2,136 research outputs found
Multimodality and multi-parametric imaging in abdominal oncology:current and future strategies to harnessing the complementary value of PET/CT and MRI
Medical imaging is essential for the diagnosis, treatment and follow-up of patients with cancer. Combinations of different, complementary imaging modalities are increasingly being used: multimodal imaging. This thesis describes recent developments and expected innovations in research (and application of) combined PET/CT and MRI in patients with abdominal cancer. To this end, the effect of integrated assessment of PET/CT and MRI scans was investigated. This resulted in a different result in 1 in 9 patients, as well as a positive effect on the confidence in the results. As a next step, the value of quantitative parameters from PET/CT and MRI was assessed, to predict the treatment outcome of patients with cancer of the rectum, uterine cervix or anus. This value appears to be limited, but the findings from conventional, visual image assessment, does contribute to the prediction
Prospective Association of Daily Steps with Cardiovascular Disease: A Harmonized Meta-Analysis
Background:
Taking fewer than the widely promoted “10 000 steps per day” has recently been associated with lower risk of all-cause mortality. The relationship of steps and cardiovascular disease (CVD) risk remains poorly described. A meta-analysis examining the dose–response relationship between steps per day and CVD can help inform clinical and public health guidelines.
Methods:
Eight prospective studies (20 152 adults [ie, ≥18 years of age]) were included with device-measured steps and participants followed for CVD events. Studies quantified steps per day and CVD events were defined as fatal and nonfatal coronary heart disease, stroke, and heart failure. Cox proportional hazards regression analyses were completed using study-specific quartiles and hazard ratios (HR) and 95% CI were meta-analyzed with inverse-variance–weighted random effects models.
Results:
The mean age of participants was 63.2±12.4 years and 52% were women. The mean follow-up was 6.2 years (123 209 person-years), with a total of 1523 CVD events (12.4 per 1000 participant-years) reported. There was a significant difference in the association of steps per day and CVD between older (ie, ≥60 years of age) and younger adults (ie, <60 years of age). For older adults, the HR for quartile 2 was 0.80 (95% CI, 0.69 to 0.93), 0.62 for quartile 3 (95% CI, 0.52 to 0.74), and 0.51 for quartile 4 (95% CI, 0.41 to 0.63) compared with the lowest quartile. For younger adults, the HR for quartile 2 was 0.79 (95% CI, 0.46 to 1.35), 0.90 for quartile 3 (95% CI, 0.64 to 1.25), and 0.95 for quartile 4 (95% CI, 0.61 to 1.48) compared with the lowest quartile. Restricted cubic splines demonstrated a nonlinear association whereby more steps were associated with decreased risk of CVD among older adults.
Conclusions:
For older adults, taking more daily steps was associated with a progressively decreased risk of CVD. Monitoring and promoting steps per day is a simple metric for clinician–patient communication and population health to reduce the risk of CVD
The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe
The preponderance of matter over antimatter in the early Universe, the
dynamics of the supernova bursts that produced the heavy elements necessary for
life and whether protons eventually decay --- these mysteries at the forefront
of particle physics and astrophysics are key to understanding the early
evolution of our Universe, its current state and its eventual fate. The
Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed
plan for a world-class experiment dedicated to addressing these questions. LBNE
is conceived around three central components: (1) a new, high-intensity
neutrino source generated from a megawatt-class proton accelerator at Fermi
National Accelerator Laboratory, (2) a near neutrino detector just downstream
of the source, and (3) a massive liquid argon time-projection chamber deployed
as a far detector deep underground at the Sanford Underground Research
Facility. This facility, located at the site of the former Homestake Mine in
Lead, South Dakota, is approximately 1,300 km from the neutrino source at
Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino
charge-parity symmetry violation and mass ordering effects. This ambitious yet
cost-effective design incorporates scalability and flexibility and can
accommodate a variety of upgrades and contributions. With its exceptional
combination of experimental configuration, technical capabilities, and
potential for transformative discoveries, LBNE promises to be a vital facility
for the field of particle physics worldwide, providing physicists from around
the globe with opportunities to collaborate in a twenty to thirty year program
of exciting science. In this document we provide a comprehensive overview of
LBNE's scientific objectives, its place in the landscape of neutrino physics
worldwide, the technologies it will incorporate and the capabilities it will
possess.Comment: Major update of previous version. This is the reference document for
LBNE science program and current status. Chapters 1, 3, and 9 provide a
comprehensive overview of LBNE's scientific objectives, its place in the
landscape of neutrino physics worldwide, the technologies it will incorporate
and the capabilities it will possess. 288 pages, 116 figure
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
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
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
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
Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial
Background
Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy
Daily steps and all-cause mortality: a meta-analysis of 15 international cohorts
Background Although 10000 steps per day is widely promoted to have health benefits, there is little evidence to support
this recommendation. We aimed to determine the association between number of steps per day and stepping rate
with all-cause mortality.
Methods In this meta-analysis, we identified studies investigating the effect of daily step count on all-cause mortality
in adults (aged ≥18 years), via a previously published systematic review and expert knowledge of the field. We asked
participating study investigators to process their participant-level data following a standardised protocol. The primary
outcome was all-cause mortality collected from death certificates and country registries. We analysed the dose–
response association of steps per day and stepping rate with all-cause mortality. We did Cox proportional hazards
regression analyses using study-specific quartiles of steps per day and calculated hazard ratios (HRs) with inversevariance weighted random effects models.
Findings We identified 15 studies, of which seven were published and eight were unpublished, with study start dates
between 1999 and 2018. The total sample included 47 471 adults, among whom there were 3013 deaths (10·1 per
1000 participant-years) over a median follow-up of 7·1 years ([IQR 4·3–9·9]; total sum of follow-up across studies was
297 837 person-years). Quartile median steps per day were 3553 for quartile 1, 5801 for quartile 2, 7842 for quartile 3,
and 10 901 for quartile 4. Compared with the lowest quartile, the adjusted HR for all-cause mortality was 0·60 (95% CI
0·51–0·71) for quartile 2, 0·55 (0·49–0·62) for quartile 3, and 0·47 (0·39–0·57) for quartile 4. Restricted cubic splines
showed progressively decreasing risk of mortality among adults aged 60 years and older with increasing number of
steps per day until 6000–8000 steps per day and among adults younger than 60 years until 8000–10000 steps per day.
Adjusting for number of steps per day, comparing quartile 1 with quartile 4, the association between higher stepping
rates and mortality was attenuated but remained significant for a peak of 30 min (HR 0·67 [95% CI 0·56–0·83]) and
a peak of 60 min (0·67 [0·50–0·90]), but not significant for time (min per day) spent walking at 40 steps per min or
faster (1·12 [0·96–1·32]) and 100 steps per min or faster (0·86 [0·58–1·28]).
Interpretation Taking more steps per day was associated with a progressively lower risk of all-cause mortality, up to a
level that varied by age. The findings from this meta-analysis can be used to inform step guidelines for public health
promotion of physical activity
Emerging collaborative research platforms for the next generation of physical activity, sleep and exercise medicine guidelines: The Prospective Physical Activity, Sitting, and Sleep consortium (ProPASS)
Galileo Galilei’s quote ‘measure what is measurable, and make measurable what is not so’
has particular relevance to health behaviours, such as physical
activity (PA), sitting and sleep, whose measurement during free living
is notoriously difficult. To date, much of what we know about how these
behaviours affect our health is based on self-report by questionnaires
which have limited validity, are prone to bias and inquire about
selective aspects of these behaviours. Although self-reported evidence
has made great contributions to shaping public health and exercise
medicine policy and guidelines until now,1
the ongoing advancements of accelerometry-based measurement and
evidence synthesis methods are set to change the landscape. The aim of
this editorial is to outline new directions in PA and sleep-related
epidemiology that open new horizons for guideline development and
improvement; and to describe a new research collaboration platform: the
Prospective Physical Activity, Sitting, and Sleep consortium (ProPASS). </p
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