How good are Global Newton methods? Part 2

Newton's method applied to certain problems with a discontinuous derivative operator is shown to be effective. A global Newton method in this setting is exhibited and its computational complexity is estimated. As an application a method is proposed to solve problems of linear inequalities (linear programming, phase 1). Using an example of the Klee-Minty type due to Blair, it was found that the simplex method (used in super-lindo) required over 2,000 iterations, while the method above required an average of 8 iterations (Newton steps) over 15 random starting values.Naval Surface Weapons Center, Dahlgren, VAhttp://archive.org/details/howgoodareglobal00goldO&MN Direct FundingApproved for public release; distribution is unlimited

Experimentally unsupervised deconvolution for light-sheet microscopy with propagation-invariant beams

This project was funded by the UK Engineering and Physical Sciences Research Council (grants EP/P030017/1 and EP/R004854/1), and has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement (EC-GA 871212) and H2020 FETOPEN project "Dynamic” (EC-GA 863203). P.W. was supported by the 1851 Research Fellowship from the Royal Commission. KRD was supported by a Mid-Career Fellowship from the Hospital Research Foundation (C-MCF-58-2019). K.D. acknowledges support from the Australian Research Council through a Laureate Fellowship. S.S. was funded by BBSRC (BB/M00905X/1).Deconvolution is a challenging inverse problem, particularly in techniques that employ complex engineered point-spread functions, such as microscopy with propagation-invariant beams. Here, we present a deep-learning method for deconvolution that, in lieu of end-to-end training with ground truths, is trained using known physics of the imaging system. Specifically, we train a generative adversarial network with images generated with the known point-spread function of the system, and combine this with unpaired experimental data that preserve perceptual content. Our method rapidly and robustly deconvolves and super-resolves microscopy images, demonstrating a two-fold improvement in image contrast to conventional deconvolution methods. In contrast to common end-to-end networks that often require 1000–10,000s paired images, our method is experimentally unsupervised and can be trained solely on a few hundred regions of interest. We demonstrate its performance on light-sheet microscopy with propagation-invariant Airy beams in oocytes, preimplantation embryos and excised brain tissue, as well as illustrate its utility for Bessel-beam LSM. This method aims to democratise learned methods for deconvolution, as it does not require data acquisition outwith the conventional imaging protocol.Publisher PDFPeer reviewe

Is social support associated with improved clinical outcomes in geriatric lung cancer patients? Observations from North Central Cancer Treatment Group Studies N9921 and N0222

Aminah Jatoi1, Shauna L Hillman1, Katie L Allen Ziegler1, Philip J Stella2, Gamini S Soori3, Kendrith M Rowland Jr41Mayo Clinic and Mayo Foundation, Rochester, MN, USA; 2Michigan Cancer Research Consortium, Ann Arbor, MI, USA; 3Missouri Valley Cancer Consortium, Omaha, NE, USA; 4Carle Cancer Center CCOP, Urbana, IL, USABackground: Social support is defined as a network of family/friends who provide practical and emotional help. A sizable literature describes a direct relationship between social support and improved cancer clinical outcomes. This study explored the extent of social support and its potential association with survival and adverse events in geriatric lung cancer patients. Methods: One hundred thirteen patients, who were aged 65 years or older, had incurable cancer, and were enrolled in one of two chemotherapy trials, completed the Lubben Social Network Scale, a validated instrument that measures social support. All were followed for survival and chemotherapy-related adverse events.Results: The median age (range) of the cohort was 74 years (65–91), and performance scores of 0, 1, or 2 were observed in 29%, 55%, and 16%, respectively. Forty-two percent were women. This cohort had a high level of social support: 81% reported they “always” had someone to take them to medical appointments. However, there were no gender-based differences in social support and no associations between social support and either survival or adverse events. Conclusion: In this cohort of geriatric lung cancer patients – all of whom were treated during a clinical trial – there was a high level of social support. However, there were no gender-based differences in extent of social support, and the latter did not predict clinical outcomes. Keywords: social support, lung cancer, elderly, adverse events, surviva

An ALMA Search for Substructure, Fragmentation, and Hidden Protostars in Starless Cores in Chamaeleon I

We present an Atacama Large Millimeter/submillimeter Array (ALMA) 106 GHz (Band 3) continuum survey of the complete population of dense cores in the Chamaeleon I molecular cloud. We detect a total of 24 continuum sources in 19 different target fields. All previously known Class 0 and Class I protostars in Chamaeleon I are detected, whereas all of the 56 starless cores in our sample are undetected. We show that the Spitzer+Herschel census of protostars in Chamaeleon I is complete, with the rate at which protostellar cores have been misclassified as starless cores calculated as <1/56, or < 2%. We use synthetic observations to show that starless cores collapsing following the turbulent fragmentation scenario are detectable by our ALMA observations when their central densities exceed ~10^8 cm^-3, with the exact density dependent on the viewing geometry. Bonnor-Ebert spheres, on the other hand, remain undetected to central densities at least as high as 10^10 cm^-3. Our starless core non-detections are used to infer that either the star formation rate is declining in Chamaeleon I and most of the starless cores are not collapsing, matching the findings of previous studies, or that the evolution of starless cores are more accurately described by models that develop less substructure than predicted by the turbulent fragmentation scenario, such as Bonnor-Ebert spheres. We outline future work necessary to distinguish between these two possibilities.Comment: Accepted by Ap

Epirubicin With Cyclophosphamide Followed by Docetaxel With Trastuzumab and Bevacizumab as Neoadjuvant Therapy for HER2-Positive Locally Advanced Breast Cancer or as Adjuvant Therapy for HER2-Positive Pathologic Stage III Breast Cancer: A Phase II Trial of the NSABP Foundation Research Group, FB-5

Background The purpose of this study was to determine the cardiac safety and clinical activity of trastuzumab and bevacizumab with docetaxel after epirubicin with cyclophosphamide (EC) in patients with HER2-positive locally advanced breast cancer (LABC) or pathologic stage 3 breast cancer (PS3BC). Patients and Methods Patients received every 3 week treatment with 4 cycles of EC (90/600 mg/m2) followed by 4 cycles of docetaxel (100 mg/m2). Targeted therapy with standard-dose trastuzumab with bevacizumab 15 mg/kg was given for a total of 1 year. Coprimary end points were (1) rate of cardiac events (CEs) in all patients defined as clinical congestive heart failure with a significant decrease in left ventricular ejection fraction or cardiac deaths; and (2) pathologic complete response (pCR) in breast and nodes in the neoadjuvant cohort. An independent cardiac review panel determined whether criteria for a CE were met. Results A total of 105 patients were accrued, 76 with LABC treated with neoadjuvant therapy and 29 with PS3BC treated with adjuvant therapy. Median follow-up was 59.2 months. Among 99 evaluable patients for cardiac safety, 4 (4%; 95% confidence interval [CI], 1.1%-10.0%) met CE criteria. The pCR percentage in LABC patients was 46% (95% CI, 34%-59%). Five-year recurrence-free survival (RFS) and overall survival (OS) for all patients was 79.9% and 90.8%, respectively. Conclusion The regimen met predefined criteria for activity of interest with an acceptable rate of CEs. Although the pCR percentage was comparable with chemotherapy regimens with trastuzumab alone the high RFS and OS are of interest in these high-risk populations

And then there were four: a study of UK market concentration - causes, consequences and the scope for market adjustment

While concentration measures are a good indicator of market structure, the link with competitiveness is more complex than often assumed. In particular, the modern theory of industrial organisation makes no clear statement regarding the impact of concentration on competition - the focus of this paper is concentration and no inferences are made about competitive aspects of the market. The extent and nature of concentration within the UK listed company audit market as at April, 2002 and, pro forma, after the collapse of Andersen is documented and analysed in detail (by firm, market segment and industry sector). The largest four firms held 90 per cent of the market (based on audit fees) in 2002, rising to 96 per cent with the demise of Andersen. A single firm, Pricewaterhouse-Coopers, held 70 per cent or more of the share of six out of 38 industry sectors, with a share of 50 per cent up to 70 per cent in a further seven sectors. The provision of non-audit services (NAS) by incumbent auditors is also considered. As at April 2002, the average ratio of non-audit fees (paid to auditor) to audit fees was 208 per cent, and exceeded 300 per cent in seven sectors. It is likely, however, that disposals by firms of their management consultancy and outsource firms, combined with the impact of the Smith Report on audit committees will serve to reduce these ratios. Another finding is that audit firms with expertise in a particular sector appeared to earn significantly higher nonaudit fees from their audit clients in that sector. The paper thus provides a solid empirical basis for debate. The subsequent discussion considers the implications for companies and audit firms of the high level of concentration in the current regulatory climate, where no direct regulatory intervention is planned

Pluripotent Stem Cells Reveal Erythroid-specific Activities Of The Gata1 N-terminus

Germline GATA1 mutations that result in the production of an amino-truncated protein termed GATA1s (where s indicates short) cause congenital hypoplastic anemia. In patients with trisomy 21, similar somatic GATA1s-producing mutations promote transient myeloproliferative disease and acute megakaryoblastic leukemia. Here, we demonstrate that induced pluripotent stem cells (iPSCs) from patients with GATA1-truncating mutations exhibit impaired erythroid potential, but enhanced megakaryopoiesis and myelopoiesis, recapitulating the major phenotypes of the associated diseases. Similarly, in developmentally arrested GATA1-deficient murine megakaryocyte-erythroid progenitors derived from murine embryonic stem cells (ESCs), expression of GATA1s promoted megakaryopoiesis, but not erythropoiesis. Transcriptome analysis revealed a selective deficiency in the ability of GATA1s to activate erythroid-specific genes within populations of hematopoietic progenitors. Although its DNA-binding domain was intact, chromatin immunoprecipitation studies showed that GATA1s binding at specific erythroid regulatory regions was impaired, while binding at many nonerythroid sites, including megakaryocytic and myeloid target genes, was normal. Together, these observations indicate that lineage-specific GATA1 cofactor associations are essential for normal chromatin occupancy and provide mechanistic insights into how GATA1s mutations cause human disease. More broadly, our studies underscore the value of ESCs and iPSCs to recapitulate and study disease phenotypes.12539931005NIH [K08 HL093290, R01 DK100854, RC2 HL10166, P30 DK090969, R01 DK065806]American Society of Hematology Scholar Awar