A simulation tool for better management of retinal services

Background: Advances in the management of retinal diseases have been fast-paced as new treatments become available, resulting in increasing numbers of patients receiving treatment in hospital retinal services. These patients require frequent and long-term follow-up and repeated treatments, resulting in increased pressure on clinical workloads. Due to limited clinic capacity, many National Health Service (NHS) clinics are failing to maintain recommended follow-up intervals for patients receiving care. As such, clear and robust, long term retinal service models are required to assess and respond to the needs of local populations, both currently and in the future. Methods: A discrete event simulation (DES) tool was developed to facilitate the improvement of retinal services by identifying efficiencies and cost savings within the pathway of care. For a mid-size hospital in England serving a population of over 500,000, we used 36 months of patient level data in conjunction with statistical forecasting and simulation to predict the impact of making changes within the service. Results: A simulation of increased demand and a potential solution of the 'Treat and Extend' (T&E) regimen which is reported to result in better outcomes, in combination with virtual clinics which improve quality, effectiveness and productivity and thus increase capacity is presented. Without the virtual clinic, where T&E is implemented along with the current service, we notice a sharp increase in the number of follow-ups, number of Anti-VEGF injections, and utilisation of resources. In the case of combining T&E with virtual clinics, there is a negligible (almost 0%) impact on utilisation of resources. Conclusions: Expansion of services to accommodate increasing number of patients seen and treated in retinal services is feasible with service re-organisation. It is inevitable that some form of initial investment is required to implement service expansion through T&E and virtual clinics. However, modelling with DES indicates that such investment is outweighed by cost reductions in the long term as more patients receive optimal treatment and retain vision with better outcomes. The model also shows that the service will experience an average of 10% increase in surplus capacity.Peer reviewedFinal Published versio

Design optimization of pixel sensors using device simulations for the phase-II CMS tracker upgrade

In order to address the problems caused by the harsh radiation environment during the high luminosity phase of the LHC (HL-LHC), all silicon tracking detectors (pixels and strips) in the CMS experiment will undergo an upgrade. And so to develop radiation hard pixel sensors, simulations have been performed using the 2D TCAD device simulator, SILVACO, to obtain design parameters. The effect of various design parameters like pixel size, pixel depth, implant width, metal overhang, p-stop concentration, p-stop depth and bulk doping density on the leakage current and critical electric field are studied for both non-irradiated as well as irradiated pixel sensors. These 2D simulation results of planar pixels are useful for providing insight into the behaviour of non-irradiated and irradiated silicon pixel sensors and further work on 3D simulation is underway. © 2015 Elsevier B.V

Tissue-specific calibration of extracellular matrix material properties by transforming growth factor-beta and Runx2 in bone is required for hearing

Publisher version: http://www.nature.com/embor/journal/v11/n10/full/embor2010135.htmlDA - 20100917 IS - 1469-3178 (Electronic) IS - 1469-221X (Linking) LA - ENG PT - JOURNAL ARTICLEDA - 20100917 IS - 1469-3178 (Electronic) IS - 1469-221X (Linking) LA - ENG PT - JOURNAL ARTICLEDA - 20100917 IS - 1469-3178 (Electronic) IS - 1469-221X (Linking) LA - ENG PT - JOURNAL ARTICLEPhysical cues, such as extracellular matrix stiffness, direct cell differentiation and support tissue-specific function. Perturbation of these cues underlies diverse pathologies, including osteoarthritis, cardiovascular disease and cancer. However, the molecular mechanisms that establish tissue-specific material properties and link them to healthy tissue function are unknown. We show that Runx2, a key lineage-specific transcription factor, regulates the material properties of bone matrix through the same transforming growth factor-beta (TGFbeta)-responsive pathway that controls osteoblast differentiation. Deregulated TGFbeta or Runx2 function compromises the distinctly hard cochlear bone matrix and causes hearing loss, as seen in human cleidocranial dysplasia. In Runx2(+/-) mice, inhibition of TGFbeta signalling rescues both the material properties of the defective matrix, and hearing. This study elucidates the unknown cause of hearing loss in cleidocranial dysplasia, and demonstrates that a molecular pathway controlling cell differentiation also defines material properties of extracellular matrix. Furthermore, our results suggest that the careful regulation of these properties is essential for healthy tissue functio

G × E interactions in QTL introgression lines of Spanish-type groundnut (Arachis hypogaea L.)

Multi-environment testing at five locations for rust and late leaf spot (LLS) resistance with 41 introgressed lines (ILs) bred using marker-assisted backcross breeding in the genetic background Spanish- type groundnut varieties identified significant genotype, and genotype 9 environment interactions (GEI) for LLS disease resistance and yield parameters. Significant GEI effects suggest the need to identify location specific breeding lines to achieve gains in pod yield and LLS resistance. The observed variable LLS disease reaction among the ILs in part suggests influence of background genotype on the level of resistance. A breeding scheme with early generation selection using molecular markers followed by phenotyping for LLS, and multi-location testing of fixed breeding lines was optimized to enhance selection intensity and accuracy in groundnut breeding. The ILs, ICGVs 14431, 14436 and 14438 with pooled LLS score at 90 DAS of 3.5–3.7 were superior to respective recurrent parent for pod yield, with early maturing similar to recurrent parents. The pod yield advantage in ILs is attributed by more number of pods, besides resistance to LLS that contributes to better filling

Measurement of the Branching Fraction of the Decay B+→π+π−ℓ+νℓ\boldsymbol{B^{+}\to\pi^{+}\pi^{-}\ell^{+}\nu_\ell} in Fully Reconstructed Events at Belle

We present an analysis of the exclusive $B^{+}\to\pi^{+}\pi^{-}\ell^{+}\nu_{\ell}$ decay, where $\ell$ represents an electron or a muon, with the assumption of charge-conjugation symmetry and lepton universality. The analysis uses the full $\Upsilon(4S)$ data sample collected by the Belle detector, corresponding to 711 fb$^{-1}$ of integrated luminosity. We select the events by fully reconstructing one $B$ meson in hadronic decay modes, subsequently determining the properties of the other $B$ meson. We extract the signal yields using a binned maximum-likelihood fit to the missing-mass squared distribution in bins of the invariant mass of the two pions or the momentum transfer squared. We measure a total branching fraction of ${{\cal B}(B^{+}\to \pi^{+}\pi^{-}\ell^{+}\nu_{\ell})= [22.7 ^{+1.9}_{-1.6} (\mathrm{stat}) \pm 3.5(\mathrm{syst}) ]\times 10^{-5}}$, where the uncertainties are statistical and systematic, respectively. This result is the first reported measurement of this decay.Comment: 23 pages, 19 figure

Evidence for a vector charmonium-like state in e+e−→Ds+Ds2∗(2573)−+c.c.e^+e^- \to D^+_sD^*_{s2}(2573)^-+c.c.

We report the measurement of $e^+e^- \to D^+_sD^*_{s2}(2573)^-+c.c.$ via initial-state radiation using a data sample of an integrated luminosity of 921.9 fb$^{-1}$ collected with the Belle detector at the $\Upsilon(4S)$ and nearby. We find evidence for an enhancement with a 3.4$\sigma$ significance in the invariant mass of $D^+_sD^*_{s2}(2573)^- +c.c.$ The measured mass and width are $(4619.8^{+8.9}_{-8.0}({\rm stat.})\pm2.3({\rm syst.}))~{\rm MeV}/c^{2}$ and $(47.0^{+31.3}_{-14.8}({\rm stat.})\pm4.6({\rm syst.}))~{\rm MeV}$, respectively. The mass, width, and quantum numbers of this enhancement are consistent with the charmonium-like state at 4626 MeV/$c^2$ recently reported by Belle in $e^+e^-\to D^+_sD_{s1}(2536)^-+c.c.$ The product of the $e^+e^-\to D^+_sD^*_{s2}(2573)^-+c.c.$ cross section and the branching fraction of $D^*_{s2}(2573)^-\to{\bar D}^0K^-$ is measured from $D^+_sD^*_{s2}(2573)^-$ threshold to 5.6 GeV.Comment: 9 pages, 4 figure

Measurement of Branching Fractions of Hadronic Decays of the Ωc0\Omega_c^0 Baryon

Using a data sample of 980 ${\rm fb}^{-1}$ of $e^+e^-$ annihilation data taken with the Belle detector operating at the KEKB asymmetric-energy $e^+e^-$ collider, we report the results of a study of the decays of the $\Omega_c^0$ charmed baryon into hadronic final states. We report the most precise measurements to date of the relative branching fractions of the $\Omega_c^0$ into $\Omega^-\pi^+\pi^0$, $\Omega^-\pi^+\pi^-\pi^+$, $\Xi^-K^-\pi^+\pi^+$, and $\Xi^0K^-\pi^+$, as well as the first measurements of the branching fractions of the $\Omega_c^0$ into $\Xi^-\bar{K}^0\pi^+$, $\Xi^0\bar{K}^0$, and $\Lambda \bar{K}^0\bar{K}^0$, all with respect to the $\Omega^-\pi^+$ decay. In addition, we investigate the resonant substructure of these modes. Finally, we present a limit on the branching fraction for the decay $\Omega_c^0\to\Sigma^+K^-K^-\pi^+$

Search for eta-mesic 4He in the dd->3He n pi0 and dd->3He p pi- reactions with the WASA-at-COSY facility

The search for 4He-eta bound states was performed with the WASA-at-COSY facility via the measurement of the excitation function for the dd->3He n pi0 and dd->3He p pi- processes. The beam momentum was varied continuously between 2.127 GeV/c and 2.422 GeV/c, corresponding to the excess energy for the dd->4He eta reaction ranging from Q=-70 MeV to Q=30 MeV. The luminosity was determined based on the dd->3He n reaction and quasi-free proton-proton scattering via dd->pp n_spectator n_spectator reactions. The excitation functions determined independently for the measured reactions do not reveal a structure which could be interpreted as a narrow mesic nucleus. Therefore, the upper limits of the total cross sections for the bound state production and decay in dd->(4He-eta)_bound->3He n pi0 and dd->(4He-eta)_bound->3He p pi- processes were determined taking into account the isospin relation between both the channels considered. The results of the analysis depend on the assumptions of the N* momentum distribution in the anticipated mesic-4He. Assuming as in the previous works, that this is identical with the distribution of nucleons bound with 20 MeV in 4He, we determined that (for the mesic bound state width in the range from 5 MeV to 50 MeV) the upper limits at 90% confidence level are about 3 nb and about 6 nb for npi0 and ppi- channels, respectively. However, based on the recent theoretical findings of the N*(1535) momentum distribution in the N*-3He nucleus bound by 3.6 MeV, we find that the WASA-at-COSY detector acceptance decreases and hence the corresponding upper limits are 5 nb and 10 nb for npi0 and ppi- channels respectively.Comment: This article will be submitted to JHE