Fat fraction mapping using bSSFP Signal Profile Asymmetries for Robust multi-Compartment Quantification (SPARCQ)

Purpose: To develop a novel quantitative method for detection of different tissue compartments based on bSSFP signal profile asymmetries (SPARCQ) and to provide a validation and proof-of-concept for voxel-wise water-fat separation and fat fraction mapping. Methods: The SPARCQ framework uses phase-cycled bSSFP acquisitions to obtain bSSFP signal profiles. For each voxel, the profile is decomposed into a weighted sum of simulated profiles with specific off-resonance and relaxation time ratios. From the obtained set of weights, voxel-wise estimations of the fractions of the different components and their equilibrium magnetization are extracted. For the entire image volume, component-specific quantitative maps as well as banding-artifact-free images are generated. A SPARCQ proof-of-concept was provided for water-fat separation and fat fraction mapping. Noise robustness was assessed using simulations. A dedicated water-fat phantom was used to validate fat fractions estimated with SPARCQ against gold-standard 1H MRS. Quantitative maps were obtained in knees of six healthy volunteers, and SPARCQ repeatability was evaluated in scan rescan experiments. Results: Simulations showed that fat fraction estimations are accurate and robust for signal-to-noise ratios above 20. Phantom experiments showed good agreement between SPARCQ and gold-standard (GS) fat fractions (fF(SPARCQ) = 1.02*fF(GS) + 0.00235). In volunteers, quantitative maps and banding-artifact-free water-fat-separated images obtained with SPARCQ demonstrated the expected contrast between fatty and non-fatty tissues. The coefficient of repeatability of SPARCQ fat fraction was 0.0512. Conclusion: The SPARCQ framework was proposed as a novel quantitative mapping technique for detecting different tissue compartments, and its potential was demonstrated for quantitative water-fat separation.Comment: 20 pages, 7 figures, submitted to Magnetic Resonance in Medicin

Blue cone monochromacy: causative mutations and associated phenotypes.

PurposeTo perform a phenotypic assessment of members of three British families with blue cone monochromatism (BCM), and to determine the underlying molecular genetic basis of disease.MethodsAffected members of three British families with BCM were examined clinically and underwent detailed electrophysiological and psychophysical testing. Blood samples were taken for DNA extraction. Molecular analysis involved the amplification of the coding regions of the long (L) and medium (M) wave cone opsin genes and the upstream locus control region (LCR) by polymerase chain reaction (PCR). Gene products were directly sequenced and analyzed.ResultsIn all three families, genetic analysis identified that the underlying cause of BCM involved an unequal crossover within the opsin gene array, with an inactivating mutation. Family 1 had a single 5'-L-M-3' hybrid gene, with an inactivating Cys203Arg (C203R) mutation. Family 3 had an array composed of a C203R inactivated 5'-L-M-3' hybrid gene followed by a second inactive gene. Families 1 and 3 had typical clinical, electrophysiological, and psychophysical findings consistent with stationary BCM. A novel mutation was detected in Family 2 that had a single hybrid gene lacking exon 2. This family presented clinical and psychophysical evidence of a slowly progressive phenotype.ConclusionsTwo of the BCM-causing family genotypes identified in this study comprised different hybrid genes, each of which contained the commonly described C203R inactivating mutation. The genotype in the family with evidence of a slowly progressive phenotype represents a novel BCM mutation. The deleted exon 2 in this family is not predicted to result in a shift in the reading frame, therefore we hypothesize that an abnormal opsin protein product may accumulate and lead to cone cell loss over time. This is the first report of slow progression associated with this class of mutation in the L or M opsin genes in BCM

Polymeric Photoacids Based on Naphthols—Design Criteria, Photostability, and Light-Mediated Release

The implementation of photoswitches within polymers offers an exciting toolbox in the design of light-responsive materials as irradiation can be controlled both spatially and temporally. Herein, we introduce a range of water-soluble copolymers featuring naphthol-based chromophores as photoacids in the side chain. With that, the resulting materials experience a drastic increase in acidity upon stimulation with UV light and we systematically studied how structure and distance of the photoacid from the copolymer backbone determines polymerizability, photo-response, and photostability. Briefly, we used RAFT (reversible addition–fragmentation chain transfer) polymerization to prepare copolymers consisting of nona(ethylene glycol) methyl ether methacrylate (MEO9MA) as water-soluble comonomer in combination with six different 1-naphthol-based (“N”) monomers. Thereby, we distinguish between methacrylates (NMA, NOeMA), methacrylamides (NMAm, NOeMAm), vinyl naphthol (VN), and post-polymerization modification based on [(1-hydroxynaphthalen-2-amido)ethyl]amine (NOeMAm, NAmeMAm). These P(MEO9MAx-co-“N”y) copolymers typically feature a 4:1 MEO9MA to “N” ratio and molar masses in the range of 10 kg mol−1. After synthesis and characterization by using NMR spectroscopy and size exclusion chromatography (SEC), we investigated how potential photo-cleavage or photo-degradation during irradiation depends on the type and distance of the linker to the copolymeric backbone and whether reversible excited state proton transfer (ESPT) occurs under these conditions. In our opinion, such materials will be strong assets as light-mediated proton sources in nanostructured environments, for example, for the site-specific creation of proton gradients. We therefore exemplarily incorporated NMA into an amphiphilic block copolymer and could demonstrate the light-mediated release of Nile red from micelles formed in water as selective solvent. © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA

Quinoline Photobasicity: Investigation within Water-Soluble Light-Responsive Copolymers

Quinoline photobases exhibit a distinctly higher pKa in their electronically excited state than in the ground state, thereby enabling light-controlled proton transfer reactions, for example, in molecular catalysis. The absorption of UV light translates to a pKa jump of approximately 10 units, as established for small-molecule photobases. This contribution presents the first synthesis of quinoline-based polymeric photobases prepared by reversible addition-fragmentation chain-transfer (RAFT) polymerization. The integration of quinolines as photobase chromophores within copolymers offers new possibilities for light-triggered proton transfer in nanostructured materials, that is, in nanoparticles, at surfaces, membranes and interfaces. To exploit the light-triggered reactivity of photobases within such materials, we first investigated how the ground- and excited-state properties of the quinoline unit changes upon polymer integration. To address this matter, we combined absorption and emission spectroscopy with time-resolved transient-absorption studies to reveal photoinduced proton-transfer dynamics in various solvents. The results yield important insights into the thermodynamic and kinetic properties of these polymeric quinoline photobases. © 2020 The Authors. Chemistry - A European Journal published by Wiley-VCH Gmb

Pesticide spraying for West Nile virus control and emergency department asthma visits in New York City, 2000

Pyrethroid pesticides were applied via ground spraying to residential neighborhoods in New York City during July–September 2000 to control mosquito vectors of West Nile virus (WNV). Case reports link pyrethroid exposure to asthma exacerbations, but population-level effects on asthma from large-scale mosquito control programs have not been assessed. We conducted this analysis to determine whether widespread urban pyrethroid pesticide use was associated with increased rates of emergency department (ED) visits for asthma. We recorded the dates and locations of pyrethroid spraying during the 2000 WNV season in New York City and tabulated all ED visits for asthma to public hospitals from October 1999 through November 2000 by date and ZIP code of patients’ residences. The association between pesticide application and asthma-related emergency visits was evaluated across date and ZIP code, adjusting for season, day of week, and daily temperature, precipitation, particulate, and ozone levels. There were 62,827 ED visits for asthma during the 14-month study period, across 162 ZIP codes. The number of asthma visits was similar in the 3-day periods before and after spraying (510 vs. 501, p = 0.78). In multivariate analyses, daily rates of asthma visits were not associated with pesticide spraying (rate ratio = 0.92; 95% confidence interval, 0.80–1.07). Secondary analyses among children and for chronic obstructive pulmonary disease yielded similar null results. This analysis shows that spraying pyrethroids for WNV control in New York City was not followed by population-level increases in public hospital ED visit rates for asthma

Cupping Therapy Does Not Influence Healthy Adult\u27s Hamstring Range of Motion Compared to Control or Sham Conditions

International Journal of Exercise Science 13(3): 216-224, 2020. Cupping therapy, a form of traditional Chinese medicine, has recently gained popularity as a therapeutic modality among sports medicine clinicians. While the use of cupping therapy to decrease musculoskeletal pain is supported by recent research findings, evaluations on the use of cupping therapy to influence range of motion (ROM) are limited. The purpose of the study was to identify if cupping therapy applied passively for 10 minutes increases flexibility compared to sham treatment or control conditions. Twenty-five participants with hamstring ROM less than 80° and no previous cupping therapy experience completed the study. Participants reported to the laboratory on three occasions for one of three randomly assigned treatment conditions (cupping, sham, or control) for 10 minutes while prone. Hamstring flexibility was evaluated three times (pre-treatment, post-treatment, and 10-minutes post-treatment) via ROM measured during an active straight leg raise. Participants returned on two other occasions to receive the remaining treatment conditions. A 3 (treatment condition) x 3 (time) repeated measures analysis of variance was utilized for statistical analysis. There was no interaction between condition and time (p= 0.78). Within-subjects effects for time (p= 0.76) was not significant. Post hoc pairwise comparison of treatment conditions found no differences between control and cupping (p= 0.36), cupping and sham (p= 0.35), or control and sham (p=0.98) conditions. Cupping therapy applied statically for 10 minutes does not increase hamstring flexibility compared to a sham treatment or control condition

Health-related quality of life impact of minor and major bleeding events during dual antiplatelet therapy::A systematic literature review and patient preference elicitation study

Background Dual antiplatelet therapy (DAPT) is the recommended preventative treatment for secondary ischaemic events, but increases the risk of bleeding, potentially affecting patients’ health-related quality-of-life (HRQoL). Varied utility decrements have been used in cost-effectiveness models assessing alternative DAPT regimens, but it is unclear which of these decrements are most appropriate. Therefore, we reviewed existing sources of utility decrements for bleeds in patients receiving DAPT and undertook primary research to estimate utility decrements through a patient elicitation exercise using vignettes and the EuroQol EQ-5D. Methods MEDLINE, PubMed and references of included studies were searched. Primary research and decision analytic modelling studies reporting utility decrements for bleeds related to DAPT were considered. For the primary research study, 21 participants completed an elicitation exercise involving vignettes describing minor and major bleeds and the EQ-5D-3 L and EQ-5D-5 L. Utility decrements were derived using linear regression and compared to existing estimates. Results Four hundred forty-two citations were screened, of which 12 studies were included for review. Reported utility decrements ranged from − 0.002 to − 0.03 for minor bleeds and − 0.007 to − 0.05 for major bleeds. Data sources used to estimate the decrements, however, lacked relevance to our population group and few studies adequately reported details of their measurement and valuation approaches. No study completely adhered to reimbursement agency requirements in the UK according to the National Institute for Health and Care Excellence reference case. Our primary research elicited utility decrements overlapped existing estimates, ranging from − 0.000848 to − 0.00828 for minor bleeds and − 0.0187 to − 0.0621 for major bleeds. However, the magnitude of difference depended on the instrument, estimation method and valuation approach applied. Conclusions Several sources of utility decrements for bleeds are available for use in cost-effectiveness analyses, but are of limited quality and relevance. Our elicitation exercise has derived utility decrements from a relevant patient population, based on standardised definitions of minor and major bleeding events, using a validated HRQoL instrument and have been valued using general population tariffs. We suggest that our utility decrements be used in future cost-effectiveness analyses of DAPT.</p