Monoamine oxidase binding not expected to significantly affect [18F]flortaucipir PET interpretation.

PURPOSE: [18F]-labeled positron emission tomography (PET) radioligands permit in vivo assessment of Alzheimer's disease biomarkers, including aggregated neurofibrillary tau (NFT) with [18F]flortaucipir. Due to structural similarities of flortaucipir with some monoamine oxidase A (MAO-A) inhibitors, this study aimed to evaluate flortaucipir binding to MAO-A and MAO-B and any potential impact on PET interpretation. METHODS: [18F]Flortaucipir autoradiography was performed on frozen human brain tissue slices, and PET imaging was conducted in rats. Dissociation constants were determined by saturation binding, association and dissociation rates were measured by kinetic binding experiments, and IC50 values were determined by competition binding. RESULTS: Under stringent wash conditions, specific [18F]flortaucipir binding was observed on tau NFT-rich Alzheimer's disease tissue and not control tissue. In vivo PET experiments in rats revealed no evidence of [18F]flortaucipir binding to MAO-A; pre-treatment with MAO inhibitor pargyline did not impact uptake or wash-out of [18F]flortaucipir. [18F]Flortaucipir bound with low nanomolar affinity to human MAO-A in a microsomal preparation in vitro but with a fast dissociation rate relative to MAO-A ligand fluoroethyl-harmol, consistent with no observed in vivo binding in rats of [18F]flortaucipir to MAO-A. Direct binding of flortaucipir to human MAO-B was not detected in a microsomal preparation. A high concentration of flortaucipir (IC50 of 1.3 µM) was found to block binding of the MAO-B ligand safinamide to MAO-B on microsomes suggesting that, at micromolar concentrations, flortaucipir weakly binds to MAO-B in vitro. CONCLUSION: These data suggest neither MAO-A nor MAO-B binding will contribute significantly to the PET signal in cortical target areas relevant to the interpretation of [18F]flortaucipir.

Sizes of pure and doped helium droplets from single shot x-ray imaging.

Advancements in x-ray free-electron lasers on producing ultrashort, ultrabright, and coherent x-ray pulses enable single-shot imaging of fragile nanostructures, such as superfluid helium droplets. This imaging technique gives unique access to the sizes and shapes of individual droplets. In the past, such droplet characteristics have only been indirectly inferred by ensemble averaging techniques. Here, we report on the size distributions of both pure and doped droplets collected from single-shot x-ray imaging and produced from the free-jet expansion of helium through a 5 µm diameter nozzle at 20 bars and nozzle temperatures ranging from 4.2 to 9 K. This work extends the measurement of large helium nanodroplets containing 109-1011 atoms, which are shown to follow an exponential size distribution. Additionally, we demonstrate that the size distributions of the doped droplets follow those of the pure droplets at the same stagnation condition but with smaller average sizes.

Geographic Distribution of the Ciclovia and Recreovia Programs by Neighborhood SES in Bogotá: How Unequal is the Geographic Access Assessed Via Distance-based Measures?

Ciclovia, also known as Open Streets initiatives in other countries, are city streets that are closed to motorized traffic and opened during certain times to residents for engaging in physical activity (PA). These initiatives are viewed by policy makers and health and community advocates as being beneficial to social, environmental, and community health. This study explores the geographic distribution of Ciclovia and Recreovia and the differences in geographic access assessed via distance-based measures, based on the socioeconomic status (SES) of the area. Results from this study show that the median distance to the Ciclovia according to SES ranges from 2930 m for SES 1 (most disadvantaged) to 482 m for SES 6 (wealthiest). The median distance to the Recreovia sites ranges from 5173 m for SES 1 to 3869 m for SES 6. This study found revealing urban inequities in the distribution of Ciclovia, whereas there was less inequalities within the Recreovia sites. This study shows that urban interventions are needed to promote recreational activity and reduce health disparities in under resourced, low SES areas.

Impact of Cardiac Cycle on Thoracic Aortic Geometry-Morphometric Analysis of Ecg Gated Computed Tomography.

BACKGROUND: Understanding morphological changes of ascending aorta, aortic arch and descending aorta with cardiac and respiratory motion is critical for planning of endovascular repair of thoracic aorta. The aim of this study was to determine the impact of the cardiac cycle on thoracic aortic geometry. METHODS: In this retrospective study, electrocardiogram-gated cardiac computed tomography from 116 patients who were evaluated for transcatheter aortic valve replacement were reviewed. A protocol for measurements of maximal diameters and lengths of the thoracic aorta and supra-aortic vessels was established. Measurements were made in multiplanar views perpendicular to the semiautomatically created centerline on both systolic and diastolic phases. RESULTS: Mean age was 77 ± 11 years of our study cohort. Mean systolic and diastolic diameter were 31.6 ± 0.42 and 30.1 ± 4.4 mm at the sinotubular junction (STJ), 35.6 ± 4.8 and 34.8 ± 4.7 mm in the ascending aorta, 29.1 ± 3.3 and 28.5 ± 3.3 mm in the aortic arch (distal left common carotid artery), and 26.7 ± 5.4 and 25.8 ± 5.4 mm in the descending aorta. Mean diameter change was 1.5 ± 0.9 mm at the STJ, 0.8 ± 0.9 mm in the ascending aorta, 0.6 ± 0.8 mm in the aortic arch, and 0.9 ± 1.2 mm in the descending aorta. Mean arterial strain was 5.0 ± 3.2% at the level of the STJ, 2.4 ± 2.7% in the ascending aorta, 2.0 ± 2.9% in the aortic arch, and 3.9 ± 5.7% in the descending aorta. CONCLUSIONS: Our results demonstrated that small but significant circumferential and longitudinal strain was present at every aortic level. These findings may have implications for endovascular thoracic aortic repair and may provide reference values for future comparison.

Neighborhood environment, self-rated health and quality of life in Latin America.

To conduct a systematic review examining the associations between neighborhood environments and self-rated health (SRH) and health-related quality of life (HR-QOL) in the urban context of Latin America. We conducted a structured search of quantitative studies in three bibliographic databases published in Spanish, English, Portuguese and French from January 1990 to December 2015. We restricted the search to studies conducted in Latin-American cities with one million and more inhabitants. Eleven studies were finally included in the analysis. Ten were cross-sectional studies and one was a cohort follow-up study. Two studies found positive associations between accessibility to parks and HR-QOL. One study found that high neighborhood social capital was positively associated with SRH. Neighborhood socioeconomic status was positively associated with both HR-QOL and SRH in two studies. A walkable neighborhood was positively associated with SRH in two studies. Three studies included attributes related with neighborhood security perception and road safety, with higher scores of HR-QOL, both in the physical and mental dimensions, while high levels of street noise were negatively associated. Narrowness and slope of streets were negatively associated with SRH. No association was found between the perception of neighborhood security and SRH. The results of this systematic review show that several studies conducted in Latin America have found significant associations between neighborhood environment and SRH and HRQOL. However, the relatively small number of studies and the heterogeneity among them require further studies to better understand this topic in the region.

HPV genotypes detected by linear array and next-generation sequencing in anal samples from HIV positive men who have sex with men in Mexico.

The incidence of anal cancer has been rising, especially in HIV+ patients and has been associated with HPV infection. HIV+ patients are more at risk of HPV coinfection and are seven times more likely to have persistent HPV infection; moreover, HIV+ men have an increased risk of developing anal cancer compared to HIV+ women. The development of screening strategies for the detection of HPV in HIV+ men is of major importance; however, there is not enough information about the HPV genotypes and variants that are colonizing the anal epithelia of HIV+ men in diverse geographical regions. Therefore, this work was aimed at identifying HPV genotypes present in the anal epithelium of HIV+ men who have sex with men (MSM), with or without anal lesions (n = 75). For HPV genotyping, two approaches were performed: Linear Array HPV Genotyping Test and next-generation sequencing (NGS). In general, the six most frequent HPV genotypes found by Linear Array were HPV6, 62, 61, 81, 16 and 51. On the other hand, employing NGS, a total of 36 HPV genotypes belonging to both alpha and beta genera were found. The genotypes with the greatest number of reads, according to the diagnostic group, were: HPV81, 45, 6, 51 and 61 in MSM without anal lesions (WAIN); HPV6, 61, 70, 62 and 66 in MSM with atypical lesions (AAL); HPV6, 11, 66, 81 and 61 in MSM with anal intraepithelial neoplasia grade I (AIN I); and HPV16, 81, 58, 61 and 52 with AIN III. Additionally, a great diversity of L1 variants was observed, especially in genotypes HPV16, 58, 61, 52, 45 and 59.

Maternal and familial correlates of anthropometric typologies in the nutrition transition of Colombia, 2000-2010.

OBJECTIVE: We aimed to assess the maternal and family determinants of four anthropometric typologies at the household level in Colombia for the years 2000, 2005 and 2010. DESIGN: We classified children 2) to assess stunting and overweight/obesity, respectively; mothers were categorized according to BMI to assess underweight (<18·5 kg/m2) and overweight/obesity (≥25·0 kg/m2). At the household level, we established four final anthropometric typologies: normal, underweight, overweight and dual-burden households. Separate polytomous logistic regression models for each of the surveyed years were developed to examine several maternal and familial determinants of the different anthropometric typologies. SETTING: National and sub-regional (urban and rural) representative samples from Colombia, South America. SUBJECTS: Drawing on data from three waves of Colombia's Demographic and Health Survey/Encuesta Nacional de Salud (DHS/ENDS), we examined individual and household information from mothers (18-49 years) and their children (birth-5 years). RESULTS: Higher parity was associated with an increased likelihood of overweight and dual burden. Higher levels of maternal education were correlated with lower prevalence of overweight, underweight and dual burden of malnutrition in all data collection waves. In 2010, participation in nutrition programmes for children <5 years, being an indigenous household, food purchase decisions by the mother and food security classification were also associated with the four anthropometric typologies. CONCLUSIONS: Results suggest that maternal and family correlates of certain anthropometric typologies at the household level may be used to better frame policies aimed at improving social conditions and nutrition outcomes.

Formation of Core-Shell Ethane-Silver Clusters in He Droplets.

Ethane core-silver shell clusters consisting of several thousand particles have been assembled in helium droplets upon capture of ethane molecules followed by Ag atoms. The composite clusters were studied via infrared laser spectroscopy in the range of the C-H stretching vibrations of ethane. The spectra reveal a splitting of the vibrational bands, which is ascribed to interaction with Ag. A rigorous analysis of band intensities for a varying number of trapped ethane molecules and Ag atoms indicates that the composite clusters consist of a core of ethane that is covered by relatively small Ag clusters. This metastable structure is stabilized due to fast dissipation in superfluid helium droplets of the cohesion energy of the clusters.

Formation of Large Ag Clusters with Shells of Methane, Ethylene, and Acetylene in He Droplets.

Helium droplets were used to assemble composite metal-molecular clusters. Produced clusters have several hundreds of silver atoms in the core, immersed in a shell consisting of methane, ethylene, or acetylene molecules. The structure of the clusters was studied via infrared spectra of the C-H stretches of the hydrocarbon molecules. The spectra of the clusters containing methane and acetylene show two distinct features due to molecules on the interface with silver core and those in the volume of the neat molecular part of the clusters. The relative intensities of the peaks are in good agreement with the estimates based on the number of the captured particles. Experiments also suggest that selection rules for infrared transitions for molecules adsorbed on metal surfaces are also valid for silver clusters as small as 300 atoms.

Upper extremity access for fenestrated endovascular aortic aneurysm repair is not associated with increased morbidity.

OBJECTIVE: Fenestrated endovascular aortic aneurysm repair (FEVAR) is an alternative to open repair in patients with complex abdominal aortic aneurysms who are neither fit nor suitable for standard open or endovascular repair. Chimney and snorkel grafts are other endovascular alternatives but frequently require bilateral upper extremity access that has been associated with a 3% to 10% risk of stroke. However, upper extremity access is also frequently required for FEVAR because of the caudal orientation of the visceral vessels. The purpose of this study was to assess the use of upper extremity access for FEVAR and the associated morbidity. METHODS: During a 5-year period, 148 patients underwent FEVAR, and upper extremity access for FEVAR was used in 98 (66%). Outcomes were compared between those who underwent upper extremity access and those who underwent femoral access alone. The primary end point was a cerebrovascular accident or transient ischemic attack, and the secondary end point was local access site complications. The mean number of fenestrated vessels was 3.07 ± 0.81 (median, 3) for a total of 457 vessels stented. Percutaneous upper extremity access was used in 12 patients (12%) and open access in 86 (88%). All patients who required a sheath size >7F underwent high brachial open access, with the exception of one patient who underwent percutaneous axillary access with a 12F sheath. The mean sheath size was 10.59F ± 2.51F (median, 12F), which was advanced into the descending thoracic aorta, allowing multiple wire and catheter exchanges. RESULTS: One hemorrhagic stroke (one of 98 [1%]) occurred in the upper extremity access group, and one ischemic stroke (one of 54 [2%]) occurred in the femoral-only access group (P = .67). The stroke in the upper extremity access group occurred 5 days after FEVAR and was related to uncontrolled hypertension, whereas the stroke in the femoral group occurred on postoperative day 3. Neither patient had signs or symptoms of a stroke immediately after FEVAR. The right upper extremity was accessed six times without a stroke (0%) compared with the left being accessed 92 times with one stroke (1%; P = .8). Four patients (4%) had local complications related to upper extremity access. One (1%) required exploration for an expanding hematoma after manual compression for a 7F sheath, one (1%) required exploration for hematoma and neurologic symptoms after open access for a 12F sheath, and two patients (2%) with small hematomas did not require intervention. Two (two of 12 [17%]) of these complications were in the percutaneous access group, which were significantly more frequent than in the open group (two of 86 [2%]; P = .02). CONCLUSIONS: Upper extremity access appears to be a safe and feasible approach for patients undergoing FEVAR. Open exposure in the upper extremity may be safer than percutaneous access during FEVAR. Unlike chimney and snorkel grafts, upper extremity access during FEVAR is not associated with an increased risk of stroke, despite the need for multiple visceral vessel stenting.

Formation of core-shell silver-ethane clusters in He droplets.

Here, we have studied the utility of large He droplets of 10(5)-10(7) atoms for the growth of composite clusters consisting of an Ag core and a shell of ethane molecules. The clusters have been assembled by doping He droplets with up to 10(3) Ag atoms and ethane molecules in two sequential pickup cells and studied via infrared spectroscopy in the C-H stretch region of the ethane molecules. We found that the ν7 band of ethane molecules at the interface with the Ag atoms has a low frequency shift of approximately 15 cm(-1) with respect to that of more distant ethane molecules away from the interface. The intensity ratio of the two bands was used for evaluation of the Ag core and ethane shell cluster structure. We found that the number of surface ethane molecules is in good agreement with a model that assumes a dense, core-shell structure for clusters containing less than about 100 atoms. However, large Ag clusters consisting of about 3000 atoms have a factor of about 5 larger surface area than that predicted by the model, indicating a ramified structure for such larger Ag clusters obtained in liquid He. Moreover, we demonstrate that He droplets behave as calorimeters for measurements of the number of captured atoms and molecules as well as the amount of absorbed laser energy.

Infrared spectra in the 3 µm region of ethane and ethane clusters in helium droplets.

Ethane and ethane clusters (N ≈ 10(2)-10(4)) were studied inside helium droplets with infrared laser spectroscopy. The spectra were measured in the 2880-3000 cm(-1) range, which covers the ν5, ν(8+11), and ν7 vibrational bands of ethane. Partially resolved rotational fine structure in the spectrum of the monomer reveals solvent-induced band origin blue shifts that are each approximately 1 cm(-1). The effective B(He) and A(He) rotational constants were found to be reduced by 52% and 16% in comparison to their gas phase values, respectively. Spectra of the clusters show the same three bands shifted toward low frequency by approximately 10 cm(-1) because of intermolecular interactions in the clusters. The spectra of the ethane clusters are dominated by the ν7 band, whereas the relative intensities of the ν5 and ν(8+11) bands are about a factor of 5 weaker than for single molecules or for solid ethane, the spectrum of which is also reported here.

Physical activity and health-related quality of life among adult women in Cali, Colombia: a cross-sectional study.

OBJECTIVES: To examine the associations of leisure-time physical activity (LTPA) and walking for transportation (WT) with the physical and mental dimensions of health-related quality of life (HR-QOL) among women. METHODS: A cross-sectional study was carried out in 2009 among 1,263 women ages 18-59 years living in neighborhoods with low and middle-low socioeconomic status in the urban area of Cali. HR-QOL was assessed using the Short Form 8 (SF-8). LTPA and WT were measured using the long version of the International Physical Activity Questionnaire (IPAQ). Associations were assessed using linear regression models adjusting for potential confounders. RESULTS: Low (10-149 min) and medium-high (at least 150 min) levels of WT were negatively associated with the mental and physical dimensions of HR-QOL. Low (10-149 min of moderate intensity PA, or 10-74 min of vigorous intensity PA) and medium-high (at least 150 or 75 min of moderate or vigorous intensity PA, respectively) levels of LTPA were positively associated with both dimensions. Significant interactions were observed between education level and perceived safety from traffic. CONCLUSIONS: This study found that WT and LTPA were associated with HR-QOL both in the physical and mental dimensions; however, the direction and magnitude of the association varied by domain. These results highlight the need to better understand the links between PA and HR-QOL in urban contexts from Latin America.

[(18)F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease.

OBJECTIVE: We wished to develop a highly selective positron emission tomography (PET) imaging agent targeting PHF-tau in human Alzheimer's disease (AD) brains. METHODS: To screen potential tau binders, human AD brain sections were used as a source of native paired helical filament (PHF)-tau and Aß rather than synthetic tau aggregates or Aß fibrils generated in vitro to measure the affinity and selectivity of [(18)F]T807 to tau and Aß. Brain uptake and biodistribution of [(18)F]T807 in mice were also tested. RESULTS: In vitro autoradiography results show that [(18)F]T807 exhibits strong binding to PHF-tau-positive human brain sections. A dissociation constant (Kd) of [(18)F]T807 (14.6 nM) was measured using brain sections from the frontal lobe of AD patients. A comparison of autoradiography and double immunohistochemical staining of PHF-tau and Aß on adjacent sections demonstrated that [(18)F]T807 binding colocalized with immunoreactive PHF-tau pathology, but did not highlight Aß plaques. In vivo studies in mice demonstrated that [(18)F]T807 was able to cross the blood-brain barrier and washed out quickly. CONCLUSIONS: [(18)F]T807 demonstrates high affinity and selectivity to PHF-tau as well as favorable in vivo properties, making this a promising candidate as an imaging agent for AD.

Exploring facial expressions and action unit domains for Parkinson detection.

BACKGROUND AND OBJECTIVE: Patients suffering from Parkinson's disease (PD) present a reduction in facial movements called hypomimia. In this work, we propose to use machine learning facial expression analysis from face images based on action unit domains to improve PD detection. We propose different domain adaptation techniques to exploit the latest advances in automatic face analysis and face action unit detection. METHODS: Three different approaches are explored to model facial expressions of PD patients: (i) face analysis using single frame images and also using sequences of images, (ii) transfer learning from face analysis to action units recognition, and (iii) triplet-loss functions to improve the automatic classification between patients and healthy subjects. RESULTS: Real face images from PD patients show that it is possible to properly model elicited facial expressions using image sequences (neutral, onset-transition, apex, offset-transition, and neutral) with accuracy improvements of up to 5.5% (from 72.9% to 78.4%) with respect to single-image PD detection. We also show that our proposed action unit domain adaptation provides improvements of up to 8.9% (from 78.4% to 87.3%) with respect to face analysis. Finally, we also show that triplet-loss functions provide improvements of up to 3.6% (from 78.8% to 82.4%) with respect to action unit domain adaptation applied upon models created from scratch. The code of the experiments is available at https://github.com/luisf-gomez/Explorer-FE-AU-in-PD. CONCLUSIONS: Domain adaptation via transfer learning methods seem to be a promising strategy to model hypomimia in PD patients. Considering the good results and also the fact that only up to five images per participant are considered in each sequence, we believe that this work is a step forward in the development of inexpensive computational systems suitable to model and quantify problems of PD patients in their facial expressions.

Prediction of Waiting Times in A&E.

Predicting waiting times in A&E is a critical tool for controlling the flow of patients in the department. The most used method (rolling average) does not account for the complex context of the A&E. Using retrospective data of patients visiting an A&E service from 2017 to 2019 (pre-pandemic). An AI-enabled method is used to predict waiting times in this study. A random forest and XGBoost regression methods were trained and tested to predict the time to discharge before the patient arrived at the hospital. When applying the final models to the 68,321 observations and using the complete set of features, the random forest algorithm's performance measurements are RMSE=85.31 and MAE=66.71. The XGBoost model obtained a performance of RMSE=82.66 and MAE=64.31. The approach might be a more dynamic method to predict waiting times.

Traces of vortices in superfluid helium droplets.

We report on the observation of vortices in superfluid 4He droplets produced in the expansion of liquid He. The vortices were traced by introducing Ag atoms, which clustered along the vortex lines, into the droplets. The Ag clusters were subsequently surface-deposited and imaged via electron microscopy. The prevalence of elongated track-shaped deposits shows that vortices are present in droplets larger than about 300 nm and that their lifetime exceeds a few milliseconds. We discuss the possible formation mechanisms and the stability of the vortices.

Photoabsorption of Ag(n)(N∼6-6000) nanoclusters formed in helium droplets: transition from compact to multicenter aggregation.

Ag(N) clusters with up to thousands of atoms were grown in large He droplets and studied by optical spectroscopy. For N≲10(3) the spectra are dominated by a surface plasmon resonance near 3.8 eV and a broad feature in the UV, consistent with absorption by individual metallic particles. Larger clusters reveal unexpectedly strong broad absorption at low frequencies, extending down to ≈0.5 eV. This suggests a transition from single-center to multicenter formation, in agreement with estimates of cluster growth kinetics in He droplets. Moreover, the spectra of large clusters develop a characteristic dispersion profile at 3.5-4.5 eV, indicative of the coexistence of localized and delocalized electronic excitations in composite clusters, as predicted theoretically.

Surface deposition and imaging of large Ag clusters formed in He droplets.

The utility of a continuous beam of He droplets for the assembly and surface deposition of Ag(N) clusters, ~ 300-6000, is studied with transmission electron microscopy. Images of the clusters on amorphous carbon substrates obtained at short deposition times have provided for a measure of the size distribution of the metal clusters. The average sizes of the deposited clusters are in good agreement with an energy balance based estimate of Ag(N) cluster growth in He droplets. Measurements of the deposition rate indicate that upon impact with the surface the He-embedded cluster is attached with high probability. The stability of the deposited clusters on the substrate is discussed.

Sizes of large He droplets.

Helium droplets spanning a wide size range, N(He) = 10(3)-10(10), were formed in a continuous-nozzle beam expansion at different nozzle temperatures and a constant stagnation pressure of 20 bars. The average sizes of the droplets have been obtained by attenuation of the droplet beam through collisions with argon and helium gases at room temperature. The results obtained are in good agreement with previous measurements in the size range N(He) = 10(5)-10(7). Moreover, the measurements give the average sizes in the previously uncharacterized range of very large droplets of 10(7)-10(10) atoms. The droplet sizes and beam flux increase rapidly at nozzle temperatures below 6 K, which is ascribed to the formation of droplets within the nozzle interior. The mass spectra of the droplet beam upon electron impact ionization have also been obtained. The spectra show a large increase in the intensity of the He(4) (+) signal upon increase of the droplet size, an effect which can be used as a secondary size standard in the droplet size range N(He) = 10(4)-10(9) atoms.