The Influence of Route Characteristics, Train Design and Maintenance Policy on Wheel Tread Damage, Wheel Life and Costs for Multiple-Unit Trains

In the UK, the use of similar vehicle types by a range of privatised operators gives the opportunity to assess the influence of different route conditions and maintenance practices on wheel tread damage, wheelset life and costs. This paper investigates these influences, using data obtained directly from the train operators and maintainers. By disseminating best practice it is expected that wheelset life can be improved on many fleets, with resultant cost savings

Association between clinical presentations before myocardial infarction and coronary mortality: a prospective population-based study using linked electronic records.

BACKGROUND: Ischaemia in different arterial territories before acute myocardial infarction (AMI) may influence post-AMI outcomes. No studies have evaluated prospectively collected information on ischaemia and its effect on short- and long-term coronary mortality. The objective of this study was to compare patients with and without prospectively measured ischaemic presentations before AMI in terms of infarct characteristics and coronary mortality. METHODS AND RESULTS: As part of the CALIBER programme, we linked data from primary care, hospital admissions, the national acute coronary syndrome registry and cause-specific mortality to identify patients with first AMI (n = 16,439). We analysed time from AMI to coronary mortality (n = 5283 deaths) using Cox regression (median 2.6 years follow-up), comparing patients with and without recent ischaemic presentations. Patients with ischaemic presentations in the 90 days before AMI experienced lower coronary mortality in the first 7 days after AMI compared with those with no prior ischaemic presentations, after adjusting for age, sex, smoking, diabetes, blood pressure and cardiovascular medications [HR: 0.64 (95% CI: 0.57-0.73) P < 0.001], but subsequent mortality was higher [HR: 1.42 (1.13-1.77) P = 0.001]. Patients with ischaemic presentations closer in time to AMI had the lowest seven day mortality (P-trend = 0.001). CONCLUSION: In the first large prospective study of ischaemic presentations prior to AMI, we have shown that those occurring closest to AMI are associated with lower short-term coronary mortality following AMI, which could represent a natural ischaemic preconditioning effect, observed in a clinical setting. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov identifier NCT01604486

Willingness to pay for preferred seat selection on UK domestic flights

This study employs a stated preference method to elicit and explore customer willingness to pay for airline ancillary products, specifically seat selection fees. Bivariate correlations are used to investigate linkages between passenger attributes and opinions with stated values for seat selection under a range of scenarios on UK domestic services. The sensitivity of consumers to ticket fares, for both business and non-business travel, is found to be negatively correlated with the stated willingness to pay for their preferred seat. On the other hand, customer perceptions of airline reputation and convenience of flight times is positively correlated to willingness to pay for seat selection on non-business travel. Additionally, the previous purchase of a seat selection product is strongly correlated to future willingness to pay for seat selection on both business and non-business travel. This is deemed to be the result of consumers being better able to value the benefits of their chosen seat from past experience. This research expands on the current literature regarding the growing importance of airline ancillary revenue. The results provide an evidence base for the development of revenue management and the marketing of seat selection fees as an ancillary product

Almanac 2012: interventional cardiology. The national society journals present selected research that has driven recent advances in clinical cardiology

Područje intervencijske kardiologije nastavlja se brzo razvijati. Učinkovitost perkutanih intervencija primjenom nove generacije stentova koji izlučuju lijekove znatno se povećala u zadnjih deset godina. Takvo poboljšanje učinkovitosti stentova proširilo je i indikacije na sve složenije intervencije poput perkutane koronarne intervencije (PCI) na glavnom stablu lijeve koronarne arterije ili intervencija na više koronarnih arterija. Najveći napredak i dalje je na području farmakološkog liječenja, kao npr. antiagregacijske terapije (bivalirudin, prasugrel, tikagrelor), što će još više poboljšati ishode PCI. Isto vrijedi i za intravaskularni slikovni prikaz intravaskularnim ultrazvukom i optičkom koherentnom tomografijom. Međutim, intervencijska kardiologija obuhvaća široko područje, koje uključuje i alkoholnu septalnu ablaciju kod hipertrofijske opstruktivne kardiomiopatije i slične postupke. Trenutno se najbrže razvija područje strukturalnih intervencija, osobito kod stenoze aortnog zaliska (transkateterska implantacija aortnog zaliska) i mitralne regurgitacije (“mitral clipping”). Ovaj pregledni članak prikazuje nova dostignuća na različitim područjima intervencijske kardiologije.The field of interventional cardiology continues to progress quickly. The efficacy of percutaneous interventions with newer generation drug-eluting stents has advanced a lot over the last decade. This improvement in stent performance has broadened the level of indication towards more complex interventions such as left main and multi- vessel PCI. Major improvements continue in the field of medical co-therapy such as antiplatelet therapies (bivalirudin, prasugrel, ticagrelor) and this will further improve outcomes of PCI. The same is true for intravascular imaging such as ultrasound IVUS and optical coherence tomography OCT. However, interventional cardiology has become a rather broad field, also including alcohol septal ablation for hypertrophic obstructive cardiomyopathy, etc. At the moment, the fastest growing area is the structural interventions, especially for aortic valve stenosis (transcatheter aortic valve implantation TAVI) and for mitral regurgitation (mitral clipping). This review covers recent advances in all these different fields of interventional cardiology

Almanac 2012: interventional cardiology. The national society journals present selected research that has driven recent advances in clinical cardiology

Područje intervencijske kardiologije nastavlja se brzo razvijati. Učinkovitost perkutanih intervencija primjenom nove generacije stentova koji izlučuju lijekove znatno se povećala u zadnjih deset godina. Takvo poboljšanje učinkovitosti stentova proširilo je i indikacije na sve složenije intervencije poput perkutane koronarne intervencije (PCI) na glavnom stablu lijeve koronarne arterije ili intervencija na više koronarnih arterija. Najveći napredak i dalje je na području farmakološkog liječenja, kao npr. antiagregacijske terapije (bivalirudin, prasugrel, tikagrelor), što će još više poboljšati ishode PCI. Isto vrijedi i za intravaskularni slikovni prikaz intravaskularnim ultrazvukom i optičkom koherentnom tomografijom. Međutim, intervencijska kardiologija obuhvaća široko područje, koje uključuje i alkoholnu septalnu ablaciju kod hipertrofijske opstruktivne kardiomiopatije i slične postupke. Trenutno se najbrže razvija područje strukturalnih intervencija, osobito kod stenoze aortnog zaliska (transkateterska implantacija aortnog zaliska) i mitralne regurgitacije (“mitral clipping”). Ovaj pregledni članak prikazuje nova dostignuća na različitim područjima intervencijske kardiologije.The field of interventional cardiology continues to progress quickly. The efficacy of percutaneous interventions with newer generation drug-eluting stents has advanced a lot over the last decade. This improvement in stent performance has broadened the level of indication towards more complex interventions such as left main and multi- vessel PCI. Major improvements continue in the field of medical co-therapy such as antiplatelet therapies (bivalirudin, prasugrel, ticagrelor) and this will further improve outcomes of PCI. The same is true for intravascular imaging such as ultrasound IVUS and optical coherence tomography OCT. However, interventional cardiology has become a rather broad field, also including alcohol septal ablation for hypertrophic obstructive cardiomyopathy, etc. At the moment, the fastest growing area is the structural interventions, especially for aortic valve stenosis (transcatheter aortic valve implantation TAVI) and for mitral regurgitation (mitral clipping). This review covers recent advances in all these different fields of interventional cardiology

Almanac 2011: acute coronary syndromes. The national society journals present selected research that has driven recent advances in clinical cardiology.

Ovaj pregledni članak ističe najnovija dostignuća u epidemiologiji, dijagnozi, stratifikaciji rizika i liječenju akutnog koronarnog sindroma (AKS). Sama količina novih studija odražava robusno stanje globalnog kardiovaskularnog istraživanja, a cilj je prikazati rezultate koji su od interesa za kliničku praksu kardiologa. Učestalost i stope smrtnosti infarkta miokarda (IM) se smanjuju, što je vjerojatno posljedica promjena životnog stila, naročito prestanka pušenja, i poboljšanja farmakološkog i intervencijskog liječenja. Troponini i dalje ostaju u ključni za postavljanje dijagnoze, a novi testovi visoke osjetljivosti dodatno snižavaju pragove detekcije i poboljšavaju ishode. Dodatna dijagnostička vrijednost ostalih cirkulirajućih biomarkera ostaje nejasna, a za stratifikaciju rizika pokazali su se korisnim jednostavni klinički algoritmi, poput GRACE ljestice. Primarna perkutana koronarna intervencija (PCI) s minimalnom odgodom liječenja predstavlja najučinkovitiju strategiju reperfuzije kod akutnog infarkta miokarda s ST elevacijom (STEMI). Radijalni pristup je povezan s manjom učestalosti krvarenja od femoralnog pristupa, no ishodi se čine identičnima. Manualna trombektomija ograničava distalnu embolizaciju i veličinu infarkta, dok stentovi koji luče lijek smanjuju potrebu za daljnjim postupcima revaskularizacije. Lezije koje nisu vodeće se najbolje rješavaju elektivno, kao dogovorni postupak, po učinjenoj primarnoj PCI. Razvoj antitrombotskih i antiagregacijskih lijekova za primjenu kod primarne PCI se i dalje nastavlja, uz nove indikacije za fondaparinuks i bivalirudin te inhibitore glikoproteina IIb/IIIa. Ako primarna PCI nije dostupna na vrijeme, fibrinolitičko liječenje preostaje kao opcija, no strategija rane angiografske procjene preporuča se za sve pacijente. Infarkt miokarda bez elevacije ST segmenta (NSTEMI) je sada dominantan fenotip i ishodi nakon akutne faze su znatno lošiji nego za STEMI. Mnogi pacijenti s NSTEMI ostaju suboptimalno liječeni te postoji mnogo novih članaka koji pokušavaju definirati najučinkovitiju antitrombotsku i antiagregacionu terapiju za ovu skupinu pacijenata. Koristi od ranog invazivnog liječenja za većinu pacijenata nisu sporne, no optimalno vrijeme zahvata i dalje ostaje neriješeno. Kardiološka rehabilitacija se preporuča kod svih pacijenata s akutnim IM, no učestalost uključivanja u program je i dalje razočaravajuća. Kućni programi su učinkoviti i mogu biti prihvatljiviji za mnoge pacijente. Dokazi za korist od promjene životnog stila i farmakoterapije za sekundarnu prevenciju su i dalje prisutni, dok je argumente za suplemente s omega-3 masnim kiselinama, nakon nedavnih negativnih studija, sada teško održati. Implantibilni kardioverter-defibrilatori štite pacijente s teškom formom IM od iznenadne smrti, no za primarnu prevenciju bi trebali biti temeljeni na mjerenjima ejekcijske frakcije lijeve klijetke kasnije (oko 40 dana) nakon početne kliničke slike, budući da njihova ranija implementacija ne pokazuje dobrobit u smanjenju smrtnosti.This overview highlights some recent advances in the epidemiology, diagnosis, risk stratification and treatment of acute coronary syndromes. The sheer volume of new studies reflects the robust state of global cardiovascular research but the focus here is on findings that are of most interest to the practising cardiologist. Incidence and mortality rates for myocardial infarction are in decline, probably owing to a combination of lifestyle changes, particularly smoking cessation, and improved pharmacological and interventional treatment. Troponins remain central for diagnosis and new high-sensitivity assays are further lowering detection thresholds and improving outcomes. The incremental diagnostic value of other circulating biomarkers remains unclear and for risk stratification simple clinical algorithms such as the GRACE score have proved more useful. Primary percutaneous coronary intervention (PCI) with minimal treatment delay is the most effective reperfusion strategy in ST elevation myocardial infarction (STEMI). Radial access is associated with less bleeding than with the femoral approach, but outcomes appear similar. Manual thrombectomy limits distal embolisation and infarct size while drug-eluting stents reduce the need for further revascularisation procedures. Non-culprit disease is best dealt with electively as a staged procedure after primary PCI has been completed. The development of antithrombotic and antiplatelet regimens for primary PCI continues to evolve, with new indications for fondaparinux and bivalirudin as well as small-molecule glycoprotein (GP)IIb/IIIa inhibitors. If timely primary PCI is unavailable, fibrinolytic treatment remains an option but a strategy of early angiographic assessment is recommended for all patients. Non-ST segment elevation myocardial infarction (NSTEMI) is now the dominant phenotype and outcomes after the acute phase are significantly worse than for STEMI. Many patients with NSTEMI remain undertreated and there is a large body of recent work seeking to define the most effective antithrombotic and antiplatelet regimens for this group of patients. The benefits of early invasive treatment for most patients are not in dispute but optimal timing remains unresolved. Cardiac rehabilitation is recommended for all patients with acute myocardial infarction but take-up rates are disappointing. Home-based programmes are effective and may be more acceptable for many patients. Evidence for the benefits of lifestyle modification and pharmacotherapy for secondary prevention continues to accumulate but the argument for omega-3 fatty acid supplements is now hard to sustain following recent negative trials. Implantable cardioverter-defibrillators for patients with severe myocardial infarction protect against sudden death but for primary prevention should be based on left ventricular ejection fraction measurements late (around 40 days) after presentation, earlier deployment showing no mortality benefit

Macrophage transactivation for chemokine production identified as a negative regulator of granulomatous inflammation using agent-based modeling

Cellular activation in trans by interferons, cytokines and chemokines is a commonly recognized mechanism to amplify immune effector function and limit pathogen spread. However, an optimal host response also requires that collateral damage associated with inflammation is limited. This may be particularly so in the case of granulomatous inflammation, where an excessive number and / or excessively florid granulomas can have significant pathological consequences. Here, we have combined transcriptomics, agent-based modeling and in vivo experimental approaches to study constraints on hepatic granuloma formation in a murine model of experimental leishmaniasis. We demonstrate that chemokine production by non-infected Kupffer cells in the Leishmania donovani-infected liver promotes competition with infected KCs for available iNKT cells, ultimately inhibiting the extent of granulomatous inflammation. We propose trans-activation for chemokine production as a novel broadly applicable mechanism that may operate early in infection to limit excessive focal inflammation