Direct and indirect orthotic management of medial compartment osteoarthritis of the knee

Osteoarthritis (OA) is a painful condition and affects approximately 80% of individuals by the age of 55 [1], with knee OA occurring two times more frequently than OA of the hand or hip [2].The condition is more prevalent in the medial compartment and restricts the daily lives of individuals due to pain and a lack of functional independence. Patients with medial compartment osteoarthritis often have a varus alignment, with the mechanical axis and load bearing passing through this compartment with a greater adduction moment leading to greater pain and progression of osteoarthritis [3]. Surgery for the condition is possible although in some cases, particularly younger patients or those not yet requiring surgery, clinical management remains a challenge. Before surgery is considered, however, conservative management is advocated, though no one treatment has been shown to be most effective, and there are few quality biomechanical or clinical studies. Of the conservative approaches the principal orthotic treatments are valgus knee braces and laterally wedged foot inlays. Studies of knee valgus bracing have consistently demonstrated an associated decreased pain and improved function [4], and greater confidence [5]. A laterally wedged foot inlay has a thicker lateral border and applies a valgus moment to the heel. It is theorised that by changing the position of the ankle and subtalar joints during weight-bearing [6] the lateral wedges may apply a valgus moment across the knee as well as the rearfoot, with the assumed reduction on load in the medial knee compartment [7]. However, there has been no study to directly compare these orthotic treatments in the same study. The aim of this research is to investigate the efficacy of valgus knee braces and laterally wedged foot inlays in reducing the varus knee moment

real world comparative effectiveness of nab paclitaxel plus gemcitabine nab p g vs folfirinox ffx in patients pts with advanced pancreatic cancer apc

n/

Burden of mild haemophilia A: Systematic literature review

Introduction Although the clinical manifestations of severe haemophilia A (HA) are well studied, the challenges, if any, of living with mild HA are not clearly delineated to date. Aim To assess available evidence of clinical risks and societal/economic impacts of disease in adult patients with mild HA using a systematic literature review. Methods Prespecified study selection criteria were applied in a comprehensive literature search. Included studies varied in design and reported outcomes of interest for adults (>= 13 years of age) with mild HA. Results Seventeen studies with a total of 3213 patients met eligibility criteria (published or presented in English, 1966-2017). Most studies were observational, and the outcomes reported were too sparse and dissimilar to support a formal meta-analysis. Mean annual bleeding rates ranged from 0.44 to 4.5 episodes per patient per year. Quality of life (QoL; SF-36 General Health) was impacted compared to healthy controls. Health care costs and productivity were seldom assessed and no robust comparisons to healthy controls were available. Conclusion Quantifying outcomes for adult patients with mild HA remains challenging, with estimates of key QoL and cost data often based on small data sets and without comparison to population norms. Therefore, the clinical impact of mild haemophilia may be under-represented and unmet needs may remain unaddressed. As paradigm-changing therapies for HA emerge, stronger knowledge of mild HA can guide the development of care options that minimize burden and enhance the QoL for this segment of the haemophilia community, and for the haemophilia community in totality

Giant Shapiro steps for two-dimensional Josephson-junction arrays with time-dependent Ginzburg-Landau dynamics

Two-dimensional Josephson junction arrays at zero temperature are investigated numerically within the resistively shunted junction (RSJ) model and the time-dependent Ginzburg-Landau (TDGL) model with global conservation of current implemented through the fluctuating twist boundary condition (FTBC). Fractional giant Shapiro steps are found for {\em both} the RSJ and TDGL cases. This implies that the local current conservation, on which the RSJ model is based, can be relaxed to the TDGL dynamics with only global current conservation, without changing the sequence of Shapiro steps. However, when the maximum widths of the steps are compared for the two models some qualitative differences are found at higher frequencies. The critical current is also calculated and comparisons with earlier results are made. It is found that the FTBC is a more adequate boundary condition than the conventional uniform current injection method because it minimizes the influence of the boundary.Comment: 6 pages including 4 figures in two columns, final versio

Development and validation of a NanoString BASE47 bladder cancer gene classifier

Background Recent molecular characterization of urothelial cancer (UC) has suggested potential pathways in which to direct treatment, leading to a host of targeted therapies in development for UC. In parallel, gene expression profiling has demonstrated that high-grade UC is a heterogeneous disease. Prognostic basal-like and luminal-like subtypes have been identified and an accurate transcriptome BASE47 classifier has been developed. However, these phenotypes cannot be broadly investigated due to the lack of a clinically viable diagnostic assay. We sought to develop and evaluate a diagnostic classifier of UC subtype with the goal of accurate classification from clinically available specimens. Methods Tumor samples from 52 patients with high-grade UC were profiled for BASE47 genes concurrently by RNAseq as well as NanoString. After design and technical validation of a BASE47 NanoString probeset, results from the RNAseq and NanoString were used to translate diagnostic criteria to the Nanostring platform. Evaluation of repeatability and accuracy was performed to derive a final Nanostring based classifier. Diagnostic classification resulting from the NanoString BASE47 classifier was validated on an independent dataset (n = 30). The training and validation datasets accurately classified 87% and 93% of samples, respectively. Results Here we have derived a NanoString-platform BASE47 classifier that accurately predicts basal-like and luminal-like subtypes in high grade urothelial cancer. We have further validated our new NanoString BASE47 classifier on an independent dataset and confirmed high accuracy when compared with our original Transcriptome BASE47 classifier. Conclusions The NanoString BASE47 classifier provides a faster turnaround time, a lower cost per sample to process, and maintains the accuracy of the original subtype classifier for better clinical implementation

Zero Temperature Glass Transition in the Two-Dimensional Gauge Glass Model

We investigate dynamic scaling properties of the two-dimensional gauge glass model for the vortex glass phase in superconductors with quenched disorder. From extensive Monte Carlo simulations we obtain static and dynamic finite size scaling behavior, where the static simulations use a temperature exchange method to ensure convergence at low temperatures. Both static and dynamic scaling of Monte Carlo data is consistent with a glass transition at zero temperature. We study a dynamic correlation function for the superconducting order parameter, as well as the phase slip resistance. From the scaling of these two functions, we find evidence for two distinct diverging correlation times at the zero temperature glass transition. The longer of these time scales is associated with phase slip fluctuations across the system that lead to finite resistance at any finite temperature, while the shorter time scale is associated with local phase fluctuations.Comment: 8 pages, 10 figures; v2: some minor correction

Age at diagnosis, obesity, smoking, and molecular subtypes in muscle-invasive bladder cancer

Background: Heterogeneity of muscle-invasive bladder cancer (MIBC) has been characterized using whole-genome mRNA expression data, showing distinct molecular and clinicopathological characteristics by subtypes. However, associations between risk factors and molecular subtypes have not been reported. Methods: Four previously published schemes were used to categorize molecular subtypes in 372 MIBC patients from the Cancer Genome Atlas (TCGA). Data on gene expression (RNA-seq), demographic, and clinicopathological characteristics were retrieved through TCGA data portal. Polytomous logistic regression was used to estimate the associations of subtypes by different schemes with age at diagnosis, obesity, and smoking. Results: While some quantitative variation was evident, distinct molecular subtype schemes showed considerable consistency in the association with the risk factors. Generally, compared to patients with luminal-like tumors, patients with basal-like subtypes were more likely to be older (OR75 + yrs vs. <60 years range = 1.32–2.89), obese (ORobese vs. normal range = 1.30–3.05), and to start smoking at early age (OR<18 years vs. 25+ years range = 1.11–4.57). Conclusions: Different molecular subtypes of MIBC may have distinct risk profiles. Large population-based studies with detailed information on bladder cancer risk factors are needed to further define etiologic heterogeneity for bladder cancer

On the existence of a finite-temperature transition in the two-dimensional gauge glass

Results from Monte Carlo simulations of the two-dimensional gauge glass supporting a zero-temperature transition are presented. A finite-size scaling analysis of the correlation length shows that the system does not exhibit spin-glass order at finite temperatures. These results are compared to earlier claims of a finite-temperature transition.Comment: 4 pages, 2 figure

Shor-Preskill Type Security-Proofs for Concatenated Bennett-Brassard 1984 Quantum Key Distribution Protocol

We discuss long code problems in the Bennett-Brassard 1984 (BB84) quantum key distribution protocol and describe how they can be overcome by concatenation of the protocol. Observing that concatenated modified Lo-Chau protocol finally reduces to the concatenated BB84 protocol, we give the unconditional security of the concatenated BB84 protocol.Comment: 4 pages, RevTe