Study of diffusion weighted MRI as a predictive biomarker of response during radiotherapy for high and intermediate risk squamous cell cancer of the oropharynx: The MeRInO study

Introduction and background: A significant proportion of patients with intermediate and high risk squamous cell cancer of the oropharynx (OPSCC) continue to relapse locally despite radical chemoradiotherapy (CRT). The toxicity of the current combination of intensified dose per fraction radiotherapy and platinum based chemotherapy limits further uniform intensification. If a predictive biomarker for outcomes from CRT can be identified during treatment then individualised and adaptive treatment strategies may be employed. Methods/design: The MeRInO study is a prospective observational imaging study of patients with intermediate and high risk, locally advanced OPSCC receiving radical RT or concurrent CRT Patients undergo diffusion weighted MRI prior to treatment (MRI_1) and during the third week of RT (MRI_2). Apparent diffusion coefficient (ADC) measurements will be made on each scan for previously specified target lesions (primary and lymph nodes) and change in ADC calculated. Patients will be followed up and disease status for each target lesion noted. The primary aim of the MeRInO study is to determine the threshold change in ADC from baseline to week 3 of RT that may identify the sub-group of non-responders during treatment. Discussion: The use of DW-MRI as a predictive biomarker during RT for SCC H&N is in its infancy but studies to date have found that response to treatment may indeed be predicted by comparison of DW-MRI carried out before and during treatment. However, previous studies have included all sub-sites and biological sub-types. Establishing ADC thresholds that predict for local failure is an essential step towards using DW-MRI to improve the therapeutic ratio in treating SCC H&N. This would be done most robustly in a specific H&N sub-site and in sub-types with similar biological behaviour. The MeRInO study will help establish these thresholds in OPSCC

Athletes’ age, sex and years of education moderate the acute neuropsychological impact of sports-related concussion: A meta-analysis

The objective of this study is to determine which pre-existing athlete characteristics, if any, are associated with greater deficits in functioning following sports-related concussion, after controlling for factors previously shown to moderate this effect (e.g., time since injury). Ninety-one independent samples of concussion were included in a fixed+systematic effects meta-analysis (n = 3,801 concussed athletes; 5,631 controls). Moderating variables were assessed using analogue-to-ANOVA and meta-regression analyses. Post-injury assessments first conducted 1-10 days following sports-related concussion revealed significant neuropsychological dysfunction, postural instability and post-concussion symptom reporting (d = -0.54, -1.10, and -1.14, respectively). During this interval, females (d = -0.87), adolescent athletes competing in high school competitions (d = -0.60), and those with 10 years of education (d = -1.32) demonstrated larger post-concussion neuropsychological deficits than males (d = -0.42), adults (d = -0.25), athletes competing at other levels of competition (d = -0.43 to -0.41), or those with 16 years of education (d = -0.15), respectively. However, these sub-groups' differential impairment/recovery beyond 10 days could not be reliably quantified from available literature. Pre-existing athlete characteristics, particularly age, sex and education, were demonstrated to be significant modifiers of neuropsychological outcomes within 10 days of a sports-related concussion. Implications for return-to-play decision-making and future research directions are discussed

Le FORUM, Vol. 38 No. 1

https://digitalcommons.library.umaine.edu/francoamericain_forum/1040/thumbnail.jp

The science case for the EISCAT_3D radar

The EISCAT (European Incoherent SCATer) Scientific Association has provided versatile incoherent scatter (IS) radar facilities on the mainland of northern Scandinavia (the EISCAT UHF and VHF radar systems) and on Svalbard (the electronically scanning radar ESR (EISCAT Svalbard Radar) for studies of the high-latitude ionised upper atmosphere (the ionosphere). The mainland radars were constructed about 30 years ago, based on technological solutions of that time. The science drivers of today, however, require a more flexible instrument, which allows measurements to be made from the troposphere to the topside ionosphere and gives the measured parameters in three dimensions, not just along a single radar beam. The possibility for continuous operation is also an essential feature. To facilitatefuture science work with a world-leading IS radar facility, planning of a new radar system started first with an EU-funded Design Study (2005–2009) and has continued with a follow-up EU FP7 EISCAT_3D Preparatory Phase project (2010–2014). The radar facility will be realised by using phased arrays, and a key aspect is the use of advanced software and data processing techniques. This type of software radar will act as a pathfinder for other facilities worldwide. The new radar facility will enable the EISCAT_3D science community to address new, significant science questions as well as to serve society, which is increasingly dependent on space-based technology and issues related to space weather. The location of the radar within the auroral oval and at the edge of the stratospheric polar vortex is also ideal for studies of the long-term variability in the atmosphere and global change. This paper is a summary of the EISCAT_3D science case, which was prepared as part of the EU-funded Preparatory Phase project for the new facility. Three science working groups, drawn from the EISCAT user community, participated in preparing this document. In addition to these working group members, who are listed as authors, thanks are due to many others in the EISCAT scientific community for useful contributions, discussions, and support

The science case for the EISCAT_3D radar

The EISCAT (European Incoherent SCATer) Scientific Association has provided versatile incoherent scatter (IS) radar facilities on the mainland of northern Scandinavia (the EISCAT UHF and VHF radar systems) and on Svalbard (the electronically scanning radar ESR (EISCAT Svalbard Radar) for studies of the high-latitude ionised upper atmosphere (the ionosphere). The mainland radars were constructed about 30 years ago, based on technological solutions of that time. The science drivers of today, however, require a more flexible instrument, which allows measurements to be made from the troposphere to the topside ionosphere and gives the measured parameters in three dimensions, not just along a single radar beam. The possibility for continuous operation is also an essential feature. To facilitatefuture science work with a world-leading IS radar facility, planning of a new radar system started first with an EU-funded Design Study (2005–2009) and has continued with a follow-up EU FP7 EISCAT_3D Preparatory Phase project (2010–2014). The radar facility will be realised by using phased arrays, and a key aspect is the use of advanced software and data processing techniques. This type of software radar will act as a pathfinder for other facilities worldwide. The new radar facility will enable the EISCAT_3D science community to address new, significant science questions as well as to serve society, which is increasingly dependent on space-based technology and issues related to space weather. The location of the radar within the auroral oval and at the edge of the stratospheric polar vortex is also ideal for studies of the long-term variability in the atmosphere and global change. This paper is a summary of the EISCAT_3D science case, which was prepared as part of the EU-funded Preparatory Phase project for the new facility. Three science working groups, drawn from the EISCAT user community, participated in preparing this document. In addition to these working group members, who are listed as authors, thanks are due to many others in the EISCAT scientific community for useful contributions, discussions, and support

Precision pulse shape simulation for proton detection at the Nab experiment

The Nab experiment at Oak Ridge National Laboratory, USA, aims to measure the beta-antineutrino angular correlation following neutron $\beta$ decay to an anticipated precision of approximately 0.1\%. The proton momentum is reconstructed through proton time-of-flight measurements, and potential systematic biases in the timing reconstruction due to detector effects must be controlled at the nanosecond level. We present a thorough and detailed semiconductor and quasiparticle transport simulation effort to provide precise pulse shapes, and report on relevant systematic effects and potential measurement schemes

Earth's ion upflow associated with polar cap patches: global and in-situ observations

We report simultaneous global monitoring of a patch of ionization and in situ observation of ion upflow at the center of the polar cap region during a geomagnetic storm. Our observations indicate strong fluxes of upwelling O+ ions originating from frictional heating produced by rapid antisunward flow of the plasma patch. The statistical results from the crossings of the central polar cap region by Defense Meteorological Satellite Program F16–F18 from 2010 to 2013 confirm that the field-aligned flow can turn upward when rapid antisunward flows appear, with consequent significant frictional heating of the ions, which overcomes the gravity effect. We suggest that such rapidly moving patches can provide an important source of upwelling ions in a region where downward flows are usually expected. These observations give new insight into the processes of ionosphere-magnetosphere coupling

Vitamin K supplementation to improve vascular stiffness in CKD:The K4Kidneys randomized controlled trial

BACKGROUND:Vascular calcification, a risk factor for cardiovascular disease, is common among patients with CKD and is an independent contributor to increased vascular stiffness and vascular risk in this patient group. Vitamin K is a cofactor for proteins involved in prevention of vascular calcification. Whether or not vitamin K supplementation could improve arterial stiffness in patients with CKD is unknown. METHODS:To determine if vitamin K supplementation might improve arterial stiffness in patients in CKD, we conducted a parallel-group, double-blind, randomized trial in participants aged 18 or older with CKD stage 3b or 4 (eGFR 15-45 ml/min per 1.73 m2). We randomly assigned participants to receive 400 μg oral vitamin K2 or matching placebo once daily for a year. The primary outcome was the adjusted between-group difference in carotid-femoral pulse wave velocity at 12 months. Secondary outcomes included augmentation index, abdominal aortic calcification, BP, physical function, and blood markers of mineral metabolism and vascular health. We also updated a recently published meta-analysis of trials to include the findings of this study. RESULTS:We included 159 randomized participants in the modified intention-to-treat analysis, with 80 allocated to receive vitamin K and 79 to receive placebo. Mean age was 66 years, 62 (39%) were female, and 87 (55%) had CKD stage 4. We found no differences in pulse wave velocity at 12 months, augmentation index at 12 months, BP, B-type natriuretic peptide, or physical function. The updated meta-analysis showed no effect of vitamin K supplementation on vascular stiffness or vascular calcification measures. CONCLUSIONS:Vitamin K2 supplementation did not improve vascular stiffness or other measures of vascular health in this trial involving individuals with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER:Vitamin K therapy to improve vascular health in patients with chronic kidney disease, ISRCTN21444964 (www.isrctn.com)

The Concussion Recognition Tool 5th Edition (CRT5): Background and rationale

The Concussion Recognition Tool 5 (CRT5) is the most recent revision of the Pocket Sport Concussion Assessment Tool 2 that was initially introduced by the Concussion in Sport Group in 2005. The CRT5 is designed to assist non-medically trained individuals to recognise the signs and symptoms of possible sport-related concussion and provides guidance for removing an athlete from play/sport and to seek medical attention. This paper presents the development of the CRT5 and highlights the differences between the CRT5 and prior versions of the instrument

Pathological Computed Tomography Features Associated with Adverse Outcomes after Mild Traumatic Brain Injury:A TRACK-TBI Study with External Validation in CENTER-TBI

Importance: A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood. Objective: To identify pathological CT features associated with adverse outcomes after mTBI. Design, Setting, and Participants: The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale-Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021. Exposures: Acute nonpenetrating head trauma. Main Outcomes and Measures: Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores <8 vs 8); and an unfavorable outcome (GOSE scores <5 vs ≥5) at 2 weeks and 3, 6, and 12 months. Results: In 1935 patients with mTBI (mean [SD] age, 41.5 [17.6] years; 1286 men [66.5%]) in the TRACK-TBI cohort and 2594 patients with mTBI (mean [SD] age, 51.8 [20.3] years; 1658 men [63.9%]) in an external validation cohort, hierarchical cluster analysis identified 3 major clusters of CT features: contusion, subarachnoid hemorrhage, and/or subdural hematoma; intraventricular and/or petechial hemorrhage; and epidural hematoma. Contusion, subarachnoid hemorrhage, and/or subdural hematoma features were associated with incomplete recovery (odds ratios [ORs] for GOSE scores <8 at 1 year: TRACK-TBI, 1.80 [95% CI, 1.39-2.33]; CENTER-TBI, 2.73 [95% CI, 2.18-3.41]) and greater degrees of unfavorable outcomes (ORs for GOSE scores <5 at 1 year: TRACK-TBI, 3.23 [95% CI, 1.59-6.58]; CENTER-TBI, 1.68 [95% CI, 1.13-2.49]) out to 12 months after injury, but epidural hematoma was not. Intraventricular and/or petechial hemorrhage was associated with greater degrees of unfavorable outcomes up to 12 months after injury (eg, OR for GOSE scores <5 at 1 year in TRACK-TBI: 3.47 [95% CI, 1.66-7.26]). Some CT features were more strongly associated with outcomes than previously validated variables (eg, ORs for GOSE scores <5 at 1 year in TRACK-TBI: neuropsychiatric history, 1.43 [95% CI.98-2.10] vs contusion, subarachnoid hemorrhage, and/or subdural hematoma, 3.23 [95% CI 1.59-6.58]). Findings were externally validated in 2594 patients with mTBI enrolled in the CENTER-TBI study. Conclusions and Relevance: In this study, pathological CT features carried different prognostic implications after mTBI to 1 year postinjury. Some patterns of injury were associated with worse outcomes than others. These results support that patients with mTBI and these CT features need TBI-specific education and systematic follow-up