Multispectral optoacoustic tomography for non-invasive disease phenotyping in pediatric spinal muscular atrophy patients

Proximal spinal muscular atrophy (SMA) is a rare progressive, life limiting genetic motor neuron disease. While promising causal therapies are available, meaningful prognostic biomarkers for therapeutic monitoring are missing. We demonstrate handheld Multispectral Optoacoustic Tomography (MSOT) as a novel non-invasive imaging approach to visualize and quantify muscle wasting in pediatric SMA. While MSOT signals were distributed homogeneously in muscles of healthy volunteers (HVs), SMA patients showed moth-eaten optoacoustic signal patterns. Further signal quantification revealed greatest differences between groups at the isosbestic point for hemoglobin (SWL 800 nm). The SWL 800 nm signal intensities further correlated with clinical phenotype tested by standard motor outcome measures. Therefore, handheld MSOT could enable non-invasive assessment of disease burden in SMA patients

Fast Multispectral Optoacoustic Tomography (MSOT) for Dynamic Imaging of Pharmacokinetics and Biodistribution in Multiple Organs

The characterization of pharmacokinetic and biodistribution profiles is an essential step in the development process of new candidate drugs or imaging agents. Simultaneously, the assessment of organ function related to the uptake and clearance of drugs is of great importance. To this end, we demonstrate an imaging platform capable of high-rate characterization of the dynamics of fluorescent agents in multiple organs using multispectral optoacoustic tomography (MSOT). A spatial resolution of approximately 150 µm through mouse cross-sections allowed us to image blood vessels, the kidneys, the liver and the gall bladder. In particular, MSOT was employed to characterize the removal of indocyanine green from the systemic circulation and its time-resolved uptake in the liver and gallbladder. Furthermore, it was possible to track the uptake of a carboxylate dye in separate regions of the kidneys. The results demonstrate the acquisition of agent concentration metrics at rates of 10 samples per second at a single wavelength and 17 s per multispectral sample with 10 signal averages at each of 5 wavelengths. Overall, such imaging performance introduces previously undocumented capabilities of fast, high resolution in vivo imaging of the fate of optical agents for drug discovery and basic biological research

Combined Forward-Backward Asymmetry Measurements in Top-Antitop Quark Production at the Tevatron

The CDF and D0 experiments at the Fermilab Tevatron have measured the asymmetry between yields of forward- and backward-produced top and antitop quarks based on their rapidity difference and the asymmetry between their decay leptons. These measurements use the full data sets collected in proton-antiproton collisions at a center-of-mass energy of $\sqrt s =1.96$ TeV. We report the results of combinations of the inclusive asymmetries and their differential dependencies on relevant kinematic quantities. The combined inclusive asymmetry is $A_{\mathrm{FB}}^{t\bar{t}} = 0.128 \pm 0.025$. The combined inclusive and differential asymmetries are consistent with recent standard model predictions

Active Travel as Stable Source of Physical Activity for One Third of German Adults: Evidence from Longitudinal Data

Walking and cycling—active travel—can help adults achieve the World Health Organization’s recommended 150+ min of moderate-intensity aerobic physical activity per week. Based on a nationally representative panel-survey of daily travel in Germany, this study assesses weekly minutes of active travel by adult respondents participating in a weeklong survey in two consecutive years. The paper first identifies person-level covariates for achieving 150+ min of active travel during a week in year 1 of panel participation. The analysis then compares the patterns of individuals falling into four groups of active travel over the two survey years: ‘high maintainers’ who achieved 150+ min in both year 1 and year 2; ‘low maintainers’ who did not achieve 150+ min in neither year 1 nor year 2; ‘adopters’ who did not achieve 150+ min in year 1, but did so in year 2; and ‘relapsers’ who achieved 150+ min in year 1, but not in year 2. About half (48%) of respondents achieved 150+ min of active travel per week in their first year of panel participation. Of those, about three-quarters were ‘high maintainers’ with 150+ min of active travel in both years. Logistic regressions showed that ‘high maintainers’ were more likely to be 30 years or older, not employed, have a monthly public transport pass, live within 2 km of a shopping destination, and less likely to own cars. Transport and land-use policies can help influence several of these factors. Compared to ‘low maintainers,’ policy interventions to increase population shares achieving health-enhancing levels of physical activity from active travel may be most promising when targeting ‘adopters’ and ‘relapsers.’ These groups are more similar to the ‘high maintainers,’ with at least one year reporting of health-enhancing physical activity from active travel—compared to the ‘low maintainers.

Active travel in Germany and the U.S. : contributions of daily walking and cycling to physical activity

Background: Travel surveys in Europe and the U.S. show large differences in the proportion of walking and cycling trips without considering implications for physical activity. Purpose: This study estimates differences between Germany and the U.S. over time in population levels of daily walking and cycling at different health-enhancing thresholds across sociodemographic groups. Methods: Uniquely comparable national travel surveys for the U.S. (NHTS 2001 and 2009) and Germany (MiD 2002 and 2008) were used to calculate the number, duration, and distance of active trips per capita. The population-weighted person and trip files for each survey were merged to calculate population levels of any walking/cycling, walking/cycling 30 minutes/day, and achieving 30 minutes in bouts of at least 10 minutes. Logistic regression models controlled for the influence of socioeconomic variables. Data were analyzed in 2010. Results: Between 2001/2002 and 2008/2009, the proportion of "any walking" was stable in the U.S. (18.5%) but increased in Germany from 36.5% to 42.3%. The proportion of "any cycling" in the U.S. remained at 1.8% but increased in Germany from 12.1% to 14.1%. In 2008/2009, the proportion of "30 minutes of walking and cycling" in Germany was 21.2% and 7.8%, respectively, compared to 7.7% and 1.0% in the U.S. There is much less variation in active travel among socioeconomic groups in Germany than in the U.S. German women, children, and seniors walk and cycle much more than their counterparts in the U.S. Conclusions: The high prevalence of active travel in Germany shows that daily walking and cycling can help a large proportion of the population to meet recommended physical activity levels

Walking and cycling in the United States, 2001-2009 : evidence from the National Household Travel Surveys

Objectives: To assess changes in walking and cycling in the United States between 2001 and 2009. Methods: The 2001 and 2009 National Household Travel Surveys were used to compute the frequency, duration, and distance of walking and cycling per capita. The population-weighted person and trip files were merged to calculate the prevalence of any walking and cycling and of walking and cycling at least 30 minutes per day. Results: The average American made 17 more walk trips in 2009 than in 2001, covering 9 more miles per year, compared with only 2 more bike trips, and 5 more miles cycling. At the population level, the prevalence of "any walking" remained unchanged (about 18%), whereas walking at least 30 minutes per day increased from 7.2% to 8.0%. The prevalence of "any cycling" and cycling 30 minutes per day remained unchanged (1.7% and 0.9%, respectively). Active travel declined for women, children, and seniors, but increased among men, the middle aged, employed, well-educated, and persons without a car. Conclusions: Walking increased slightly, whereas cycling levels stagnated, and the overall prevalence of active travel remained low. Improved infrastructure for walking and cycling must be combined with programs to encourage active travel among more groups, especially children, seniors, and women

In vitro effects of bethanechol on smooth muscle preparations from abomasal fundus, corpus, and antrum of dairy cows

Abomasal displacement has been associated with gastric hypomotility. The supply of prokinetic drugs available to address this problem is insufficient. The goal of the study was to investigate the effect of the muscarinic agonist bethanechol (BeCh) on contractility parameters of smooth muscle preparations from several regions of the bovine abomasum (fundus, corpus, and antrum). Cumulative concentration-response curves were constructed using BeCh in vitro with and without pre-incubation with antagonists targeted at M(2) and M(3) muscarinic acetylcholine receptor (mAChR) subtypes. In all preparations investigated, BeCh induced a significant and concentration-dependent increase in all contractility parameters investigated. The maximal attainable effect (V(max)) was more pronounced in circular specimens, and V(max) of antral specimens in circular orientation were significantly lower when compared to the other preparations. Both antagonists caused a rightward shift of the concentration-response curve, suggesting that the effect of BeCh is mediated at least partly by M(2) and M(3) AChRs

Media 1: Real-time handheld multispectral optoacoustic imaging

Originally published in Optics Letters on 01 May 2013 (ol-38-9-1404

Endovascular thrombectomy for the treatment of acute ischemic stroke

ABSTRACT Few patients benefit from the current standard treatment for acute ischemic stroke (AIS), encouraging the development of new treatments. Objective To systematically review the literature on the efficacy and/or safety of endovascular thrombectomy in AIS compared to standard treatment and to identify ongoing randomized controlled trials (RCTs). Method Searches for RCTs were performed in Medline/Embase, and for ongoing trials: International Clinical Trial Registry Platform, Clinicaltrials.gov and ISRCTN registry (to June 15th, 2015). Results From the eight published RCTs, five showed the superiority of treatment that includes thrombectomy compared to standard care alone. From the 13 ongoing RCTs, 3 have been halted, one has not started, one has unknown status and eight will end between 2016 - 2020. Conclusion Evidence favours a combination of the standard therapy with endovascular thrombectomy. The selection criteria however limit the number of people who can benefit. Further studies are needed to prove its cost-effectiveness