The interobserver reliability of a novel qualitative point of care assay for heart-type fatty acid binding protein.

BACKGROUND: Heart-type fatty acid-binding protein (h-FABP) may help to improve the early diagnosis of acute coronary syndromes in patients presenting to the Emergency Department (ED) with chest pain. A novel qualitative point of care h-FABP lateral flow immunoassay (True Rapid, FABPulous BV) could provide results to clinicians within just 5min. Given the qualitative nature of this test and prior to evaluation in a large diagnostic study, we aimed to determine inter-observer reliability when interpreted contemporaneously by staff in the ED. METHODS: In a nested prospective cohort study including adult patients with suspected cardiac chest pain, venous blood samples were tested for h-FABP (FABPulous BV) on arrival and 3h later. Each test result was independently interpreted by two different investigators after 5min. The investigators were blinded to each other's interpretation and recorded their findings on separate case report forms. We determined interobserver reliability by calculating the Cohen's kappa score and 95% confidence intervals. RESULTS: A total of 43 test results (from 31 patients) were each interpreted by two independent investigators. Absolute agreement between investigators was 93.0%, with a Cohen's kappa of 0.81 (95% CI 0.6-1.0), indicating near perfect agreement. In total there were three (7.0%) disagreements. In each case one investigator reported a 'weak positive' result while the other interpreted the result as 'negative'. CONCLUSIONS: These findings demonstrate the interobserver reliability of a qualitative point of care h-FABP assay. Further work must evaluate diagnostic accuracy and determine the clinical implications of the small rate of disagreement

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Global temperature definition affects achievement of long-term climate goals

The Paris Agreement on climate change aims to limit 'global average temperature' rise to 'well below 2 °C' but reported temperature depends on choices about how to blend air and water temperature data, handle changes in sea ice and account for regions with missing data. Here we use CMIP5 climate model simulations to estimate how these choices affect reported warming and carbon budgets consistent with the Paris Agreement. By the 2090s, under a low-emissions scenario, modelled global near-surface air temperature rise is 15% higher (5%-95% range 6%-21%) than that estimated by an approach similar to the HadCRUT4 observational record. The difference reduces to 8% with global data coverage, or 4% with additional removal of a bias associated with changing sea-ice cover. Comparison of observational datasets with different data sources or infilling techniques supports our model results regarding incomplete coverage. From high-emission simulations, we find that a HadCRUT4 like definition means higher carbon budgets and later exceedance of temperature thresholds, relative to global near-surface air temperature. 2 °C warming is delayed by seven years on average, to 2048 (2035-2060), and CO2 emissions budget for a >50% chance of <2 °C warming increases by 67 GtC (246 GtCO2)

Additive growth inhibitory effects of ibandronate and antiestrogens in estrogen receptor-positive breast cancer cell lines

INTRODUCTION: Bisphosphonates are inhibitors of osteoclast-mediated tumor-stimulated osteolysis, and they have become standard therapy for the management of bone metastases from breast cancer. These drugs can also directly induce growth inhibition and apoptosis of osteotropic cancer cells, including estrogen receptor-positive (ER+) breast cancer cells. METHODS: We examined the anti-proliferative properties of ibandronate on two ER+ breast cancer cell lines (MCF-7 and IBEP-2), and on one ER negative (ER-) cell line (MDA-MB-231). Experiments were performed in steroid-free medium to assess ER regulation and the effect of ibandronate in combination with estrogen or antiestrogens. RESULTS: Ibandronate inhibited cancer cell growth in a dose- and time-dependent manner (approximate IC(50): 10(-4 )M for MCF-7 and IBEP-2 cells; 3 × 10(-4 )M for MDA-MB-231 cells), partly through apoptosis induction. It completely abolished the mitogenic effect induced by 17β-estradiol in ER+ breast cancer cells, but affected neither ER regulation nor estrogen-induced progesterone receptor expression, as documented in MCF-7 cells. Moreover, ibandronate enhanced the growth inhibitory action of partial (4-hydroxytamoxifen) and pure (ICI 182,780, now called fluvestrant or Faslodex™) antiestrogens in estrogen-sensitive breast cancer cells. Combination analysis identified additive interactions between ibandronate and ER antagonists. CONCLUSION: These data constitute the first in vitro evidence for additive effects between ibandronate and antiestrogens, supporting their combined use for the treatment of bone metastases from breast cancer

On order and disorder during the COVID-19 pandemic

Funding: Canadian Institute for Advanced Research.In this paper, we analyse the conditions under which the COVID‐19 pandemic will lead either to social order (adherence to measures put in place by authorities to control the pandemic) or to social disorder (resistance to such measures and the emergence of open conflict). Using examples from different countries (principally the United Kingdom, the United States, and France), we first isolate three factors which determine whether people accept or reject control measures. These are the historical context of state‐public relations, the nature of leadership during the pandemic and procedural justice in the development and operation of these measures. Second, we analyse the way the crisis is policed and how forms of policing determine whether dissent will escalate into open conflict. We conclude by considering the prospects for order/disorder as the pandemic unfolds.Publisher PDFPeer reviewe

Cardiac troponin and natriuretic peptide analytical interferences from hemolysis and biotin: educational aids from the IFCC Committee on Cardiac Biomarkers (IFCC C-CB).

Two interferences recently brought to the forefront as patient safety issues include hemolysis (hemoglobin) and biotin (vitamin B7). The International Federation for Clinical Chemistry Committee on Cardiac Biomarkers (IFCC-CB) obtained input from a majority of cTn and NP assay manufacturers to collate information related to high-sensitivity (hs)-cTnI, hs-cTnT, contemporary, and POC cTn assays, and NP assays interferences due to hemolysis and biotin. The information contained in these tables was designed as educational tools to aid laboratory professionals and clinicians in troubleshooting cardiac biomarker analytical results that are discordant with the clinical situation