Cost-effectiveness and programmatic benefits of maternal vaccination against pertussis in England.

: Maternal pertussis immunisation was introduced during the pertussis resurgence in England in 2012 as a temporary measure to protect infants too young to be vaccinated. The programme was shown to be safe and highly effective. However, continuation of maternal vaccination as a routine programme requires a cost-effectiveness analysis. : The estimated prevented disease burden among mothers and their infants was obtained assuming 89% (95% CI: 19%-99%) vaccine efficacy for mothers and 91% (95% CI: 84%-95%) for infants. Future incidence was projected based on the disease rates in 2010-2012, including the four-year cycle of low and high incidence years. Full probabilistic sensitivity analysis was performed for different scenarios. : Assuming a vaccine coverage of 60%, there were 1650 prevented hospitalisations in infants (3.5% discounting, the first 10 years), including 55-60 deaths and ∼20,500 cases among mothers, of which around 1800 would be severe. The annual costs of the programme are £7.3 million assuming a price of £10 per dose and £9.4 million assuming £15 per dose. Using discounting of 3.5%, a 200 year time horizon and a price of £10 per dose (+£7.5 administration costs) only 25% of the iterations were below £30,000 per QALY. Using a 35% higher incidence resulted in 88% of the scenarios below this threshold. Assuming that the incidence remains at the level at the height of 2012, then the programme would be highly cost effective, with an ICER of £16,865 (£12,209-£25,976; price of £10 and 3.5%/3.5% discounting). : Maternal vaccination is effective in preventing severe illness and deaths in infants but the cost-effectiveness of the programme is highly dependent on future incidence which is necessarily uncertain. However, the duration and magnitude of protection against transmission afforded by the current acellular vaccines is also uncertain as are the associated effects on future herd immunity. The direct protection offered by the maternal dose provides the only certain way of protecting vulnerable infants from birth.<br/

Canonical Generations and the British Left: The Narrative Construction of the Miners’ Strike 1984–85

‘Generations’ have been invoked to describe a variety of social and cultural relationships, and to understand the development of self-conscious group identity. Equally, the term can be an applied label and politically useful construct; generations can be retrospectively produced. Drawing on the concept of ‘canonical generations’ – those whose experiences come to epitomise an event of historic and symbolic importance – this article examines the narrative creation and functions of ‘generations’ as collective memory shapes and re-shapes the desire for social change. Building a case study of the canonical role of the miners’ strike of 1984–85 in the narrative history of the British left, it examines the selective appropriation and transmission of the past in the development of political consciousness. It foregrounds the autobiographical narratives of activists who, in examining and legitimising their own actions and prospects, (re)produce a ‘generation’ in order to create a relatable and useful historical understanding

Deletion of the Polycomb-Group Protein EZH2 Leads to Compromised Self-Renewal and Differentiation Defects in Human Embryonic Stem Cells

Through the histone methyltransferase EZH2, the Polycomb complex PRC2 mediates H3K27me3 and is associated with transcriptional repression. PRC2 regulates cell-fate decisions in model organisms; however, its role in regulating cell differentiation during human embryogenesis is unknown. Here, we report the characterization of $\small \textit{EZH2}$-deficient human embryonic stem cells (hESCs). H3K27me3 was lost upon $\small \textit{EZH2}$ deletion, identifying an essential requirement for EZH2 in methylating H3K27 in hESCs, in contrast to its non-essential role in mouse ESCs. Developmental regulators were derepressed in $\small \textit{EZH2}$-deficient hESCs, and single-cell analysis revealed an unexpected acquisition of lineage-restricted transcriptional programs. $\small \textit{EZH2}$-deficient hESCs show strongly reduced self-renewal and proliferation, thereby identifying a more severe phenotype compared to mouse ESCs. $\small \textit{EZH2}$-deficient hESCs can initiate differentiation toward developmental lineages; however, they cannot fully differentiate into mature specialized tissues. Thus, $\small \textit{EZH2}$ is required for stable ESC self-renewal, regulation of transcriptional programs, and for late-stage differentiation in this model of early human development.Wellcome Trust (Grant ID: WT093736), Biotechnology and Biological Sciences Research Council (Grant ID: BBS/E/B/000C0402), Medical Research Council (DTG Studentships, Grant ID: MR/J003808/1

Crack-Like Processes Governing the Onset of Frictional Slip

We perform real-time measurements of the net contact area between two blocks of like material at the onset of frictional slip. We show that the process of interface detachment, which immediately precedes the inception of frictional sliding, is governed by three different types of detachment fronts. These crack-like detachment fronts differ by both their propagation velocities and by the amount of net contact surface reduction caused by their passage. The most rapid fronts propagate at intersonic velocities but generate a negligible reduction in contact area across the interface. Sub-Rayleigh fronts are crack-like modes which propagate at velocities up to the Rayleigh wave speed, VR, and give rise to an approximate 10% reduction in net contact area. The most efficient contact area reduction (~20%) is precipitated by the passage of slow detachment fronts. These fronts propagate at anomalously slow velocities, which are over an order of magnitude lower than VR yet orders of magnitude higher than other characteristic velocity scales such as either slip or loading velocities. Slow fronts are generated, in conjunction with intersonic fronts, by the sudden arrest of sub-Rayleigh fronts. No overall sliding of the interface occurs until either of the slower two fronts traverses the entire interface, and motion at the leading edge of the interface is initiated. Slip at the trailing edge of the interface accompanies the motion of both the slow and sub-Rayleigh fronts. We might expect these modes to be important in both fault nucleation and earthquake dynamics.Comment: 19 page, 5 figures, to appear in International Journal of Fractur

Ureterolithiasis after Cohen re-implantation – case report

BACKGROUND: In the past decades, the widespread use of cross-trigonal ureteral reimplants for the treatment of children with vesicoureteral reflux has resulted in a large population of patients with transversely lying ureters. As this population gets older they will consequently be entering an age group at higher risk for stone and urothelial cancer formation. If ureteroscopy becomes necessary, the transverse position of the ureter makes ureteric access often impossible. CASE PRESENTATION: We present the case of a young man who not only suffered from urolithiasis due to hyperparathyroidism, but also further jeopardized his treatment by omitting the fact that as a child he underwent Cohen reimplantation of the right ureter. CONCLUSIONS: This case illustrates the particular difficulties the endoscopist may face in this group of patients. Patients with difficult ureteric access, abnormal anatomy, or those with known cross-trigonal ureteric reimplantations should be managed in a specialised endourology unit

Saturn Plasma Sources and Associated Transport Processes

This article reviews the different sources of plasma for Saturn’s magnetosphere, as they are known essentially from the scientific results of the Cassini-Huygens mission to Saturn and Titan. At low and medium energies, the main plasma source is the H2OH2O cloud produced by the “geyser” activity of the small satellite Enceladus. Impact ionization of this cloud occurs to produce on the order of 100 kg/s of fresh plasma, a source which dominates all the other ones: Titan (which produces much less plasma than anticipated before the Cassini mission), the rings, the solar wind (a poorly known source due to the lack of quantitative knowledge of the degree of coupling between the solar wind and Saturn’s magnetosphere), and the ionosphere. At higher energies, energetic particles are produced by energy diffusion and acceleration of lower energy plasma produced by the interchange instabilities induced by the rapid rotation of Saturn, and possibly, for the highest energy range, by contributions from the CRAND process acting inside Saturn’s magnetosphere. Discussion of the transport and acceleration processes acting on these plasma sources shows the importance of rotation-induced radial transport and energization of the plasma, and also shows how much the unexpected planetary modulation of essentially all plasma parameters of Saturn’s magnetosphere remains an unexplained mystery

Spherical Functions Associated With the Three Dimensional Sphere

In this paper, we determine all irreducible spherical functions \Phi of any K -type associated to the pair (G,K)=(\SO(4),\SO(3)). This is accomplished by associating to \Phi a vector valued function H=H(u) of a real variable u, which is analytic at u=0 and whose components are solutions of two coupled systems of ordinary differential equations. By an appropriate conjugation involving Hahn polynomials we uncouple one of the systems. Then this is taken to an uncoupled system of hypergeometric equations, leading to a vector valued solution P=P(u) whose entries are Gegenbauer's polynomials. Afterward, we identify those simultaneous solutions and use the representation theory of \SO(4) to characterize all irreducible spherical functions. The functions P=P(u) corresponding to the irreducible spherical functions of a fixed K-type \pi_\ell are appropriately packaged into a sequence of matrix valued polynomials (P_w)_{w\ge0} of size (\ell+1)\times(\ell+1). Finally we proved that \widetilde P_w={P_0}^{-1}P_w is a sequence of matrix orthogonal polynomials with respect to a weight matrix W. Moreover we showed that W admits a second order symmetric hypergeometric operator \widetilde D and a first order symmetric differential operator \widetilde E.Comment: 49 pages, 2 figure

Current-density functional theory of time-dependent linear response in quantal fluids: recent progress

Vignale and Kohn have recently formulated a local density approximation to the time-dependent linear response of an inhomogeneous electron system in terms of a vector potential for exchange and correlation. The vector potential depends on the induced current density through spectral kernels to be evaluated on the homogeneous electron-gas. After a brief review of their theory, the case of inhomogeneous Bose superfluids is considered, with main focus on dynamic Kohn-Sham equations for the condensate in the linear response regime and on quantal generalized hydrodynamic equations in the weak inhomogeneity limit. We also present the results of calculations of the exchange-correlation spectra in both electron and superfluid boson systems.Comment: 12 pages, 2 figures, Postscript fil

Investigating spillover of multidrug-resistant tuberculosis from a prison: a spatial and molecular epidemiological analysis.

BACKGROUND: Congregate settings may serve as institutional amplifiers of tuberculosis (TB) and multidrug-resistant tuberculosis (MDR-TB). We analyze spatial, epidemiological, and pathogen genetic data prospectively collected from neighborhoods surrounding a prison in Lima, Peru, where inmates experience a high risk of MDR-TB, to investigate the risk of spillover into the surrounding community. METHODS: Using hierarchical Bayesian statistical modeling, we address three questions regarding the MDR-TB risk: (i) Does the excess risk observed among prisoners also extend outside the prison? (ii) If so, what is the magnitude, shape, and spatial range of this spillover effect? (iii) Is there evidence of additional transmission across the region? RESULTS: The region of spillover risk extends for 5.47 km outside of the prison (95% credible interval: 1.38, 9.63 km). Within this spillover region, we find that nine of the 467 non-inmate patients (35 with MDR-TB) have MDR-TB strains that are genetic matches to strains collected from current inmates with MDR-TB, compared to seven out of 1080 patients (89 with MDR-TB) outside the spillover region (p values: 0.022 and 0.008). We also identify eight spatially aggregated genetic clusters of MDR-TB, four within the spillover region, consistent with local transmission among individuals living close to the prison. CONCLUSIONS: We demonstrate a clear prison spillover effect in this population, which suggests that interventions in the prison may have benefits that extend to the surrounding community

Galaxy and Mass Assembly (GAMA): Panchromatic data release (far-UV–far-IR) and the low-z energy budget

We present the Galaxy And Mass Assembly (GAMA) Panchromatic Data Release (PDR) constituting over 230 deg2 of imaging with photometry in 21 bands extending from the farUV to the far-IR. These data complement our spectroscopic campaign of over 300k galaxies, and are compiled from observations with a variety of facilities including: GALaxy Evolution eXplorer, Sloan Digital Sky Survey, Visible and Infrared Telescope for Astronomy (VISTA), Wide-field Infrared Survey Explorer, and Herschel, with the GAMA regions currently being surveyedbyVLTSurveyTelescope(VST)andscheduledforobservationsbyAustralianSquare Kilometer Array Pathfinder (ASKAP). These data are processed to a common astrometric solution, from which photometry is derived for ∼221373 galaxies with r < 19.8 mag. Online tools are provided to access and download data cutouts, or the full mosaics of the GAMA regions in each band. We focus, in particular, on the reduction and analysis of the VISTA VIsta Kilo-degree INfrared Galaxy data, and compare to earlier data sets (i.e. 2MASS and UKIDSS) before combining the data and examining its integrity. Having derived the 21-band photometric catalogue, we proceed to fit the data using the energy balance code MAGPHYS. These measurements are then used to obtain the first fully empirical measurement of the 0.1–500 μm energy output of the Universe. Exploring the cosmic spectral energy distribution across three time-intervals (0.3–1.1, 1.1–1.8, and 1.8–2.4 Gyr), we find that the Universe is currently generating (1.5 ± 0.3) × 1035 h70 W Mpc−3, down from (2.5 ± 0.2) × 1035 h70 W Mpc−3 2.3 Gyr ago. More importantly, we identify significant and smooth evolution in the integrated photon escape fraction at all wavelengths, with the UV escape fraction increasing from 27(18) per cent at z= 0.18 in NUV(FUV) to 34(23) per cent at z= 0.06. The GAMA PDR can be found at: http://gama-psi.icrar.org/