Development and validation of the first high performance-lateral flow immunoassay (HP-LFIA) for the rapid screening of domoic acid from shellfish extracts

A lateral flow immunoassay (LFIA) has been developed and fully validated to detect the primary amnesic shellfish poisoning (ASP) toxin, domoic acid (DA). The performance characteristics of two versions of the test were investigated using spiked and naturally contaminated shellfish (mussels, scallops, oysters, clams, and cockles). The tests provide a qualitative result, to indicate the absence or presence of DA in extracts of shellfish tissues, at concentrations that are relevant to regulatory limits. The new rapid assay (LFIA version 2) was designed to overcome the performance limitations identified in the first version of the assay. The improved test uses an electronic reader to remove the subjective nature of the generated results, and the positive cut-off for screening of DA in shellfish was increased from 10 ppm (version 1) to 17.5 ppm (version 2). A simple extraction and test procedure was employed, which required minimal equipment and materials; results were available 15 min after sample preparation. Stability of the aqueous extracts at room temperature (22 C) at four time points (up to 245 min after extraction) and across a range of DA concentrations was 100.3±1.3% and 98.8±2.4% for pre- and post-buffered extracts, respectively. The assay can be used both within laboratory settings and in remote locations. The accuracy of the new assay, to indicate negative results at or below 10 ppm DA, and positive results at or above 17.5 ppm, was 99.5% (n=216 tests). Validation data were obtained from a 2-day, randomised, blind study consisting of multiple LFIA lots (n=3), readers (n=3) and operators (n=3), carrying out multiple extractions of mussel tissue (n=3) at each concentration (0, 10, 17.5, and 20 ppm). No matrix effects were observed on the performance of the assay with different species (mussels, scallops, oysters, clams, and cockles). There was no impact on accuracy or interference from other phycotoxins, glutamic acid or glutamine with various strip incubations (8, 10, and 12 min). The accuracy of the assay, using naturally contaminated samples to indicate negative results at or below 12.5 ppm and positive results at or above 17.5 ppm, was 100%. Variability between three LFIA lots across a range of DA concentrations, expressed as coefficient of variation (% CV), was 1.1±0.4% (n=2 days) based on quantitative readings from the electronic reader. During an 8 week stability study, accuracy of the method with test strips stored at various temperatures (6, 22, 37 and 50 C) was 100%. Validation for both versions included comparisons with results obtained using reference LC-UV methods. © 2013 Elsevier B.V.

Multi-Dimensional Deprivation in Ireland Among 9-Year-Olds in Ireland:An Analysis of the Growing Up in Ireland Survey’

In this paper we make use of the 9-year old wave of the Growing Up in Ireland study to analyse multidimensional deprivation in Ireland. The Alkire and Foster adjusted head count ratio approach (AHCR; 2007, 2011a, 2011b) applied here constitutes a significant improvement on union and intersection approaches and allows for the decomposition of multidimensional poverty in terms of dimensions and sub-groups. The approach involves a censoring of data such that deprivations count only for those above the specified multidimensional threshold leading to a stronger set of interrelationships between deprivation dimensions. Our analysis shows that the composition of the adjusted head ratio is influenced by a range of socio-economic factors. For less-favoured socio-economic groups dimensions relating to material deprivation are disproportionately represented while for the more advantaged groups, those relating to behavioral and emotional issues and social interaction play a greater role. Notwithstanding such variation in composition, our analysis showed that the AHCR varied systematically across categories of household type, and the social class, education and age group of the primary care giver. Furthermore, these variables combined in a cumulative manner. The most systematic variation was in relation to the head count of those above the multidimensional threshold rather than intensity, conditional on being above that cut-off point. Without seeking to arbitrate on the relative value of composite indices versus disaggregated profiles, our analysis demonstrates that there is much to be gained from adopting an approach with clearly understood axiomatic properties. Doing so allows one to evaluate the consequences of the measurement strategy employed for the understanding of levels of multidimensional deprivation, the nature of such deprivation profiles and socio-economic risk patterns. Ultimately it permits an informed assessment of the strengths and weaknesses of the particular choices made.

Holocene floodplain palaeoecology of the Humberhead Levels; implications for regional wetland development

The acquisition of high quality, well-dated local site records is essential for progressing regional environmental reconstructions. As part of a wider study designed to examine intra- and extra- site ecosystem responses to environmental change, this paper presents new palaeoecological data from the floodplain of the River Torne in the Humberhead Levels, South Yorkshire. The sampling site lies adjacent to the lowland raised mire of Hatfield Moors, a location with a long history of palaeoecological investigations. The potential of using floodplain records to reconstruct local variations in ecosystem response to environmental change is also considered. Coleoptera and pollen are used to reconstruct floodplain ecosystem dynamics, whilst chronologies are established using Bayesian age–depth modelling. Between 10,200 cal BP and 2300 cal BP, the floodplain experienced multiple phases of ecological change. At 10,200–9910 cal BP, a cut-off channel began to infill with peat, while the surrounding floodplain remained relatively dry with Pinus forest growing nearby. Between 9630–9500 cal BP and 7270–7020 cal BP, a depositional hiatus occurred in the sedimentary record. By the end of this period, the local woodland had diversified and expanded to mixed deciduous tree cover. A wet shift identified at 6870–6160 cal BP was shortly followed by a rise in Alnus and Tilia from 6410–6160 cal BP. At this time, widespread floodplain paludification had occurred in the Humberhead Levels, which was largely controlled by relative sea-level (RSL) rise and the associated rise in regional water tables. Floodplain expansion also resulted in the widespread occurrence of Alnus dominated fen woodland. The local Torne floodplain experienced varying levels of wetness that influenced the decline and subsequent regeneration of the woodland from 5870–5640 cal BP. At this time, the Ulmus decline is identified in the pollen stratigraphic record. Floodplain hydrology appears to have been controlled by a combination of water table fluctuations and changes in channel pattern/flow, both of which can be linked to RSL variations recorded in the Humber Estuary. Floodplain alluviation, also linked to rising water tables, is dated to 4360–4160 cal BP. Anthropogenic woodland clearance further upstream may have further compounded this event.

The influence of the magnetic field on running penumbral waves in the solar chromosphere

We use images of high spatial and temporal resolution, obtained using both ground- and space-based instrumentation, to investigate the role magnetic field inclination angles play in the propagation characteristics of running penumbral waves in the solar chromosphere. Analysis of a near-circular sunspot, close to the center of the solar disk, reveals a smooth rise in oscillatory period as a function of distance from the umbral barycenter. However, in one directional quadrant, corresponding to the north direction, a pronounced kink in the period-distance diagram is found. Utilizing a combination of the inversion of magnetic Stokes vectors and force-free field extrapolations, we attribute this behavior to the cut-off frequency imposed by the magnetic field geometry in this location. A rapid, localized inclination of the magnetic field lines in the north direction results in a faster increase in the dominant periodicity due to an accelerated reduction in the cut-off frequency. For the first time, we reveal how the spatial distribution of dominant wave periods, obtained with one of the highest resolution solar instruments currently available, directly reflects the magnetic geometry of the underlying sunspot, thus opening up a wealth of possibilities in future magnetohydrodynamic seismology studies. In addition, the intrinsic relationships we find between the underlying magnetic field geometries connecting the photosphere to the chromosphere, and the characteristics of running penumbral waves observed in the upper chromosphere, directly supports the interpretation that running penumbral wave phenomena are the chromospheric signature of upwardly propagating magneto-acoustic waves generated in the photosphere.

Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States

Objective: To investigate the association between serum 25-hydroxyvitamin D concentrations (25(OH)D) and mortality in a large consortium of cohort studies paying particular attention to potential age, sex, season, and country differences.

Design: Meta-analysis of individual participant data of eight prospective cohort studies from Europe and the US.

Setting: General population.

Participants: 26 018 men and women aged 50-79 years

Main outcome measures: All-cause, cardiovascular, and cancer mortality.

Results: 25(OH)D concentrations varied strongly by season (higher in summer), country (higher in US and northern Europe) and sex (higher in men), but no consistent trend with age was observed. During follow-up, 6695 study participants died, among whom 2624 died of cardiovascular diseases and 2227 died of cancer. For each cohort and analysis, 25(OH)D quintiles were defined with cohort and subgroup specific cut-off values. Comparing bottom versus top quintiles resulted in a pooled risk ratio of 1.57 (95% CI 1.36 to 1.81) for all-cause mortality. Risk ratios for cardiovascular mortality were similar in magnitude to that for all-cause mortality in subjects both with and without a history of cardiovascular disease at baseline. With respect to cancer mortality, an association was only observed among subjects with a history of cancer (risk ratio, 1.70 (1.00 to 2.88)). Analyses using all quintiles suggest curvilinear, inverse, dose-response curves for the aforementioned relationships. No strong age, sex, season, or country specific differences were detected. Heterogeneity was low in most meta-analyses.

Conclusions: Despite levels of 25(OH)D strongly varying with country, sex, and season, the association between 25(OH)D level and all-cause and cause-specific mortality was remarkably consistent. Results from a long term randomised controlled trial addressing longevity are being awaited before vitamin D supplementation can be recommended in most individuals with low 25(OH)D levels.

Flawed Premises and Unexpected Consequences: Support of Regional Languages in Europe:Support of Regional Languages in Europe

This article discusses the relationship between three language communities in Europe with variant levels of official recognition, namely Kashub, Sorb, and Silesian, and the institutions of their host states as regards their respective use, promotion, and revital-ization. Most language communities across the world campaign for recognition within a geographic/political region, or on the basis of a historic/group identity to ensure their language's use and status. The examples discussed here illustrate that language recognition and policies resulting therefrom and promoting official monolin-gualism strengthen the symbolic status of the language but contribute little to the functionality of language communities outside the area. As this article illustrates, in increasingly multilingual societies, language policies cut off its speakers from the political, economic, and social opportunities accessible through the medium of languages that lack official recognition locally. © 2014 Taylor & Francis Group, LLC.

Monte Carlo calculations of quantum yield in inhomogeneous PtSi/p-Si Schottky barriers

Monte Carlo calculations of quantum yield in PtSi/p-Si infrared detectors are carried out taking into account the presence of a spatially distributed barrier potential. In the 1-4 mu m wavelength range it is found that the spatial inhomogeneity of the barrier has no significant effect on the overall device photoresponse. However, above lambda = 4.0 mu m and particularly as the cut-off wavelength (lambda approximate to 5.5 mu m) is approached, these calculations reveal a difference between the homogeneous and inhomogeneous barrier photoresponse which becomes increasingly significant and exceeds 50% at lambda = 5.3 mu m. It is, in fact, the inhomogeneous barrier which displays an increased photoyield, a feature that is confirmed by approximate analytical calculations assuming a symmetric Gaussian spatial distribution of the barrier. Furthermore, the importance of the silicide layer thickness in optimizing device efficiency is underlined as a trade-off between maximizing light absorption in the silicide layer and optimizing the internal yield. The results presented here address important features which determine the photoyield of PtSi/Si Schottky diodes at energies below the Si absorption edge and just above the Schottky barrier height in particular.

Optical coherence tomography (OCT) for detection of macular oedema in patients with diabetic retinopathy

Background

Diabetic macular oedema (DMO) is a thickening of the central retina, or the macula, and is associated with long-term visual loss in people with diabetic retinopathy (DR). Clinically significant macular oedema (CSMO) is the most severe form of DMO. Almost 30 years ago, the Early Treatment Diabetic Retinopathy Study (ETDRS) found that CSMO, diagnosed by means of stereoscopic fundus photography, leads to moderate visual loss in one of four people within three years. It also showed that grid or focal laser photocoagulation to the macula halves this risk. Recently, intravitreal injection of antiangiogenic drugs has also been used to try to improve vision in people with macular oedema due to DR.Optical coherence tomography (OCT) is based on optical reflectivity and is able to image retinal thickness and structure producing cross-sectional and three-dimensional images of the central retina. It is widely used because it provides objective and quantitative assessment of macular oedema, unlike the subjectivity of fundus biomicroscopic assessment which is routinely used by ophthalmologists instead of photography. Optical coherence tomography is also used for quantitative follow-up of the effects of treatment of CSMO.

Objectives

To determine the diagnostic accuracy of OCT for detecting DMO and CSMO, defined according to ETDRS in 1985, in patients referred to ophthalmologists after DR is detected. In the update of this review we also aimed to assess whether OCT might be considered the new reference standard for detecting DMO.

Search methods

We searched the Cochrane Database of Systematic Reviews (CDSR), the Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment Database (HTA) and the NHS Economic Evaluation Database (NHSEED) (The Cochrane Library 2013, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2013), EMBASE (January 1950 to June 2013), Web of Science Conference Proceedings Citation Index - Science (CPCI-S) (January 1990 to June 2013), BIOSIS Previews (January 1969 to June 2013), MEDION and the Aggressive Research Intelligence Facility database (ARIF). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 25 June 2013. We checked bibliographies of relevant studies for additional references.

Selection Criteria

We selected studies that assessed the diagnostic accuracy of any OCT model for detecting DMO or CSMO in patients with DR who were referred to eye clinics. Diabetic macular oedema and CSMO were diagnosed by means of fundus biomicroscopy by ophthalmologists or stereophotography by ophthalmologists or other trained personnel.

Data collection and analysis

Three authors independently extracted data on study characteristics and measures of accuracy. We assessed data using random-effects hierarchical sROC meta-analysis models.

Main results

We included 10 studies (830 participants, 1387 eyes), published between 1998 and 2012. Prevalence of CSMO was 19% to 65% (median 50%) in nine studies with CSMO as the target condition. Study quality was often unclear or at high risk of bias for QUADAS 2 items, specifically regarding study population selection and the exclusion of participants with poor quality images. Applicablity was unclear in all studies since professionals referring patients and results of prior testing were not reported. There was a specific 'unit of analysis' issue because both eyes of the majority of participants were included in the analyses as if they were independent.In nine studies providing data on CSMO (759 participants, 1303 eyes), pooled sensitivity was 0.78 (95% confidence interval (CI) 0.72 to 0.83) and specificity was 0.86 (95% CI 0.76 to 0.93). The median central retinal thickness cut-off we selected for data extraction was 250 µm (range 230 µm to 300 µm). Central CSMO was the target condition in all but two studies and thus our results cannot be applied to non-central CSMO.Data from three studies reporting accuracy for detection of DMO (180 participants, 343 eyes) were not pooled. Sensitivities and specificities were about 0.80 in two studies and were both 1.00 in the third study.Since this review was conceived, the role of OCT has changed and has become a key ingredient of decision-making at all levels of ophthalmic care in this field. Moreover, disagreements between OCT and fundus examination are informative, especially false positives which are referred to as subclinical DMO and are at higher risk of developing clinical CSMO.

Authors' conclusions

Using retinal thickness thresholds lower than 300 µm and ophthalmologist's fundus assessment as reference standard, central retinal thickness measured with OCT was not sufficiently accurate to diagnose the central type of CSMO in patients with DR referred to retina clinics. However, at least OCT false positives are generally cases of subclinical DMO that cannot be detected clinically but still suffer from increased risk of disease progression. Therefore, the increasing availability of OCT devices, together with their precision and the ability to inform on retinal layer structure, now make OCT widely recognised as the new reference standard for assessment of DMO, even in some screening settings. Thus, this review will not be updated further.

Clinical and Cost-Effectiveness of Procalcitonin Test for Prodromal Meningococcal Disease-A Meta-Analysis

BACKGROUND: Despite vaccines and improved medical intensive care, clinicians must continue to be vigilant of possible Meningococcal Disease in children. The objective was to establish if the procalcitonin test was a cost-effective adjunct for prodromal Meningococcal Disease in children presenting at emergency department with fever without source.

METHODS AND FINDINGS: Data to evaluate procalcitonin, C-reactive protein and white cell count tests as indicators of Meningococcal Disease were collected from six independent studies identified through a systematic literature search, applying PRISMA guidelines. The data included 881 children with fever without source in developed countries.The optimal cut-off value for the procalcitonin, C-reactive protein and white cell count tests, each as an indicator of Meningococcal Disease, was determined. Summary Receiver Operator Curve analysis determined the overall diagnostic performance of each test with 95% confidence intervals. A decision analytic model was designed to reflect realistic clinical pathways for a child presenting with fever without source by comparing two diagnostic strategies: standard testing using combined C-reactive protein and white cell count tests compared to standard testing plus procalcitonin test. The costs of each of the four diagnosis groups (true positive, false negative, true negative and false positive) were assessed from a National Health Service payer perspective. The procalcitonin test was more accurate (sensitivity=0.89, 95%CI=0.76-0.96; specificity=0.74, 95%CI=0.4-0.92) for early Meningococcal Disease compared to standard testing alone (sensitivity=0.47, 95%CI=0.32-0.62; specificity=0.8, 95% CI=0.64-0.9). Decision analytic model outcomes indicated that the incremental cost effectiveness ratio for the base case was £-8,137.25 (US $ -13,371.94) per correctly treated patient.

CONCLUSIONS: Procalcitonin plus standard recommended tests, improved the discriminatory ability for fatal Meningococcal Disease and was more cost-effective; it was also a superior biomarker in infants. Further research is recommended for point-of-care procalcitonin testing and Markov modelling to incorporate cost per QALY with a life-time model.

Enhanced clinical pharmacy service targeting tools: risk-predictive algorithms

Rationale, aims and objectives: This study aimed to determine the value of using a mix of clinical pharmacy data and routine hospital admission spell data in the development of predictive algorithms. Exploration of risk factors in hospitalized patients, together with the targeting strategies devised, will enable the prioritization of clinical pharmacy services to optimize patient outcomes. 

Methods: Predictive algorithms were developed using a number of detailed steps using a 75% sample of integrated medicines management (IMM) patients, and validated using the remaining 25%. IMM patients receive targeted clinical pharmacy input throughout their hospital stay. The algorithms were applied to the validation sample, and predicted risk probability was generated for each patient from the coefficients. Risk threshold for the algorithms were determined by identifying the cut-off points of risk scores at which the algorithm would have the highest discriminative performance. Clinical pharmacy staffing levels were obtained from the pharmacy department staffing database. 

Results: Numbers of previous emergency admissions and admission medicines together with age-adjusted co-morbidity and diuretic receipt formed a 12-month post-discharge and/or readmission risk algorithm. Age-adjusted co-morbidity proved to be the best index to predict mortality. Increased numbers of clinical pharmacy staff at ward level was correlated with a reduction in risk-adjusted mortality index (RAMI). 

Conclusions: Algorithms created were valid in predicting risk of in-hospital and post-discharge mortality and risk of hospital readmission 3, 6 and 12 months post-discharge. The provision of ward-based clinical pharmacy services is a key component to reducing RAMI and enabling the full benefits of pharmacy input to patient care to be realized.

Prioritisation of citizen centric information for disaster response

In the aftermath of a disaster event, and in the absence of trained professionals, many responsibilities are taken on by uninjured citizens who are willing and able to help, such as care of the injured or search and rescue. These citizens are constrained by communications and logistics problems but are less equipped to deal with them as most often they are cut off from any coordinated assistance. The method proposed in this study would increase the survivability of those injured or trapped by a disaster event by providing a facility to allow citizens to coordinate and share information among themselves. This is facilitated by the proposed deployment and the autonomous management of an ad hoc infrastructure that liaises (OK?) directly with survivors without central control. Furthermore, as energy concerns present critical constraints to these networks, this research proposes a system of categorising information elements within the network to ensure efficient information exchange.

Galleria mellonella as a novel in vivo model for assessment of the toxicity of 1-alkyl-3-methylimidazolium chloride ionic liquids

The larval form of the Greater Wax Moth (Galleria mellonella) was evaluated as a model system for the study of the acute in vivo toxicity of 1-alkyl-3-methylimidazolium chloride ionic liquids. 24-h median lethal dose (LD50) values for nine of these ionic liquids bearing alkyl chain substituents ranging from 2 to 18 carbon atoms were determined. The in vivo toxicity of the ionic liquids was found to correlate directly with the length of the alkyl chain substituent, and the pattern of toxicity observed was in accordance with previous studies of ionic liquid toxicity in other living systems, including a characteristic toxicity ‘cut-off’ effect. However, G. mellonella appeared to be more susceptible to the toxic effects of the ionic liquids tested, possibly as a result of their high body fat content. The results obtained in this study indicate that G. mellonella represents a sensitive, reliable and robust in vivo model organism for the evaluation of ionic liquid toxicity.

A comparison of endoscopy versus pathology sizing of colorectal adenomas and potential implications for surveillance colonoscopy

Background and AimsTo compare endoscopy and pathology sizing in a large population-based series of colorectal adenomas and to evaluate the implications for patient stratification into surveillance colonoscopy.MethodsEndoscopy and pathology sizes available from intact adenomas removed at colonoscopies performed as part of the Northern Ireland Bowel Cancer Screening Programme, from 2010 to 2015, were included in this study. Chi-squared tests were applied to compare size categories in relation to clinicopathological parameters and colonoscopy surveillance strata according to current American Gastroenterology Association and British Society of Gastroenterology guidelines.ResultsA total of 2521 adenomas from 1467 individuals were included. There was a trend toward larger endoscopy than pathology sizing in 4 of the 5 study centers, but overall sizing concordance was good. Significantly greater clustering with sizing to the nearest 5 mm was evident in endoscopy versus pathology sizing (30% vs 19%, p<0.001), which may result in lower accuracy. Applying a 10-mm cut-off relevant to guidelines on risk stratification, 7.3% of all adenomas and 28.3% of those 8 to 12 mm in size had discordant endoscopy and pathology size categorization. Depending upon which guidelines are applied, 4.8% to 9.1% of individuals had differing risk stratification for surveillance recommendations, with the use of pathology sizing resulting in marginally fewer recommended surveillance colonoscopies.ConclusionsChoice of pathology or endoscopy approaches to determine adenoma size will potentially influence surveillance colonoscopy follow-up in 4.8% to 9.1% of individuals. Pathology sizing appears more accurate than endoscopy sizing, and preferential use of pathology size would result in a small, but clinically important, decreased burden on surveillance colonoscopy demand. Careful endoscopy sizing is required for adenomas removed piecemeal.

Numerical study of neutron beam divergence in a beam-fusion scenario employing laser driven ions

The most established route to create a laser-based neutron source is by employing laser accelerated, low atomic-number ions in fusion reactions. In addition to the high reaction cross-sections at moderate energies of the projectile ions, the anisotropy in neutron emission is another important feature of beam-fusion reactions. Using a simple numerical model based on neutron generation in a pitcher–catcher scenario, anisotropy in neutron emission was studied for the deuterium–deuterium fusion reaction. Simulation results are consistent with the narrow-divergence ( ∼ 70 ° full width at half maximum) neutron beam recently served in an experiment employing multi-MeV deuteron beams of narrow divergence (up to 30° FWHM, depending on the ion energy) accelerated by a sub-petawatt laser pulse from thin deuterated plastic foils via the Target Normal Sheath Acceleration mechanism. By varying the input ion beam parameters, simulations show that a further improvement in the neutron beam directionality (i.e. reduction in the beam divergence) can be obtained by increasing the projectile ion beam temperature and cut-off energy, as expected from interactions employing higher power lasers at upcoming facilities.

Progression of left atrial volume index in a population at risk for heart failure:a substudy of the STOP-HF (St Vincent's Screening TO Prevent Heart Failure) trial

AIMS: Limited data are available concerning the evolution of the left atrial volume index (LAVI) in pre-heart failure (HF) patients. The aim of this study was to investigate clinical characteristics and serological biomarkers in a cohort with risk factors for HF and evidence of serial atrial dilatation.

METHODS AND RESULTS: This was a prospective substudy within the framework of the STOP-HF cohort (NCT00921960) involving 518 patients with risk factors for HF electively undergoing serial clinical, echocardiographic, and natriuretic peptide assessment. Mean follow-up time between assessments was 15 ± 6 months. 'Progressors' (n = 39) were defined as those with serial LAVI change ≥3.5 mL/m(2) (and baseline LAVI between 20 and 34 mL/m(2)). This cut-off was derived from a calculated reference change value above the biological, analytical, and observer variability of serial LAVI measurement. Multivariate analysis identified significant baseline clinical associates of LAVI progression as increased age, beta-blocker usage, and left ventricular mass index (all P < 0.05). Serological biomarkers were measured in a randomly selected subcohort of 30 'Progressors' matched to 30 'Non-progressors'. For 'Progressors', relative changes in matrix metalloproteinase 9 (MMP9), tissue inhibitor of metalloproteinase 1 (TIMP1), and the TIMP1/MMP9 ratio, markers of interstitial remodelling, tracked with changes in LAVI over time (all P < 0.05).

CONCLUSION: Accelerated LAVI increase was found to occur in up to 14% of all pre-HF patients undergoing serial echocardiograms over a relatively short follow-up period. In a randomly selected subcohort of 'Progressors', changes in LAVI were closely linked with alterations in MMP9, TIMP1, and the ratio of these enzymes, a potential aid in highlighting this at-risk group.