The standard Lambda Cold Dark Matter (Lambda CDM) cosmological model provides a good description of a wide range of astrophysical and cosmological data. However, there are a few big open questions... Show moreThe standard Lambda Cold Dark Matter (Lambda CDM) cosmological model provides a good description of a wide range of astrophysical and cosmological data. However, there are a few big open questions that make the standard model look like an approximation to a more realistic scenario yet to be found. In this paper, we list a few important goals that need to be addressed in the next decade, taking into account the current discordances between the different cosmological probes, such as the disagreement in the value of the Hubble constant H-0, the sigma(8)-S-8 tension, and other less statistically significant anomalies. While these discordances can still be in part the result of systematic errors, their persistence after several years of accurate analysis strongly hints at cracks in the standard cosmological scenario and the necessity for new physics or generalisations beyond the standard model. In this paper, we focus on the 5.0 sigma tension between the Planck CMB estimate of the Hubble constant H-0 and the SH0ES collaboration measurements. After showing the H-0 evaluations made from different teams using different methods and geometric calibrations, we list a few interesting new physics models that could alleviate this tension and discuss how the next decade's experiments will be crucial. Moreover, we focus on the tension of the Planck CMB data with weak lensing measurements and redshift surveys, about the value of the matter energy density Omega(m), and the amplitude or rate of the growth of structure (sigma(8), f sigma(8)). We list a few interesting models proposed for alleviating this tension, and we discuss the importance of trying to fit a full array of data with a single model and not just one parameter at a time. Additionally, we present a wide range of other less discussed anomalies at a statistical significance level lower than the H-0-S-8 tensions which may also constitute hints towards new physics, and we discuss possible generic theoretical approaches that can collectively explain the non-standard nature of these signals. Finally, we give an overview of upgraded experiments and next-generation space missions and facilities on Earth that will be of crucial importance to address all these open questions. (C) 2022 The Author(s). Published by Elsevier B.V. Show less
Diener, H.C.; Tassorelli, C.; Dodick, D.W.; Silberstein, S.D.; Lipton, R.B.; Ashina, M.; ... ; Int Headache Soc Clinical Trials C 2020
Clinical trials are a key component of the evidence base for the treatment of headache disorders. In 1991, the International Headache Society Clinical Trials Standing Committee developed and... Show moreClinical trials are a key component of the evidence base for the treatment of headache disorders. In 1991, the International Headache Society Clinical Trials Standing Committee developed and published the first edition of theGuidelines for Controlled Trials of Drugs in Migraine. Advances in drugs, devices, and biologicals, as well as novel trial designs, have prompted several updates over the nearly 30 years since, including most recently theGuidelines for controlled trials of preventive treatment of chronic migraine(2018), theGuidelines for controlled trials of acute treatment of migraine attacks in adults(2019), andGuidelines for controlled trials of preventive treatment of migraine in children and adolescents(2019). The present update incorporates findings from new research and is intended to optimize the design of controlled trials of preventive pharmacological treatment of episodic migraine in adults. A guideline for clinical trials with devices will be published separately. Show less
The purpose of this study was the prospective comparison of objective and subjective effects of target volume region of interest (ROI) delineation using mouse-keyboard and pen-tablet user input... Show moreThe purpose of this study was the prospective comparison of objective and subjective effects of target volume region of interest (ROI) delineation using mouse-keyboard and pen-tablet user input devices (UIDs). The study was designed as a prospective test/retest sequence, with Wilcoxon signed rank test for matched-pair comparison. Twenty-one physician-observers contoured target volume ROIs on four standardized cases (representative of brain, prostate, lung, and head and neck malignancies) twice: once using QWERTY keyboard/scroll-wheel mouse UID and once with pen-tablet UID (DTX2100, Wacom Technology Corporation, Vancouver, WA, USA). Active task time, ROI manipulation task data, and subjective survey data were collected. One hundred twenty-nine target volume ROI sets were collected, with 62 paired pen-tablet/mouse-keyboard sessions. Active contouring time was reduced using the pen-tablet UID, with mean +/- SD active contouring time of 26 +/- 23 min, compared with 32 +/- 25 with the mouse (p a parts per thousand currency signaEuro parts per thousand 0.01). Subjective estimation of time spent was also reduced from 31 +/- 26 with mouse to 27 +/- 22 min with the pen (p = 0.02). Task analysis showed ROI correction task reduction (p = 0.045) and decreased panning and scrolling tasks (p < 0.01) with the pen-tablet; drawing, window/level changes, and zoom commands were unchanged (p = n.s.) Volumetric analysis demonstrated no detectable differences in ROI volume nor intra- or inter-observer volumetric coverage. Fifty-two of 62 (84%) users preferred the tablet for each contouring task; 5 of 62 (8%) denoted no preference, and 5 of 62 (8%) chose the mouse interface. The pen-tablet UID reduced active contouring time and reduced correction of ROIs, without substantially altering ROI volume/coverage. Show less
Purpose: Variations in target volume delineation represent a significant hurdle in clinical trials involving conformal radiotherapy. We sought to determine the effect of a consensus guideline-based... Show morePurpose: Variations in target volume delineation represent a significant hurdle in clinical trials involving conformal radiotherapy. We sought to determine the effect of a consensus guideline-based visual atlas on contouring the target volumes.Methods and Materials: A representative case was contoured (Scan 1) by 14 physician observers and a reference expert with and without target volume delineation instructions derived from a proposed rectal cancer clinical trial involving conformal radiotherapy. The gross tumor volume (GTV), and two clinical target volumes (CTVA, including the internal iliac, presacral, and perirectal nodes, and CTVB, which included the external iliac nodes) were contoured. The observers were randomly assigned to receipt (Group A) or nonreceipt (Group B) of a consensus guideline and atlas for anorectal cancers and then instructed to recontour the same case/images (Scan 2). Observer variation was analyzed volumetrically using the conformation number (CN, where CN = 1 equals total agreement).Results: Of 14 evaluable contour sets (1 expert and 7 Group A and 6 Group B observers), greater agreement was found for the GTV (mean CN, 0.75) than for the CTVs (mean CN, 0.46-0.65). Atlas exposure for Group A led to significantly increased interobserver agreement for CTVA (mean initial CN, 0.68, after atlas use, 0.76; p = .03) and increased agreement with the expert reference (initial mean CN, 0.58; after atlas use, 0.69; p = .02). For the GTV and CTVB, neither the interobserver nor the expert agreement was altered after atlas exposure.Conclusion: Consensus guideline atlas implementation resulted in a detectable difference in interobserver agreement and a greater approximation of expert volumes for the CTVA but not for the GTV or CTVB in the specified case. Visual atlas inclusion should be considered as a feature in future clinical trials incorporating conformal RT. (C) 2011 Elsevier Inc. Show less
