Chronobiology and chronotherapy of osteoporosis

Physiological circadian (ie, 24-hour) rhythms are critical for bone health. Animal studies have shown that genes involved in the intrinsic molecular clock demonstrate potent circadian expression patterns in bone and that genetic disruption of these clock genes results in a disturbed bone structure and quality. More importantly, circulating markers of bone remodeling show diurnal variation in mice as well as humans, and circadian disruption by, eg, working night shifts is associated with the bone remodeling disorder osteoporosis. In this review, we provide an overview of the current literature on rhythmic bone remodeling and its underlying mechanisms and identify critical knowledge gaps. In addition, we discuss novel (chrono)therapeutic strategies to reduce osteoporosis by utilizing our knowledge on circadian regulation of bone. (c) 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.Diabetes mellitus: pathophysiological changes and therap

Insulating and Conducting Phases of RbC60

Optical measurements were performed on thin films of Rb$_{x}$C$_{60}$, identified by X-ray diffraction as mostly $x=1$ material. The samples were subjected to various heat treatments, including quenching and slow cooling from 400K. The dramatic increase in the transmission of the quenched samples, and the relaxation towards the transmission observed in slow cooled samples provides direct evidence for the existence of a metastable insulating phase. Slow cooling results in a phase transition between two electrically conducting phases.Comment: Minor revisions. Submitted to PRB, RevTeX 3.0 file, 2 postscript figures included, ir_dop

Ophthalmic magnetic resonance imaging at 7.0 T using a 6-channel transceiver radiofrequency coil array in healthy subjects and patients with intraocular masses

OBJECTIVES: This study was designed to examine the feasibility of ophthalmic magnetic resonance imaging (MRI) at 7.0 T using a local 6-channel transmit/receive radiofrequency (RF) coil array in healthy volunteers and patients with intraocular masses. MATERIALS AND METHODS: A novel 6-element transceiver RF coil array that makes uses of loop elements and that is customized for eye imaging at 7.0 T is proposed. Considerations influencing the RF coil design and the characteristics of the proposed RF coil array are presented. Numerical electromagnetic field simulations were conducted to enhance the RF coil characteristics. Specific absorption rate simulations and a thorough assessment of RF power deposition were performed to meet the safety requirements. Phantom experiments were carried out to validate the electromagnetic field simulations and to assess the real performance of the proposed transceiver array. Certified approval for clinical studies was provided by a local notified body before the in vivo studies. The suitability of the RF coil to image the human eye, optical nerve, and orbit was examined in an in vivo feasibility study including (a) 3-dimensional (3D) gradient echo (GRE) imaging, (b) inversion recovery 3D GRE imaging, and (c) 2D T2-weighted fast spin-echo imaging. For this purpose, healthy adult volunteers (n = 17; mean age, 34 +- 11 years) and patients with intraocular masses (uveal melanoma, n = 5; mean age, 57 +- 6 years) were investigated. RESULTS: All subjects tolerated all examinations well with no relevant adverse events. The 6-channel coil array supports high-resolution 3D GRE imaging with a spatial resolution as good as 0.2 × 0.2 × 1.0 mm, which facilitates the depiction of anatomical details of the eye. Rather, uniform signal intensity across the eye was found. A mean signal-to-noise ratio of approximately 35 was found for the lens, whereas the vitreous humor showed a signal-to-noise ratio of approximately 30. The lens-vitreous humor contrast-to-noise ratio was 8, which allows good differentiation between the lens and the vitreous compartment. Inversion recovery prepared 3D GRE imaging using a spatial resolution of 0.4 × 0.4 × 1.0 mm was found to be feasible. T2-weighted 2D fast spin-echo imaging with the proposed RF coil afforded a spatial resolution of 0.25 × 0.25 × 0.7 mm. CONCLUSIONS: This work provides valuable information on the feasibility of ophthalmic MRI at 7.0 T using a dedicated 6-channel transceiver coil array that supports the acquisition of high-contrast, high-spatial resolution images in healthy volunteers and patients with intraocular masses. The results underscore the challenges of ocular imaging at 7.0 T and demonstrate that these issues can be offset by using tailored RF coil hardware. The benefits of such improvements would be in positive alignment with explorations that are designed to examine the potential of MRI for the assessment of spatial arrangements of the eye segments and their masses with the ultimate goal to provide imaging means for guiding treatment decisions in ophthalmological diseases

Monte Carlo Methods for Estimating Interfacial Free Energies and Line Tensions

Excess contributions to the free energy due to interfaces occur for many problems encountered in the statistical physics of condensed matter when coexistence between different phases is possible (e.g. wetting phenomena, nucleation, crystal growth, etc.). This article reviews two methods to estimate both interfacial free energies and line tensions by Monte Carlo simulations of simple models, (e.g. the Ising model, a symmetrical binary Lennard-Jones fluid exhibiting a miscibility gap, and a simple Lennard-Jones fluid). One method is based on thermodynamic integration. This method is useful to study flat and inclined interfaces for Ising lattices, allowing also the estimation of line tensions of three-phase contact lines, when the interfaces meet walls (where "surface fields" may act). A generalization to off-lattice systems is described as well. The second method is based on the sampling of the order parameter distribution of the system throughout the two-phase coexistence region of the model. Both the interface free energies of flat interfaces and of (spherical or cylindrical) droplets (or bubbles) can be estimated, including also systems with walls, where sphere-cap shaped wall-attached droplets occur. The curvature-dependence of the interfacial free energy is discussed, and estimates for the line tensions are compared to results from the thermodynamic integration method. Basic limitations of all these methods are critically discussed, and an outlook on other approaches is given

Acute Gain in Minimal Lumen Area Following Implantation of Everolimus-Eluting ABSORB Biodegradable Vascular Scaffolds or Xience Metallic Stents: Intravascular Ultrasound Assessment From the ABSORB II Trial

Objectives The study compared, by intravascular ultrasound (IVUS), acute gain (AG) at the site of the pre-procedural minimal lumen area (MLA) achieved by either the Absorb (Abbott Vascular, Santa Clara, California) scaffold or the Xience stent and identified the factors contributing to the acute performance of these devices. Background It is warranted that the acute performance of Absorb matches that of metallic stents; however, concern exists about acute expansion and lumen gain with the use of Absorb. Methods Of a total of 501 patients (546 lesions) in the ABSORB II (ABSORB II Randomized Controlled Trial) randomized trial, 445 patients with 480 lesions were investigated by IVUS pre- and post-procedure. Comparison of MLA pre- and post-procedure was performed at the MLA site by matching pre- and post-procedural IVUS pullbacks. Results Lower AG on IVUS (lowest tertile) occurred more frequently in the Absorb arm than in the Xience arm (3.46\ua0mm 2 vs. 4.27 mm 2 , respectively; p\ua0< 0.001; risk ratio: 3.04; 95% confidence interval: 1.94 to 4.76). The plaque morphology at the MLA cross-section was not independently associated with IVUS acute gain. The main difference in AG in MLD by angiography was observed at the time of device implantation (Xience vs. Absorb, \u394+1.50 mm vs. \u394+1.23 mm, respectively), whereas the gain from post-dilation was similar between the 2 arms (\u394+0.16 mm vs. \u394+0.16 mm) when patients underwent post-dilation, although expected balloon diameter was smaller in the Absorb arm than in the Xience arm (p\ua0= 0.003) during post-dilation. Conclusions At the site of the pre-procedural MLA, the increase of the lumen post-procedure was smaller in the Absorb-arm than in the Xience arm. To achieve equivalent AG to Xience, the implantation of Absorb may require more aggressive strategies at implantation, pre- and post-dilation than the technique used in the ABSORB II trial

Hiring New Key Inventors to Improve Firms’ Post-M&A Inventive Output

Although merger and acquisitions (M&As) are acknowledged as an important means to access innovative assets and know-how, firms’ inventive output often declines in the post-M&A period. Financial, managerial and organizational constraints related to the M&A event contribute to inventive output declines and inventors’ departure. Prior literature treats the acquiring firm as a passive observer of invention declines. This study argues that acquiring firms can take measures by hiring new key inventors. We show that the hiring of new key inventors in the post-M&A period can counteract invention declines in two ways. First, these newly hired inventors are associated with an increase of corporate inventive output after the M&A. Second, they are also associated with an improved inventive output of inventors already working for the acquiring firm. These results suggest that an appropriate hiring policy can counteract declining inventive output of firms in the aftermath of M&As

The performance of the jet trigger for the ATLAS detector during 2011 data taking

The performance of the jet trigger for the ATLAS detector at the LHC during the 2011 data taking period is described. During 2011 the LHC provided proton–proton collisions with a centre-of-mass energy of 7 TeV and heavy ion collisions with a 2.76 TeV per nucleon–nucleon collision energy. The ATLAS trigger is a three level system designed to reduce the rate of events from the 40 MHz nominal maximum bunch crossing rate to the approximate 400 Hz which can be written to offline storage. The ATLAS jet trigger is the primary means for the online selection of events containing jets. Events are accepted by the trigger if they contain one or more jets above some transverse energy threshold. During 2011 data taking the jet trigger was fully efficient for jets with transverse energy above 25 GeV for triggers seeded randomly at Level 1. For triggers which require a jet to be identified at each of the three trigger levels, full efficiency is reached for offline jets with transverse energy above 60 GeV. Jets reconstructed in the final trigger level and corresponding to offline jets with transverse energy greater than 60 GeV, are reconstructed with a resolution in transverse energy with respect to offline jets, of better than 4 % in the central region and better than 2.5 % in the forward direction