226 research outputs found
Factors Influencing the Participation of Older People in Clinical Trials : Data Analysis from the MAVIS Trial
Peer reviewedPostprin
Ultrarelativistic electron-hole pairing in graphene bilayer
We consider ground state of electron-hole graphene bilayer composed of two
independently doped graphene layers when a condensate of spatially separated
electron-hole pairs is formed. In the weak coupling regime the pairing affects
only conduction band of electron-doped layer and valence band of hole-doped
layer, thus the ground state is similar to ordinary BCS condensate. At strong
coupling, an ultrarelativistic character of electron dynamics reveals and the
bands which are remote from Fermi surfaces (valence band of electron-doped
layer and conduction band of hole-doped layer) are also affected by the
pairing. The analysis of instability of unpaired state shows that s-wave
pairing with band-diagonal condensate structure, described by two gaps, is
preferable. A relative phase of the gaps is fixed, however at weak coupling
this fixation diminishes allowing gapped and soliton-like excitations. The
coupled self-consistent gap equations for these two gaps are solved at zero
temperature in the constant-gap approximation and in the approximation of
separable potential. It is shown that, if characteristic width of the pairing
region is of the order of magnitude of chemical potential, then the value of
the gap in the spectrum is not much different from the BCS estimation. However,
if the pairing region is wider, then the gap value can be much larger and
depends exponentially on its energy width.Comment: 13 pages with 8 figures; accepted to Eur. Phys. J.
Intrauterine devices and endometrial cancer risk : a pooled analysis of the Epidemiology of Endometrial Cancer Consortium
Intrauterine devices (IUDs), long-acting and reversible contraceptives, induce a number of immunological and biochemical changes in the uterine environment that could affect endometrial cancer (EC) risk. We addressed this relationship through a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We combined individual-level data from 4 cohort and 14 case-control studies, in total 8,801 EC cases and 15,357 controls. Using multivariable logistic regression, we estimated pooled odds ratios (pooled-ORs) and 95% confidence intervals (CIs) for EC risk associated with ever use, type of device, ages at first and last use, duration of use and time since last use, stratified by study and adjusted for confounders. Ever use of IUDs was inversely related to EC risk (pooled-OR = 0.81, 95% CI = 0.74-0.90). Compared with never use, reduced risk of EC was observed for inert IUDs (pooled-OR = 0.69, 95% CI = 0.58-0.82), older age at first use (≥35 years pooled-OR = 0.53, 95% CI = 0.43-0.67), older age at last use (≥45 years pooled-OR = 0.60, 95% CI = 0.50-0.72), longer duration of use (≥10 years pooled-OR = 0.61, 95% CI = 0.52-0.71) and recent use (within 1 year of study entry pooled-OR = 0.39, 95% CI = 0.30-0.49). Future studies are needed to assess the respective roles of detection biases and biologic effects related to foreign body responses in the endometrium, heavier bleeding (and increased clearance of carcinogenic cells) and localized hormonal changes
Mineralocorticoid receptors dampen glucocorticoid receptor sensitivity to stress via regulation of FKBP5
Responding to different dynamic levels of stress is critical for mammalian survival. Disruption of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) signaling is proposed to underlie hypothalamic-pituitary-adrenal (HPA) axis dysregulation observed in stress-related psychiatric disorders. In this study, we show that FK506-binding protein 51 (FKBP5) plays a critical role in fine-tuning MR:GR balance in the hippocampus. Biotinylated-oligonucleotide immunoprecipitation in primary hippocampal neurons reveals that MR binding, rather than GR binding, to the Fkbp5 gene regulates FKBP5 expression during baseline activity of glucocorticoids. Notably, FKBP5 andMR exhibit similar hippocampal expression patterns in mice and humans, which are distinct from that of the GR. Pharmacological inhibition and region- and cell type-specific receptor deletion in mice further demonstrate that lack of MR decreases hippocampal Fkbp5 levels and dampens the stress-induced increase in glucocorticoid levels. Overall, our findings demonstrate that MR-dependent changes in baseline Fkbp5 expression modify GR sensitivity to glucocorticoids, providing insight into mechanisms of stress homeostasis.Diabetes mellitus: pathophysiological changes and therap
Implementable deep learning for multi-sequence proton MRI lung segmentation: a multi-center, multi-vendor, and multi-disease study
Background
Recently, deep learning via convolutional neural networks (CNNs) has largely superseded conventional methods for proton (1H)-MRI lung segmentation. However, previous deep learning studies have utilized single-center data and limited acquisition parameters.
Purpose
Develop a generalizable CNN for lung segmentation in 1H-MRI, robust to pathology, acquisition protocol, vendor, and center.
Study type
Retrospective.
Population
A total of 809 1H-MRI scans from 258 participants with various pulmonary pathologies (median age (range): 57 (6–85); 42% females) and 31 healthy participants (median age (range): 34 (23–76); 34% females) that were split into training (593 scans (74%); 157 participants (55%)), testing (50 scans (6%); 50 participants (17%)) and external validation (164 scans (20%); 82 participants (28%)) sets.
Field Strength/Sequence
1.5-T and 3-T/3D spoiled-gradient recalled and ultrashort echo-time 1H-MRI.
Assessment
2D and 3D CNNs, trained on single-center, multi-sequence data, and the conventional spatial fuzzy c-means (SFCM) method were compared to manually delineated expert segmentations. Each method was validated on external data originating from several centers. Dice similarity coefficient (DSC), average boundary Hausdorff distance (Average HD), and relative error (XOR) metrics to assess segmentation performance.
Statistical Tests
Kruskal–Wallis tests assessed significances of differences between acquisitions in the testing set. Friedman tests with post hoc multiple comparisons assessed differences between the 2D CNN, 3D CNN, and SFCM. Bland–Altman analyses assessed agreement with manually derived lung volumes. A P value of <0.05 was considered statistically significant.
Results
The 3D CNN significantly outperformed its 2D analog and SFCM, yielding a median (range) DSC of 0.961 (0.880–0.987), Average HD of 1.63 mm (0.65–5.45) and XOR of 0.079 (0.025–0.240) on the testing set and a DSC of 0.973 (0.866–0.987), Average HD of 1.11 mm (0.47–8.13) and XOR of 0.054 (0.026–0.255) on external validation data.
Data Conclusion
The 3D CNN generated accurate 1H-MRI lung segmentations on a heterogenous dataset, demonstrating robustness to disease pathology, sequence, vendor, and center.
Evidence Level
4.
Technical Efficacy
Stage 1
Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers
While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood appr
Reforming Watershed Restoration: Science in Need of Application and Applications in Need of Science
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