Inclusion body myositis: therapeutic approaches.

The idiopathic inflammatory myopathies are a heterogeneous group of diseases that include dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) and other less common myopathies. These are clinically and histopathologically distinct diseases with many shared clinical features. IBM, the most commonly acquired inflammatory muscle disease occurs in individuals aged over 50 years, and is characterized by slowly progressive muscle weakness and atrophy affecting proximal and distal muscle groups, often asymmetrically. Unlike DM and PM, IBM is typically refractory to immunotherapy. Although corticosteroids have not been tested in randomized controlled trials, the general consensus is that they are not efficacious. There is some suggestion that intravenous immunoglobulin slows disease progression, but its long-term effectiveness is unclear. The evidence for other immunosuppressive therapies has been derived mainly from case reports and open studies and the results are discouraging. Only a few clinical trials have been conducted on IBM, making it difficult to provide clear recommendations for treatment. Moreover, IBM is a slowly progressive disease so assessment of treatment efficacy is problematic due to the longer-duration trials needed to determine treatment effects. Newer therapies may be promising, but further investigation to document efficacy would be expensive given the aforementioned need for longer trials. In this review, various treatments that have been employed in IBM will be discussed even though none of the interventions has sufficient evidence to support its routine use

Joint Scheduling and Resource Allocation in the OFDMA Downlink: Utility Maximization under Imperfect Channel-State Information

We consider the problem of simultaneous user-scheduling, power-allocation, and rate-selection in an OFDMA downlink, with the goal of maximizing expected sum-utility under a sum-power constraint. In doing so, we consider a family of generic goodput-based utilities that facilitate, e.g., throughput-based pricing, quality-of-service enforcement, and/or the treatment of practical modulation-and-coding schemes (MCS). Since perfect knowledge of channel state information (CSI) may be difficult to maintain at the base-station, especially when the number of users and/or subchannels is large, we consider scheduling and resource allocation under imperfect CSI, where the channel state is described by a generic probability distribution. First, we consider the "continuous" case where multiple users and/or code rates can time-share a single OFDMA subchannel and time slot. This yields a non-convex optimization problem that we convert into a convex optimization problem and solve exactly using a dual optimization approach. Second, we consider the "discrete" case where only a single user and code rate is allowed per OFDMA subchannel per time slot. For the mixed-integer optimization problem that arises, we discuss the connections it has with the continuous case and show that it can solved exactly in some situations. For the other situations, we present a bound on the optimality gap. For both cases, we provide algorithmic implementations of the obtained solution. Finally, we study, numerically, the performance of the proposed algorithms under various degrees of CSI uncertainty, utilities, and OFDMA system configurations. In addition, we demonstrate advantages relative to existing state-of-the-art algorithms

Negative Blogs, Positive Outcomes: When Should Firms Permit Employees toBlog Honestly

Weblogs or blogs have recently received a lot of attention, especially in the business community, with a number of firms encouraging their employees to publish blogs to reach out and connect to a wider audience. It is beginning to be recognized that employee blogs can cast a firm in either a positive or a negative light, thereby enhancing or harming the firm’s reputation. Paradoxically, under certain conditions negative postings by employees can actually help the overall reputation of the firm. The rationale for this is that negative posts raise the credibility of an employee blog and attract more readers, who then will also be exposed to the positive posts on the blog. Drawing from the literature on customer advocacy and the stage model theory of information processing in cognitive psychology, we develop a model to decipher the relationship between the extent of negative posts and the overall positive Word of Mouth (WOM) generated by the employee blogs for the firm. An empirical model is developed to account for the inherent non-linearities, endogeneity and unobserved heterogeneity concerns, and potential alternative specifications. Our results suggest that negative posts act as a catalyst to increase the readership of an employee blog, with readership increasing exponentially in the initial stages and then stabilizing. The empirical findings are used to generate an analytical framework that firms can use to formulate employee blogging policies. We illustrate the application of the framework using blogging data from Sun Microsystems

Strike a happy medium: the effect of it knowledge on venture capitalists' overconfidence in it investments

In this article, the effect of IT knowledge on the overconfidence of venture capitalists (VCs) in their IT investments is examined. Our findings show that the effect of IT knowledge on overconfidence is nonlinear. VCs with moderate levels of IT knowledge are least overconfident. At the same time, VCs with moderate levels of IT knowledge are most resistant to the biasing effects of past successes. Past failures show a negative association with overconfidence independent of the level of the VC's IT knowledge. Finally, the negative association between stakes and VC overconfidence is stronger with greater levels of IT knowledge. These results shed light on the highly disputed role of IT knowledge in the domain of IT investments.info:eu-repo/semantics/publishedVersio

Moir\'e fractals in twisted graphene layers

Twisted bilayer graphene (TBLG) subject to a sequence of commensurate external periodic potentials reveals the formation of moir\'{e} fractals (MF) that share striking similarities with the central place theory (CPT) of economic geography, thus uncovering a remarkable connection between twistronics and the geometry of economic zones. MFs arise from the self-similarity of the emergent hierarchy of Brillouin zones (BZ), forming a nested subband structure within the bandwidth of the original moir\'{e} bands. We derive the fractal generators (FG) for TBLG under these external potentials and explore their impact on the hierarchy of the BZ edges and the wavefunctions at the Dirac point. By examining realistic super-moir\'{e} structures (SMS) and demonstrating their equivalence to MFs with periodic perturbations under specific conditions, we establish MFs as a general description for such systems. Furthermore, we uncover parallels between the modification of the BZ hierarchy and magnetic BZ formation in Hofstadter's butterfly (HB), allowing us to construct an incommensurability measure for MFs \textit{vs.} twist angle. The resulting bandstructure hierarchy bolsters correlation effects, pushing more bands within the same energy window for both commensurate and incommensurate TBLG.Comment: revised main text latex 17 pages including bibliography and appendices. Accepted for publication in Physical Review

A primer on Twistronics: Massless Dirac Fermion's journey to Moir\'e patterns and Flat bands in Twisted Bilayer Graphene

The recent discovery of the strongly correlated phases in magic angle twisted bilayer graphene heralded a new area of investigation into the strongly-correlation physics in graphene. This is remarkably different from the initial period of graphene research which was dominated by interest in one body physics of massless Dirac fermions. This pedagogical review article provides a self-contained theoretical perspective of the journey of the wonder material graphene from its single-particle physics dominated regime to the flat band regime of strong-correlation physics. Starting from the origin of Dirac points in condensed matter systems, along this road, this review discusses the effect of superlattice on the Fermi velocity and Van Hove singularities in the dispersion relation of the graphene, and how it naturally leads to investigation into Moir\'e pattern in Van der Wall's heterostructure such as graphene-hexagonal boron-nitride and twisted bilayer graphene. Subsequently It discusses in detail the origin of flat bands in twisted bilayer graphene at the magic angles. by analysing in detail a number of prominent theoretical works in this direction. The theoretical description is intercepted at appropriate places by connecting it with the relevant experimental works. In a final section we also provide a list of the topics in the field of twisted bilayer graphene that are not covered in this review, but can be approached with the help of this primer.Comment: Invited Topical Review (Submitted for Publication

Joint Scheduling and Resource Allocation in OFDMA Downlink Systems via ACK/NAK Feedback

In this paper, we consider the problem of joint scheduling and resource allocation in the OFDMA downlink, with the goal of maximizing an expected long-term goodput-based utility subject to an instantaneous sum-power constraint, and where the feedback to the base station consists only of ACK/NAKs from recently scheduled users. We first establish that the optimal solution is a partially observable Markov decision process (POMDP), which is impractical to implement. In response, we propose a greedy approach to joint scheduling and resource allocation that maintains a posterior channel distribution for every user, and has only polynomial complexity. For frequency-selective channels with Markov time-variation, we then outline a recursive method to update the channel posteriors, based on the ACK/NAK feedback, that is made computationally efficient through the use of particle filtering. To gauge the performance of our greedy approach relative to that of the optimal POMDP, we derive a POMDP performance upper-bound. Numerical experiments show that, for slowly fading channels, the performance of our greedy scheme is relatively close to the upper bound, and much better than fixed-power random user scheduling (FP-RUS), despite its relatively low complexity

Management of interstitial lung disease (ILD) in myositis syndromes: A practical guide for clinicians

Inflammatory myopathies are heterogeneous clinico-serological syndromes, with variable clinical manifestations. Interstitial lung disease (ILD) is a major cause of morbidity and mortality in patients with myositis. The clinical manifestation of myositis-ILD is heterogeneous, e.g., with acute-on-chronic presentations, as well as the chronic aftermath of acute disease. Here, we have largely divided myositis-ILD into three main prognostic groups which require different treatment approaches: mild-moderate (subacute), severe or progressive (acute or subacute) and rapidly progressive, life-threatening. In current clinical practice, the treatment of myositis-ILD involves immunomodulation in an induction-maintenance treatment paradigm. There is now an option to add antifibrotics to slow the progression of established fibrosis in selected cases with chronic progressive phenotype. Here, we describe current concepts in myositis-ILD and aim to provide a practical guide for clinicians on how to approach assessment, including early identification of ILD, phenotyping of patients according to clinical trajectory and likely prognosis and stratified management adopting multi-disciplinary cross-speciality expertise, with close collaboration between rheumatology and respiratory physicians