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

The Power of Action Plots: Unveiling Reaction Selectivity of Light‐Stabilized Dynamic Covalent Chemistry

Exploiting the optimum wavelength of reactivity for efficient photochemical reactions has been well-established based on the development of photochemical action plots. We herein demonstrate the power of such action plots by a remarkable example of the wavelength-resolved photochemistry of two triazolinedione (TAD) substrates, i.e., aliphatic and aromatic substituted, that exhibit near identical absorption spectra yet possess vastly disparate photoreactivity. We present our findings in carefully recorded action plots, from which reaction selectivity is identified. The profound difference in photoreactivity is exploited by designing a ‘hybrid’ bisfunctional TAD molecule, enabling the formation of a dual-gated reaction manifold that demonstrates the exceptional and site-selective (photo)chemical behavior of both TAD substrates within a single small molecule

Revisiting the effects of organized mammography programs on inequalities in breast screening uptake : a multilevel analysis of nationwide data from 1997 to 2017

This study revisits the effects of mammography screening programs on inequalities in breast screening uptake in Switzerland. The progressive introduction of regional mammography programs by 12 out of the 26 Swiss cantons (regions) since 1999 offers an opportunity to perform an ecological quasi-experimental study. We examine absolute income and marital status inequalities in mammography uptake, and whether the cantons' implementation of mammography programs moderate these inequalities, as previous research has devoted little attention to this. We use five waves of the Swiss Health Interview Survey covering the 1997–2017 period and comprising data on 14,267 women aged 50–70. Both up-to-date and ever-screening outcomes are analyzed with multilevel models which assess the mammography programs' within-canton effect. Findings show that higher income women and married women (compared to unmarried women) had significantly higher mammography uptake probabilities. Mammography programs did not moderate absolute income differences in up-to-date screening; however, they were associated with smaller absolute income differences in ever-screening uptake. Mammography programs related to higher screening uptake for married women, more than for unmarried women. In conclusion, we showed absolute income inequalities in mammography uptake which were not revealed by previous studies using relative inequality measures. Mammography programs may have contributed to reducing income inequalities in ever-screening, yet this was not observed for up-to-date screening. This study has implication for preventive health interventions—e.g., cancer screening promotion should pay attention to women's marital status since screening programs may widen the screening gap between married and unmarried women

Total Directional Variation for Video Denoising

In this paper, we propose a variational approach for video denoising, based on a total directional variation (TDV) regulariser proposed in Parisotto et al. (2018), for image denoising and interpolation. In the TDV regulariser, the underlying image structure is encoded by means of weighted derivatives so as to enhance the anisotropic structures in images, e.g. stripes or curves with a dominant local directionality. For the extension of TDV to video denoising, the space-time structure is captured by the volumetric structure tensor guiding the smoothing process. We discuss this and present our whole video denoising work-flow. Our numerical results are compared with some state-of-the-art video denoising methods.SP acknowledges UK EPSRC grant EP/L016516/1 for the CCA DTC. CBS acknowledges support from Leverhulme Trust project on Breaking the non-convexity barrier, EPSRC grant Nr. EP/M00483X/1, the EPSRC Centre EP/N014588/1, the RISE projects CHiPS and NoMADS, the CCIMI and the Alan Turing Institute

SOWL QL: Querying Spatio - Temporal Ontologies in OWL

We introduce SOWL QL, a query language for spatio-temporal information in ontologies. Buildingupon SOWL (Spatio-Temporal OWL), an ontology for handling spatio-temporal information in OWL, SOWL QL supports querying over qualitative spatio-temporal information (expressed using natural language expressions such as “before”, “after”, “north of”, “south of”) rather than merely quantitative information (exact dates, times, locations). SOWL QL extends SPARQL with a powerful set of temporal and spatial operators, including temporal Allen topological, spatial directional and topological operations or combinations of the above. SOWL QL maintains simplicity of expression and also, upward and downward compatibility with SPARQL. Query translation in SOWL QL yields SPARQL queries implying that, querying spatio-temporal ontologies using SPARQL is still feasible but suffers from several drawbacks the most important of them being that, queries in SPARQL become particularly complicated and users must be familiar with the underlying spatio-temporal representation (the “N-ary relations” or the “4D-fluents” approach in this work). Finally, querying in SOWL QL is supported by the SOWL reasoner which is not part of the standard SPARQL translation. The run-time performance of SOWL QL has been assessed experimentally in a real data setting. A critical analysis of its performance is also presented

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

Advances in ab-initio theory of Multiferroics. Materials and mechanisms: modelling and understanding

Within the broad class of multiferroics (compounds showing a coexistence of magnetism and ferroelectricity), we focus on the subclass of "improper electronic ferroelectrics", i.e. correlated materials where electronic degrees of freedom (such as spin, charge or orbital) drive ferroelectricity. In particular, in spin-induced ferroelectrics, there is not only a {\em coexistence} of the two intriguing magnetic and dipolar orders; rather, there is such an intimate link that one drives the other, suggesting a giant magnetoelectric coupling. Via first-principles approaches based on density functional theory, we review the microscopic mechanisms at the basis of multiferroicity in several compounds, ranging from transition metal oxides to organic multiferroics (MFs) to organic-inorganic hybrids (i.e. metal-organic frameworks, MOFs)Comment: 22 pages, 9 figure

The interaction of bacterial pathogens with platelets.

In recent years, the frequency of serious cardiovascular infections such as endocarditis has increased, particularly in association with nosocomially acquired antibiotic-resistant pathogens. Growing evidence suggests a crucial role for the interaction of bacteria with human platelets in the pathogenesis of cardiovascular infections. Here, we review the nature of the interactions between platelets and bacteria, and the role of these interactions in the pathogenesis of endocarditis and other cardiovascular diseases

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