221 research outputs found

    Refining the risk of HTLV-1-associated myelopathy in people living with HTLV-1: identification of a HAM-like phenotype in a proportion of asymptomatic carriers

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    Up to 3.8% of human T-lymphotropic virus type-1 (HTLV-1)-infected asymptomatic carriers (AC) eventually develop HTLV-1-associated myelopathy (HAM). HAM occurs in patients with high (>ā€‰1%) HTLV proviral load (PVL). However, this cut-off includes more than 50% of ACs and therefore the risk needs to be refined. As HAM is additionally characterised by an inflammatory response to HTLV-1, markers of T cell activation (TCA), Ī²2-microglobulin (Ī²2M) and neuronal damage were accessed for the identification of ACs at high risk of HAM. Retrospective analysis of cross-sectional and longitudinal routine clinical data examining differences in TCA (CD4/CD25, CD4/HLA-DR, CD8/CD25 & CD8/HLA-DR), Ī²2M and neurofilament light (NfL) in plasma in ACs with high or low PVL and patients with HAM. Comparison between 74 low PVL ACs, 84 high PVL ACs and 58 patients with HAM revealed a significant, stepwise, increase in TCA and Ī²2M. Construction of receiver operating characteristic (ROC) curves for each of these blood tests generated a profile that correctly identifies 88% of patients with HAM along with 6% of ACs. The 10 ACs with this 'HAM-like' profile had increased levels of NfL in plasma and two developed myelopathy during follow-up, compared to none of the 148 without this viral-immune-phenotype. A viral-immuno-phenotype resembling that seen in patients with HAM identifies asymptomatic carriers who are at increased risk of developing HAM and have markers of subclinical neuronal damage

    Airborne Measurements of Atmospheric Methane Using Pulsed Laser Transmitters

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    Atmospheric methane (CH4) is the second most important anthropogenic greenhouse gas with approximately 25 times the radiative forcing of carbon dioxide (CO2) per molecule. At NASA Goddard Space Flight Center (GSFC) we have been developing a laser-based technology needed to remotely measure CH4 from orbit. We report on our development effort for the methane lidar, especially on our laser transmitters and recent airborne demonstration. Our lidar transmitter is based on an optical parametric process to generate near infrared laser radiation at 1651 nanometers, coincident with a CH4 absorption. In an airborne flight campaign in the fall of 2015, we tested two kinds of laser transmitters --- an optical parametric amplifier (OPA) and an optical parametric oscillator (OPO). The output wavelength of the lasers was rapidly tuned over the CH4 absorption by tuning the seed laser to sample the CH4 absorption line at several wavelengths. This approach uses the same Integrated Path Differential Absorption (IPDA) technique we have used for our CO2 lidar for ASCENDS. The two laser transmitters were successfully operated in the NASAs DC-8 aircraft, measuring methane from 3 to 13 kilometers with high precision

    Improving medication management in multimorbidity: development of the MultimorbiditY COllaborative Medication Review And DEcision Making (MY COMRADE) intervention using the Behaviour Change Wheel.

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    BACKGROUND: Multimorbidity, the presence of two or more chronic conditions, affects over 60Ā % of patients in primary care. Due to its association with polypharmacy, the development of interventions to optimise medication management in patients with multimorbidity is a priority. The Behaviour Change Wheel is a new approach for applying behavioural theory to intervention development. Here, we describe how we have used results from a review of previous research, original research of our own and the Behaviour Change Wheel to develop an intervention to improve medication management in multimorbidity by general practitioners (GPs), within the overarching UK Medical Research Council guidance on complex interventions. METHODS: Following the steps of the Behaviour Change Wheel, we sought behaviours associated with medication management in multimorbidity by conducting a systematic review and qualitative study with GPs. From the modifiable GP behaviours identified, we selected one and conducted a focused behavioural analysis to explain why GPs were or were not engaging in this behaviour. We used the behavioural analysis to determine the intervention functions, behavioural change techniques and implementation plan most likely to effect behavioural change. RESULTS: We identified numerous modifiable GP behaviours in the systematic review and qualitative study, from which active medication review (rather than passive maintaining the status quo) was chosen as the target behaviour. Behavioural analysis revealed GPs' capabilities, opportunities and motivations relating to active medication review. We combined the three intervention functions deemed most likely to effect behavioural change (enablement, environmental restructuring and incentivisation) to form the MultimorbiditY COllaborative Medication Review And DEcision Making (MY COMRADE) intervention. MY COMRADE primarily involves the technique of social support: two GPs review the medications prescribed to a complex multimorbid patient together. Four other behavioural change techniques are incorporated: restructuring the social environment, prompts/cues, action planning and self-incentives. CONCLUSIONS: This study is the first to use the Behaviour Change Wheel to develop an intervention targeting multimorbidity and confirms the usability and usefulness of the approach in a complex area of clinical care. The systematic development of the MY COMRADE intervention will facilitate a thorough evaluation of its effectiveness in the next phase of this work

    Single nucleotide polymorphism discovery in albacore and Atlantic bluefin tuna provides insights into worldwide population structure.

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    The optimal management of the commercially important, but mostly over-exploited, pelagic tunas, albacore (Thunnus alalunga Bonn., 1788) and Atlantic bluefin tuna (BFT; Thunnus thynnus L., 1758), requires a better understanding of population structure than has been provided by previous molecular methods. Despite numerous studies of both species, their population structures remain controversial. This study reports the development of single nucleotide polymorphisms (SNPs) in albacore and BFT and the application of these SNPs to survey genetic variability across the geographic ranges of these tunas. A total of 616 SNPs were discovered in 35 albacore tuna by comparing sequences of 54 nuclear DNA fragments. A panel of 53 SNPs yielded FST values ranging from 0.0 to 0.050 between samples after genotyping 460 albacore collected throughout the distribution of this species. No significant heterogeneity was detected within oceans, but between-ocean comparisons (Atlantic, Pacific and Indian oceans along with Mediterranean Sea) were significant. Additionally, a 17-SNP panel was developed in Atlantic BFT by cross-species amplification in 107 fish. This limited number of SNPs discriminated between samples from the two major spawning areas of Atlantic BFT (FST = 0.116). The SNP markers developed in this study can be used to genotype large numbers of fish without the need for standardizing alleles among laboratories.This work was supported by ATM2010Hegaluze (351BI20090047), ATM2009Hegalabur (351BI20090034) and ATM2008Bonorte (ACM2008BONORTE) projects funded by the Basque Government, and the ACEITUNA (CTM2011-27505) project funded by the Spanish Ministerio de EconomĆ­a y Competitividad

    Fiber-Based Laser MOPA Transmitter Packaging for Space Environment

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    NASAs Goddard Space Flight Center has been developing lidar to remotely measure CO2 and CH4 in the Earths atmosphere. The ultimate goal is to make space-based satellite measurements with global coverage. We are working on maturing the technology readiness of a fiber-based, 1.57-micron wavelength laser transmitter designed for use in atmospheric CO2 remote-sensing. To this end, we are building a ruggedized prototype to demonstrate the required power and performance and survive the required environment. We are building a fiber-based master oscillator power amplifier (MOPA) laser transmitter architecture. The laser is a wavelength-locked, single frequency, externally modulated DBR operating at 1.57-micron followed by erbium-doped fiber amplifiers. The last amplifier stage is a polarization-maintaining, very-large-mode-area fiber with ~1000 m2 effective area pumped by a Raman fiber laser. The optical output is single-frequency, one microsecond pulses with >450 J pulse energy, 7.5 KHz repetition rate, single spatial mode, and > 20 dB polarization extinction
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