Phase phonon spectrum and melting in a quantum rotor model with diagonal disorder

We study the zero-temperature ($T = 0$) quantum rotor model with on-site disorder in the charging energy. Such a model may serve as an idealized Hamiltonian for an array of Josephson-coupled small superconducting grains, or superfluid $^4$He in a disordered environment. In the approximation of small-amplitude phase fluctuations, the Hamiltonian maps onto a system of coupled harmonic oscillators with on-site disorder. We study the effects of disorder in this harmonic regime, using the coherent potential approximation (CPA), obtaining the density of states and the lifetimes of the spin-wave-like excitations for several choices of the parameters which characterize the disorder. Finally, we estimate the parameters characterizing the $T = 0$ quantum melting of the phase order, using a suitable Lindemann criterion.Comment: 8 pages, 5 figures. To be published in Phys. Rev. B. Minor change

Using Swallowing Quality of Life to Compare Oropharyngeal Dysphagia Following Cervical Disc Arthroplasty or Anterior Cervical Discectomy and Fusion

Objective To evaluate dysphagia outcomes using the swallowing quality of life (SWAL-QOL) questionnaire between patients undergoing cervical disk arthroplasty (CDA) or anterior cervical discectomy and fusion (ACDF). Methods Patient-reported outcome measures (PROMs) were collected using SWAL-QOL, VAS, NDI, and SF-12 PCS. All measures were recorded preoperatively to 6-month postoperatively. Patients were grouped according to cervical procedure and instrumentation used. Differences in PROMs and SWAL-QOL domains were evaluated by t-test and one-way ANOVA with post-hoc testing, respectively. Simple linear regression was employed to evaluate the relationship between number of levels operated on and postoperative outcomes. Results 161 patients were included. CDA patients had significantly worse SWAL-QOL scores at 6-months. Preoperative VAS neck was significantly worse for patients who underwent either an ACDF procedure with a stand-alone cage or CDA as compared to patients who underwent an ACDF with anterior plating. At 6-months postoperatively, CDA patients reported a significantly worse “fatigue” score compared to ACDF patients. At 6-months postoperatively, ACDF patients reported a significantly better “sleep” scores compared to CDA patients with both recipients of an anterior plate and stand-alone cage reporting significantly better scores compared to the CDA cohort (p=0.024; p<0.001). The SWAL-QOL domain of symptom frequency at 6-weeks postoperatively was significantly associated with number of levels operated (p=0.032). Conclusion Patients undergoing either an ACDF or CDA procedure largely did not demonstrate differences in pain, disability, and dysphagia scores. However, at more longitudinal timepoints CDA patients reported worse fatigue and sleep scores compared to ACDF patients

Diffusion of MMPs on the Surface of Collagen Fibrils: The Mobile Cell Surface – Collagen Substratum Interface

Remodeling of the extracellular matrix catalyzed by MMPs is central to morphogenetic phenomena during development and wound healing as well as in numerous pathologic conditions such as fibrosis and cancer. We have previously demonstrated that secreted MMP-2 is tethered to the cell surface and activated by MT1-MMP/TIMP-2-dependent mechanism. The resulting cell-surface collagenolytic complex (MT1-MMP)2/TIMP-2/MMP-2 can initiate (MT1-MMP) and complete (MMP-2) degradation of an underlying collagen fibril. The following question remained: What is the mechanism of substrate recognition involving the two structures of relatively restricted mobility, the cell surface enzymatic complex and a collagen fibril embedded in the ECM? Here we demonstrate that all the components of the complex are capable of processive movement on a surface of the collagen fibril. The mechanism of MT1-MMP movement is a biased diffusion with the bias component dependent on the proteolysis of its substrate, not adenosine triphosphate (ATP) hydrolysis. It is similar to that of the MMP-1 Brownian ratchet we described earlier. In addition, both MMP-2 and MMP-9 as well as their respective complexes with TIMP-1 and -2 are capable of Brownian diffusion on the surface of native collagen fibrils without noticeable dissociation while the dimerization of MMP-9 renders the enzyme immobile. Most instructive is the finding that the inactivation of the enzymatic activity of MT1-MMP has a detectable negative effect on the cell force developed in miniaturized 3D tissue constructs. We propose that the collagenolytic complex (MT1-MMP)2/TIMP-2/MMP-2 represents a Mobile Cell Surface – Collagen Substratum Interface. The biological implications of MT1-MMP acting as a molecular ratchet tethered to the cell surface in complex with MMP-2 suggest a new mechanism for the role of spatially regulated peri-cellular proteolysis in cell-matrix interactions

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Using Adipose Measures from Health Care Provider-Based Imaging Data for Discovery

The location and type of adipose tissue is an important factor in metabolic syndrome. A database of picture archiving and communication system (PACS) derived abdominal computerized tomography (CT) images from a large health care provider, Geisinger, was used for large-scale research of the relationship of volume of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) with obesity-related diseases and clinical laboratory measures. Using a “greedy snake” algorithm and 2,545 CT images from the Geisinger PACS, we measured levels of VAT, SAT, total adipose tissue (TAT), and adipose ratio volumes. Sex-combined and sex-stratified association testing was done between adipose measures and 1,233 disease diagnoses and 37 clinical laboratory measures. A genome-wide association study (GWAS) for adipose measures was also performed. SAT was strongly associated with obesity and morbid obesity. VAT levels were strongly associated with type 2 diabetes-related diagnoses (p = 1.5 × 10−58), obstructive sleep apnea (p = 7.7 × 10−37), high-density lipoprotein (HDL) levels (p = 1.42 × 10−36), triglyceride levels (p = 1.44 × 10−43), and white blood cell (WBC) counts (p = 7.37 × 10−9). Sex-stratified tests revealed stronger associations among women, indicating the increased influence of VAT on obesity-related disease outcomes particularly among women. The GWAS identified some suggestive associations. This study supports the utility of pursuing future clinical and genetic discoveries with existing imaging data-derived adipose tissue measures deployed at a larger scale