R.A.Fisher, design theory, and the Indian connection

Design Theory, a branch of mathematics, was born out of the experimental statistics research of the population geneticist R. A. Fisher and of Indian mathematical statisticians in the 1930s. The field combines elements of combinatorics, finite projective geometries, Latin squares, and a variety of further mathematical structures, brought together in surprising ways. This essay will present these structures and ideas as well as how the field came together, in itself an interesting story.Comment: 11 pages, 3 figure

Higgs mass and vacuum stability in the Standard Model at NNLO

We present the first complete next-to-next-to-leading order analysis of the Standard Model Higgs potential. We computed the two-loop QCD and Yukawa corrections to the relation between the Higgs quartic coupling (lambda) and the Higgs mass (Mh), reducing the theoretical uncertainty in the determination of the critical value of Mh for vacuum stability to 1 GeV. While lambda at the Planck scale is remarkably close to zero, absolute stability of the Higgs potential is excluded at 98% C.L. for Mh < 126 GeV. Possible consequences of the near vanishing of lambda at the Planck scale, including speculations about the role of the Higgs field during inflation, are discussed.Comment: 35 pages, 8 figures. Final published version, misprints fixed, figures update

Testing the running of the cosmological constant with Type Ia Supernovae at high z

Within the Quantum Field Theory context the idea of a "cosmological constant" (CC) evolving with time looks quite natural as it just reflects the change of the vacuum energy with the typical energy of the universe. In the particular frame of Ref.[30], a "running CC" at low energies may arise from generic quantum effects near the Planck scale, M_P, provided there is a smooth decoupling of all massive particles below M_P. In this work we further develop the cosmological consequences of a "running CC" by addressing the accelerated evolution of the universe within that model. The rate of change of the CC stays slow, without fine-tuning, and is comparable to H^2 M_P^2. It can be described by a single parameter, \nu, that can be determined from already planned experiments using SNe Ia at high z. The range of allowed values for \nu follow mainly from nucleosynthesis restrictions. Present samples of SNe Ia can not yet distinguish between a "constant" CC or a "running" one. The numerical simulations presented in this work show that SNAP can probe the predicted variation of the CC either ruling out this idea or confirming the evolution hereafter expected.Comment: LaTeX, 51 pages, 13 figures, 1 table, references added, typos corrected, version accepted in JCA

Effects and feasibility of a multi-disciplinary orientation program for newly registered cancer patients: design of a randomised controlled trial

Background Diagnosis and treatment of cancer can contribute to psychological distress and anxiety amongst patients. Evidence indicates that information giving can be beneficial in reducing patient anxiety, so oncology specific information may have a major impact on this patient group. This study investigates the effects of an orientation program on levels of anxiety and self-efficacy amongst newly registered cancer patients who are about to undergo chemotherapy and/or radiation therapy in the cancer care centre of a large tertiary Australian hospital. Methods The concept of interventions for orienting new cancer patients needs revisiting due to the dynamic health care system. Historically, most orientation programs at this cancer centre were conducted by one nurse. A randomised controlled trial has been designed to test the effectiveness of an orientation program with bundled interventions; a face-to-face program which includes introduction to the hospital facilities, introduction to the multi-disciplinary team and an overview of treatment side effects and self care strategies. The aim is to orientate patients to the cancer centre and to meet the health care team. We hypothesize that patients who receive this orientation will experience lower levels of anxiety and distress, and a higher level of self-efficacy. Discussion An orientation program is a common health care service provided by cancer care centres for new cancer patients. Such programs aim to give information to patients at the beginning of their encounter at a cancer care centre. It is clear in the literature that interventions that aim to improve self-efficacy in patients may demonstrate potential improvement in health outcomes. Yet, evidence on the effects of orientation programs for cancer patients on self-efficacy remains scarce, particularly with respect to the use of multidisciplinary team members. This paper presents the design of a randomised controlled trial that will evaluate the effects and feasibility of a multidisciplinary orientation program for new cancer patients

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment