Grounding event references in news

Events are frequently discussed in natural language, and their accurate identification is central to language understanding. Yet they are diverse and complex in ontology and reference; computational processing hence proves challenging. News provides a shared basis for communication by reporting events. We perform several studies into news event reference. One annotation study characterises each news report in terms of its update and topic events, but finds that topic is better consider through explicit references to background events. In this context, we propose the event linking task which—analogous to named entity linking or disambiguation—models the grounding of references to notable events. It defines the disambiguation of an event reference as a link to the archival article that first reports it. When two references are linked to the same article, they need not be references to the same event. Event linking hopes to provide an intuitive approximation to coreference, erring on the side of over-generation in contrast with the literature. The task is also distinguished in considering event references from multiple perspectives over time. We diagnostically evaluate the task by first linking references to past, newsworthy events in news and opinion pieces to an archive of the Sydney Morning Herald. The intensive annotation results in only a small corpus of 229 distinct links. However, we observe that a number of hyperlinks targeting online news correspond to event links. We thus acquire two large corpora of hyperlinks at very low cost. From these we learn weights for temporal and term overlap features in a retrieval system. These noisy data lead to significant performance gains over a bag-of-words baseline. While our initial system can accurately predict many event links, most will require deep linguistic processing for their disambiguation

Prospective evaluation of improving fluoroquinolone exposure using centralised therapeutic drug monitoring (TDM) in patients with tuberculosis (PERFECT): a study protocol of a prospective multicentre cohort study

Introduction Global multidrug-resistant tuberculosis (MDR-TB) treatment success rates remain suboptimal. Highly active WHO group A drugs moxifloxacin and levofloxacin show intraindividual and interindividual pharmacokinetic variability which can cause low drug exposure. Therefore, therapeutic drug monitoring (TDM) of fluoroquinolones is recommended to personalise the drug dosage, aiming to prevent the development of drug resistance and optimise treatment. However, TDM is considered laborious and expensive, and the clinical benefit in MDR-TB has not been extensively studied. This observational multicentre study aims to determine the feasibility of centralised TDM and to investigate the impact of fluoroquinolone TDM on sputum conversion rates in patients with MDR-TB compared with historical controls. Methods and analysis Patients aged 18 years or older with sputum smear and culture-positive pulmonary MDR-TB will be eligible for inclusion. Patients receiving TDM using a limited sampling strategy (t=0 and t=5 hours) will be matched to historical controls without TDM in a 1:2 ratio. Sample analysis and dosing advice will be performed in a centralised laboratory. Centralised TDM will be considered feasible if >80% of the dosing recommendations are returned within 7 days after sampling and 100% within 14 days. The number of patients who are sputum smear and culture-negative after 2 months of treatment will be determined in the prospective TDM group and will be compared with the control group without TDM to determine the impact of TDM. Ethics and dissemination Ethical clearance was obtained by the ethical review committees of the 10 participating hospitals according to local procedures or is pending (online supplementary file 1). Patients will be included after obtaining written informed consent. We aim to publish the study results in a peer-reviewed journal. Trial registration number ClinicalTrials.gov Registry (NCT03409315)

Exposure of anti-infective drugs and the dynamic changes of the gut microbiota during gastrointestinal mucositis in autologous stem cell transplant patients: a pilot study

Published online: 17 January 2023Gastrointestinal mucositis could potentially compromise drug absorption due to functional loss of mucosa and other pathophysiological changes in the gastrointestinal microenvironment. Little is known about this effect on commonly used anti-infectives. This study aimed to explore the association between different stages of gastrointestinal mucositis, drug exposure, and gut microbiota. A prospective, observational pilot study was performed in HSCT patients aged ≥ 18 years receiving anti-infectives orally. Left-over blood samples and fecal swabs were collected from routine clinical care until 14 days after HSCT to analyze drug and citrulline concentrations and to determine the composition of the gut microbiota. 21 patients with a median age of 58 (interquartile range 54-64) years were included with 252 citrulline, 155 ciprofloxacin, 139 fluconazole, and 76 acyclovir concentrations and 48 fecal swabs obtained. Severe gastrointestinal mucositis was observed in all patients. Due to limited data correlation analysis was not done for valacyclovir and fluconazole, however we did observe a weak correlation between ciprofloxacin and citrulline concentrations. This could suggest that underexposure of ciprofloxacin can occur during severe mucositis. A follow-up study using frequent sampling rather than the use of left-over would be required to investigate the relationship between gastrointestinal mucositis, drug exposure, and gut microbiome.Anne-Grete Märtson, Ana Rita da Silva Ferreira, Anette Veringa, Lei Liu, Hannah R. Wardill, Lenneke A. T. Junier, Tjip S. van der Werf, Hermie J. M. Harmsen, Marieke G. G. Sturkenboom, Lambert F. Span, Wim J. E. Tissing, Jan-Willem C. Alffenaa

Calsequestrin as a risk factor in Graves’ hyperthyroidism and Graves’ ophthalmopathy patients

Background: The pathogenesis of Graves’ ophthalmopathy (GO), Graves’ hyperthyroidism (GH) and the mechanisms for its link to thyroid autoimmunity are poorly understood. Our research focuses on the role of the skeletal muscle calcium binding protein calsequestrin (CASQ1) in thyroid. We measured the concentration of the CASQ1 protein correlating levels with parameters of the eye signs, CASQ1 antibody levels and CASQ1 gene polymorphism rs3838284. Methods: CASQ1 protein was measured by quantitative Western Blotting. The protein concentrations were expressed as pmol/mg total protein by reference to CASQ1 standards. Results: Western blot analysis showed the presence of two forms of CASQ1 in the thyroid. The mean concentration of CASQ1 protein was significantly reduced in patients with Graves’ disease, compared to thyroid from control subjects with multi-nodular goitre or thyroid cancer. Although in patients with GO it was lower than that, compared with patients with GH this difference was not significant. Reduced CASQ1 in Graves’ thyroid correlated with the homozygous genotype of the rs3838284 CASQ1 polymorphism. Conclusions: Decreased CASQ1 in the thyroid of patients with Graves’ disease compared to thyroid from control subjects is not explained but may reflect consumption of the protein during an autoimmune reaction against CASQ1 in the thyroid

Treatment Outcomes of Patients With Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis According to Drug Susceptibility Testing to First- and Second-line Drugs: An Individual Patient Data Meta-analysis

The clinical validity of drug susceptibility testing (DST) for pyrazinamide, ethambutol, and second-line antituberculosis drugs is uncertain. In an individual patient data meta-analysis of 8955 patients with confirmed multidrug-resistant tuberculosis, DST results for these drugs were associated with treatment outcome

Physicians' and nurses' opinions on selective decontamination of the digestive tract and selective oropharyngeal decontamination: a survey

Contains fulltext : 89741.pdf (publisher's version ) (Open Access)INTRODUCTION: Use of selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) in intensive care patients has been controversial for years. Through regular questionnaires we determined expectations concerning SDD (effectiveness) and experience with SDD and SOD (workload and patient friendliness), as perceived by nurses and physicians. METHODS: A survey was embedded in a group-randomized, controlled, cross-over multicenter study in the Netherlands in which, during three 6-month periods, SDD, SOD or standard care was used in random order. At the end of each study period, all nurses and physicians from participating intensive care units received study questionnaires. RESULTS: In all, 1024 (71%) of 1450 questionnaires were returned by nurses and 253 (82%) of 307 by physicians. Expectations that SDD improved patient outcome increased from 71% and 77% of respondents after the first two study periods to 82% at the end of the study (P = 0.004), with comparable trends among nurses and physicians. Nurses considered SDD to impose a higher workload (median 5.0, on a scale from 1 (low) to 10 (high)) than SOD (median 4.0) and standard care (median 2.0). Both SDD and SOD were considered less patient friendly than standard care (medians 4.0, 4.0 and 6.0, respectively). According to physicians, SDD had a higher workload (median 5.5) than SOD (median 5.0), which in turn was higher than standard care (median 2.5). Furthermore, physicians graded patient friendliness of standard care (median 8.0) higher than that of SDD and SOD (both median 6.0). CONCLUSIONS: Although perceived effectiveness of SDD increased as the trial proceeded, both among physicians and nurses, SOD and SDD were, as compared to standard care, considered to increase workload and to reduce patient friendliness. Therefore, education about the importance of oral care and on the effects of SDD and SOD on patient outcomes will be important when implementing these strategies. TRIAL REGISTRATION: ISRCTN35176830