Ice crushing occurs to varying degrees in many situations including those that involve a sliding frictional component, such as in sports involving ice contact, ice interaction with bridges, piers, ...ship hulls, vehicle wheels, rock beds under glaciers and ice-on-ice sliding/crushing interaction within glaciers and extraterrestrial ice masses (on Saturn's moon Enceladus). Here results of ice crushing-friction experiments on high-roughness surfaces with regular arrays of small prominences are presented. Friction coefficients were extraordinarily low and were proportional to the ratio of the tangential sliding rate and the normal crushing rate. All of the friction coefficient variation was determined by the fluid dynamics of a slurry that flowed through channels that developed between leeward-facing facets of the prominences and the moving ice. The slurry originated from a highly-lubricating self-generating squeeze film of ice particles and melt located between the encroaching intact ice and the surfaces.
•Fluid-dynamic mechanisms govern ice crushing-friction on high-roughness surfaces.•Very low friction coefficients occur when ice is crushed on high-roughness surfaces.•An ice/melt slurry flows through channels at leeward faces of surface prominences.•A highly-lubricating ice/melt squeeze film occurs when ice is crushed on surfaces.
Medical Education 2012: 46: 552–563
Context Programmes of assessment should measure the various components of clinical competence. Clinical reasoning has been traditionally assessed using written ...tests and performance‐based tests. The script concordance test (SCT) was developed to assess clinical data interpretation skills. A recent review of the literature examined the validity argument concerning the SCT. Our aim was to provide potential users with evidence‐based recommendations on how to construct and implement an SCT.
Methods A systematic review of relevant databases (MEDLINE, ERIC Education Resources Information Centre, PsycINFO, the Research and Development Resource Base RDRB, University of Toronto) and Google Scholar, medical education journals and conference proceedings was conducted for references in English or French. It was supplemented by ancestry searching and by additional references provided by experts.
Results The search yielded 848 references, of which 80 were analysed. Studies suggest that tests with around 100 items (25–30 cases), of which 25% are discarded after item analysis, should provide reliable scores. Panels with 10–20 members are needed to reach adequate precision in terms of estimated reliability. Panellists’ responses can be analysed by checking for moderate variability among responses. Studies of alternative scoring methods are inconclusive, but the traditional scoring method is satisfactory. There is little evidence on how best to determine a pass/fail threshold for high‐stakes examinations.
Conclusions Our literature search was broad and included references from medical education journals not indexed in the usual databases, conference s and dissertations. There is good evidence on how to construct and implement an SCT for formative purposes or medium‐stakes course evaluations. Further avenues for research include examining the impact of various aspects of SCT construction and implementation on issues such as educational impact, correlations with other assessments, and validity of pass/fail decisions, particularly for high‐stakes examinations.
Discuss ideas arising from this article at ‘discuss’
The receptors for hepatocyte and vascular endothelial cell growth factors (MET and VEGFR2, respectively) are critical oncogenic mediators in gastric adenocarcinoma. The purpose is to examine the ...safety and efficacy of foretinib, an oral multikinase inhibitor targeting MET, RON, AXL, TIE-2, and VEGFR2 receptors, for the treatment of metastatic gastric adenocarcinoma.
Foretinib safety and tolerability, and objective response rate (ORR) were evaluated in patients using intermittent (240 mg/day, for 5 days every 2 weeks) or daily (80 mg/day) dosing schedules. Thirty evaluable patients were required to achieve alpha = 0.10 and beta = 0.2 to test the alternative hypothesis that single-agent foretinib would result in an ORR of ≥ 25%. Up to 10 additional patients could be enrolled to ensure at least eight with MET amplification. Correlative studies included tumor MET amplification, MET signaling, pharmacokinetics and plasma biomarkers of foretinib activity.
From March 2007 until October 2009, 74 patients were enrolled; 74% male; median age, 61 years (range, 25-88); 93% had received prior therapy. Best response was stable disease (SD) in 10 (23%) patients receiving intermittent dosing and five (20%) receiving daily dosing; SD duration was 1.9-7.2 months (median 3.2 months). Of 67 patients with tumor samples, 3 had MET amplification, one of whom had SD. Treatment-related adverse events occurred in 91% of patients. Rates of hypertension (35% vs. 15%) and elevated aspartate aminotransferase (23% vs. 8%) were higher with intermittent dosing. In both patients with high baseline tumor phospho-MET (pMET), the pMET:total MET protein ratio decreased with foretinib treatment.
These results indicate that few gastric carcinomas are driven solely by MET and VEGFR2, and underscore the diverse molecular oncogenesis of this disease. Despite evidence of MET inhibition by foretinib, single-agent foretinib lacked efficacy in unselected patients with metastatic gastric cancer.
To describe the etiology of vasa previa and the risk factors and associated condition, to identify the various clinical presentations of vasa previa, to describe the ultrasound tools used in its ...diagnosis, and to describe the management of vasa previa.
Reduction of perinatal mortality, short-term neonatal morbidity, long-term infant morbidity, and short-term and long-term maternal morbidity and mortality.
Published literature on randomized trials, prospective cohort studies, and selected retrospective cohort studies was retrieved through searches of PubMed or Medline, CINAHL, and the Cochrane Library, using appropriate controlled vocabulary (e.g., selected epidemiological studies comparing delivery by Caesarean section with vaginal delivery; studies comparing outcomes when vasa previa is diagnosed antenatally vs. intrapartum) and key words (e.g., vasa previa). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Searches were updated on a regular basis and incorporated into the guideline to October 1, 2008. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and from national and international medical specialty societies.
The evidence collected was reviewed by the Diagnostic Imaging Committee and the Maternal Fetal Medicine Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) and quantified using the evaluation of evidence guidelines developed by the Canadian Task Force on Preventive Health Care.
The benefit expected from this guideline is facilitation of optimal and uniform care for pregnancies complicated by vasa previa.
The Society of Obstetricians and Gynaecologists of Canada.
A comparison of women who were diagnosed antenatally and those who were not shows respective neonatal survival rates of 97% and 44%, and neonatal blood transfusion rates of 3.4% and 58.5%, respectively. Vasa previa can be diagnosed antenatally, using combined abdominal and transvaginal ultrasound and colour flow mapping; however, many cases are not diagnosed, and not making such a diagnosis is still acceptable. Even under the best circumstances the false positive rate is extremely low. (II-2) RECOMMENDATIONS.
A full-scale 3D numerical simulation model of ice-induced vibration of structures has been developed (using LS-Dyna™) and applied to the Molikpaq facility for an ice-encroachment event similar to ...that which occurred on May 12, 1986 in the Beaufort Sea. The bulk ice sheet used for the simulations had elastic properties, and its dimensions were 6 km × 6 km × 2.5 m. Where ice crushing occurred at the structure-ice interface the ice model used was a crushable foam that incorporated regular spallation events. Typical characteristics of ice-crushing in the brittle regime were manifested by the model. That is, a narrow horizontal hard zone (relatively-intact high-interface-pressure ice) was present in the mid-height region of the ice-edge contact area. Soft-zone material (shattered spall debris from the hard zone) was also represented. Evolution of the hard-zone contact area involved rapid reductions in size during spallation events, immediately followed by fast growth during consequent elastic surging of the near-field ice sheet and structure towards each other, and then some slower growth (due to the bulk ice-sheet velocity) until the next spalling event. The specified ‘thickness’ of the spalls was 5.4 cm, as previously determined from Molikpaq records of the frequency of the spalling events as a function of ice-sheet speed. Spallation (and associated rapid drops in load) occurred at regular intervals whenever a critical amount of hard-zone stress was reached at the ice-structure interface. The amplitude of the Molikpaq repetitive movements in response to the sawtooth loading from the spalling events depended on whether the resonant frequency of the structure/ice system was higher (for a strong response) or lower (for a weak response) than the spalling frequency, where the spalling frequency is directly proportional to the ice-sheet speed. The continuously variable resonant frequency of the structure/ice system had a maximal limiting value (~ 2.1 Hz), designated as the At-Spallation-Resonant-Frequency (ASRF), that was essentially determined by the time duration of load drops at spallation events. The simulations inherently accounted for the variable effective mass and effective spring constant of the ice sheet.
•A 3D numerical simulation of ice-induced vibration of structures was developed•Ice spallations from hard zones generate sawtooth load patterns in the model•The resonant frequency of the structure-ice system influences the structure response•The At-Spallation-Resonant-Frequency of the structure/ice system is maximal•The resonant frequency of the structure-ice system varies with the spalling rate
Introduction
In a script concordance test (SCT), examinees are asked to judge the effect of a new piece of clinical information on a proposed hypothesis. Answers are collected using a Likert-type ...scale (ranging from −2 to +2, with ‘0’ indicating no effect), and compared with those of a reference panel of ‘experts’. It has been argued, however, that SCT may be susceptible to the influences of gaming and guesswork. This study aims to address some of the mounting concern over the response process validity of SCT scores.
Method
Using published datasets from three independent SCTs, we investigated examinee response patterns, and computed the score a hypothetical examinee would obtain on each of the tests if he 1) guessed random answers and 2) deliberately answered ‘0’ on all test items.
Results
A simulated random guessing strategy led to scores 2 SDs below mean scores of actual respondents (Z-scores −3.6 to −2.1). A simulated ‘all-0’ strategy led to scores at least 1 SD
above
those obtained by random guessing (Z-scores −2.2 to −0.7). In one dataset, stepwise exclusion of items with modal panel response ‘0’ to fewer than 10% of the total number of test items yielded hypothetical scores 2 SDs below mean scores of actual respondents.
Discussion
Random guessing was not an advantageous response strategy. An ‘all-0’ response strategy, however, demonstrated evidence of artificial score inflation. Our findings pose a significant threat to the SCT’s validity argument. ‘Testwiseness’ is a potential hazard to all testing formats, and appropriate countermeasures must be established. We propose an approach that might be used to mitigate a potentially real and troubling phenomenon in script concordance testing. The impact of this approach on the content validity of SCTs merits further discussion.
Preeclampsia (PrE) is a leading complication of pregnancy characterized by vascular dysfunction. Characterizing the longitudinal changes in vascular function prior to PrE onset is critical to the ...identification of optimal timepoints for vascular assessment and the development of effective early screening strategies.
In this prospective longitudinal study of women with singleton high-risk pregnancies, arterial stiffness and wave reflection parameters were assessed using applanation tonometry at 10–13 weeks' gestation and repeated every 4 weeks throughout pregnancy. Changepoints in carotid-femoral pulse wave velocity (cfPWV), carotid-radial PWV (crPWV), augmentation index (AIx), time to wave reflection (T1R), pulse pressure amplification (PPA), and subendocardial viability ratio (SEVR) were compared between women who did and did not subsequently develop PrE.
A changepoint in cfPWV and crPWV was detected at 14–17 weeks' gestation. cfPWV then increased in women who went on to develop PrE but decreased in women who did not; a 1.2 m/s difference in cfPWV between the groups was observed at 22–25 weeks' gestation. Conversely, crPWV converged in the two groups from a baseline difference of 1.05 m/s (95% credible interval: 0.37, 1.72). Women who subsequently developed PrE demonstrated an increase in AIx at 18–21 weeks' gestation that was not seen in women who did not develop PrE until 30–33 weeks. No differences in T1R, PPA, or SEVR were observed between the groups.
Altered vascular adaptations were detected using measures of arterial stiffness and wave reflection in the early second trimester of pregnant women who developed PrE compared to those who did not. These findings demonstrate the potential clinical utility of arterial stiffness and wave reflection parameters as an early screening tool for PrE, which can be used to inform clinical management of high-risk pregnancies.
•Altered vascular adaptations in women with PrE were noted early in the second trimester.•A changepoint in cfPWV was detected at 14–17 weeks.•cfPWV was higher by 1.2 m/s at 22–25 weeks in women who developed PrE.•AIx increased at 18–21 weeks in women with PrE, while at 30–33 weeks in those without.
Diabetes in Pregnancy Berger, Howard; Gagnon, Robert; Sermer, Mathew ...
Journal of obstetrics and gynaecology Canada,
07/2016, Letnik:
38, Številka:
7
Journal Article
Recenzirano
This guideline reviews the evidence relating to the diagnosis and obstetrical management of diabetes in pregnancy.
The outcomes evaluated were short- and long-term maternal outcomes, including ...preeclampsia, Caesarean section, future diabetes, and other cardiovascular complications, and fetal outcomes, including congenital anomalies, stillbirth, macrosomia, birth trauma, hypoglycemia, and long-term effects.
Published literature was retrieved through searches of PubMed and the Cochrane Library using appropriate controlled vocabulary (MeSH terms "diabetes" and "pregnancy"). Where appropriate, results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date limits, but results were limited to English or French language materials.
The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1).
Recommendations It is recognized that the use of different diagnostic thresholds for the "preferred" and "alternative" strategies could cause confusion in certain settings. Despite this, the committee has identified the importance of remaining aligned with the current Canadian Diabetes Association 2013 guidelines as being a priority. It is thus recommended that each care centre strategically align with 1 of the 2 strategies and implement protocols to ensure consistent and uniform reporting of test results.
This phase I/II single-arm study evaluated the safety, pharmacokinetics, pharmacodynamics, and activity of foretinib, an oral multikinase inhibitor of MET, ROS, RON, AXL, TIE-2, and VEGFR2, in the ...first-line setting in advanced hepatocellular carcinoma patients.
In the phase I part, advanced hepatocellular carcinoma patients were dose escalated on foretinib (30-60 mg) every day using the standard 3+3 design. Once the maximum tolerated dose (MTD) was determined, an additional 32 patients were dosed at the MTD in the phase II expansion cohort for assessment of efficacy and safety. Exploratory analyses were conducted to assess potential biomarkers that might correlate with clinical efficacy and survival.
The MTD of foretinib was established as 30 mg every day. The most frequent adverse events were hypertension, decreased appetite, ascites, and pyrexia. When dosed at 30 mg every day in the first-line setting, foretinib demonstrated promising antitumor activity. According to the modified mRECIST, the objective response rate was 22.9%, the disease stabilization rate 82.9%, and the median duration of response 7.6 months. The median time to progression was 4.2 months and the median overall survival (OS) was 15.7 months. Fifteen candidate biomarkers whose levels in the circulation were significantly altered in response to foretinib treatment were elucidated. Multivariate analyses identified IL6 and IL8 as independent predictors of OS.
Foretinib demonstrated promising antitumor activity and good tolerability in the first-line setting in Asian advanced hepatocellular carcinoma patients. Baseline plasma levels of IL6 or IL8 might predict the response to foretinib.
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