Achieving provider engagement: providers' perceptions of implementing and delivering integrated care

The literature on integrated care is limited with respect to practical learning and experience. Although some attention has been paid to organizational processes and structures, not enough is paid to people, relationships, and the importance of these in bringing about integration. Little is known, for example, about provider engagement in the organizational change process, how to obtain and maintain it, and how it is demonstrated in the delivery of integrated care. Based on qualitative data from the evaluation of a large-scale integrated care initiative in London, United Kingdom, we explored the role of provider engagement in effective integration of services. Using thematic analysis, we identified an evolving engagement narrative with three distinct phases: enthusiasm, antipathy, and ambivalence, and argue that health care managers need to be aware of the impact of professional engagement to succeed in advancing the integrated care agenda

Self and Microbiota-Derived Epitopes Induce CD4⁺ T Cell Anergy and Conversion into CD4⁺Foxp3⁺ Regulatory Cells

The physiological role of T cell anergy induction as a key mechanism supporting self-tolerance remains undefined, and natural antigens that induce anergy are largely unknown. In this report, we used TCR sequencing to show that the recruitment of CD4+CD44+Foxp3−CD73+FR4+ anergic (Tan) cells expands the CD4+Foxp3+ (Tregs) repertoire. Next, we report that blockade in peripherally-induced Tregs (pTregs) formation due to mutation in CNS1 region of Foxp3 or chronic exposure to a selecting self-peptide result in an accumulation of Tan cells. Finally, we show that microbial antigens from Akkermansia muciniphila commensal bacteria can induce anergy and drive conversion of naive CD4+CD44-Foxp3− T (Tn) cells to the Treg lineage. Overall, data presented here suggest that Tan induction helps the Treg repertoire to become optimally balanced to provide tolerance toward ubiquitous and microbiome-derived epitopes, improving host ability to avert systemic autoimmunity and intestinal inflammation

Thymus-derived regulatory T cells control tolerance to commensal microbiota

Peripheral mechanisms preventing autoimmunity and maintaining tolerance to commensal microbiota involve CD4+Foxp3+ regulatory T cells1,2 generated in the thymus (tTregs) or extrathymically by induction of naive CD4+Foxp3− T cells (iTregs). Prior studies suggested that the T cell receptor (TCR) repertoires of tTregs and iTregs are biased towards self and non-self antigens, respectively 3–6 but their relative contribution in controlling immunopathology, e.g. colitis and other untoward inflammatory responses triggered by different types of antigens, remains unresolved 7. The intestine, and especially the colon, is a particularly suitable organ to study this question, given the variety of self-, microbiota- and food-derived antigens to which Tregs and other T cell populations are exposed. Intestinal environments can enhance conversion to a regulatory lineage 8,9 and favor tolerogenic presentation of antigens to naive CD4+ T cells 10,11, suggesting that intestinal homeostasis depends on microbiota-specific iTregs 12–15. Here, to identify the origin and antigen-specificity of intestinal Tregs, we performed single cell as well as high-throughput (HT) sequencing of the TCR repertoires of CD4+Foxp3+ and CD4+Foxp3− T cells and analyzed their reactivity against specific commensal species. We show that tTregs constitute the majority of Tregs in all lymphoid and intestinal organs, including colon, where their repertoire is heavily influenced by the composition of the microbiota. Our results suggest that tTregs, and not iTregs, dominantly mediate tolerance to antigens produced by intestinal commensals

General thoughts to the Kaon pair production in the threshold region

Simple--minded thoughts about the cross sections for the reactions pp-->ppK+K- and pp-->ppK0K0 are presented, which certainly do not account for the complex coupled channel problem but rather provide some ideas into the mutual reaction dynamics.Comment: Talk given at 9th International Workshop on Meson Production, Properties and Interaction, Cracow, Poland, 9-13 June 2006. 3 pages, 2 figure

Isospin dependence of the eta' meson production in nucleon--nucleon collisions

According to the quark model, the masses of eta and eta' mesons should be almost equal. However, the empirical values of these masses differ by more than the factor of two. Similarly, though the almost the same quark-antiquark content, the total cross section for the creation of these mesons close to the kinematical thresholds in the pp --> ppX reaction differs significantly. Using the COSY-11 detection setup we intend to determine whether this difference will also be so significant in the case of the production of these mesons in the proton-neutron scattering. Additionally, the comparison of the pp --> pp eta' and pn --> pn eta' total cross sections will allow to learn about the production of the eta' meson in the channels of isospin I = 0 and I = 1 and to investigate aspects of the gluonium component of the eta' meson.Comment: Presented at LEAP05: International conference on Low Energy Antiproton Physics, Bonn - Juelich, Germany, May 16-22, 200

COSY-11: an experimental facility for studying meson production in free and quasi-free nucleon-nucleon collisions

The COSY-11 experimental setup is an internal facility installed at the COoler SYnchrotron COSY in Juelich. It allows to investigate meson production in free and quasi-free nucleon-nucleon collisions, eg. pp --> pp meson and pd --> p_sp np meson reactions. Drift chambers and scintillators permit to measure outgoing protons, separated in magnetic field of COSY-11 dipole. Neutrons are registered in the neutron modular detector installed downstream the beam. Recently, the experimental setup has been extended with spectator detector, deuteron drift chamber and polarization monitoring system, and since then meson production can be investigated also as a function of spin and isospin of colliding nucleons.Comment: Presented at LEAP05: International conference on Low Energy Antiproton Physics, Bonn - Juelich, Germany, May 16-22, 200

Associated strangeness production in pp collisions near threshold

Motivated by the ongoing discussion concerning the nature of the scalar resonances f0(980) and a0(980), the COSY-11 collaboration has taken exclusive data on the pp->ppK+K- reaction near the production threshold. A first total cross section sigma=(1.80+-0.27+0.28-0.35)nb for the excess energy Q=17 MeV has been determined. In contrary to the eta, omega and eta' single meson production studies which clearly show the strong pp final state interaction (FSI), the cross section values obtained at COSY-11 and DISTO can be both described by a fit with a four-body phase space including the proton-proton final state interaction as well as with one-meson exchange calculations neglecting FSI effects. Therefore, one might think about a compensation of the strong pp interaction through a pK- FSI effect or an additional degree of freedom caused by the four-body final state. In the latter case, strong FSI effects can be expected at Q-values very close to the K+K- production threshold. Such a motivation triggered -- in combination with the investigation of the kaon-Antikaon interaction being relevant to the structure of the f0(980) -- further measurements at the excess energies Q=10 and Q=28 MeV at COSY-11.Comment: 5 pages, 4 figures, Presented at X. International Conference On Hadron Spectroscopy (Hadron 2003), Aschaffenburg, Germany, 31 Aug - 6 Sep 200

Non-equilibrium emission of complex fragments from p+Au collisions at 2.5 GeV proton beam energy

Energy and angular dependence of double differential cross sections d$^2\sigma$/d$\Omega$dE was measured for reactions induced by 2.5 GeV protons on Au target with isotopic identification of light products (H, He, Li, Be, and B) and with elemental identification of heavier intermediate mass fragments (C, N, O, F, Ne, Na, Mg, and Al). It was found that two different reaction mechanisms give comparable contributions to the cross sections. The intranuclear cascade of nucleon-nucleon collisions followed by evaporation from an equilibrated residuum describes low energy part of the energy distributions whereas another reaction mechanism is responsible for high energy part of the spectra of composite particles. Phenomenological model description of the differential cross sections by isotropic emission from two moving sources led to a very good description of all measured data. Values of the extracted parameters of the emitting sources are compatible with the hypothesis claiming that the high energy particles emerge from pre-equilibrium processes consisting in a breakup of the target into three groups of nucleons; small, fast and hot fireball of $\sim$ 8 nucleons, and two larger, excited prefragments, which emits the light charged particles and intermediate mass fragments. The smaller of them contains $\sim$ 20 nucleons and moves with velocity larger than the CM velocity of the proton projectile and the target. The heavier prefragment behaves similarly as the heavy residuum of the intranuclear cascade of nucleon-nucleon collisions. %The mass and charge dependence of the total production cross %sections was extracted from the above analysis for all observed %reaction products. This dependence follows the power low behavior %(A$^{-\tau}$ or Z$^{-\tau}$)