Search

Clear prospective associations exist between grip strength and multiple indices of health and well-being, including frailty, morbidity, and mortality. The usual explanation is that low grip strength arises from loss of muscle function, indicative of a more general decline in physical health.1 However, the relationship that also exists between grip strength and preservation of cognitive capacity2, 3—when cognitive and muscle function are not linked,4 suggests that this account is incomplete. Beyond middle age, individual variations in grip strength may predominantly be a marker of brain health, rather than physical status.5 Application of grip force demands sophisticated neuromuscular coordination and control. Advances in brain imaging make clear that neural degeneration is an orderly and sequential process6 affecting networks that mediate functionally related processes such as cognition and motor control.7 From this perspective, the proximate cause of the relationship between grip strength and cognitive decline is weakening of the functional integrity of brain networks. The distal cause is the dysregulation of multiple physiological systems, which ultimately also becomes manifested in the associations of grip strength (and cognitive function) with frailty, morbidity, and mortality.

We provide estimates of health priorities during the COVID-19 pandemic based on web-surveys administered in seven developing countries in Africa, Asia, and Latin America in 2022. Using the best-worst scaling method, respondents ranked the importance of seven health problems, including COVID-19 (the others were alcohol and drugs, HIV/AIDS, malaria, TB, other respiratory diseases, and water-borne diseases). Respondents in most countries considered COVID-19 a serious problem but ranked other respiratory illness as more serious. Respondents’ rankings were generally consistent with relative disease prevalence when it can be reasonably well measured (i.e., malaria and TB). Differences in priorities across countries were generally larger than within-country differences. The importance respondents assigned to COVID-19 was associated with their knowledge of COVID-19. These results have implications for the allocation of health resources: policymakers may face resistance if their actions are viewed as focusing too much on COVID-19 while neglecting other, potentially serious health problems.

The activity of passive content consumers on social media sites is typically difficult to measure. This paper explores the activity of a subset of such consumers by looking at the influence on Wikipedia pageviews of one large Reddit community which frequently links to Wikipedia articles. The subreddit used in this analysis, /r/todayilearned (TIL), features a large number of posts on an eclectic set of topics, but excludes current events, which helps rule out the primary threat to being able to make causal statements. Wikipedia's public hourly pageview data provides a unique opportunity to study the influence of a Reddit post on a Wikipedia page at different time horizons. We here present analyses using posts from 2012 in TIL, showing that the week in which a post references a specific Wikipedia article is associated with a substantial increase in pageviews relative to prior and successive weeks. We then apply functional PCA to the dataset in order to characterize pageview dynamics. We also provide a qualitative analysis of the subset of Wikipedia topics posted to Reddit.

Objectives Cortisol is known to promote adipocyte differentiation and maturation, and prolonged exposure to excess cortisol contributes to the development of obesity and metabolic dysregulation. The intracellular 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme catalyzes the conversion of inactive cortisone to active cortisol. Recently, we demonstrated reduced brain 11β-HSD1 levels in vivo with increasing body mass index (BMI), using positron emission tomography (PET) radioligands [11C]- and [18F]AS2471907(1). PET imaging can simultaneously quantify uptake in multiple organs (e.g., liver/brain). [18F]AS2471907 has high uptake and specific binding in the brain and liver(2). Liver and brain 11β-HSD1 measured by PET imaging may help elucidate the roles of cortisol activation in the setting of metabolic dysregulation. Thus, we performed PET imaging studies to examine 11β-HSD1 levels in the liver and brain. Methods Nine individuals (5F/4M) with a range of BMIs (22.6-34.4 kg/m2) underwent a 90 min PET/CT acquisition with arterial plasma sampling after injection of [18F]AS2471907. Regions-of-interest (ROI) for the liver were manually drawn on a summed PET image (60-90 min). Seventeen brain ROIs were selected from the anatomical automatic labeling (AAL) template and applied to the dynamic PET images to generate time-activity-curves (TACs). Brain volume of distribution (VT, mL/cm3), the target tissue to plasma ratio of radioligand at equilibrium, was estimated for each ROI using the multilinear analysis-1 method with plasma input function. Mean whole-brain VT values were calculated by averaging all ROIs. Given the appearance of irreversible kinetics in the liver, Ki (min-1), the rate of irreversible tracer uptake, was calculated using the Patlak method. Results Qualitative brain and liver uptake was assessed by examining a summed PET image (SUV 60-90min). The parent fraction in plasma was 88±1% at 90 min, indicating negligible plasma radiolabeled-metabolites contributing the measured signal in the liver. Kinetic modeling estimates demonstrated decreasing whole brain VT with increasing BMI (R2=0.53), similar to our previously published study examining only brain in a larger cohort(1). Patlak methods provided good estimates of Ki. In an opposite manner from the brain, correlations seen in the liver using Ki were positively correlated with BMI (R2=0.57). Conclusions These preliminary studies suggest obesity is associated with increased 11β-HSD1 levels in the liver but decreased 11β-HSD1 levels in the brain. Clinically, liver specific 11β-HSD1 inhibitors may prove beneficial in treating metabolic sequalae of obesity such non-alcoholic fatty liver disease (NAFLD) by inhibiting activity of higher 11β-HSD1 levels. Further studies in NAFLD and obesity are necessary to determine appropriate populations that would benefit from 11β-HSD1 inhibitors and longitudinal in vivo PET imaging to help inform development of future therapeutics. References [1] Bini, et al, Molecular Imaging and Biology, 2020. [2] Bini, et al, IEEE Trans on Radiation and Plasma Medical Sciences, 2021 Presentation: Saturday, June 11, 2022 1:42 p.m. - 1:47 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

HIV continues to be an important public health issue. Voluntary community-based HIV testing (VCBT) helps to reduce the undiagnosed population of HIV-positive individuals, enabling early diagnosis and treatment. Monitoring is essential to determine whether at-risk groups are being effectively reached. Our aim was to pilot and then introduce sustained monitoring of VCBT in Ireland, through collaboration between statutory and non-statutory organisations. The study was initiated by the Health Protection Surveillance Centre in 2018. Steps included forming a multisectoral steering group and developing a minimum standardised dataset. De-identified case-based data were requested for VCBT carried out from 1 January 2017 onwards; this paper includes data for 2018. Six organisations participated; all four NGOs involved in VCBT, one medical charity, and the Health Service Executive National Social Inclusion Office. Methods were rapid point-of-care testing (POCT) (54%) or laboratory based (46%). Total HIV test reactivity was 1.7% (1.5% excluding persons later identified as previously diagnosed HIV positive). All POCT data were case based; the test reactivity rate was 0.8% and was higher in bar/club settings (1.2%). Most (74%) laboratory testing data were in aggregate format; the test positivity rate in one asylum centre was 5.0%. Ongoing challenges include testing among persons later identified as previously diagnosed HIV positive, monitoring case-based testing in asylum settings, and suboptimal data on confirmatory testing and linkage to care. Sustained national monitoring in community settings will help inform HIV testing guidelines and will enable assessment of the impact of local and regional community HIV testing strategies.

During the spring of 2020 ChoiceFlows Inc. (Choiceflows) researchers document an approach for small and medium-sized businesses to make informed decisions about equitable and resilient reopening after COVID-19 pandemic shutdowns and restrictions. The client is 501(c)(3) chartered Restart Partners in Washington State and their client, the State of Washington Department of Commerce. After several revisions, an agreement is signed on December 30, 2020 to make the approach real with development and deployment in 2021 using Cares Act Grant money from the U.S. Federal Government. The result is Smart WA – and can be freely accessed online here: https://smartwa.us Smart WA is the result of unique primary research conducted by Choiceflows involving citizens and residents of Washington State, and many days of secondary research finding publicly available data sources and bringing them together in one place to provide both comprehensive and easier to use data to make informed decisions. The research behind Smart WA is the first study to comprehensively examine how specific COVID-19 transmission reduction actions influence planned visits to different types of businesses. Data on Smart WA is organized by Human Health, Economic Health, and Community Experience metrics – and displayed as composite scores. The entire online system is powered by Tanjo.ai machine learning, a Choiceflows business partner, and is updated from all data sources daily.The advent of the COVID pandemic disrupts a wide range of businesses that directly serve the public and causes a dramatic fall in visits to these establishments. Businesses face a wide range of options in how to respond ranging from the pre-pandemic status quo and doing nothing to prevent the spread of the virus to shutting down businesses due to a lack of customers.Recognizing this, Smart WA has a “what-if” game-like section that allows a business to model the choices that they can make for reopening, and what they can expect from customers based on real data from people in the state. The relevant question from a small business perspective is: If we take an action or actions that influence COVID-19 transmission and make it known to our customers, how will that influence those customers to visit? The research supporting this function was conducted in four waves of surveys designed and administered during 2021, making it one of the most comprehensive research programs of its type during COVID with snapshots of customer preferences being collected over several month intervals.We document the development of this COVID Choices research using the Choiceflows pioneered Volumetric Choice Experiment (VCE) method and design and in parallel the online system. This provides a platform for projecting how the insights and methods from this work can be used for other issues facing small and medium size businesses to aid in and speed decision making and choice. This includes and dashboards for policymakers and main street for allocating resources for commerce, including economic development, ongoing community health, and supporting quality of life indicators.

Purpose GluN2B containing N-methyl-D-aspartate receptors (NMDARs) play an essential role in neurotransmission and are a potential treatment target for multiple neurological and neurodegenerative diseases, including stroke, Alzheimer’s disease, and Parkinson’s disease. (R)-[18F]OF-Me-NB1 was reported to be more specific and selective than (S)-[18F]OF-Me-NB1 for the GluN2B subunits of the NMDAR based on their binding affinity to GluN2B and sigma-1 receptors. Here we report a comprehensive evaluation of (R)-[18F]OF-Me-NB1 and (S)-[18F]OF–Me-NB1 in nonhuman primates. Methods The radiosynthesis of (R)-[18F]OF-Me-NB1 and (S)-[18F]OF-Me-NB1 started from 18F-fluorination of the boronic ester precursor, followed by removal of the acetyl protecting group. PET scans in two rhesus monkeys were conducted on the Focus 220 scanner. Blocking studies were performed after treatment of the animals with the GluN2B antagonist Co101,244 or the sigma-1 receptor antagonist FTC-146. One-tissue compartment (1TC) model and multilinear analysis-1 (MA1) method with arterial input function were used to obtain the regional volume of distribution (VT, mL/cm3). Occupancy values by the two blockers were obtained by the Lassen plot. Regional non-displaceable binding potential (BPND) was calculated from the corresponding baseline VT and the VND derived from the occupancy plot of the Co101,244 blocking scans. Results (R)- and (S)-[18F]OF-Me-NB1 were produced in > 99% radiochemical and enantiomeric purity, with molar activity of 224.22 ± 161.69 MBq/nmol at the end of synthesis (n = 10). Metabolism was moderate, with ~ 30% parent compound remaining for (R)-[18F]OF-Me-NB1 and 20% for (S)-[18F]OF-Me-NB1 at 30 min postinjection. Plasma free fraction was 1–2%. In brain regions, both (R)- and (S)-[18F]OF-Me-NB1 displayed fast uptake with slower clearance for the (R)- than (S)-enantiomer. For (R)-[18F]OF-Me-NB1, both the 1TC model and MA1 method gave reliable estimates of regional VT values, with MA1 VT (mL/cm3) values ranging from 8.9 in the cerebellum to 12.8 in the cingulate cortex. Blocking with 0.25 mg/kg of Co101,244 greatly reduced the uptake of (R)-[18F]OF-Me-NB1 across all brain regions, resulting in occupancy of 77% and VND of 6.36, while 0.027 mg/kg of FTC-146 reduced specific binding by 30%. Regional BPND, as a measure of specific binding signals, ranged from 0.40 in the cerebellum to 1.01 in the cingulate cortex. Conclusions In rhesus monkeys, (R)-[18F]OF-Me-NB1 exhibited fast kinetics and heterogeneous uptake across brain regions, while the (S)-enantiomer displayed a narrower dynamic range of uptake across regions. A Blocking study with a GluN2B antagonist indicated binding specificity. The value of BPND was > 0.5 in most brain regions, suggesting good in vivo specific binding signals. Taken together, results from the current study demonstrated the potential of (R)-[18F]OF-Me-NB1 as a useful radiotracer for imaging the GluN2B receptors.

OBJECTIVES/SPECIFIC AIMS: The serotonin receptor 6 (5-HT6) is a potential therapeutic target given its distribution in brain regions that are important in depression, anxiety, and cognition. This study sought to investigate the effects of age on 5-HT6 receptor availability using 11C GSK215083, a PET ligand with affinity for 5-HT6 in the striatum and 5-HT2A in the cortex. METHODS/STUDY POPULATION: In total, 28 healthy male subjects (age range: 23–52 years) were scanned with 11C-GSK215083 on the HR+PET scanner. Time-activity curves in regions-of-interest were fitted with multilinear analysis-1 method. Binding potentials (BPND) were calculated using cerebellum as the reference region and corrected for partial volume effects. RESULTS/ANTICIPATED RESULTS: In 5-HT6 rich areas, regional 11C-GSK215083 displayed a negative correlation between BPND and age in the caudate (r=−0.41, p=0.03) (14% change per decade), and putamen (r=−0.30, p=0.04) (11% change per decade), but not in the ventral striatum and pallidum. Negative correlation with age was also seen in cortical regions (r=−0.41, p=0.03) (7% change per decade), consistent with the literature on 5-HT2A availability. DISCUSSION/SIGNIFICANCE OF IMPACT: This is the first in vivo study in humans to examine the effect of age on 5-HT6 receptor availability. The study demonstrated a significant age-related decline in 5-HT6 availability (BPND) in the caudate and putamen.

The analysis of wind data collected throughout the Southern Appalachian Mountain region of the Southeastern US is presented. Data were collected at 50 m above ground level on nine ridge top sites between 2002 and 2005. Monthly average wind speeds, power densities, wind sheers, and turbulence intensities, along with monthly maximum gusts, are presented. Measured annual average wind speeds are compared to AWS TrueWind predictions. Diurnal variations in wind speed are also reported. Annual wind roses for each site are presented. Annual wind speeds range from 5.5 to 7.4 m/s with the highest annual average wind speeds found on ridges near the northern TN–NC border. A 20% winter and nighttime enhancement of the wind speed was observed. The prevailing wind is from the westerly directions. The estimated annual energy outputs from a small wind farm consisting of fifteen 1.5 MW GE turbines range from 50 to 75 MkWh, and estimated capacity factors range from 25% to 35%. This analysis suggests that ridges in the region are suitable for utility-scale wind development.

The price, output, and quality of a monopolistic competitor are determined by maximizing the difference between its revenue and its cost, where cost is measured exclusive of the rent on its product-specialized inputs. It can be argued that such a firm must have unique inputs that are specialized to its unique product—since product differentiation is otherwise compatible with perfect competition—and the uniqueness of these inputs allows them to earn positive rent, even in long-run equilibrium. The inclusion of rent in cost gives rise to the traditional Chamberlinian solution, in which (rent-inclusive) average cost is tangent to demand and therefore downward-sloping. But if rent is excluded, average cost may be constant or even upward-sloping in equilibrium, and in this sense, monopolistic competition need not give rise to excess capacity or to production facilities that are too small. The basic conclusion is that monopolistic competition improves welfare—that is to say, it creates consumer and producer surplus—by creating variety without necessarily reducing output.

We analyze three years (1998-2000) of OGLE observations of microlensing events to place limits on the abundance of planets with a planet-to-star mass ratio $q=10^{-3}$ at distances $\sim 1-4$AU from their host stars, i.e. `cool Jupiters'. We fit a total of 145 events using a maximum likelihood fit that adjusts 6 parameters. Each data point on the lightcurve allows us to exclude planets close to the two images of the source appearing on opposite sides of the Einstein ring of the lens star. We proceed to compute detection probability maps for each event, using $����^2$ threshold values of 25, 60, 100 and combine the results from all events to place global constraints. Our selection criteria returned 5 candidate events for a planet with mass ratio $q=10^{-3}$. Only two of these remained as plausible candidates after three were rejected due to poor data quality at the time of the anomalies. Our results suggest that less than 21 ($n$)% of the lens stars have Jupiter-mass planets orbiting them at an orbital radius of $1 < a < 4$ AU. $n \le 2$ is the number of planet anomaly candidates that are actually due to planets. The datasets presented here were obtained from the DoPhot analysis of the events available at the OGLE website. The main conclusion of this work is that observing time is more efficiently allocated by observing many events with sampling intervals that produce non-overlapping detection zones than using intensive sampling on a small number of events.

In 2012, immigrants constitute 63 % of new cases of heterosexually transmitted HIV among individuals born outside Ireland. Current strategies to encourage testing can be ineffective if immigrants perceive them as culturally insensitive. We obtained qualitative data to explore challenges to voluntary HIV-testing for immigrants in Ireland. Content analysis was undertaken to identify and describe pertinent themes. Widespread beliefs that HIV is primarily a disease of African immigrants were identified as challenges that constrain access to testing and care. The organization and location of testing services, attitude of health workers, and beliefs regarding mandatory HIV-testing for immigrants seeking access to welfare benefits were also identified. Immigrants in Ireland encounter a variety of structural, cultural and personal constraints to HIV testing. Opportunities exist in the Irish Health system to increase testing among immigrants through greater acknowledgement of cultural sensitivities of immigrant groups.

Item does not contain fulltext

Traditional solutions to vibration problems often employ viscoelastic materials which can be heavy, temperature-sensitive and bulky. Active solutions can provide useful damping but are often complex and expensive. This paper outlines a passive piezoelectric damping system with an adaptive controller capable of not only providing useful damping levels, but of modifying the components so as to change the circuit resonant frequency and thereby the damping effort. Experiments on simple beams and more realistic structures are described and the potential benefits and power requirements of such a system discussed. Increases in loss factor up to a factor of 10 and a high level of tuning repeatability were seen.

A comparative study has been made to explore the potential benefits of newly available single-crystal ferroelectric materials when used in a practical device, in this case an ultrasonic micro-motor. This type of micro-motor exhibits exceptional power-to-weight characteristics, which could be exploited beneficially, for example, in unmanned air-vehicle (UAV) systems. The operating principles of a range of commercial and experimental motor designs were evaluated objectively in order to identify areas of performance that can potentially be enhanced using PMN-PT single-crystal piezoelectric ceramics. Based on this analysis a practical motor design was selected for construction and experimentation. Detailed numerical analysis indicated that a motor constructed from single crystal PMN-PT could be expected to provide an improvement in motor stall-torque by up to a factor of 2.8 and a no-load speed improvement by a factor of 1.5 when compared with motors based on standard polycrystalline lead-zirconate-titanate (PZT) ceramics. In practice single-crystal versions of the motor were found to produce double the power output of their polycrystalline counterparts. Overall efficiency was found to be improved two-fold. There were significant discrepancies between the numerical predictions for the single-crystal devices and their measured performance, whereas the polycrystalline devices were found to perform closely in line with predictions.

E048 Maximising Signal-To-Noise Ratio in Transient EM Data A.M. Ziolkowski* (MTEM Ltd) & R. Carson (MTEM Ltd) SUMMARY We describe the multi-transient electromagnetic method and focus on new technology to maximise the signal-to-noise ratio. The amplitude of the transient EM impulse response decays with offset r as 1/r^5. We employ a variety of techniques to maximize the signal: maximizing the input current ; increasing the source bi-pole length proportional to offset r but satisfying the constraint that the length must be less than a quarter of the offset; choosing the order of the PRBS source time function to be large

Summary We describe the multi-transient electromagnetic method and focus on new technology for realtime quality control and rapid interpretation of subsurface resistivities for both land and marine environments. The amplitude of the transient EM impulse response decays with offset r as 5 / 1 r and the corresponding step response decays as 3 / 1 r . Parameters that must be optimized to maximize the signal include: input current; source bi-pole length; order of the pseudo-random binary sequence (PRBS) source time function; and source bit rate. By exploiting the symmetry of the bi-pole field of the source we are able to measure noise essentially uncontaminated by the signal and use this measurement to reduce the noise in the transient EM measurements. The variation of the arrival time of the peak of the earth impulse response with offset can be mapped to an apparent interval resistivity, creating a pseudo-resistivity section beneath the line. We plan to illustrate the concepts presented here with both land and marine data.

Recent widespread damage from oil spills in Europe suggests that the current legal and economic framework does not provide a mechanism for preventing oil spill damages. The process by which a preventative mechanism arose in the United States following the Exxon Valdez oil spill may provide some lessons for Europe. The key to reducing oil spill damages is to create an incentive for prevention by increasing the damages a shipper of oil has to pay for a major oil spill. The simple economic argument is that shippers facing greater liability for damages will make greater efforts to prevent oil spills and to contain oil spills that have occurred. These greater efforts will be taken up to the point where the expected marginal prevention/containment cost is equal to the expected marginal change in the level of liability. Translating this economic solution into a preventative legal and economic framework for oil spill damages requires ensuring that an optimal level of prevention is achieved by using appropriate damage assessment methods that are part of a coherent administrative and legal framework. This framework must also address the potential for undesired responses, provide prior planning to facilitate prevention and containment, and make decisions about how to allocate resources to initial response, restoration, and compensation. These key issues are discussed by examining the process surrounding the Exxon Valdez oil spill in the United States.

Summary We present a test of the Multi-Transient Electro-Magnetic (MTEM) method in water 10 – 20 m deep in the Firth of Forth, Scotland. Using a low-cost experimental system and currents of less than 50 A, we recovered earth impulse responses at offsets in the range 600 – 8000 m, corresponding to target depths up to 2 km.