A pedagogic appraisal of the Priority Heuristic

We have explored how science and mathematics teachers made decisions when confronted with a dilemma in which a fictitious young woman, Deborah, may choose to have an operation that might address a painful spinal condition. We sought to explore the extent to which psychological heuristic models, in particular the Priority Heuristic, might successfully describe the decision-making process of these teachers and how an analysis of the role of personal and emotional factors in shaping the decision-making process might inform pedagogical design. A novel aspect of this study is that the setting in which the decision-making process is examined contrasts sharply with those used in psychological experiments. We found that to some extent, even in this contrasting setting, the Priority Heuristic could describe these teachers' decision-making. Further analysis of the transcripts yielded some insights into limitations on scope as well the richness and complexity in how personal factors were brought to bear. We see these limitations as design opportunities for educational intervention

Maternal psychological distress in primary care and association with child behavioural outcomes at age three

Observational studies indicate children whose mothers have poor mental health are at increased risk of socio-emotional behavioural difficulties, but it is unknown whether these outcomes vary by the mothers’ mental health recognition and treatment status. To examine this question, we analysed linked longitudinal primary care and research data from 1078 women enrolled in the Born in Bradford cohort. A latent class analysis of treatment status and self-reported distress broadly categorised women as (a) not having a common mental disorder (CMD) that persisted through pregnancy and the first 2 years after delivery (N = 756, 70.1 %), (b) treated for CMD (N = 67, 6.2 %), or (c) untreated (N = 255, 23.7 %). Compared to children of mothers without CMD, 3-year-old children with mothers classified as having untreated CMD had higher standardised factor scores on the Strengths and Difficulties Questionnaire (d = 0.32), as did children with mothers classified as having treated CMD (d = 0.27). Results were only slightly attenuated in adjusted analyses. Children of mothers with CMD may be at risk for socio-emotional and behavioural difficulties. The development of effective treatments for CMD needs to be balanced by greater attempts to identify and treat women. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00787-015-0777-2) contains supplementary material, which is available to authorized users

Identifying Resistance Mechanisms against Five Tyrosine Kinase Inhibitors Targeting the ERBB/RAS Pathway in 45 Cancer Cell Lines

Because of the low overall response rates of 10-47% to targeted cancer therapeutics, there is an increasing need for predictive biomarkers. We aimed to identify genes predicting response to five already approved tyrosine kinase inhibitors. We tested 45 cancer cell lines for sensitivity to sunitinib, erlotinib, lapatinib, sorafenib and gefitinib at the clinically administered doses. A resistance matrix was determined, and gene expression profiles of the subsets of resistant vs. sensitive cell lines were compared. Triplicate gene expression signatures were obtained from the caArray project. Significance analysis of microarrays and rank products were applied for feature selection. Ninety-five genes were also measured by RT-PCR. In case of four sunitinib resistance associated genes, the results were validated in clinical samples by immunohistochemistry. A list of 63 top genes associated with resistance against the five tyrosine kinase inhibitors was identified. Quantitative RT-PCR analysis confirmed 45 of 63 genes identified by microarray analysis. Only two genes (ANXA3 and RAB25) were related to sensitivity against more than three inhibitors. The immunohistochemical analysis of sunitinib-treated metastatic renal cell carcinomas confirmed the correlation between RAB17, LGALS8, and EPCAM and overall survival. In summary, we determined predictive biomarkers for five tyrosine kinase inhibitors, and validated sunitinib resistance biomarkers by immunohistochemistry in an independent patient cohort. © 2013 Pénzváltó et al

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

Endotracheal tubes and fluid aspiration: An in vitro evaluation of new cuff technologies

© 2017 The Author(s). Background: Aspiration of subglottic secretions past the endotracheal tube (ETT) cuff is a prerequisite for developing ventilator-associated pneumonia (VAP). Subglottic secretion drainage (SSD) ETTs reduce aspiration of subglottic secretions and have demonstrated lower VAP rates. We compared the performance of seven SSD ETTs against a non-SSD ETT in preventing aspiration below inflated cuffs. Methods: ETTs were positioned vertically in 2 cm diameter cylinders. Four ml of a standard microbial suspension was added above inflated cuffs. After 1 h, aspiration was measured and ETTs demonstrating no leakage were subjected to rotational movement and evaluation over 24 h. Collected aspirated fluid was used to inoculate agar media and incubated aerobically at 37 °C for 24 h. The aspiration rate, volume and number of microorganisms that leaked past the cuff was measured. Experiments were repeated (×10) for each type of ETT, with new ETTs used for each repeat. Best performing ETTs were then tested in five different cylinder diameters (1.6, 1.8, 2.0, 2.2 and 2.4 cm). Experiments were repeated as above using sterile water. Volume and time taken for aspiration past the cuff was measured. Experiments were repeated (×10) for each type of ETT. Results were analysed using non-parametric tests for repeated measures. Results: The PneuX ETT prevented aspiration past the cuff in all experiments. All other ETTs allowed aspiration, with considerable variability in performance. The PneuX ETT was statistically superior in reducing aspiration compared to the SealGuard (p < 0.009), KimVent (p < 0.002), TaperGuard (p < 0.004), Lanz (p < 0.001), ISIS (p < 0.001), SACETT (p < 0.001) and Soft Seal (p < 0.001) ETTs. Of the 4 ETTs tested in differing cylinder sizes, the PneuX significantly reduced aspiration across the range of diameters compared to the SealGuard (p < 0.0001), TaperGuard (p < 0.0001) and KimVent (p < 0.0001) ETTs. Conclusions: ETTs showed substantial variation in fluid aspiration, relating to cuff material and design. Variability in performance was likely due to the random manner in which involutional folds form in the inflated ETT cuff. The PneuX ETT was the only ETT able to consistently prevent aspiration past the cuff in all experiments