A Demand and Capacity Model For Home-Based Intermediate Care: Optimizing The ‘Step Down’ Pathway

This is the author accepted manuscript. The final version is available from IEEE via the DOI in this recordIntermediate care supports timely discharge from hospital for patients with complex healthcare needs. The purpose of 'step-down' care is to enable patients to leave hospital as soon as medically fit, avoiding costly discharge delays and consequent risks to patient health and wellbeing. Determining optimal intermediate care capacity requires balancing costs to both acute hospital and community care providers. Too much community capacity results in underutilized resources and poor economic efficiency, while too little risks excessive hospital discharge delays. Application of discrete-time simulation shows that total costs across the acute-community interface can be minimized by identifying optimal community capacity in terms of the maximum number of patients for which home visits can be provided by the service. To our knowledge, this is the first simulation study to model the patient pathway from hospital discharge through to community visits. Simulation modeling has supported short-term resource planning in a major English healthcare system.Health Data Research U

A logistic map approach to economic cycles I. The best adapted companies

A birth-death lattice gas model about the influence of an environment on the fitness and concentration evolution of economic entities is analytically examined. The model can be mapped onto a high order logistic map. The control parameter is a (scalar) "business plan". Conditions are searched for growth and decay processes, stable states, upper and lower bounds, bifurcations, periodic and chaotic solutions. The evolution equation of the economic population for the best fitted companies indicates "microscopic conditions" for cycling. The evolution of a dynamic exponent is shown as a function of the business plan parameters.Comment: 10 pages, 5 postscript figure

Absence of system xc⁻ on immune cells invading the central nervous system alleviates experimental autoimmune encephalitis

Background: Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System x(c)- or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration. Methods: Semi-quantitative Western blotting served to study protein expression of xCT, the specific subunit of system x(c)-, as well as of regulators of xCT transcription, in the normal appearing white matter (NAWM) of MS patients and in the CNS and spleen of mice exposed to experimental autoimmune encephalomyelitis (EAE), an accepted mouse model of MS. We next compared the clinical course of the EAE disease, the extent of demyelination, the infiltration of immune cells and microglial activation in xCT-knockout (xCT(-/-)) mice and irradiated mice reconstituted in xCT(-/-) bone marrow (BM), to their proper wild type (xCT(+/+)) controls. Results: xCT protein expression levels were upregulated in the NAWM of MS patients and in the brain, spinal cord, and spleen of EAE mice. The pathways involved in this upregulation in NAWM of MS patients remain unresolved. Compared to xCT(+/+) mice, xCT(-/-) mice were equally susceptible to EAE, whereas mice transplanted with xCT(-/-) BM, and as such only exhibiting loss of xCT in their immune cells, were less susceptible to EAE. In none of the above-described conditions, demyelination, microglial activation, or infiltration of immune cells were affected. Conclusions: Our findings demonstrate enhancement of xCT protein expression in MS pathology and suggest that system x(c)- on immune cells invading the CNS participates to EAE. Since a total loss of system x(c)- had no net beneficial effects, these results have important implications for targeting system x(c)- for treatment of MS

Blocking TGF-β signaling pathway preserves mitochondrial proteostasis and reduces early activation of PDGFRβ+ pericytes in aristolochic acid induced acute kidney injury in wistar male rats

The platelet-derived growth factor receptor β (PDGFRβ)+ perivascular cell activation becomes increasingly recognized as a main source of scar-associated kidney myofibroblasts and recently emerged as a new cellular therapeutic target.In this regard, we first confirmed the presence of PDGFRβ+ perivascular cells in a human case of end-stage aristolochic acid nephropathy (AAN) and thereafter we focused on the early fibrosis events of transforming growth factor β (TGFβ) inhibition in a rat model of AAN.Neutralizing anti-TGFβ antibody (1D11) and its control isotype (13C4) were administered (5 mg/kg, i.p.) at Days -1, 0, 2 and 4; AA (15 mg/kg, sc) was injected daily.At Day 5, 1D11 significantly suppressed p-Smad2/3 signaling pathway improving renal function impairment, reduced the score of acute tubular necrosis, peritubular capillaritis, interstitial inflammation and neoangiogenesis. 1D11 markedly decreased interstitial edema, disruption of tubular basement membrane loss of brush border, cytoplasmic edema and organelle ultrastructure alterations (mitochondrial disruption and endoplasmic reticulum edema) in proximal tubular epithelial cells. Moreover, 1D11 significantly inhibited p-PERK activation and attenuated dysregulation of unfolded protein response (UPR) pathways, endoplasmic reticulum and mitochondrial proteostasis in vivo and in vitro.The early inhibition of p-Smad2/3 signaling pathway improved acute renal function impairment, partially prevented epithelial-endothelial axis activation by maintaining PTEC proteostasis and reduced early PDGFRβ+ pericytes-derived myofibroblasts accumulation

Search for Supersymmetry in pp Collisions at root s=13 TeV in the Single-Lepton Final State Using the Sum of Masses of Large-Radius Jets

Peer reviewe

Search for the bcb_c meson in hadronic Z decays

A search for the Bc meson decaying into the channels J/psi pi+ and J/psi l nu (l = e or mu) is performed in a sample of 3.9 million hadronic Z decays collected by the ALEPH detector. This search results in the observation of 0 and 2 candidates in each of these channels, respectively, while 0.44 and 0.81 background events are expected. The following 90\% confidence level upper limits are derived: Br(Z->Bc X)/Br(Z->q q )*Br(Bc->J/psi pi+) 3.6 10^-5 Br(Z->Bc X)/Br(Z->q q )*Br(Bc->J/psi l nu) 5.2 10^-5 An additional Bc->J/psi(e+e-) mu nu candidate with very low background probability, found in an independent analysis, is also described in detail

Study of muon-pair production at centre-of-mass energies from 20 to 136 GeV with the Aleph detector

The total cross section and the forward-backward asymmetry for the process $e^+ e^- \rightarrow \mu^+ \mu^- (n \gamma)$ are measured in the energy range 20-136 GeV by reconstructing the effective centre-of-mass energy after initial state radiation. The analysis is based on the data recorded with the ALEPH detector at LEP between 1990 and 1995, corresponding to a total integrated luminosity of 143.5 $\mathrm{pb}^{-1}$. Two different approaches are used: in the first one an exclusive selection of events with hard initial state radiation in the energy range 20-88 GeV is directly compared with the Standard Model predictions showing good agreement. In the second one, all events are used to obtain a precise measurement of the energy dependence of $\sigma^0$ and $A_{\mathrm{FB}}^0$ from a model independent fit, enabling constraints to be placed on models with extra Z bosons