Chemometric classification of casework arson samples based on gasoline content.

Detection and identification of ignitable liquids (ILs) in arson debris is a critical part of arson investigations. The challenge of this task is due to the complex and unpredictable chemical nature of arson debris, which also contains pyrolysis products from the fire. ILs, most commonly gasoline, are complex chemical mixtures containing hundreds of compounds that will be consumed or otherwise weathered by the fire to varying extents depending on factors such as temperature, air flow, the surface on which IL was placed, etc. While methods such as ASTM E-1618 are effective, data interpretation can be a costly bottleneck in the analytical process for some laboratories. In this study, we address this issue through the application of chemometric tools. Prior to the application of chemometric tools such as PLS-DA and SIMCA, issues of chromatographic alignment and variable selection need to be addressed. Here we use an alignment strategy based on a ladder consisting of perdeuterated n-alkanes. Variable selection and model optimization was automated using a hybrid backward elimination (BE) and forward selection (FS) approach guided by the cluster resolution (CR) metric. In this work, we demonstrate the automated construction, optimization, and application of chemometric tools to casework arson data. The resulting PLS-DA and SIMCA classification models, trained with 165 training set samples, have provided classification of 55 validation set samples based on gasoline content with 100% specificity and sensitivity.

Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3): a multicentre randomised controlled trial.

BACKGROUND: Venous thromboembolism is a common, potentially avoidable cause of death and morbidity in patients in hospital, including those with stroke. In surgical patients, intermittent pneumatic compression (IPC) reduces the risk of deep vein thrombosis (DVT), but no reliable evidence exists about its effectiveness in patients who have had a stroke. We assessed the effectiveness of IPC to reduce the risk of DVT in patients who have had a stroke. METHODS: The CLOTS 3 trial is a multicentre parallel group randomised trial assessing IPC in immobile patients (ie, who cannot walk to the toilet without the help of another person) with acute stroke. We enrolled patients from day 0 to day 3 of admission and allocated them via a central randomisation system (ratio 1:1) to receive either IPC or no IPC. A technician who was masked to treatment allocation did a compression duplex ultrasound (CDU) of both legs at 7-10 days and, wherever practical, at 25-30 days after enrolment. Caregivers and patients were not masked to treatment assignment. Patients were followed up for 6 months to determine survival and later symptomatic venous thromboembolism. The primary outcome was a DVT in the proximal veins detected on a screening CDU or any symptomatic DVT in the proximal veins, confirmed on imaging, within 30 days of randomisation. Patients were analysed according to their treatment allocation. TRIAL REGISTRATION: ISRCTN93529999. FINDINGS: Between Dec 8, 2008, and Sept 6, 2012, 2876 patients were enrolled in 94 centres in the UK. The included patients were broadly representative of immobile stroke patients admitted to hospital and had a median age of 76 years (IQR 67-84). The primary outcome occurred in 122 (8·5%) of 1438 patients allocated IPC and 174 (12·1%) of 1438 patients allocated no IPC; an absolute reduction in risk of 3·6% (95% CI 1·4-5·8). Excluding the 323 patients who died before any primary outcome and 41 without any screening CDU, the adjusted OR for the comparison of 122 of 1267 patients vs 174 of 1245 patients was 0·65 (95% CI 0·51-0·84; p=0·001). Deaths in the treatment period occurred in 156 (11%) patients allocated IPC and 189 (13%) patients allocated no IPC died within the 30 days of treatment period (p=0·057); skin breaks on the legs were reported in 44 (3%) patients allocated IPC and in 20 (1%) patients allocated no IPC (p=0·002); falls with injury were reported in 33 (2%) patients in the IPC group and in 24 (2%) patients in the no-IPC group (p=0·221). INTERPRETATION: IPC is an effective method of reducing the risk of DVT and possibly improving survival in a wide variety of patients who are immobile after stroke. FUNDING: National Institute of Health Research (NIHR) Health Technology Assessment (HTA) programme, UK; Chief Scientist Office of Scottish Government; Covidien (MA, USA).

CRASH-2 (Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage) intracranial bleeding study: the effect of tranexamic acid in traumatic brain injury--a nested randomised, placebo-controlled trial.

BACKGROUND: Tranexamic acid (TXA) has been shown to reduce blood loss in surgical patients and the risk of death in patients with traumatic bleeding, with no apparent increase in vascular occlusive events. These findings raise the possibility that it might also be effective in traumatic brain injury (TBI). OBJECTIVE: The Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage Intracranial Bleeding Study (CRASH-2 IBS) was conducted to quantify the effect of an early short course of TXA on intracranial haemorrhage and new focal cerebral ischaemic lesions in patients with TBI. DESIGN: CRASH-2 IBS was a prospective randomised controlled trial nested within the CRASH-2 trial. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight. We used a local pack system that selected the lowest numbered treatment pack from a box containing eight numbered packs. Apart from the pack number, the treatment packs were identical. The pack number was recorded on the entry form, which was sent to the international trial co-ordinating centre in London, UK. Once the treatment pack number was recorded, the patient was included in the trial whether or not the treatment pack was opened or the allocated treatment started. All site investigators and trial co-ordinating centre staff were masked to treatment allocation. SETTING: Ten hospitals: (India) Aditya Neuroscience Centre, Sanjivani Hospital, CARE Hospital, Christian Medical College, Medical Trust Hospital, Jeevan Jyoti Hospital and (Colombia) Hospital Universitario San Vicente de Paul, Hospital Pablo Tobón Uribe, Hospital Universitario San José de Popayán and Fundación Valle del Lili. PARTICIPANTS: The trial was conducted in a subset of 270 CRASH-2 trial participants. Patients eligible for inclusion in the CRASH-2 IBS fulfilled the inclusion criteria for the CRASH-2 trial, and also had TBI [Glasgow Coma Scale score of ≤ 14 and a brain computerised tomography (CT) scan compatible with TBI]. Pregnant women and patients for whom a second brain CT scan was not possible were excluded. INTERVENTIONS: Participants were randomly allocated to receive either a loading dose of 1 g of TXA infused over 10 minutes followed by an intravenous infusion of 1 g over 8 hours or matching placebo. MAIN OUTCOME MEASURE: The primary outcome was the increase in size of intracranial haemorrhage growth between a CT scan at hospital admission and a second scan 24-48 hours later. RESULTS: One hundred and thirty-three patients were allocated to TXA and 137 to placebo, of whom information on the primary (imaging) outcome was available for 123 (92%) and 126 (92%) respectively. The analysis suggested that TXA was likely to be associated with a reduction in haemorrhage growth [adjusted difference -3.8 ml, 95% credibility interval (CrI) -11.5 ml to 3.9 ml], fewer focal ischaemic lesions [adjusted odds ratio (OR) 0.54, 95% CrI 0.20 to 1.46] and fewer deaths (adjusted OR 0.49, 95% CrI 0.22 to 1.06). CONCLUSIONS: This was the first randomised controlled study to evaluate the effect of TXA in TBI patients and it found that neither moderate benefits nor moderate harmful effects can be excluded. However, although uncertainty remains, our analyses suggest that TXA administration might improve outcome in TBI patients and provide grounds for evaluating this hypothesis in future research. TRIAL REGISTRATION: Current Controlled Trials ISRCTN86750102. SOURCE OF FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 13. See the HTA programme website for further project information.

Preparation of pyrolysis reference samples: evaluation of a standard method using a tube furnace.

A new, simple method for the reproducible creation of pyrolysis products from different materials that may be found at a fire scene is described. A temperature programmable steady-state tube furnace was used to generate pyrolysis products from different substrates, including softwoods, paper, vinyl sheet flooring, and carpet. The temperature profile of the tube furnace was characterized, and the suitability of the method to reproducibly create pyrolysates similar to those found in real fire debris was assessed. The use of this method to create proficiency tests to realistically test an examiner's ability to interpret complex gas chromatograph-mass spectrometric fire debris data, and to create a library of pyrolsates generated from materials commonly found at a fire scene, is demonstrated.

Principal component analysis and analysis of variance on the effects of Entellan New on the Raman spectra of fibers.

During the forensic examination of textile fibers, fibers are usually mounted on glass slides for visual inspection and identification under the microscope. One method that has the capability to accurately identify single textile fibers without subsequent demounting is Raman microspectroscopy. The effect of the mountant Entellan New on the Raman spectra of fibers was investigated to determine if it is suitable for fiber analysis. Raman spectra of synthetic fibers mounted in three different ways were collected and subjected to multivariate analysis. Principal component analysis score plots revealed that while spectra from different fiber classes formed distinct groups, fibers of the same class formed a single group regardless of the mounting method. The spectra of bare fibers and those mounted in Entellan New were found to be statistically indistinguishable by analysis of variance calculations. These results demonstrate that fibers mounted in Entellan New may be identified directly by Raman microspectroscopy without further sample preparation.

The timing, extent, progression and regression of deep vein thrombosis in immobile stroke patients: observational data from the CLOTS multicenter randomized trials.

BACKGROUND: Deep vein thrombosis (DVT) is an important complication of stroke, but the evidence to support commonly used prophylactic strategies is conflicting. OBJECTIVES: To describe the incidence, extent, associated clinical features and evolution of DVT after stroke. PATIENTS/METHODS: The CLOTS trials 1 and 2 together randomized 5632 immobile stroke patients in 135 hospitals in nine countries. We screened patients for asymptomatic DVT with compression duplex ultrasound (CDU) at about 7-10 days and again at about 25-30 days after enrollment. RESULTS: Six hundred and forty-one (11.4%) of 5632 patients had DVT detected on the first CDU scan at a median of 8 days (interquartile range [IQR] 7-10 days) after enrollment, and an additional 176 (3.1%) had a DVT on the second CDU scan at a median of 28 days (IQR 26-30 days). Of the 817 with DVTs, 289 (35%) were symptomatic and 39 (5%) had pulmonary embolism (PE) confirmed by imaging. Six hundred and seventy-six (83%) were unilateral, 141 (17%) were bilateral, 322 (39%) were limited to calf veins, 172 (21%) were popliteal, and 323 (40%) were femoral. Among the 542 patients with DVT and a weak leg, the DVT affected the weaker leg in 396 (73%), the stronger leg in 59 (11%), and was bilateral in 87 (16%). Among the 318 patients with a DVT detected on the first CDU scan who had a second scan, the DVT regressed in 148 (47%), stayed the same in 140 (44%), and progressed in only 30 (9%). CONCLUSIONS: Although most DVTs develop within the first week, some develop later, and some early DVTs progress. Any prophylaxis needs to be started early but ideally continued for at least 4 weeks.

Automated optimization and construction of chemometric models based on highly variable raw chromatographic data.

Direct chemometric interpretation of raw chromatographic data (as opposed to integrated peak tables) has been shown to be advantageous in many circumstances. However, this approach presents two significant challenges: data alignment and feature selection. In order to interpret the data, the time axes must be precisely aligned so that the signal from each analyte is recorded at the same coordinates in the data matrix for each and every analyzed sample. Several alignment approaches exist in the literature and they work well when the samples being aligned are reasonably similar. In cases where the background matrix for a series of samples to be modeled is highly variable, the performance of these approaches suffers. Considering the challenge of feature selection, when the raw data are used each signal at each time is viewed as an individual, independent variable; with the data rates of modern chromatographic systems, this generates hundreds of thousands of candidate variables, or tens of millions of candidate variables if multivariate detectors such as mass spectrometers are utilized. Consequently, an automated approach to identify and select appropriate variables for inclusion in a model is desirable. In this research we present an alignment approach that relies on a series of deuterated alkanes which act as retention anchors for an alignment signal, and couple this with an automated feature selection routine based on our novel cluster resolution metric for the construction of a chemometric model. The model system that we use to demonstrate these approaches is a series of simulated arson debris samples analyzed by passive headspace extraction, GC-MS, and interpreted using partial least squares discriminant analysis (PLS-DA).

Current controversies: thrombolysis for patients with acute ischaemic stroke aged over 80.

Stroke is the major cause of disability in the community. Most strokes are due to blocked arteries in the brain. Evidence is accumulating that clot-busting drugs improve outcome after ischaemic stroke. Recombinant tissue plasminogen activator (rt-PA) is licensed for the treatment of selected patients within three hours of acute ischaemic stroke in many parts of the world, and stroke services are being developed so that eligible patients can receive this treatment as soon as possible after the onset of stroke symptoms. However, thrombolysis can cause bleeding into the brain, so the treatment should only be given when the benefits outweigh the risks. Controversy still exists about the risks and benefits in certain groups of patients, and there is variation in practice between stroke physicians, reflecting these uncertainties.

The molecular basis of thrombolysis and its clinical application in stroke.

The rationale for thrombolysis, the most promising pharmacological approach in acute ischaemic stroke, is centred on the principal cause of most ischaemic strokes: the thrombus that occludes the cerebral artery, and renders part of the brain ischaemic. The occluding thrombus is bound together within fibrin. Fibrinolysis acts by activation of plasminogen to plasmin; plasmin splits fibrinogen and fibrin and lyses the clot, which then allows reperfusion of the ischaemic brain. Thrombolytic agents include streptokinase (SK) and recombinant tissue-type plasminogen activator (rt-PA) amongst others under test or development. SK is nonfibrin-specific, has a longer half-life than tissue-type plasminogen activator (t-PA), prevents re-occlusion and is degraded enzymatically in the circulation. rt-PA is more fibrin-specific and clot-dissolving, and is metabolized during the first passage in the liver. In animal models of ischaemic stroke, the effects of rt-PA are remarkably consistent with the effects seen in human clinical trials. For clinical application, some outcome data from the Cochrane Database of Systematic Reviews which includes all randomized evidence available on thrombolysis in man were used. Trials included tested urokinase, SK, rt-PA, pro-urokinase, or desmoteplase. The chief immediate hazard of thrombolytic therapy is fatal intracranial bleeding. However, despite the risk, the human trial data suggest the immediate hazards and the apparent substantial scope for net benefit of thrombolytic therapy given up to 6 h of acute ischaemic stroke. So far the fibrin-specific rt-PA is the only agent to be approved for use in stroke. This may be due to its short half-life and its absence of any specific amount of circulating fibrinogen degradation products, thereby leaving platelet function intact. The short half-life does not leave rt-PA without danger for haemorrhage after the infusion. Due to its fibrin-specificity, it can persist within a fibrin-rich clot for one or more days. The molecular mechanisms with regards to fibrin-specificity in thrombolytic agents should, if further studied, be addressed in within-trial comparisons. rt-PA has antigenic properties and although their long-term clinical relevance is unclear there should be surveillance for allergic reactions in relation to treatment. Although rt-PA is approved for use in selected patients, there is scope for benefit in a much wider variety of patients. A number of trials are underway to assess which additional patients - beyond the age and time limits of the current approval - might benefit, and how best to identify them.

Characterization of the products formed by the reaction of trichlorocyanuric acid with 2-propanol.

We report a recent investigation into the death of a cat that was initially thought to involve intentionally burning the animal via the use of an ignitable liquid. The exposure of the animal to flame was ruled out. Instead, forensic investigation revealed the intentional mixing together of a common outdoor swimming pool chlorinator, trichlorocyanuric acid (TCCA), and 2-propanol (aka, isopropyl alcohol or rubbing alcohol). The reaction of these two chemicals resulted in the formation of cyanuric acid residue, hydrochloric acid, and the evolution of a significant volume of chlorine gas. Further alpha-chlorination side reactions also occurred between 2-propanol and TCCA to produce a variety of chlorinated 2-propanone species that were detected on the submitted evidence. The identification of the products of both the main reaction and the side reactions allowed the authors to determine what chemicals were originally mixed together by the culprit.

Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS trial 1): a multicentre, randomised controlled trial.

BACKGROUND: Deep vein thrombosis (DVT) and pulmonary embolism are common after stroke. In small trials of patients undergoing surgery, graduated compression stockings (GCS) reduce the risk of DVT. National stroke guidelines extrapolating from these trials recommend their use in patients with stroke despite insufficient evidence. We assessed the effectiveness of thigh-length GCS to reduce DVT after stroke. METHODS: In this outcome-blinded, randomised controlled trial, 2518 patients who were admitted to hospital within 1 week of an acute stroke and who were immobile were enrolled from 64 centres in the UK, Italy, and Australia. Patients were allocated via a central randomisation system to routine care plus thigh-length GCS (n=1256) or to routine care plus avoidance of GCS (n=1262). A technician who was blinded to treatment allocation undertook compression Doppler ultrasound of both legs at about 7-10 days and, when practical, again at 25-30 days after enrolment. The primary outcome was the occurrence of symptomatic or asymptomatic DVT in the popliteal or femoral veins. Analyses were by intention to treat. This study is registered, number ISRCTN28163533. FINDINGS: All patients were included in the analyses. The primary outcome occurred in 126 (10.0%) patients allocated to thigh-length GCS and in 133 (10.5%) allocated to avoid GCS, resulting in a non-significant absolute reduction in risk of 0.5% (95% CI -1.9% to 2.9%). Skin breaks, ulcers, blisters, and skin necrosis were significantly more common in patients allocated to GCS than in those allocated to avoid their use (64 [5%] vs 16 [1%]; odds ratio 4.18, 95% CI 2.40-7.27). INTERPRETATION: These data do not lend support to the use of thigh-length GCS in patients admitted to hospital with acute stroke. National guidelines for stroke might need to be revised on the basis of these results. FUNDING: Medical Research Council (UK), Chief Scientist Office of Scottish Government, Chest Heart and Stroke Scotland, Tyco Healthcare (Covidien) USA, and UK Stroke Research Network.

Evaluation of internal standards for the analysis of ignitable liquids in fire debris.

An evaluation of eight compounds for use as an internal standard in fire debris analysis was conducted. Tests were conducted on tetrachloroethylene, chlorobenzene, n-octylbenzene, 3-phenyltolune, and deuterated compounds toluene-d8, styrene-d8, naphthalene-d8, and diphenyl-d10 to measure the extraction efficiency of each compound in the presence of an interfering volatile compound (carbon disulfide). Other tests were conducted to evaluate whether or not the presence of an ignitable liquid or pyrolysis/combustion products from fire debris would interfere with the identification of these compounds when used as an internal standard. The results showed that while any of the eight compounds could be used as an internal standard in fire debris analysis, the more volatile compounds (toluene-d8, tetrachloroethylene, chlorobenzene, and styrene-d8) showed better extraction efficiencies at room temperature than when heated to 60 degrees C. Each of the less volatile compounds (naphthalene-d8, diphenyl-d10, n-octylbenzene, and 3-phenyltolune) performed well during extraction at 60 degrees C, while naphthalene-d8 showed better extraction efficiency in the presence of competing volatiles when extracted at room temperature.

Fire investigation and ignitable liquid residue analysis--a review: 2001-2007.

Next to natural disasters fires cause some of the greatest losses to property and human life around the world. Arson, the deliberate setting of a fire to destroy property or to take a human life, is one of the most difficult crimes to investigate because much of the evidence at the scene is destroyed by the fire. Fortunately, the science of fire investigation is not static and more information to help investigators determine the origin and cause of a fire through careful examination of the scene and laboratory analysis of fire debris is published every year. This review article provides an overview of the scientific literature describing research and best practices in the fields of fire scene investigation as well as ignitable liquid residue analysis. This review is a compilation of articles published between late 2001 and early 2007. Conference proceedings for which full papers have not been published were intentionally excluded from this review. Some of the information contained in this review was presented at the 14th Interpol Forensic Science Symposium held in Lyon, France in October 2004.

WITHDRAWN: Surgery for cervical radiculomyelopathy.

BACKGROUND: Cervical spondylosis causes pain and disability by compressing the spinal cord or roots. Surgery to relieve the compression may reduce the pain and disability, but is associated with a small but definite risk. We sought to assess the balance of risk and benefit from surgery. OBJECTIVES: To determine whether: 1) surgical treatment of cervical radiculopathy or myelopathy is associated with improved outcome, compared with conservative management and 2) timing of surgery (immediate or delayed upon persistence/progression of relevant symptoms and signs) has an impact on outcome. SEARCH STRATEGY: We searched Medline (between 1966 and 1998), Embase (between 1980 and 1998) and the Cochrane Controlled Trials Register. Authors of the identified randomised controlled trials were contacted to detect any additional published or unpublished data. SELECTION CRITERIA: All unconfounded truly or quasi-randomised controlled trials allocating patients with cervical radiculopathy or myelopathy to 1) "best medical management" or "decompressive surgery (with or without some form of fusion) plus best medical management" 2) "early decompressive surgery" or "delayed decompressive surgery". DATA COLLECTION AND ANALYSIS: Two authors independently selected trials for inclusion, assessed trial quality and extracted the data. MAIN RESULTS: Two trials involving a total of 130 patients were included. One trial with 81 patients compared surgical decompression with either physiotherapy or cervical collar immobilization in patients with cervical radiculopathy. The short-term effects of surgery, in terms of pain, weakness or sensory loss were superior, however, at one year no significant differences between groups were present. One trial with 49 patients compared the effects of surgery with those of conservative treatment in patients with mild functional deficit associated with cervical myelopathy. No significant differences were observed between groups, up to two years following treatment. AUTHORS' CONCLUSIONS: The available small randomised trials do not provide reliable evidence on the effects of surgery for cervical spondylotic radiculopathy or myelopathy. It is not clear whether the short-term risks of surgery are offset by any long-term benefits.

Use of a solid absorbent and an accelerant detection canine for the detection of ignitable liquids burned in a structure fire.

Ignitable Liquid Absorbent (ILA), a commercial solid absorbent intended to assist fire scene investigators in sample location and collection, has been field tested in three separate room fires. The ability of the ILA to detect and absorb different amounts of gasoline, odorless paint thinner, and camp fuel on two different substrates after a full-scale burn was assessed against results from an accelerant detection canine and laboratory analysis using gas chromatography-mass spectrometry (GC-MS). The canine correctly alerted on most of the panels that contained an ignitable liquid after the fire, while the ILA indicator dye failed to indicate in the presence of gasoline and camp fuel. GC-MS results for ignitable liquid residue from each panel and from the ILA showed that ILA absorbed odorless paint thinner and camp fuel from most of the test panels, but failed to absorb gasoline from the panels on which gasoline was confirmed to be present.