Economic analysis of participation in physical activity in England: implications for health policy.

BACKGROUND: Changing the relative price of (in) activity is an important tool for health policies. Nonetheless, to date, analyses of correlates of physical activity (PA) have excluded the notion of price. Using the first nationwide dataset on prices of PA for England, we explore for the first time how money and time prices are associated with PA (in general) and specific activities. METHODS: A nationally representative telephone follow-up survey to Health Survey for England (HSE) 2008 was undertaken in 2010. The sample covered individuals who reported to have undertaken some PA in the HSE 2008. Questions focussed on: ex-post money and time prices; type and quantity of PA; perceived benefits of PA and socio-economic details. Count regression models (all activities together, and swimming, workout, walking separately) were fitted to investigate the variation in quantity of PA. RESULTS: Of 1683 respondents, 83% participated in PA (one or more activities), and spent an average of £2.40 per occasion of participation in PA and 23 minutes travelling. Participation in PA was negatively associated with money prices per occasion (i.e. family member/child care fees, parking fees, and facility charges) and travel time price. Participation in PA was more sensitive to travel time price than money price. Among the specific activities, the money price effect was highest for swimming with a 10% higher price associated with 29% fewer occasions of swimming; followed by workout (3% fewer occasions) and walking (2% fewer occasions). Only swimming and workout were sensitive to travel time price. People who felt doing PA could help them 'get outdoors', 'have fun', or 'lose weight' were likely to do more PA. CONCLUSIONS: Two main policy implications emerge from the findings. First, the results support the notion that positive financial incentives, e.g. subsidising price of participation, could generally lead to an increase in quantity of PA among those already exercising. Second, such policies could lead to desired policy goals if implemented at an individual activity level (e.g. 50% subsidy on swimming entrance charges) rather than a blanket implementation (e.g. subsidising average entrance charges across all activities by 50%).Department of Health’s Policy Research Programm

Understanding the HERA Phase i receiver system with simulations and its impact on the detectability of the EoR delay power spectrum

The detection of the Epoch of Reionization (EoR) delay power spectrum using a "foreground avoidance method" highly depends on the instrument chromaticity. The systematic effects induced by the radio-telescope spread the foreground signal in the delay domain, which contaminates the EoR window theoretically observable. Applied to the Hydrogen Epoch of Reionization Array (HERA), this paper combines detailed electromagnetic and electrical simulations in order to model the chromatic effects of the instrument, and quantify its frequency and time responses. In particular, the effects of the analogue receiver, transmission cables, and mutual coupling are included. These simulations are able to accurately predict the intensity of the reflections occurring in the 150-m cable which links the antenna to the back-end. They also show that electromagnetic waves can propagate from one dish to another one through large sections of the array due to mutual coupling. The simulated system time response is attenuated by a factor $10^{4}$ after a characteristic delay which depends on the size of the array and on the antenna position. Ultimately, the system response is attenuated by a factor $10^{5}$ after 1400 ns because of the reflections in the cable, which corresponds to characterizable ${k_\parallel}$-modes above 0.7 $h\;\rm{Mpc}^{-1}$ at 150 MHz. Thus, this new study shows that the detection of the EoR signal with HERA Phase I will be more challenging than expected. On the other hand, it improves our understanding of the telescope, which is essential to mitigate the instrument chromaticity

Polo kinase recruitment via the constitutive centromere-associated network at the kinetochore elevates centromeric RNA

The kinetochore, a multi-protein complex assembled on centromeres, is essential to segregate chromosomes during cell division. Deficiencies in kinetochore function can lead to chromosomal instability and aneuploidy-a hallmark of cancer cells. Kinetochore function is controlled by recruitment of regulatory proteins, many of which have been documented, however their function often remains uncharacterized and many are yet to be identified. To identify candidates of kinetochore regulation we used a proteome-wide protein association strategy in budding yeast and detected many proteins that are involved in post-translational modifications such as kinases, phosphatases and histone modifiers. We focused on the Polo-like kinase, Cdc5, and interrogated which cellular components were sensitive to constitutive Cdc5 localization. The kinetochore is particularly sensitive to constitutive Cdc5 kinase activity. Targeting Cdc5 to different kinetochore subcomplexes produced diverse phenotypes, consistent with multiple distinct functions at the kinetochore. We show that targeting Cdc5 to the inner kinetochore, the constitutive centromere-associated network (CCAN), increases the levels of centromeric RNA via an SPT4 dependent mechanism

First Results from HERA Phase I: Upper Limits on the Epoch of Reionization 21 cm Power Spectrum

We report upper-limits on the Epoch of Reionization (EoR) 21 cm power spectrum at redshifts 7.9 and 10.4 with 18 nights of data ($\sim36$ hours of integration) from Phase I of the Hydrogen Epoch of Reionization Array (HERA). The Phase I data show evidence for systematics that can be largely suppressed with systematic models down to a dynamic range of $\sim10^9$ with respect to the peak foreground power. This yields a 95% confidence upper limit on the 21 cm power spectrum of $\Delta^2_{21} \le (30.76)^2\ {\rm mK}^2$ at $k=0.192\ h\ {\rm Mpc}^{-1}$at$z=7.9$, and also$\Delta^2_{21} \le (95.74)^2\ {\rm mK}^2$at$k=0.256\ h\ {\rm Mpc}^{-1}$at$z=10.4$. At$z=7.9$, these limits are the most sensitive to-date by over an order of magnitude. While we find evidence for residual systematics at low line-of-sight Fourier$k_\parallel$modes, at high$k_\parallel$ modes we find our data to be largely consistent with thermal noise, an indicator that the system could benefit from deeper integrations. The observed systematics could be due to radio frequency interference, cable sub-reflections, or residual instrumental cross-coupling, and warrant further study. This analysis emphasizes algorithms that have minimal inherent signal loss, although we do perform a careful accounting in a companion paper of the small forms of loss or bias associated with the pipeline. Overall, these results are a promising first step in the development of a tuned, instrument-specific analysis pipeline for HERA, particularly as Phase II construction is completed en route to reaching the full sensitivity of the experiment

Engineering and functional analysis of mitotic kinases through chemical genetics

During mitosis, multiple protein kinases transform the cytoskeleton and chromosomes into new and highly dynamic structures that mediate the faithful transmission of genetic information and cell division. However, the large number and strong conservation of mammalian kinases in general pose significant obstacles to interrogating them with small molecules, due to the difficulty in identifying and validating those which are truly selective. To overcome this problem, a steric complementation strategy has been developed, in which a bulky “gatekeeper” residue within the active site of the kinase of interest is replaced with a smaller amino acid, such as glycine or alanine. The enlarged catalytic pocket can then be targeted in an allele-specific manner with bulky purine analogs. This strategy provides a general framework for dissecting kinase function with high selectivity, rapid kinetics, and reversibility. In this chapter we discuss the principles and techniques needed to implement this chemical genetic approach in mammalian cells

Understanding the HERA Phase i receiver system with simulations and its impact on the detectability of the EoR delay power spectrum

The detection of the Epoch of Reionization (EoR) delay power spectrum using a "foreground avoidance method" highly depends on the instrument chromaticity. The systematic effects induced by the radio-telescope spread the foreground signal in the delay domain, which contaminates the EoR window theoretically observable. Applied to the Hydrogen Epoch of Reionization Array (HERA), this paper combines detailed electromagnetic and electrical simulations in order to model the chromatic effects of the instrument, and quantify its frequency and time responses. In particular, the effects of the analogue receiver, transmission cables, and mutual coupling are included. These simulations are able to accurately predict the intensity of the reflections occurring in the 150-m cable which links the antenna to the back-end. They also show that electromagnetic waves can propagate from one dish to another one through large sections of the array due to mutual coupling. The simulated system time response is attenuated by a factor $10^{4}$ after a characteristic delay which depends on the size of the array and on the antenna position. Ultimately, the system response is attenuated by a factor $10^{5}$ after 1400 ns because of the reflections in the cable, which corresponds to characterizable ${k_\parallel}$-modes above 0.7 $h\;\rm{Mpc}^{-1}$ at 150 MHz. Thus, this new study shows that the detection of the EoR signal with HERA Phase I will be more challenging than expected. On the other hand, it improves our understanding of the telescope, which is essential to mitigate the instrument chromaticity

Decoding Polo-like kinase 1 signaling along the kinetochore–centromere axis

Protein kinase signaling along the kinetochore-centromere axis is crucial to assure mitotic fidelity, yet its spatial coordination is obscure. Here, we examined how pools of human Polo-like kinase 1 (Plk1) within this axis control signaling events to elicit mitotic functions. To do this, we restricted active Plk1 to discrete subcompartments within the kinetochore-centromere axis using chemical genetics and decoded functional and phosphoproteomic signatures of each. We observe distinct phosphoproteomic and functional roles, suggesting that Plk1 exists and functions in discrete pools along this axis. Deep within the centromere, Plk1 operates to assure proper chromosome alignment and segregation. Thus, Plk1 at the kinetochore is a conglomerate of an observable bulk pool coupled with additional functional pools below the threshold of microscopic detection/resolution. Although complex, this multiplicity of locales provides an opportunity to decouple functional and phosphoproteomic signatures for a comprehensive understanding of Plk1’s kinetochore functions