908 research outputs found
Statistical Mechanics of Semi-Supervised Clustering in Sparse Graphs
We theoretically study semi-supervised clustering in sparse graphs in the
presence of pairwise constraints on the cluster assignments of nodes. We focus
on bi-cluster graphs, and study the impact of semi-supervision for varying
constraint density and overlap between the clusters. Recent results for
unsupervised clustering in sparse graphs indicate that there is a critical
ratio of within-cluster and between-cluster connectivities below which clusters
cannot be recovered with better than random accuracy. The goal of this paper is
to examine the impact of pairwise constraints on the clustering accuracy. Our
results suggests that the addition of constraints does not provide automatic
improvement over the unsupervised case. When the density of the constraints is
sufficiently small, their only impact is to shift the detection threshold while
preserving the criticality. Conversely, if the density of (hard) constraints is
above the percolation threshold, the criticality is suppressed and the
detection threshold disappears.Comment: 8 pages, 4 figure
Changes to healthcare utilisation and symptoms for common mental health problems over the first 21 months of the COVID-19 pandemic: parallel analyses of electronic health records and survey data in England
BACKGROUND:
Few studies have investigated the effect of the COVID-19 pandemic on mental health beyond 2020. This study quantifies changes to healthcare utilisation and symptoms for common mental health problems over the pandemic’s first 21 months.
METHODS:
Parallel cohort studies using primary care database and survey data for adults (≥16 years) in England from January 2015 to December 2021: 16,551,842 from the Clinical Practice Research Datalink (CPRD) and 40,699 from the UK Household Longitudinal Survey (UKHLS). Interrupted time-series models estimated changes in monthly prevalence of presentations and prescribed medications for anxiety and depression (CPRD); and self-reported psychological distress (UKHLS). The pandemic period was divided into five phases: 1st Wave (April–May 2020); post-1st Wave (June–September 2020); 2nd Wave (October 2020–February 2021); post 2nd Wave (March–May 2021); 3rd Wave (June–December 2021).
FINDINGS:
Primary care presentations for depression or anxiety dropped during the first wave (4.6 fewer monthly appointments per 1000 patients, 4.4–4.8) and remained lower than expected throughout follow-up. Self-reported psychological distress exceeded expected levels during the first (Prevalence Ratio = 1.378, 95% CI 1.289–1.459) and second waves (PR = 1.285, 1.189–1.377), returning towards expected levels during the third wave (PR = 1.038, 0.929–1.154). Increases in psychological distress and declines in presentations were greater for women. The decrease in primary care presentations for depression and anxiety exceeded that for physical health conditions (rheumatoid arthritis, diabetes, urinary tract infections). Anxiety and depression prescriptions returned to pre-pandemic levels during the second wave due to increased repeat prescriptions.
INTERPRETATION:
Despite periods of distress during the pandemic, we did not find an enduring effect on common mental health problems. The fall in primary care presentations for anxiety or depression suggests changing healthcare utilisation for mental distress and a potential treatment gap.
FUNDING:
National Institute for Health and Care Research (NIHR)
High Preservation of CpG Cytosine Methylation Patterns at Imprinted Gene Loci in Liver and Brain of Aged Mice
A gradual loss of the correct patterning of 5-methyl cytosine marks in gene promoter regions has been implicated in aging and age-related diseases, most notably cancer. While a number of studies have examined DNA methylation in aging, there is no consensus on the magnitude of the effects, particularly at imprinted loci. Imprinted genes are likely candidate to undergo age-related changes because of their demonstrated plasticity in utero, for example, in response to environmental cues. Here we quantitatively analyzed a total of 100 individual CpG sites in promoter regions of 11 imprinted and non-imprinted genes in liver and cerebral cortex of young and old mice using mass spectrometry. The results indicate a remarkably high preservation of methylation marks during the aging process in both organs. To test if increased genotoxic stress associated with premature aging would destabilize DNA methylation we analyzed two DNA repair defective mouse models showing a host of premature aging symptoms in liver and brain. However, also in these animals, at the end of their life span, we found a similarly high preservation of DNA methylation marks. We conclude that patterns of DNA methylation in gene promoters of imprinted genes are surprisingly stable over time in normal, postmitotic tissues and that the
Entanglement, recoherence and information flow in an accelerated detector - quantum field system: Implications for black hole information issue
We study an exactly solvable model where an uniformly accelerated detector is
linearly coupled to a massless scalar field initially in the Minkowski vacuum.
Using the exact correlation functions we show that as soon as the coupling is
switched on one can see information flowing from the detector to the field and
propagating with the radiation into null infinity. By expressing the reduced
density matrix of the detector in terms of the two-point functions, we
calculate the purity function in the detector and study the evolution of
quantum entanglement between the detector and the field. Only in the ultraweak
coupling regime could some degree of recoherence in the detector appear at late
times, but never in full restoration. We explicitly show that under the most
general conditions the detector never recovers its quantum coherence and the
entanglement between the detector and the field remains large at late times. To
the extent this model can be used as an analog to the system of a black hole
interacting with a quantum field, our result seems to suggest in the prevalent
non-Markovian regime, assuming unitarity for the combined system, that black
hole information is not lost but transferred to the quantum field degrees of
freedom. Our combined system will evolve into a highly entangled state between
a remnant of large area (in Bekenstein's black hole atom analog) without any
information of its initial state, and the quantum field, now imbued with
complex information content not-so-easily retrievable by a local observer.Comment: 16 pages, 12 figures; minor change
Coronary artery endothelial dysfunction is positively correlated with low density lipoprotein and inversely correlated with high density lipoprotein subclass particles measured by nuclear magnetic resonance spectroscopy.
OBJECTIVE: The association between cholesterol and endothelial dysfunction remains controversial. We tested the hypothesis that lipoprotein subclasses are associated with coronary endothelial dysfunction.
METHODS AND RESULTS: Coronary endothelial function was assessed in 490 patients between November 1993 and February 2007. Fasting lipids and nuclear magnetic resonance (NMR) lipoprotein particle subclasses were measured. There were 325 females and 165 males with a mean age of 49.8+/-11.6 years. Coronary endothelial dysfunction (epicardial constriction>20% or increase in coronary blood flow<50% in response to intracoronary acetylcholine) was diagnosed in 273 patients, the majority of whom (64.5%) had microvascular dysfunction. Total cholesterol and LDL-C (low density lipoprotein cholesterol) were not associated with endothelial dysfunction. One-way analysis and multivariate methods adjusting for age, gender, diabetes, hypertension and lipid-lowering agent use were used to determine the correlation between lipoprotein subclasses and coronary endothelial dysfunction. Epicardial endothelial dysfunction was significantly correlated with total (p=0.03) and small LDLp (LDL particles) (p<0.01) and inversely correlated with total and large HDLp (high density lipoprotein particles) (p<0.01).
CONCLUSIONS: Epicardial, but not microvascular, coronary endothelial dysfunction was associated directly with LDL particles and inversely with HDL particles, suggesting location-dependent impact of lipoprotein particles on the coronary circulation
Identification and validation of genes with expression patterns inverse to multiple metastasis suppressor genes in breast cancer cell lines
Metastasis suppressor genes (MSGs) have contributed to an understanding of regulatory pathways unique to the lethal metastatic process. When re-expressed in experimental models, MSGs block cancer spread to, and colonization of distant sites without affecting primary tumor formation. Genes have been identified with expression patterns inverse to a single MSG, and found to encode functional, druggable signaling pathways. We now hypothesize that common signaling pathways mediate the effects of multiple MSGs. By gene expression profiling of human MCF7 breast carcinoma cells expressing a scrambled siRNA, or siRNAs to each of 19 validated MSGs (NME1, BRMS1, CD82, CDH1, CDH2, CDH11, CASP8, MAP2K4, MAP2K6, MAP2K7, MAPK14, GSN, ARHGDIB, AKAP12, DRG1, CD44, PEBP1, RRM1, KISS1), we identified genes whose expression was significantly opposite to at least five MSGs. Five genes were selected for further analysis: PDE5A, UGT1A, IL11RA, DNM3 and OAS1. After stable downregulation of each candidate gene in the aggressive human breast cancer cell line MDA-MB-231T, in vitro motility was significantly inhibited. Two stable clones downregulating PDE5A (phosphodiesterase 5A), an enzyme involved in the regulation of cGMP-specific signaling, exhibited no difference in cell proliferation, but reduced motility by 47 and 66 % compared to the empty vector-expressing cells (p = 0.01 and p = 0.005). In an experimental metastasis assay, two shPDE5A-MDA-MB-231T clones produced 47-62 % fewer lung metastases than shRNA-scramble expressing cells (p = 0.045 and p = 0.009 respectively). This study demonstrates that previously unrecognized genes are inversely related to the expression of multiple MSGs, contribute to aspects of metastasis, and may stand as novel therapeutic targets
Epidemic processes in complex networks
In recent years the research community has accumulated overwhelming evidence
for the emergence of complex and heterogeneous connectivity patterns in a wide
range of biological and sociotechnical systems. The complex properties of
real-world networks have a profound impact on the behavior of equilibrium and
nonequilibrium phenomena occurring in various systems, and the study of
epidemic spreading is central to our understanding of the unfolding of
dynamical processes in complex networks. The theoretical analysis of epidemic
spreading in heterogeneous networks requires the development of novel
analytical frameworks, and it has produced results of conceptual and practical
relevance. A coherent and comprehensive review of the vast research activity
concerning epidemic processes is presented, detailing the successful
theoretical approaches as well as making their limits and assumptions clear.
Physicists, mathematicians, epidemiologists, computer, and social scientists
share a common interest in studying epidemic spreading and rely on similar
models for the description of the diffusion of pathogens, knowledge, and
innovation. For this reason, while focusing on the main results and the
paradigmatic models in infectious disease modeling, the major results
concerning generalized social contagion processes are also presented. Finally,
the research activity at the forefront in the study of epidemic spreading in
coevolving, coupled, and time-varying networks is reported.Comment: 62 pages, 15 figures, final versio
Inference of hidden structures in complex physical systems by multi-scale clustering
We survey the application of a relatively new branch of statistical
physics--"community detection"-- to data mining. In particular, we focus on the
diagnosis of materials and automated image segmentation. Community detection
describes the quest of partitioning a complex system involving many elements
into optimally decoupled subsets or communities of such elements. We review a
multiresolution variant which is used to ascertain structures at different
spatial and temporal scales. Significant patterns are obtained by examining the
correlations between different independent solvers. Similar to other
combinatorial optimization problems in the NP complexity class, community
detection exhibits several phases. Typically, illuminating orders are revealed
by choosing parameters that lead to extremal information theory correlations.Comment: 25 pages, 16 Figures; a review of earlier work
The Academics Athletics Trade-off: Universities and Intercollegiate Athletics
This analysis focuses on several key issues in the Football Bowl Subdivision (FBS). The intrinsic benefits of athletic programs are discussed in the first section. Trends in graduation rates and academic performance among athletes and how they correlate with the general student body are discussed in the second section. Finally, an overview of the revenues and expenses of athletic department budgets are discussed in an effort to gain a better understanding of the allocation of funds to athletics. In spite of recent growth in revenues and expenses, the athletic department budget comprises on average only 5 percent of the entire university budget at an FBS school, though spending and revenues have increased dramatically in recent years. In the grand scheme of things, American higher education faces several other, arguably more pressing, areas of reform. However, athletics is a significant and growing dimension of higher education that warrants in-depth examination
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A BRCA1 deficient-like signature is enriched in breast cancer brain metastases and predicts DNA damage-induced poly (ADP-ribose) polymerase inhibitor sensitivity
Introduction: There is an unmet clinical need for biomarkers to identify breast cancer patients at an increased risk of developing brain metastases. The objective is to identify gene signatures and biological pathways associated with human epidermal growth factor receptor 2-positive (HER2+) brain metastasis. Methods: We combined laser capture microdissection and gene expression microarrays to analyze malignant epithelium from HER2+ breast cancer brain metastases with that from HER2+ nonmetastatic primary tumors. Differential gene expression was performed including gene set enrichment analysis (GSEA) using publicly available breast cancer gene expression data sets. Results: In a cohort of HER2+ breast cancer brain metastases, we identified a gene expression signature that anti-correlates with overexpression of BRCA1. Sequence analysis of the HER2+ brain metastases revealed no pathogenic mutations of BRCA1, and therefore the aforementioned signature was designated BRCA1 Deficient-Like (BD-L). Evaluation of an independent cohort of breast cancer metastases demonstrated that BD-L values are significantly higher in brain metastases as compared to other metastatic sites. Although the BD-L signature is present in all subtypes of breast cancer, it is significantly higher in BRCA1 mutant primary tumors as compared with sporadic breast tumors. Additionally, BD-L signature values are significantly higher in HER2-/ER- primary tumors as compared with HER2+/ER + and HER2-/ER + tumors. The BD-L signature correlates with breast cancer cell line pharmacologic response to a combination of poly (ADP-ribose) polymerase (PARP) inhibitor and temozolomide, and the signature outperformed four published gene signatures of BRCA1/2 deficiency. Conclusions: A BD-L signature is enriched in HER2+ breast cancer brain metastases without pathogenic BRCA1 mutations. Unexpectedly, elevated BD-L values are found in a subset of primary tumors across all breast cancer subtypes. Evaluation of pharmacological sensitivity in breast cancer cell lines representing all breast cancer subtypes suggests the BD-L signature may serve as a biomarker to identify sporadic breast cancer patients who might benefit from a therapeutic combination of PARP inhibitor and temozolomide and may be indicative of a dysfunctional BRCA1-associated pathway
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