER1 testing may be helpful given the poor sensitivity of CT for identifying malignant pathology.

We analytically and numerically solve the PCP equation, u x x u y y = 1 , with homogeneous Dirichlet boundary conditions on the unit square. Chebyshev and Fourier spectral methods with low degree truncations yield moderate accuracy but the usual exponential rate of convergence of spectral methods is destroyed by the boundary singularities of the solution. In the sequel to this work, we will apply a variety of strategies including a change-of-coordinates and singular basis functions to recover spectral accuracy in spite of the boundary singularities. As preparation for this numerical study, we find explicit solutions to related problems to the two-dimensional PCP equation in a domain with a boundary that is an ellipse and the three-dimensional PCP equation in a cubic domain. We also analyze the boundary behavior of these solutions: all have complicated singularities with unbounded first derivatives.

People with brain cancer and their support persons (SPs) are critical sources of information on the components of care that contribute to psychosocial outcomes.To determine the proportion of studies that examined (1) at least one of 14 nominated components of psychosocial cancer care and (2) more than one component of care.Medline, The Cochrane Library, PsycINFO and Embase were electronically searched for publications from January 1999 to December 2019. Publications that met the inclusion criteria were coded according to the number and type of psychosocial care components assessed from 14 listed components, and whether patient and/or SPs' views about care were elicited.Of the 113 included publications, 61 publications included patient-reported data only (54%), 27 included both patient and SP-reported data (24%) and 25 included SP-reported data only (22%). Most assessed a single component of care (77% of patient-reported and 71% of SP-reported). No publications assessed all 14 components. The "Psychosocial" component was the most frequently assessed component of care for patient-reported (n = 80/88, 91%) and SP-reported publications (n = 46/52, 88%).Publications reporting on psychosocial care in brain cancer present a relatively narrow view of patient and support person experiences. The inclusion of both patient and support person perspectives and the assessment of multiple components of care are required in future research to optimize psychosocial outcomes in brain cancer.

Childhood obesity is a serious health problem in the United States that affects millions of children and adolescents. Obese children are more prone to chronic illnesses, and these risks persist into adulthood. The Richard B. Russell National School Lunch Act (42 U.S.C. 1751 et seq.) sought to promote better nutrition among children, especially those who may otherwise not have access to healthy meals, by providing lunches that meet defined nutritional standards. Despite this effort, obesity rates continue to rise and there is little evidence favoring the effectiveness of the National School Lunch Act in reducing obesity incidence among children. Recently, policymakers proposed expanding nutrition education efforts to the classroom to address the current limitations of the National School Lunch Act (i.e., H.R.5892 and S.3293). However, education efforts alone are insufficient to foster long-lasting healthy eating patterns among children. Therefore, we propose that Congress amend the National School Lunch Act to include three evidence-based approaches: a 50-hour education program (H.R.5892), equitable partnerships between schools, local businesses and nonprofit organizations (S.3293), and a community engagement program designed to impact dietary behavior beyond the classroom.

PURPOSE Low-grade serous ovarian carcinomas (LGSOCs) have historically low chemotherapy responses. Alterations affecting the MAPK pathway, most commonly KRAS/BRAF, are present in 30%-60% of LGSOCs. The purpose of this study was to evaluate binimetinib, a potent MEK1/2 inhibitor with demonstrated activity across multiple cancers, in LGSOC. METHODS This was a 2:1 randomized study of binimetinib (45 mg twice daily) versus physician’s choice chemotherapy (PCC). Eligible patients had recurrent measurable LGSOC after ≥ 1 prior platinum-based chemotherapy but ≤ 3 prior chemotherapy lines. The primary end point was progression-free survival (PFS) by blinded independent central review (BICR); additional assessments included overall survival (OS), overall response rate (ORR), duration of response (DOR), clinical-benefit rate, biomarkers, and safety. RESULTS A total of 303 patients were randomly assigned to an arm of the study at the time of interim analysis (January 20, 2016). Median PFS by BICR was 9.1 months (95% CI, 7.3 to 11.3) for binimetinib and 10.6 months (95% CI, 9.2 to 14.5) for PCC (hazard ratio,1.21; 95%CI, 0.79 to 1.86), resulting in early study closure according to a prespecified futility boundary after 341 patients had enrolled. Secondary efficacy end points were similar in the two groups: ORR 16% (complete response [CR]/partial responses[PRs], 32) versus 13% (CR/PRs, 13); median DOR, 8.1 months (range, 0.03 to ≥ 12.0 months) versus 6.7 months (0.03 to ≥ 9.7 months); and median OS, 25.3 versus 20.8 months for binimetinib and PCC, respectively. Safety results were consistent with the known safety profile of binimetinib; the most common grade ≥ 3 event was increased blood creatine kinase level (26%). Post hoc analysis suggests a possible association between KRAS mutation and response to binimetinib. Results from an updated analysis (n = 341; January 2019) were consistent. CONCLUSION Although the MEK Inhibitor in Low-Grade Serous Ovarian Cancer Study did not meet its primary end point, binimetinib showed activity in LGSOC across the efficacy end points evaluated. A higher response to chemotherapy than expected was observed and KRAS mutation might predict response to binimetinib.

We revisit the spectral solution of the Thomas–Fermi problem for neutral atoms, u r r − ( 1 / r ) u 3 / 2 = 0 on r ∈ [ 0 , ∞ ] with u ( 0 ) = 1 and u ( ∞ ) = 0 to illustrate some themes in solving differential equations when there are complications, and also to make improvements in our earlier treatment. By “complications” we mean features of the problem that either destroy the exponential accuracy of a standard Chebyshev series, or render the classic Chebyshev approach inapplicable. The Thomas–Fermi problem has four complications: (i) a semi-infinite domain r ∈ [ 0 , ∞ ] (ii) a square root singularity in u ( r ) at the origin (iii) a fractional power nonlinearity and (iv) asymptotic decay as r → ∞ that includes negative powers of r with fractional exponents. Our earlier treatment determined the slope at the origin to twenty-five decimal places, but no fewer than 600 basis functions were required to approximate a univariate solution that is everywhere monotonic, and all of the earlier tricks failed to recover an exponential rate of convergence in the truncation of the spectral series N, but only a high order convergence in negative powers of N. Here, using the coordinate z ≡ r to neutralize the square root singularity as before, we show that accuracy and rate of convergence are significantly improved by solving for the original unknown u ( r ) instead of the modified unknown v ( r ) = u ( r ) used previously. Without a further change of coordinate, a rational Chebyshev basis T L n ( z ; L ) yields twelve decimal place accuracy for the slope at the origin, u r ( 0 ) , with 70 basis functions and twenty-four decimal places with a truncation N = 100 . True exponential accuracy can be restored by using an appropriate change of coordinate, z = G ( Z ) , where G is some species of exponential. However, the various Chebyshev and Fourier series for the Thomas–Fermi function have “plural asymptotics”, that is, a n ∼ a intermediate ( n ) for 1 ≪ n ≪ n I but a n ∼ a far ( n ) for n ≫ n I for some positive constant n I . The “far-asymptotics” as n → ∞ are often of no practical significance. For this problem, the TL-with-sinh method, theoretically the best for huge n, is bedeviled with numerical ill-conditioning and its asymptotic superiority is realized only when the goal is at least forty decimal places of accuracy. This is absurd for engineering, but useful perhaps for benchmarking. To sixty decimal places, u r ( 0 ) = − 1.588071022611375312718684509423950109452746621674825616765677 . To nineteen digits after the decimal point, the constant in the Coulson–March asymptotic series is improved to F = 13.2709738480269351535 .

Strongly nonlinear perturbation theory would seem to be an oxymoron, that is, a contradiction of terms. Nonetheless, we here describe perturbation methods for wave categories that are intrinsically nonlinear including solitons (solitary waves), bound states of solitons (bions) and spatially periodic traveling waves (cnoidal waves). Examples include the Kortweg-deVries and Benjamin-Ono equations with general power law nonlinearity and the Fifth Order KdV equation. The perturbation strategies include (ⅰ) the Gorshkov-Ostrovsky-Papko near-equal-amplitude soliton interaction theory (ⅱ) perturbation series in the Newton-homotopy parameter and (ⅲ) approximations for large values of the nonlinearity exponent. A long section places strongly nonlinear perturbation theory for waves in a larger context as a subset of unconventional perturbation expansions including phase transition theory in \begin{document}$ 4 - \epsilon $\end{document} dimensions, the \begin{document}$ \epsilon = 1/D $\end{document} expansion where \begin{document}$ D $\end{document} is the dimension in quantum chemistry, the renormalized quantum anharmonic oscillator, the Yakhot-Orszag expansion in the exponent of the energy spectrum in hydrodynamic turbulence, and the Newton homotopy expansion.

The system presented herein consists of a custom 200 kV electron tube with deflection magnets and stationary water-cooled targets for radiotherapy (RT) and imaging. The electron beam is deflected and dwelled along 41 discrete anode locations equally spaced by 1 cm in a line, at equivalent speeds of 1000 cm/s, to create a focused radiotherapy source. The treatment beam is collimated into a triangular polyhedron shape, producing a 4 cm focal spot at the isocenter and corresponding planning-treatment-volume (PTV). This beam shape would allow entry dose to be distributed over large areas for skin sparing. The source is mounted on a ring gantry that rotates at speeds up to 1.5 rpm. Preliminary dose rate measurements were collected in air at 140 kV beam energy, up to 80 mA beam current. Radiographic film was used to collect an image of the treatment beam at isocenter. Results are presented and can be extrapolated to a dose rate of 2 Gy/min for a 140 kV, 200 mA beam. The electron beam can be deflected within 1 ms from therapy path to an additional array of 19 imaging targets, which provides hardware capabilities for real-time tomosynthesis and image-guided RT. Onboard cone beam CT for patient positioning is also available. The utilization of 200 kV beam treatment energies compared to MV greatly reduces the required shielding (4-6 mm lead vs. 1-2 m concrete) and the cost of radiotherapy system installations. Systems can be mounted onto standard mobile trailers for use at remote locations.

Baroclinic instability generates the cyclones and anticyclones of midlatitude weather. Charney developed the first effective theory for the infancy of this cyclogenesis in 1947. His linear eigenproblem is analytically solvable by confluent hypergeometric functions. It is also, with extension of the domain of the coordinate from [0,∞] to [−∞,∞] by reflection about the origin, the point-jet model of barotropic instability, important for tropical cyclogenesis. (Note that the coordinate is height z in the Charney model, but latitude y for the point-jet bartropic instability. It is a great simplification that the Charney and point-jet instability problems are mathematically identical, but it also is confusing that the mathematical analysis in y also applies to the Charney problem with the substitution of z for y.) Unfortunately, the theory is full of distributions like the Dirac delta-function and the reflected Charney eigenfunction has a discontinuous first derivative at y = 0. Here we regularize the Charney problem by replacing a linear mean current, U = |y|, by either U = є log(cosh(y/є)) or U = є y erf(y/є), followed by matched asymptotic perturbation expansions in powers of the small regularization parameter є. The series is carried to third order because the lowest nonzero correction to the phase speed is O(є2) and this correction is determined simultaneously with the third order approximation to the eigenfunction. The result is both an explicit, analytic regularization of a problem important in atmospheric and ocean dynamics, but also a good school problem because the series is explicit with nothing worse than polylogarithms and confluent hypergeometric functions. The primary meteorological conclusion is that the delta functions in the Charney problem are harmless as demonstrated both by third order perturbation theory and by spectrally-accurate numerical solutions. The physics of the regularized Charney problem is not significantly changed from that of the original Charney problem.

We have used different metallic magnetic calorimeter (MMC) gamma detectors to measure the low-energy emissions of 233U with an accuracy of a few eV. 233U is of interest in nuclear safeguards because it is a fissile isotope that is produced by neutron irradiation of 232Th in the thorium fuel cycle. However, some of the nuclear decay data of 233U in the literature have relatively high uncertainties, especially at lower energies where lines can overlap or be dominated by a high Compton background. MMC gamma detectors operated at a temperature of 10 mK can have an energy resolution below 50 eV and can resolve lines with similar energy and reduce these uncertainties. We present recent MMC measurements of 233U and discuss the contributions of statistical and systematic errors. Importantly, we have performed the experiments with different MMC gamma detectors and different SQUID readout systems to increase the confidence in some observed deviations from literature values. The consistency of the results suggest that observed deviations are not due to detector artifacts and that a predictable quadratic response is intrinsic to the properties of MMCs.

Metallic magnetic microcalorimeters (MMCs) achieve energy resolution comparable to transition-edge sensors (TESs) but rely on different measurement physics that may allow MMCs to surpass TESs in some future applications. We have recently completed fabrication of new MMC γ-ray detector arrays using several exploratory sensor designs. All designs integrate the SQUID and sensor on the same chip and use a superconducting cap layer on the paramagnet, but explore different combinations of combined/separate sensing and magnetization coils and direct/flux transformer coupling to the input SQUIDs. This report describes the design and initial testing of one of these devices, which has so far demonstrated an energy resolution of 38 eV at 60 keV near 10 mK using natural-abundance silver–erbium paramagnet.