Digital and technological innovation in vector-borne disease surveillance to predict, detect, and control climate-driven outbreaks

Vector-borne diseases are particularly sensitive to changes in weather and climate. Timely warnings from surveillance systems can help to detect and control outbreaks of infectious disease, facilitate effective management of finite resources, and contribute to knowledge generation, response planning, and resource prioritisation in the long term, which can mitigate future outbreaks. Technological and digital innovations have enabled the incorporation of climatic data into surveillance systems, enhancing their capacity to predict trends in outbreak prevalence and location. Advance notice of the risk of an outbreak empowers decision makers and communities to scale up prevention and preparedness interventions and redirect resources for outbreak responses. In this Viewpoint, we outline important considerations in the advent of new technologies in disease surveillance, including the sustainability of innovation in the long term and the fundamental obligation to ensure that the communities that are affected by the disease are involved in the design of the technology and directly benefit from its application

Effectiveness of omalizumab in a patient with severe asthma and atopic dermatitis

The anti-IgE antibody omalizumab is currently indicated in severe asthma not controlled by standard drug therapy. Recently, new indications for omalizumab were suggested, which include atopic dermatitis (AD), a skin disorder characterized by elevated levels of IgE. We report the case of a 39-year old woman with severe asthma and severe AD, both resistant to conventional drug treatment. The patient had a IgE level of 1304 kU/L, which exceeded the recommended maximum level for treating asthma with omalizumab (stated in 700 Ku/L) but was far lower than previously reported in cases of AD treated with anti-IgE. The treatment consisted of a dose of omalizumab 375 mg every two weeks, and induced a rapid improvement of asthma, with no need of other drugs after three months, along with a progressive decline of severity of AD, which after five months was completely cured. These findings suggest the usefulness of omalizumab in patients with concomitant severe asthma and AD, also considering the pharmaco-economic balance obtained by withdrawing the multiple drugs used to treat both diseases

Cortical depth dependent functional responses in humans at 7T: improved specificity with 3D GRASE

Ultra high fields (7T and above) allow functional imaging with high contrast-to-noise ratios and improved spatial resolution. This, along with improved hardware and imaging techniques, allow investigating columnar and laminar functional responses. Using gradient-echo (GE) (T2* weighted) based sequences, layer specific responses have been recorded from human (and animal) primary visual areas. However, their increased sensitivity to large surface veins potentially clouds detecting and interpreting layer specific responses. Conversely, spin-echo (SE) (T2 weighted) sequences are less sensitive to large veins and have been used to map cortical columns in humans. T2 weighted 3D GRASE with inner volume selection provides high isotropic resolution over extended volumes, overcoming some of the many technical limitations of conventional 2D SE-EPI, whereby making layer specific investigations feasible. Further, the demonstration of columnar level specificity with 3D GRASE, despite contributions from both stimulated echoes and conventional T2 contrast, has made it an attractive alternative over 2D SE-EPI. Here, we assess the spatial specificity of cortical depth dependent 3D GRASE functional responses in human V1 and hMT by comparing it to GE responses. In doing so we demonstrate that 3D GRASE is less sensitive to contributions from large veins in superficial layers, while showing increased specificity (functional tuning) throughout the cortex compared to GE

A simple device for multiplex ELISA made from melt-extruded plastic microcapillary film

We present a simple device for multiplex quantitative enzyme-linked immunosorbant assays (ELISA) made from a novel melt-extruded microcapillary film (MCF) containing a parallel array of 200µm capillaries along its length. To make ELISA devices different protein antigens or antibodies were immobilised inside individual microcapillaries within long reels of MCF extruded from fluorinated ethylene propylene (FEP). Short pieces of coated film were cut and interfaced with a pipette, allowing sequential uptake of samples and detection solutions into all capillaries from a reagent well. As well as being simple to produce, these FEP MCF devices have excellent light transmittance allowing direct optical interrogation of the capillaries for simple signal quantification. Proof of concept experiments demonstrate both quantitative and multiplex assays in FEP MCF devices using a standard direct ELISA procedure and read using a flatbed scanner. This new multiplex immunoassay platform should find applications ranging from lab detection to point-of-care and field diagnostics

Choice of Cell-Delivery Route for Skeletal Myoblast Transplantation for Treating Post-Infarction Chronic Heart Failure in Rat

Intramyocardial injection of skeletal myoblasts (SMB) has been shown to be a promising strategy for treating post-infarction chronic heart failure. However, insufficient therapeutic benefit and occurrence of ventricular arrhythmias are concerns. We hypothesised that the use of a retrograde intracoronary route for SMB-delivery might favourably alter the behaviour of the grafted SMB, consequently modulating the therapeutic effects and arrhythmogenicity.Three weeks after coronary artery ligation in female wild-type rats, 5x10(6) GFP-expressing SMB or PBS only (control) were injected via either the intramyocardial or retrograde intracoronary routes. Injection of SMB via either route similarly improved cardiac performance and physical activity, associated with reduced cardiomyocyte-hypertrophy and fibrosis. Grafted SMB via either route were only present in low numbers in the myocardium, analysed by real-time PCR for the Y-chromosome specific gene, Sry. Cardiomyogenic differentiation of grafted SMB was extremely rare. Continuous ECG monitoring by telemetry revealed that only intramyocardial injection of SMB produced spontaneous ventricular tachycardia up to 14 days, associated with local myocardial heterogeneity generated by clusters of injected SMB and accumulated inflammatory cells. A small number of ventricular premature contractions with latent ventricular tachycardia were detected in the late-phase of SMB injection regardless of the injection-route.Retrograde intracoronary injection of SMB provided significant therapeutic benefits with attenuated early-phase arrhythmogenicity in treating ischaemic cardiomyopathy, indicating the promising utility of this route for SMB-delivery. Late-phase arrhythmogenicity remains a concern, regardless of the delivery route

Ethnicity, consanguinity, and genetic architecture of hypertrophic cardiomyopathy

AIMS: Hypertrophic cardiomyopathy (HCM) is characterized by phenotypic heterogeneity that is partly explained by the diversity of genetic variants contributing to disease. Accurate interpretation of these variants constitutes a major challenge for diagnosis and implementing precision medicine, especially in understudied populations. The aim is to define the genetic architecture of HCM in North African cohorts with high consanguinity using ancestry-matched cases and controls. METHODS AND RESULTS: Prospective Egyptian patients (n = 514) and controls (n = 400) underwent clinical phenotyping and genetic testing. Rare variants in 13 validated HCM genes were classified according to standard clinical guidelines and compared with a prospective HCM cohort of majority European ancestry (n = 684). A higher prevalence of homozygous variants was observed in Egyptian patients (4.1% vs. 0.1%, P = 2 × 10-7), with variants in the minor HCM genes MYL2, MYL3, and CSRP3 more likely to present in homozygosity than the major genes, suggesting these variants are less penetrant in heterozygosity. Biallelic variants in the recessive HCM gene TRIM63 were detected in 2.1% of patients (five-fold greater than European patients), highlighting the importance of recessive inheritance in consanguineous populations. Finally, rare variants in Egyptian HCM patients were less likely to be classified as (likely) pathogenic compared with Europeans (40.8% vs. 61.6%, P = 1.6 × 10-5) due to the underrepresentation of Middle Eastern populations in current reference resources. This proportion increased to 53.3% after incorporating methods that leverage new ancestry-matched controls presented here. CONCLUSION: Studying consanguineous populations reveals novel insights with relevance to genetic testing and our understanding of the genetic architecture of HCM

MRI T2 and T1ρ relaxation in patients at risk for knee osteoarthritis: A systematic review and meta-analysis

© 2019 The Author(s). Background: Magnetic resonance imaging (MRI) T2 and T1ρ relaxation are increasingly being proposed as imaging biomarkers potentially capable of detecting biochemical changes in articular cartilage before structural changes are evident. We aimed to: 1) summarize MRI methods of published studies investigating T2 and T1ρ relaxation time in participants at risk for but without radiographic knee OA; and 2) compare T2 and T1ρ relaxation between participants at-risk for knee OA and healthy controls. Methods: We conducted a systematic review of studies reporting T2 and T1ρ relaxation data that included both participants at risk for knee OA and healthy controls. Participant characteristics, MRI methodology, and T1ρ and T2 relaxation data were extracted. Standardized mean differences (SMDs) were calculated within each study. Pooled effect sizes were then calculated for six commonly segmented knee compartments. Results: 55 articles met eligibility criteria. There was considerable variability between scanners, coils, software, scanning protocols, pulse sequences, and post-processing. Moderate risk of bias due to lack of blinding was common. Pooled effect sizes indicated participants at risk for knee OA had lengthened T2 relaxation time in all compartments (SMDs from 0.33 to 0.74; p \u3c 0.01) and lengthened T1ρ relaxation time in the femoral compartments (SMD from 0.35 to 0.40; p \u3c 0.001). Conclusions: T2 and T1ρ relaxation distinguish participants at risk for knee OA from healthy controls. Greater standardization of MRI methods is both warranted and required for progress towards biomarker validation

Higher Order Statistics in a mmWave Propagation Environment

(c) 2019 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/ republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works.[EN] A thorough measurement campaign in an indoor environment at the millimeter-wave band is carried out with an aim at characterizing the short-term fading channel in terms of its higher-order statistics. The measurements are conducted in a variety of scenarios, with frequencies ranging from 55 to 65 GHz, in line-of-sight and non-line-of-sight conditions, and combinations of horizontal and vertical polarizations at both the transmitter and the receiver. A number of fading models are tested, namely Rayleigh, Rice, Nakagami-m, alpha-mu, kappa-mu, eta-mu, and alpha-eta-kappa-mu. The main second-order statistics under analysis are the level crossing rate (LCR) and average fade duration (AFD) both given per distance unit. From the experimental data, the parameters of these statistics are estimated, and the corresponding curves of the theoretical models are compared with the empirical ones and the best model is selected. Additionally, the study of the very general distribution, namely alpha-eta-kappa-mu, is advanced, in which new expressions for time-/distance-domain LCR and Al-ll are derived using an envelope-based approach. Such an approach leads to integral-form formulations with much less computational complexity and computes rapidly compared with the already existing ones presented elsewhere, also given in the integral form. Furthermore, a series of expansion expression for the alpha-eta-kappa-mu time-/distance-domain LCR is then derived that improves even further the computational time.This work was supported in part by the Conselho Nacional de Desenvolvimento Cientico e Tecnologico (CNPq) under Grant 304248/2014-2 and Grant 308365/2017-8, in part by the Rede Nacional de Ensino e Pesquisa (RNP), with resources from Ministerio da Ciencia, Tecnologia, Inovacoes e Comunicacoes (MCTIC), through the Radiocommunication Reference Center [Centro de Referencia em Radiocomunicacoes (CRR)] Project of the National Institute of Telecommunications [Instituto Nacional de Telecomunicacoes (INATEL)], Brazil, under Grant 01250.075413/2018-04, and in part by the Ministerio de Economia, Industria y Competitividad of the Spanish Government through the Agencia Estatal de Investigacion (AEI) and the Fondo Europeo de Desarrollo Regional (FEDER) under Project TEC2017-86779-C2-2-R.Dos Anjos, AA.; Rufino-Marins, TR.; Nogueira Da Silva, CR.; Rodrigo Peñarrocha, VM.; Rubio Arjona, L.; Reig, J.; Amaral De Souza, RA.... (2019). Higher Order Statistics in a mmWave Propagation Environment. IEEE Access. 7:103876-103892. https://doi.org/10.1109/ACCESS.2019.2930931S103876103892