Convolutional neural networks for automated targeted analysis of gas chromatography-mass spectrometry data

Through their breath, humans exhale hundreds of volatile organic compounds (VOCs) that can reveal pathologies, including many types of cancer at early stages. Gas chromatography–mass spectrometry (GC-MS) is an analytical method used to separate and detect compounds in the mixture contained in breath samples. The identification of VOCs is based on the recognition of their specific ion patterns in GC-MS data, which requires labour-intensive and time-consuming preprocessing and analysis by domain experts. This paper explores the original idea of applying supervised machine learning, and in particular convolutional neural networks (CNNs), to learn ion patterns directly from raw GC-MS data. The method adapts to machine specific characteristics, and once trained, can quickly analyse breath samples bypassing the time-consuming preprocessing phase. The CNN classification performance is compared to those of shallow neural networks and support vector machines. All considered machine learning tools achieved high accuracy in experiments with clinical data from participants. In particular, the CNN-based approach detected the lowest number of false positives. The results indicate that the proposed method is a promising tool to improve accuracy, specificity, and in particular speed in the detection of VOCs of interest in large-scale data analysis

Estimated ingested profenofos dose in the two patient groups, with and without a history of alcohol co-ingestion.

<p>Estimated ingested profenofos dose in the two patient groups, with and without a history of alcohol co-ingestion.</p

Red cell AChE values taken on admission in the two profenofos poisoned patient groups, with and without a history of alcohol co-ingestion.

<p>Data were available for 94 (64 no alcohol, 30 with alcohol) patients.</p

Antivenom for European <i>Vipera</i> species envenoming

<p><b>Background:</b> European viper bite is relatively uncommon but can cause serious envenoming, particularly swelling and hemorrhage spreading from limb to trunk that can cause long term disability. Systemic features are relatively mild compared to many other venomous species. Moderate-to-severe envenoming requires antivenom, which is given many hundreds of times each year across the continent. Several <i>Vipera</i> spp antivenoms are produced in Europe, but there is little comparative information available for the antivenoms and none is licensed with the European Medicines Agency. We aimed to collect descriptive data on European viper antivenoms and assess their relative effectiveness.</p> <p><b>Methods:</b> A systematic review of articles relating to antivenom in Europe was performed using the Medline medical database. The following keywords “Europ*” or the individual names of each European country and “antiven*” or “immun*” or “envenom*” and “snake” or “viper*” or “adder” were used. Articles published between 1 January 1996 and 11 March 2016 pertaining to clinical outcome, including case reports, were selected. Referenced articles in the indexed articles were explored for suitability and included if they met any of the criteria: specific antivenom used, route of antivenom administration, adverse reactions to antivenom therapy and length of hospital admission. All accepted abstracts from EAPCCT conferences since 2000 were searched and abstracts relating to <i>Vipera</i> spp envenoming were assessed for suitability. We extracted data on study type, safety and effectiveness. We sought information on antivenoms from manufacturers and individual patient data from authors of publications. Since individual patient data were only rarely available, we compared median length of stay between case series reporting each antivenom. We identified 40 papers and six published abstracts, and one unpublished paper that reported clinical cases and case series of envenomed patients treated with antivenom. No publication reported randomized controlled trials comparing any European <i>Vipera</i> antivenom with either placebo or another antivenom. 25 reports were of retrospective hospital- (<i>n</i> = 13) or poison center-based (<i>n</i> = 12) case series including five or more patients; a further 12 reports were either case reports or case series with less than five patients and one paper was a limited literature review. An additional nine papers reported prospective data; seven collected data remotely through poison service telephone communication with the attending physicians.</p> <p><b>Antivenoms available in Europe:</b> Eight antivenoms are available for European <i>Vipera</i> spp envenoming; a material safety data sheet providing information on manufacture was available for seven. Six are raised against <i>V. berus or V. ammodytes</i> venom; the seventh is raised against a mixture of <i>V. ammodytes, V. aspis and V. berus</i> venom and the eighth is raised against <i>V. ammodytes</i>, <i>Macrovipera lebetina</i> and <i>Montivipera xanthina</i> venom. Six manufacturers recommended intramuscular administration while two recommended intravenous administration. No randomized control trials comparing the effectiveness of antivenoms were identified.</p> <p><b>Pre-clinical data:</b> We found two papers presenting comparative preclinical data.</p> <p><b>Clinical data:</b> Clinical studies were predominantly retrospective and contained clinical data on antivenom used in 2602 patients; where the antivenom was identified (<i>n</i> = 2174), 2061 (94.8%) received Zagreb, ViperFAV or ViperaTAb antivenoms. There were few published data on the other antivenoms.</p> <p><b>Repeated use of antivenom:</b> Repeat doses were reported in 230/1491 of cases (15.4%) where this information was recorded.</p> <p><b>Outcome and length of hospital stay:</b> Intravenous administration of antivenom was associated with shorter length of hospital stay (median length of hospital stay in studies of intravenous ViperFAV or ViperaTAb ranged from 1 to 4.8 days versus 2 to 18 days for intramuscular Bulbio or Zagreb antivenoms).</p> <p><b>Antivenom versus no antivenom:</b> Some small studies demonstrated no difference in the length of hospital stay in patients with equivalent envenomation grading who either did or did not receive antivenom.</p> <p><b>Adverse events:</b> Adverse reactions were reported in 37 of 2408 cases (1.5%) including seven cases of anaphylaxis.</p> <p><b>Conclusions:</b> There are very limited pre-clinical comparative data and no randomised controlled trials assessing effectiveness of the antivenoms against different <i>Vipera</i> species. Most descriptive data suggest the efficacy of Zagreb, ViperFAV and ViperaTAb antivenoms by the intravenous route but not intramuscular route, although this is level D evidence. Reported adverse reactions were rare, suggesting that the modern intravenous antivenoms are of good quality. Better and more systematic data, including perhaps randomized controlled trials comparing different antivenoms, are required for the many hundreds of antivenom administrations that occur annually across Europe.</p

Intent for different methods of death from injury.

*<p>Assault injuries due to violence include deaths from munitions and roadside bombs, whether exploded intentionally or unintentionally.</p

Incidence of fatal injury by gender and age.

<p>The incidence was calculated from the gender and age specific 2001 census results. The Government of Sri Lanka estimates that the population of the province has increased by 1.2% each year since the census, reducing the incidences shown here.</p

Deaths from injury in the WHO SEAR-B region of South East Asia during 2002 [16] and the North Central Province of Sri Lanka during 2003–4.

*<p>Sear-B South-East Asia with low child and low adult mortality [Indonesia, Sri Lanka, Thailand]</p>**<p>Estimated mid year population for 2003</p>***<p>Since a ceasefire was in effect for the civil war during this period, all deaths due to bombs and shootings were included under Violence rather than War.</p

Deaths from injury in North Central Province by cause, age, and gender during the 18 months, Jan 2003–Jun 2004.

<p>Deaths from injury in North Central Province by cause, age, and gender during the 18 months, Jan 2003–Jun 2004.</p

Rate ratios and change in the number of suicides in years 2011–2015 after the phased bans of paraquat, dimethoate and fenthion relative to those expected based on trend 2001–10.

<p>Rate ratios and change in the number of suicides in years 2011–2015 after the phased bans of paraquat, dimethoate and fenthion relative to those expected based on trend 2001–10.</p

Additional file 1: of Vendor-based restrictions on pesticide sales to prevent pesticide self-poisoning - a pilot study

Appendix 1. Questionnaire for baseline and follow-up survey. (DOCX 40 kb