Many real-world networks exhibit the phenomenon of edge clustering,which is typically measured by the average clustering coefficient. Recently,an alternative measure, the average closure coefficient, ...is proposed to quantify local clustering. It is shown that the average closure coefficient possesses a number of useful properties and can capture complementary information missed by the classical average clustering coefficient. In this paper, we study the asymptotic distribution of the average closure coefficient of a heterogeneous Erdős–Rényi random graph. We prove that the standardized average closure coefficient converges in distribution to the standard normal distribution. In the Erdős–Rényi random graph,the variance of the average closure coefficient exhibits the same phase transition phenomenon as the average clustering coefficient.
Abstract Background Older major depressive disorder (MDD) patients have more complex clinical symptoms and higher abnormal lipid metabolism (ALM) rates. This study aimed to compare clinical ...differences between those with and without ALM in a sample of older first-episode drug naïve (FEDN) patients. Methods We recruited 266 older MDD patients. Socio-demographic variables, clinical data, and lipid parameters were obtained. The Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), and the positive subscale of the Positive and Negative Syndrome Scale (PANSS-P) were conducted to evaluate patients’ depression, anxiety and psychotic symptoms, respectively. Results In this study, we found that the prevalence of comorbid ALM was 86.1% in older MDD patients. Compared with the non-abnormal lipid metabolism (NALM) group, the ALM group had a higher duration of illness, higher clinical global impression of severity scale (CGI-S) and HAMD scores, higher thyroid stimulating hormone (TSH) and glucose levels. Logistic regression analysis indicated that duration of illness (OR = 1.11, P = 0.023, 95%CI = 1.015–1.216) and CGI-S score (OR = 2.28, P = 0.014, 95%CI = 1.18–4.39) were associated with ALM in older MDD patients. Conclusion The importance of regular lipid assessment in older MDD patients needs to be taken into account.
The global epidemiology of end-stage kidney disease (ESKD) reflects each nation's unique genetic, environmental, lifestyle, and sociodemographic characteristics. The response to ESKD, particularly ...regarding kidney replacement therapy (KRT), depends on local disease burden, culture, and socioeconomics. Here, we explore geographic variation and global trends in ESKD incidence and prevalence and examine variations in KRT modality, practice patterns, and mortality. We conclude with a discussion on disparities in access to KRT and strategies to reduce ESKD global burden and to improve access to treatment in low- and middle-income countries (LMICs).
From 2003 to 2016, incidence rates of treated ESKD were relatively stable in many higher income countries but rose substantially predominantly in East and Southeast Asia. The prevalence of treated ESKD has increased worldwide, likely due to improving ESKD survival, population demographic shifts, higher prevalence of ESKD risk factors, and increasing KRT access in countries with growing economies. Unadjusted 5-year survival of ESKD patients on KRT was 41% in the USA, 48% in Europe, and 60% in Japan. Dialysis is the predominant KRT in most countries, with hemodialysis being the most common modality. Variations in dialysis practice patterns account for some of the differences in survival outcomes globally. Worldwide, there is a greater prevalence of KRT at higher income levels, and the number of people who die prematurely because of lack of KRT access is estimated at up to 3 times higher than the number who receive treatment. Key Messages: Many people worldwide in need of KRT as a life-sustaining treatment do not receive it, mostly in LMICs where health care resources are severely limited. This large treatment gap demands a focus on population-based prevention strategies and development of affordable and cost-effective KRT. Achieving global equity in KRT access will require concerted efforts in advocating effective public policy, health care delivery, workforce capacity, education, research, and support from the government, private sector, nongovernmental, and professional organizations.
Aims
It has been proposed that an increase of myocardial adiposity is related to left ventricular (LV) diastolic dysfunction. The specific roles of myocardial steatosis including epicardial fat and ...intramyocardial fat for diastolic function are unknown in those patients suffering heart failure (HF) with reduced (HFrEF) or preserved ejection fraction (HFpEF). This study aims to determine the complex relationship between myocardial adiposity in patients with HFrEF or HFpEF.
Methods and results
Using cardiac magnetic resonance imaging (CMRI), myocardial steatosis was measured in 305 subjects (34 patients with HFrEF, 163 with HFpEF, and 108 non‐HF controls). We also evaluated cardiac structure and diastolic and systolic function by echocardiography and CMRI. Patients with HFpEF had significantly more intramyocardial fat than HFrEF patients or non‐HF controls intramyocardial fat content (%), 1.56 (1.26, 1.89) vs. 0.75 (0.50, 0.87) and 1.0 (0.79, 1.15), P < 0.05. Intramyocardial fat amount (%) was higher in HFpEF women than in men 1.91% (1.17%, 2.32%) vs. 1.22 (0.87%, 2.02%), P = 0.01. When estimated by CMRI (left ventricular peak filling rate), echocardiographic E/e′ level, or left atrial volume index, intramyocardial fat correlated with LV diastolic dysfunction parameters in HFpEF patients, and this was independent of age, co‐morbidities, body mass index, gender, and myocardial fibrosis (standardized coefficient: β = −0.34, P = 0.03; β = 0.29, P = 0.025; and β = 0.25, P = 0.02, respectively).
Conclusions
Patients with HFpEF had significantly more intramyocardial fat than HFrEF patients or non‐HF controls. Independent of risk factors or gender, intramyocardial fat correlated with LV diastolic dysfunction parameters in HFpEF patients.
Hyperactive ribosomal biogenesis is widely observed in cancer, which has been partly attributed to the increased rDNA transcription by Pol I in cancer. However, whether small nucleolar RNAs ...(snoRNAs), a class of non-coding RNAs crucial in ribosomal RNA (rRNA) maturation and functionality, are involved in cancer remains elusive. We report that snoRNAs and fibrillarin (FBL, an enzymatic small nucleolar ribonucleoprotein, snoRNP) are frequently overexpressed in both murine and human breast cancer as well as in prostate cancers, and significantly, that this overexpression is essential for tumorigenicity in vitro and in vivo. We demonstrate that when the elevated snoRNA pathway is suppressed, the tumor suppressor p53 can act as a sentinel of snoRNP perturbation, the activation of which mediates the growth inhibitory effect. On the other hand, high level of FBL interferes with the activation of p53 by stress. We further show that p53 activation by FBL knockdown is not only regulated by the ribosomal protein-MDM2-mediated protein stabilization pathway, but also by enhanced PTB-dependent, cap-independent translation. Together, our data uncover an essential role of deregulated snoRNA biogenesis in tumors and a new mechanism of nucleolar modulation of p53.
A discrete degree of freedom can be engineered to match the Hamiltonian of particles moving in a real-space lattice potential. Such synthetic dimensions are powerful tools for quantum simulation ...because of the control they offer and the ability to create configurations difficult to access in real space. Here, in an ultracold
Sr atom, we demonstrate a synthetic-dimension based on Rydberg levels coupled with millimeter waves. Tunneling amplitudes between synthetic lattice sites and on-site potentials are set by the millimeter-wave amplitudes and detunings respectively. Alternating weak and strong tunneling in a one-dimensional configuration realizes the single-particle Su-Schrieffer-Heeger (SSH) Hamiltonian, a paradigmatic model of topological matter. Band structure is probed through optical excitation from the ground state to Rydberg levels, revealing symmetry-protected topological edge states at zero energy. Edge-state energies are robust to perturbations of tunneling-rates that preserve chiral symmetry, but can be shifted by the introduction of on-site potentials.
Abstract Objectives The purpose of this study was to investigate diffuse myocardial fibrosis in patients with systolic heart failure (SHF) and in patients with heart failure with preserved ejection ...fraction (HFpEF) and the association with diastolic dysfunction of the left ventricle (LV). Background Increased diffuse myocardial fibrosis may impair LV diastolic function. However, no study has verified the association between the degree of diffuse myocardial fibrosis and the severity of impaired diastolic function in SHF and HFpEF. Methods Forty patients with SHF, 62 patients with HFpEF, and 22 patients without HF underwent cardiac magnetic resonance (CMR), including T1 mapping and cine CMR on a 3-T system. Extracellular volume fraction (ECV), a measure of diffuse myocardial fibrosis, was quantified from T1 mapping. Systolic and diastolic functions of the LV were assessed by cine CMR. The ECV values and LV functional indexes were compared among the 3 groups. Associations between ECV and LV diastolic function were also investigated. Results Compared with patients without HF, significantly higher ECV was found in patients with SHF (31.2% interquartile range (IQR): 29.0% to 34.1% vs. 27.9% IQR: 26.2% to 29.4%, p < 0.001) and HFpEF (28.9% IQR: 27.8% to 31.3% vs. 27.9% IQR: 26.2% to 29.4%, p = 0.006). Peak filling rate, a diastolic functional index assessed by cine CMR, was significantly decreased in patients with SHF (1.00 s−1 IQR: 0.79 to 1.49 s−1 vs. 3.86 s−1 IQR: 3.34 to 4.48 s−1 , p < 0.001) and HFpEF (2.89 s−1 IQR: 2.13 to 3.50 s−1 vs. 3.86 s−1 IQR: 3.34 to 4.48 s−1 , p < 0.001). Myocardial ECV was significantly correlated with peak filling rate in the HFpEF group (r = −0.385, p = 0.002), but no correlation was found in the SHF and non-HF groups (r = 0.030, p = 0.856 and r = −0.238, p = 0.285, respectively). Conclusions In patients with HF, only those with HFpEF show a significant correlation between increased diffuse myocardial fibrosis and impaired diastolic function. Diffuse myocardial fibrosis plays a unique role in the pathogenesis of HFpEF.
On August 2, 2014 a catastrophic dust explosion occurred in a large industrial plant for polishing various aluminium-alloy parts in Kunshan, China. The explosion occurred during manual polishing of ...the surfaces of aluminium-alloy wheel hubs for the car industry. 75 people lost their lives immediately and another 185 were injured. Subsequently, 71 of the seriously injured also died, which increased the total loss of lives to 146. The direct economic loss of was 351 million yuan. This is probably one of the most serious dust explosion catastrophes known apart from some very major coal dust explosion disasters in coal mines.
Based on measurements of explosion parameters of dust samples collected on the explosion site and on-site investigations and interviews, it was concluded that a series of consecutive explosions was initiated in one of the external dust filters. Then it propagated into the main building via the dust extraction ducting and further onto the second floor. At the same time the propagating in-house dust flame was sucked into the ducts leading to seven other external dust filters, which also exploded.
On the basis of investigations on site after the explosion and subsequent laboratory experiments and data analyses it was concluded that the explosion was most probably initiated by self-ignition of contaminated aluminium-alloy dust in the dust collecting barrel below the external bag filter unit in which the initial primary explosion took place.
General ignorance of the potential risk of dust explosions in industries producing fine metal dusts as a low-mass waste by-product is the most probable basic root cause of this catastrophic accident. Therefore, avoiding accumulation of deposits of such dusts indoors by good regular housekeeping and other means is regarded the most effective and practical way of loss prevention due to metal dust explosions in such plants. In addition, explosion isolation between dust collecting systems and workshops appears to be another important measure towards minimizing the consequences of such explosions.
•Features of a recent catastrophic dust explosion in China are presented and analysed in detail.•The most likely ignition source was auto-ignition of moistened Al–alloy dust in a dust collecting barrel.•Important practical lessons have been learnt from this catastrophe.
Disease progression in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib has been attributed to histologic transformation or acquired mutations in BTK and PLCG2. The rate of ...resistance and clonal composition of PD are incompletely characterized. We report on CLL patients treated with single-agent ibrutinib on an investigator-initiated phase 2 trial. With median follow-up of 34 months, 15 of 84 evaluable patients (17.9%) progressed. Relapsed/refractory disease at study entry, TP53 aberration, advanced Rai stage, and high β-2 microglobulin were independently associated with inferior progression-free survival (P < .05 for all tests). Histologic transformation occurred in 5 patients (6.0%) and was limited to the first 15 months on ibrutinib. In contrast, progression due to CLL in 10 patients (11.9%) occurred later, diagnosed at a median 38 months on study. At progression, mutations in BTK (Cys481) and/or PLCG2 (within the autoinhibitory domain) were found in 9 patients (10.7%), in 8 of 10 patients with progressive CLL, and in 1 patient with prolymphocytic transformation. Applying high-sensitivity testing (detection limit ∼1 in 1000 cells) to stored samples, we detected mutations up to 15 months before manifestation of clinical progression (range, 2.9-15.4 months). In 5 patients (6.0%), multiple subclones carrying different mutations arose independently, leading to subclonal heterogeneity of resistant disease. For a seamless transition to alternative targeted agents, patients progressing with CLL were continued on ibrutinib for up to 3 months, with 19.8 months median survival from the time of progression. This trial was registered at www.clinicaltrials.gov as #NCT01500733.
•Most cases of ibrutinib-resistant CLL were due to mutations in BTK and/or PLCG2 and often composed of multiple independent subclones.•High sensitivity testing identified resistance mutations up to 15 months before manifestation of clinical progression.
Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, significantly improves cardiovascular outcomes in diabetic patients; however, the mechanism is unclear. We hypothesized that ...empagliflozin might have beneficial effects on cardiac function, structure, adiposity, and myocardial diffuse fibrosis. This prospective study enrolled 35 patients (48.6% men, age 63.5 ± 9.7 years) with type 2 diabetes mellitus (T2DM) from June 1, 2017, to November 31, 2018. The patients received an SGLT2 inhibitor (empagliflozin 25 or 12.5 mg/d) for 6 months in addition to stable oral hypoglycaemic treatment. All patients underwent cardiac magnetic resonance imaging (CMRI) before and after empagliflozin treatment. Left ventricular (LV) function and structure were quantified using cine CMRI. Cardiac adiposity was defined based on pericardial fat and intracardiac triglyceride contents, whereas myocardial diffuse fibrosis was indicated by extracellular volume (ECV). The statistical significance of parameter changes was assessed using paired t-test and stepwise multiple linear regression. There were no significant differences in LV function and structure changes. Cardiac adiposity and diffuse fibrosis indices were also not different before and after empagliflozin treatment. Concerning clinical parameters, only a significant decrease in systolic blood pressure (by 6.4 mmHg) was observed (p = 0.013). Stepwise multiple linear regression revealed that worse baseline MRI parameters were associated with better improvements. Intracardiac triglyceride content decrease was inversely associated with baseline intracardiac triglyceride content (p < 0.001). Pericardial fat changes were negatively correlated with baseline pericardial fat (p < 0.001) and ECV changes (p = 0.028). ECV changes were inversely associated with baseline ECV (p < 0.001), baseline LV ejection fraction (p < 0.001), and LV mass index changes (p = 0.020). This study demonstrated that 6 months of empagliflozin treatment did not significantly improve the LV function, structure, adiposity, and diffuse fibrosis in patients with T2DM. Further, the beneficial effects of empagliflozin treatment might be more evident in patients with worse baseline LV substrate and structure.
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