The medium-term sustainability of organisational innovations in the national health service

Background: There is a growing recognition of the importance of introducing new ways of working into the UK's National Health Service (NHS) and other health systems, in order to ensure that patient care is provided as effectively and efficiently as possible. Researchers have examined the challenges of introducing new ways of working-'organisational innovations'-into complex organisations such as the NHS, and this has given rise to a much better understanding of how this takes place-and why seemingly good ideas do not always result in changes in practice. However, there has been less research on the medium-and longer-term outcomes for organisational innovations and on the question of how new ways of working, introduced by frontline clinicians and managers, are sustained and become established in day-to-day practice. Clearly, this question of sustainability is crucial if the gains in patient care that derive from organisational innovations are to be maintained, rather than lost to what the NHS Institute has called the 'improvement-evaporation effect'. Methods: The study will involve research in four case-study sites around England, each of which was successful in sustaining its new model of service provision beyond an initial period of pilot funding for new genetics services provided by the Department of Health. Building on findings relating to the introduction and sustainability of these services already gained from an earlier study, the research will use qualitative methods-in-depth interviews, observation of key meetings, and analysis of relevant documents-to understand the longer-term challenges involved in each case and how these were surmounted. The research will provide lessons for those seeking to sustain their own organisational innovations in wide-ranging clinical areas and for those designing the systems and organisations that make up the NHS, to make them more receptive contexts for the sustainment of innovation. Discussion: Through comparison and contrast across four sites, each involving different organisational innovations, different forms of leadership, and different organisational contexts to contend with, the findings of the study will have wide relevance. The research will produce outputs that are useful for managers and clinicians responsible for organisational innovation, policy makers and senior managers, and academics

Structural effects in UO2_2 thin films irradiated with fission-energy Xe ions

Uranium dioxide thin films have been successfully grown on LSAT (Al$_{10}$La$_3$O$_{51}$Sr$_{14}$Ta$_7$) substrates by reactive magnetron sputtering. Irradiation by 92 MeV $^{129}$Xe$^{23+}$ ions to simulate fission damage that occurs within nuclear fuels caused microstructural and crystallographic changes. Initially flat and continuous thin films were produced by magnetron sputtering with a root mean square roughness of 0.35 nm determined by AFM. After irradiation, this roughness increased to 60-70 nm, with the films developing discrete microstructural features: small grains (~3 $\mu$m), along with larger circular (up to 40 $\mu$m) and linear formations with non-uniform composition according to the SEM, AFM and EDX results. The irradiation caused significant restructuring of the UO$_2$ films that was manifested in significant filmsubstrate mixing, observed through EDX analysis. Diffusion of Al from the substrate into the film in unirradiated samples was also observed.Engineering and Physical Sciences Research Council (Grant ID: EP/ I036400/1), Radioactive Waste Management Ltd (formerly the Radioactive Waste Management Directorate of the UK Nuclear Decommissioning Authority, contract NPO004411A-EPS02), Russian Foundation for Basic Research (projects 13-03-90916), CSAR, Grand Accelélérateur National d’Ions Lourds (GANIL) Caen France, French Network EMIR, CIMAP-CIRIL, M.V.Lomonosov Moscow State University Program of Development, CKP FMI IPCE RA

The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis

Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P = 1.34×10<sup>−8</sup>, OR = 1.22, CI 95% = 1.14–1.30; rs2004640: P = 4.60×10<sup>−7</sup>, OR = 0.84, CI 95% = 0.78–0.90; rs10488631: P = 7.53×10<sup>−20</sup>, OR = 1.63, CI 95% = 1.47–1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P = 9.04×10<sup>−22</sup>, OR = 1.75, CI 95% = 1.56–1.97) better explained the observed association (likelihood P-value = 1.48×10<sup>−4</sup>), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific

Taking forward the Stop TB Partnership and World Health Organization joint theme for World TB Day March 24th 2018 - "Wanted: Leaders for a TB-Free World. You can make history. End TB"

World TB Day, March 24th commemorates the day in March 1882 when Professor Robert Koch made the groundbreaking announcement in Berlin of his discovery of Mycobacterium tuberculosis as the cause of Tuberculosis (TB) (Koch, 1882). At the time of his announcement, there was a deadly TB epidemic, rampaging throughout Europe and the Americas, causing the death of one out of every seven people. Since Koch’s announcement, Mycobacterium tuberculosis has defied worldwide efforts by public health systems, researchers, governments and the World Health Organization (WHO) to eradicate it. The data presented in the WHO Global TB Report 2017 (World Health Organization, 2017a) makes very gruesome reading. In 2016 there were an estimated 10.4 million people who developed TB disease worldwide, of which 90% were adults, 35% female and 10% were HIV-co-infected people. An estimated 40% of active TB cases go undiagnosed each year. One hundred and thirty-six years since Koch’s announcement, TB remains a major global public health issue and TB has surpassed HIV/AIDS and malaria as the world’s top cause of death from an infectious disease! On World TB Day, March 24th, 2018, we need to reflect on the current status quo of the continuing devastating global TB epidemic

Revealing the velocity structure of the filamentary nebula in NGC 1275 in its entirety

We have produced for the first time a detailed velocity map of the giant filamentary nebula surrounding NGC 1275, the Perseus cluster’s brightest galaxy, and revealed a previously unknown rich velocity structure across the entire nebula. These new observations were obtained with the optical imaging Fourier transform spectrometer SITELLE at CFHT. With its wide field of view ( ∼11 arcmin × 11 arcmin), SITELLE is the only integral field unit spectroscopy instrument able to cover the 80 kpc  ×  55 kpc ( 3.8 arcmin × 2.6 arcmin) large nebula in NGC 1275. Our analysis of these observations shows a smooth radial gradient of the [N II]λ6583/H α line ratio, suggesting a change in the ionization mechanism and source across the nebula. The velocity map shows no visible general trend or rotation, indicating that filaments are not falling uniformly onto the galaxy, nor being uniformly pulled out from it. Comparison between the physical properties of the filaments and Hitomi measurements of the X-ray gas dynamics in Perseus is also explored

Structural effects in UO2_2 thin films irradiated with U ions

This work presents the results of a detailed structural characterisation of irradiated and unirradiated single crystal thin films of UO$_2$. Thin films of UO$_2$ were produced by reactive magnetron sputtering onto (0 0 1), (1 1 0) and (1 1 1) single crystal yttria-stabilised zirconia (YSZ) substrates. Half of the samples were irradiated with 110 MeV $^{238}$U$^{31+}$ ions to fluences of 5 $\times$ 10$^{10}$, 5 $\times$ 10$^{11}$ and 5 $\times$ 10$^{12}$ ions/cm$^2$ to induce radiation damage, with the remainder kept for reference measurements. It was observed that as-produced UO$_2$ films adopted the crystallographic orientation of their YSZ substrates. The irradiation fluences used in this study however, were not sufficient to cause any permanent change in the crystalline nature of UO$_2$. It has been demonstrated that the effect of epitaxial re-crystallisation of the induced radiation damage can be quantified in terms of kernel average misorientation (KAM) and different crystallographic orientations of UO$_2$ respond differently to ion irradiation.The irradiation experiment was performed at the Grand Accélérateur National d’Ions Lourds (GANIL) Caen, France, and supported by the French Network EMIR. A.J. Popel acknowledges funding from the UK EPSRC (grant EP/ I036400/1) and Radioactive Waste Management Ltd (formerly the Radioactive Waste Management Directorate of the UK Nuclear Decommissioning Authority, contract NPO004411A-EPS02)

The effect of surgery on the outcome of treatment for multidrug-resistant tuberculosis: a systematic review and meta-analysis.

BACKGROUND: In 2014 only 50 % of multidrug-resistant tuberculosis (MDR-TB) patients achieved a successful treatment outcome. With limited options for medical treatment, surgery has re-emerged as an adjuvant therapeutic strategy. We conducted a systematic review and meta-analysis to assess the evidence for the effect of surgery as an adjunct to chemotherapy on outcomes of adults treated for MDR-TB. METHODS: Databases and grey literature sources were searched using terms incorporating surgery and MDR-TB. No language or publication type limits were applied. Articles published pre-1990, without a comparator group, or reporting <10 surgical participants were excluded. Two-stage sifting in duplicate was employed. Data on WHO-defined treatment outcomes were abstracted into a standardised database. Study-level risk of bias was evaluated using standardised tools. Outcome-level evidence quality was assessed using GRADE. Forest plots were generated, random effects meta-analysis conducted, and heterogeneity assessed using the I(2) statistic. RESULTS: Of 1024 unique citations identified, 62 were selected for full-text review and 15 retained for inclusion. A further four articles were included after bibliography/citation searching, and one additional unpublished manuscript was identified, giving 20 articles for final inclusion. Six were meta-analyses/systematic reviews and 14 were primary research articles (observational studies). From the 14 primary research articles, a successful outcome (cured/treatment completed) was reported for 81.9 % (371/453) and 59.7 % (1197/2006) in the surgical and non-surgical group respectively, giving a summary odds ratio of 2.62 (95 % confidence interval 1.94-3.54). Loss to follow-up and treatment failure were lower in the surgery group (both p = 0.01). Overall GRADE quality of evidence for all outcomes considered was "very low". CONCLUSIONS: This meta-analysis suggests that surgery as an adjunct to chemotherapy is associated with improved treatment outcomes in MDR-TB patients. However, inherent limitations in observational study design, insufficient reporting, and lack of adjustment for confounders, led to grading of the evidence as very low quality. Data on rationale for surgical referral, subsequent outcomes and resource-limited settings are scarce, precluding evidence-based recommendations on the suitability of surgery by patient characteristics or setting. It is hoped that highlighted methodological and reporting gaps will encourage improved design and reporting of future surgical studies for MDR-TB

Deterministic polarization chaos from a laser diode

Fifty years after the invention of the laser diode and fourty years after the report of the butterfly effect - i.e. the unpredictability of deterministic chaos, it is said that a laser diode behaves like a damped nonlinear oscillator. Hence no chaos can be generated unless with additional forcing or parameter modulation. Here we report the first counter-example of a free-running laser diode generating chaos. The underlying physics is a nonlinear coupling between two elliptically polarized modes in a vertical-cavity surface-emitting laser. We identify chaos in experimental time-series and show theoretically the bifurcations leading to single- and double-scroll attractors with characteristics similar to Lorenz chaos. The reported polarization chaos resembles at first sight a noise-driven mode hopping but shows opposite statistical properties. Our findings open up new research areas that combine the high speed performances of microcavity lasers with controllable and integrated sources of optical chaos.Comment: 13 pages, 5 figure

On Multi-objective Policy Optimization as a Tool for Reinforcement Learning

Many advances that have improved the robustness and efficiency of deep reinforcement learning (RL) algorithms can, in one way or another, be understood as introducing additional objectives, or constraints, in the policy optimization step. This includes ideas as far ranging as exploration bonuses, entropy regularization, and regularization toward teachers or data priors when learning from experts or in offline RL. Often, task reward and auxiliary objectives are in conflict with each other and it is therefore natural to treat these examples as instances of multi-objective (MO) optimization problems. We study the principles underlying MORL and introduce a new algorithm, Distillation of a Mixture of Experts (DiME), that is intuitive and scale-invariant under some conditions. We highlight its strengths on standard MO benchmark problems and consider case studies in which we recast offline RL and learning from experts as MO problems. This leads to a natural algorithmic formulation that sheds light on the connection between existing approaches. For offline RL, we use the MO perspective to derive a simple algorithm, that optimizes for the standard RL objective plus a behavioral cloning term. This outperforms state-of-the-art on two established offline RL benchmarks