The radical ion HCl+, a key intermediate in the chlorine chemistry of the interstellar gas, has been identified for the first time in the interstellar medium with the Herschel Space Observatory's ...Heterodyne Instrument for the Far-Infrared. The ground-state rotational transition of H super(35)Cl+, super(2)Pi sub(3/2)J = 5/2-3/2, showing Lambda-doubling and hyperfine structure, is detected in absorption toward the Galactic star-forming regions W31C (G10.6-0.4) and W49N. The complex interstellar absorption features are modeled by convolving in velocity space the opacity profiles of other molecular tracers toward the same sources with the fine and hyperfine structure of HCl+. This structure is derived from a combined analysis of optical data from the literature and new laboratory measurements of pure rotational transitions, reported in the accompanying Letter by Gupta et al. The models reproduce well the interstellar absorption, and the frequencies inferred from the astronomical observations are in exact agreement with those calculated using spectroscopic constants derived from the laboratory data. The detection of H super(37)Cl+ toward W31C, with a column density consistent with the expected super(35)Cl/ super(37)Cl isotopic ratio, provides additional evidence for the identification. A comparison with the chemically related molecules HCl and H sub(2)Cl+ yields an abundance ratio of unity with both species (HCl+ : H sub(2)Cl+ : HCl ~ 1). These observations also yield the unexpected result that HCl+ accounts for 3%-5% of the gas-phase chlorine toward W49N and W31C, values several times larger than the maximum fraction (~1%) predicted by chemical models.
Large Phase III trials across Asia and Latin America have recently demonstrated the efficacy of a recombinant, live-attenuated dengue vaccine (Dengvaxia) over the first 25 mo following vaccination. ...Subsequent data collected in the longer-term follow-up phase, however, have raised concerns about a potential increase in hospitalization risk of subsequent dengue infections, in particular among young, dengue-naïve vaccinees. We here report predictions from eight independent modelling groups on the long-term safety, public health impact, and cost-effectiveness of routine vaccination with Dengvaxia in a range of transmission settings, as characterised by seroprevalence levels among 9-y-olds (SP9). These predictions were conducted for the World Health Organization to inform their recommendations on optimal use of this vaccine.
The models adopted, with small variations, a parsimonious vaccine mode of action that was able to reproduce quantitative features of the observed trial data. The adopted mode of action assumed that vaccination, similarly to natural infection, induces transient, heterologous protection and, further, establishes a long-lasting immunogenic memory, which determines disease severity of subsequent infections. The default vaccination policy considered was routine vaccination of 9-y-old children in a three-dose schedule at 80% coverage. The outcomes examined were the impact of vaccination on infections, symptomatic dengue, hospitalised dengue, deaths, and cost-effectiveness over a 30-y postvaccination period. Case definitions were chosen in accordance with the Phase III trials. All models predicted that in settings with moderate to high dengue endemicity (SP9 ≥ 50%), the default vaccination policy would reduce the burden of dengue disease for the population by 6%-25% (all simulations: -3%-34%) and in high-transmission settings (SP9 ≥ 70%) by 13%-25% (all simulations: 10%- 34%). These endemicity levels are representative of the participating sites in both Phase III trials. In contrast, in settings with low transmission intensity (SP9 ≤ 30%), the models predicted that vaccination could lead to a substantial increase in hospitalisation because of dengue. Modelling reduced vaccine coverage or the addition of catch-up campaigns showed that the impact of vaccination scaled approximately linearly with the number of people vaccinated. In assessing the optimal age of vaccination, we found that targeting older children could increase the net benefit of vaccination in settings with moderate transmission intensity (SP9 = 50%). Overall, vaccination was predicted to be potentially cost-effective in most endemic settings if priced competitively. The results are based on the assumption that the vaccine acts similarly to natural infection. This assumption is consistent with the available trial results but cannot be directly validated in the absence of additional data. Furthermore, uncertainties remain regarding the level of protection provided against disease versus infection and the rate at which vaccine-induced protection declines.
Dengvaxia has the potential to reduce the burden of dengue disease in areas of moderate to high dengue endemicity. However, the potential risks of vaccination in areas with limited exposure to dengue as well as the local costs and benefits of routine vaccination are important considerations for the inclusion of Dengvaxia into existing immunisation programmes. These results were important inputs into WHO global policy for use of this licensed dengue vaccine.
Defining the boundary of children's ‘neighborhoods’ has important implications for understanding the contextual influences on child health. Additionally, insight into activities that occur outside ...people's neighborhoods may indicate exposures that place-based studies cannot detect. This study aimed to 1) extend current neighborhood research, using data from wearable cameras and GPS devices that were worn over several days in an urban setting; 2) define the boundary of children's neighborhoods by using leisure time activity space data; and 3) determine the destinations visited by children in their leisure time, outside their neighborhoods.
One hundred and fourteen children (mean age 12y) from Wellington, New Zealand wore wearable cameras and GPS recorders. Residential Euclidean buffers at incremental distances were paired with GPS data (thereby identifying time spent in different places) to explore alternative definitions of neighborhood boundaries. Children's neighborhood boundary was at 500 m. A newly developed software application was used to identify ‘destinations’ visited outside the neighborhood by specifying space-time parameters. Image data from wearable cameras were used to determine the type of destination.
Children spent over half of their leisure time within 500 m of their homes. Children left their neighborhood predominantly to visit school (for leisure purposes), other residential locations (e.g. to visit friends) and food retail outlets (e.g. convenience stores, fast food outlets). Children spent more time at food retail outlets than at structured sport and in outdoor recreation locations combined.
Person-centered neighborhood definitions may serve to better represent children's everyday experiences and neighborhood exposures than previous methods based on place-based measures. As schools and other residential locations (friends and family) are important destinations outside the neighborhood, such destinations should be taken into account. The combination of image data and activity space GPS data provides a more robust approach to understanding children's neighborhoods and activity spaces.
•Assessed children's neighborhood extent using wearable cameras and GPS devices.•We used GPS derived criteria to determine person-centered neighborhood definitions.•Children spend the majority of their non-school time within 500 m of home.•Children left their neighborhoods to visit school, residential, food retailers.•Combined image and GPS data enabled detailed analyses of children's neighborhoods.
We present precision Penning trap mass measurements of neutron-rich calcium and potassium isotopes in the vicinity of neutron number N=32. Using the TITAN system, the mass of 51K was measured for the ...first time, and the precision of the (51,52)Ca mass values were improved significantly. The new mass values show a dramatic increase of the binding energy compared to those reported in the atomic mass evaluation. In particular, 52Ca is more bound by 1.74 MeV, and the behavior with neutron number deviates substantially from the tabulated values. An increased binding was predicted recently based on calculations that include three-nucleon (3N) forces. We present a comparison to improved calculations, which agree remarkably with the evolution of masses with neutron number, making neutron-rich calcium isotopes an exciting region to probe 3N forces.
To determine if mexiletine is safe and effective in reducing myotonia in myotonic dystrophy type 1 (DM1).
Myotonia is an early, prominent symptom in DM1 and contributes to decreased dexterity, gait ...instability, difficulty with speech/swallowing, and muscle pain. A few preliminary trials have suggested that the antiarrhythmic drug mexiletine is useful, symptomatic treatment for nondystrophic myotonic disorders and DM1.
We performed 2 randomized, double-blind, placebo-controlled crossover trials, each involving 20 ambulatory DM1 participants with grip or percussion myotonia on examination. The initial trial compared 150 mg of mexiletine 3 times daily to placebo, and the second trial compared 200 mg of mexiletine 3 times daily to placebo. Treatment periods were 7 weeks in duration separated by a 4- to 8-week washout period. The primary measure of myotonia was time for isometric grip force to relax from 90% to 5% of peak force after a 3-second maximum grip contraction. EKG measurements and adverse events were monitored in both trials.
There was a significant reduction in grip relaxation time with both 150 and 200 mg dosages of mexiletine. Treatment with mexiletine at either dosage was not associated with any serious adverse events, or with prolongation of the PR or QTc intervals or of QRS duration. Mild adverse events were observed with both placebo and mexiletine treatment.
Mexiletine at dosages of 150 and 200 mg 3 times daily is effective, safe, and well-tolerated over 7 weeks as an antimyotonia treatment in DM1.
This study provides Class I evidence that mexiletine at dosages of 150 and 200 mg 3 times daily over 7 weeks is well-tolerated and effective in reducing handgrip relaxation time in DM1.
PDF
