Genetic determinants of Paget’s Disease of Bone

PURPOSE OF REVIEW: To provide an overview of the role of genes and loci that predispose to Paget’s disease of bone and related disorders. RECENT FINDINGS: Studies over the past ten years have seen major advances in knowledge on the role of genetic factors in Paget’s disease of bone (PDB). Genome wide association studies have identified six loci that predispose to the disease whereas family based studies have identified a further eight genes that cause PDB. This brings the total number of genes and loci implicated in PDB to fourteen. Emerging evidence has shown that a number of these genes also predispose to multisystem proteinopathy syndromes where PDB is accompanied by neurodegeneration and myopathy due to the accumulation of abnormal protein aggregates, emphasising the importance of defects in autophagy in the pathogenesis of PDB. SUMMARY: Genetic factors play a key role in the pathogenesis of PDB and the studies in this area have identified several genes previously not suspected to play a role in bone metabolism. Genetic testing coupled to targeted therapeutic intervention is being explored as a way of halting disease progression and improving outcome before irreversible skeletal damage has occurred

Total Hip Arthroplasty When Utilised in Young Adults Is a Cost-Effective Procedure:A 10-Year and Lifetime Cost-Utility Analysis

Purpose The primary aim of this study was to determine the cost-effectiveness of total hip arthroplasty (THA) in patients aged 25 years and under by calculating the cost per quality-adjusted life year (QALY) gained at 10 years post-operatively, and over the course of a lifetime. Secondary aims were to describe the change in health-related quality of life (HRQoL), Oxford hip score (OHS), and satisfaction in these patients. Methods From 2000 to 2016, 33 patients undergoing THA aged 25 and under had pre-operative and one-year post-operative EuroQol five-dimensions (EQ-5D) scores and OHS recorded prospectively. Post-operative change in EQ-5D allowed calculation of a health-utility score, which, when combined with life expectancy, gave total QALYs gained. Results The mean age was 20 years (range 13.3-24.9), with 23 females (72.7%). Mean number of QALYs gained was 21.1 (95% CI 14.1-28.2). Total lifetime cost per patient was £14641, giving a mean cost per QALY of £4183 at 10 years post-operatively, and £694 over the total remaining lifetime. Discounting total QALYs gained at a rate of 3.5% and 5% per remaining year of life expectancy increased the mean cost per QALY to £1652 and £2187, respectively. Mean pre- and post-operative EQ-5D index were 0.27 (SD 0.27) and 0.63 (SD 0.29), respectively (p=0.0001). Mean pre-operative and post-operative OHS was 37.5 (SD 7.9) and 19.7 (SD 6.94), respectively (p<0.00001). Conclusion THA remains a cost-effective intervention for patients aged 25 years and under. It is also associated with significant improvement in HRQoL, OHS, and high levels of patient satisfaction in this unique patient group

Pathway Analysis of Major Genes Affecting Osteosarcoma Metastasis

Faculty advisor: David LargaespadaThis research was supported by the Undergraduate Research Opportunities Program (UROP)

Semiquantitative Classification of Two Oxidizing Gases with Graphene-Based Gas Sensors

Miniature and low-power gas sensing elements are urgently needed for a portable electronic nose, especially for outdoor pollution monitoring. Hereby we prepared chemiresistive sensors based on wide-area graphene (grown by chemical vapor deposition) placed on Si/Si3N4 substrates with interdigitated electrodes and built-in microheaters. Graphene of each sensor was individually functionalized with ultrathin oxide coating (CuO-MnO2, In2O3 or Sc2O3) by pulsed laser deposition. Over the course of 72 h, the heated sensors were exposed to randomly generated concentration cycles of 30 ppb NO2, 30 ppb O3, 60 ppb NO2, 60 ppb O3 and 30 ppb NO2 + 30 ppb O3 in synthetic air (21% O2, 50% relative humidity). While O3 completely dominated the response of sensors with CuO-MnO2 coating, the other sensors had comparable sensitivity to NO2 as well. Various response features (amplitude, response rate, and recovery rate) were considered as machine learning inputs. Using just the response amplitudes of two complementary sensors allowed us to distinguish these five gas environments with an accuracy of ~ 85%. Misclassification was mostly due to an overlap in the case of the 30 ppb O3, and 30 ppb O3 + 30 ppb NO2 responses, and was largely caused by the temporal drift of these responses. The addition of recovery rates to machine learning input variables enabled us to very clearly distinguish different gases and increase the overall accuracy to ~94%

Challenges and perspectives in continuous glucose monitoring

Diabetes is a global epidemic that threatens the health and well-being of hundreds of millions of people. The first step in patient treatment is to monitor glucose levels. Currently this is most commonly done using enzymatic strips. This approach suffers from several limitations, namely it requires a blood sample and is therefore invasive, the quality and the stability of the enzymatic strips vary widely, and the patient is burdened by performing the measurement themselves. This results in dangerous fluctuations in glucose levels often going undetected. There is currently intense research towards new approaches in glucose detection that would enable non-invasive continuous glucose monitoring (CGM). In this review, we explore the state-of-the-art in glucose detection technologies. In particular, we focus on the physical mechanisms behind different approaches, and how these influence and determine the accuracy and reliability of glucose detection. We begin by reviewing the basic physical and chemical properties of the glucose molecule. Although these play a central role in detection, especially the anomeric ratio, they are surprisingly often overlooked in the literature. We then review state-of-the art and emerging detection methods. Finally, we survey the current market for glucometers. Recent results show that past challenges in glucose detection are now being overcome, thereby enabling the development of smart wearable devices for non-invasive continuous glucose monitoring. These new directions in glucose detection have enormous potential to improve the quality of life of millions of diabetics, as well as offer insight into the development, treatment and even prevention of the disease