Tolerogenic vaccines for Multiple Sclerosis

Tolerogenic vaccines represent a new class of vaccine designed to re-establish immunological tolerance, restore immune homeostasis, and thereby reverse autoimmune disease. Tolerogenic vaccines induce long-term, antigen-specific, inhibitory memory that blocks pathogenic T cell responses via loss of effector T cells and gain of regulatory T cell function. Substantial advances have been realized in the generation of tolerogenic vaccines that inhibit experimental autoimmune encephalomyelitis in a preclinical setting, and these vaccines may be a prequel of the tolerogenic vaccines that may have therapeutic benefit in Multiple Sclerosis. The purpose here is to provide a snapshot of the current concepts and future prospects of tolerogenic vaccination for Multiple Sclerosis, along with the central challenges to clinical application

Validation of an experimental setup to study atmospheric heterogeneous ozonolysis of semi-volatile organic compounds

International audienceThere is currently a need for reliable experimental procedures to follow the heterogeneous processing simulating the atmospheric conditions. This work offers an alternative experimental device to study the behaviour of semi-volatile organic compounds (SVOC) that presumably exhibit extremely slow reactivity (e.g. pesticides) towards the atmospheric oxidants such as ozone and OH. Naphthalene was chosen as a test compound since it was widely studied in the past and hence represents a good reference. Prior to ozone exposure, the gaseous naphthalene was adsorbed via gas-solid equilibrium on silica and XAD-4 particles. Then, the heterogeneous reaction of ozone with adsorbed naphthalene was investigated in specially designed flow tube reactors. After the reaction, the remaining naphthalene (adsorbed on particles surface) was extracted, filtered and analyzed by Gas Chromatography-Flame Ionization Detector (GC-FID). Thus, the kinetics results were obtained following the consumption of naphthalene. Using this procedure, the rate constants of heterogeneous ozonolysis of naphthalene (kO3 silica=2.26 (±0.09)×10−17 cm3 molec−1 s−1 and kO3 XAD-4=4.29 (±1.06)×10−19 cm3 molec−1 s−1) were determined for silica and XAD-4 particles, at 25°C and relative humidity <0.7%. The results show that the nature of the particles significantly affects the kinetics and that heterogeneous ozonolysis of naphthalene is faster than its homogeneous ozonolysis in the gas phase

Accuracy of nature of call screening tool in identifying patients requiring treatment for out of hospital cardiac arrest

BackgroundA new pre-triage screening tool, Nature of Call (NoC), has been introduced into the telephone triage system of UK ambulance services which employ National Health Service Pathways (NHSP). Its function is to provide rapid recognition of patients who may need immediate ambulance dispatch for out-of-hospital cardiac arrest (OHCA) and withholding dispatch for other calls while further triage is undertaken. In this study, we evaluated the accuracy of NoC and NHSP in identifying patients with potentially treatable or imminent OHCA.MethodsThis retrospective, observational study reviewed consecutive calls to a UK ambulance service between October 2016 and February 2017 in which NOC, and then NHSP were applied sequentially. Only those calls for which a corresponding electronic Patient Clinical Record was available were included. Sensitivity and specificity of NOC and NHSP for recognition of an OHCA were determined by comparing allocated priority dispositions with an OHCA Treatment Registry (OHCATR).ResultsOf 96 423 calls received, 71 373 were reviewed. For 590 (0.8%) of these calls, the patients received treatment for OHCA. NOC identified 458 OHCATR patients; NHSP identified 467; together they identified 496. NoC captured 29 patients not identified by NHSP; NHSP captured 38 patients not identified by NOC. For NOC sensitivity was 77.6% (95% CI 74.1 to 80.8) and specificity 86.9% (95% CI 86.6 to 87.1). NHSP sensitivity was 79.2% (95% CI 75.7 to 82.2) and specificity 93.4% (95% CI 93.2 to 93.6). NoC and NHSP combined had a sensitivity of 84.1% (95% CI 80.9 to 86.8) and specificity of 85.3% (95% CI 85.1 to 85.6).ConclusionsNoC and NHSP call categorisation each achieved similar sensitivity for the identification of OHCATR, identifying most of the same patients, but each captured unique patients. Using both methods sequentially improved accuracy. The 16% of OHCATR patients not identified by either method present a challenge to ambulance dispatch systems.</jats:sec

PP12 New ‘nature of call’ telephone screening tool, employed prior to nhs pathways triage, can accurately identify those later treated for out of hospital cardiac arrest: analysis of sensitivity and specificity using routine ambulance service data

BackgroundA new pre-triage emergency medical call screening tool, Nature of Call (NoC), has been introduced into UK ambulance services which employ the NHS Pathways (NHSP) triage system. Its current function is to provide a rapid sieve, differentiating between patients who may need treatment for Out-of-Hospital Cardiac Arrest (OHCA), and therefore require immediate ambulance dispatch, and all other calls, for which ambulance dispatch is withheld whilst further triage is undertaken.ObjectiveTo evaluate the accuracy of NoC in identifying patients with potentially treatable OHCA or peri-arrest conditions.MethodsStudy of diagnostic accuracy. The sample was a retrospective cohort of consecutive calls to a UK ambulance service, taken over a four-month period. Sensitivity and specificity were determined, comparing allocated priority dispositions with an OHCA Treatment Registry. Context was supplied by the evaluation of subsequent categorisation by NHSP. The accuracy of the combined NoC and NHSP allocations was also investigated.ResultsA total of 1 87 419 emergency calls were received. Of these, 71 373 were allocated both NoC and NHSP priority dispositions and were associated with electronic Patient Clinical Records. 590 (0.8%) of these patients received treatment for OHCA. NoC, sensitivity=77.6% (95% CI 74.1 to 80.8); specificity=86.9% (95% CI 86.6 to 87.1). NHSP, sensitivity=79.2% (95% CI 75.7 to 82.2); specificity=93.4% (93.2 to 93.6). NoC and NHSP combined, sensitivity=84.1% (95% CI 80.9 to 86.8); specificity=95.0% (95% CI 94.8 to 95.3).ConclusionsNoC and subsequent NHSP call categorisation each achieved relatively high sensitivity for the identification of treated OHCA, predicting similar groups of registry patients (although 6% were identified by NoC alone). Overall accuracy was enhanced when NoC and subsequent NHSP Results were combined. The unidentified group of treated OHCA patients (16%) present a challenge to the current dispatch system which relies on the early recognition of patients who may require treatment for OHCA.</jats:sec

PP13 The NHS pathways (NHSP) medical call triage system and new ‘nature of call’ telephone screening tool, employed prior to NHSP, can accurately identify high acuity patients: analysis of sensitivity and specificity using routine ambulance service data

BackgroundThe NHS Pathways (NHSP) medical call triage system is employed by UK ambulance services. One function is to identify a broad category of ‘high-acuity calls’, distinguishing them from those that do not require an emergency response. A new pre-triage screening tool, Nature of Call (NoC), designed to augment NHSP could be employed as a rapid initial sieve of broad acuity.ObjectivesTo identify the accuracy of NHSP (and NoC) in recognising patients who require an emergency ambulance response (and therefore those who may not).MethodsDiagnostic accuracy. The sample is a retrospective cohort of consecutive calls, over a 4 month period, to a UK ambulance service. Sensitivity and specificity were determined, comparing allocated NoC and NHS Pathways priority dispositions with a composite reference standard comprised of administered medications, procedures, observations and clinical impressions associated with high-acuity, as recorded on ambulance electronic Patient Clinical Records.ResultsA total of 1 87 408 emergency calls were received. Of these, 71 373 were allocated both NoC and NHSP priority dispositions and were associated with electronic Patient Clinical Records. 40 997 (57%) of these patients met the high-acuity reference criteria. NHSP, sensitivity=98.1% (95% CI 98.0 to 98.2); specificity=5.9% (95% CI 5.6 to 6.1). NoC, sensitivity=84.0% (95% CI 83.7 to 84.4); specificity=26.5% (95% CI 26.0 to 27.0).ConclusionsNHSP is effective in identifying high-acuity patients (as is NoC). Sensitivity analysis therefore supports the this function of NHSP and NoC/NHSP to inform initial ambulance dispatch decisions, particularly if NoC categorisation is reviewed in the light of subsequent NHSP triage. However, both systems appear to achieve high sensitivity by also allocating most low-acuity calls to high-acuity categories. This significantly restricts operational application. Only one quarter of low-acuity calls are allocated the lowest priority category by NoC and one-in-seventeen by NHSP, severely restricting the group likely to be considered for alternative care pathways.</jats:sec

LSD1-mediated enhancer silencing attenuates retinoic acid signalling during pancreatic endocrine cell development.

Developmental progression depends on temporally defined changes in gene expression mediated by transient exposure of lineage intermediates to signals in the progenitor niche. To determine whether cell-intrinsic epigenetic mechanisms contribute to signal-induced transcriptional responses, here we manipulate the signalling environment and activity of the histone demethylase LSD1 during differentiation of hESC-gut tube intermediates into pancreatic endocrine cells. We identify a transient requirement for LSD1 in endocrine cell differentiation spanning a short time-window early in pancreas development, a phenotype we reproduced in mice. Examination of enhancer and transcriptome landscapes revealed that LSD1 silences transiently active retinoic acid (RA)-induced enhancers and their target genes. Furthermore, prolonged RA exposure phenocopies LSD1 inhibition, suggesting that LSD1 regulates endocrine cell differentiation by limiting the duration of RA signalling. Our findings identify LSD1-mediated enhancer silencing as a cell-intrinsic epigenetic feedback mechanism by which the duration of the transcriptional response to a developmental signal is limited

Model efekata radijacijskog prijenosa topline u graničnom sloju atmosfere

During nighttime clear-sky conditions and in the absence of significant advection the influence of divergence of net longwave radiative flux on thermodynamic processes could be dominant in the atmospheric boundary layer. The model which parameterizes such processes by height (35 grid points up to 2000 m) is accomplished based on the emissivity concept. The test of the model is performed on the Wangara experiment data. The results are analyzed and discussed concerning a complex structure of the total cooling rate, especially in the lower part of the nocturnal boundary layer (region of smaller wind speeds)

Grasping the dialogical nature of acculturation

In this interesting article, Andreouli (2013). Identity and acculturation: The case of naturalised citizens in Britain. Culture & Psychology, 19, 1–47) presents a dialogical perspective on acculturation. To support this perspective, the author integrates the Dialogical Self Theory and the Social Representations Theory. Drawing on her theoretical explanation, we develop a conceptual review focused on two pairs of constructs – social representations/I-positions and polyphasia/polyphonia. Andreouli’s empirical study allowed her to operationalize some critiques about the two-dimensional perspective and its strategies on acculturation. Nevertheless, it seems that the author ends up replicating a more conventional and dual way of thinking. Their results give us privileged access to the negotiation of meanings and activation of promoter signs or, in other words, to the dialogical dynamics between I-positions. In this respect, we suggest that the assumption of a more dialogic and semiotic lens could be an interesting further development to this study