437 research outputs found
Preservice teachers’ pictorial strategies for a multistep multiplicative fraction problem
Previous research has documented that preservice teachers (PSTs) struggle with under- standing fraction concepts and operations, and misconceptions often stem from their understanding of the referent whole. This study expands research on PSTs’ understanding of wholes by investigating pictorial strategies that 85 PSTs constructed for a multistep fraction task in a multiplicative context. The results show that many PSTs were able to construct valid pictorial strategies, and the strategies were widely diverse with respect to how they made sense of an unknown referent whole of a fraction in multiple steps, how they represented the wholes in their drawings, in which order they did multiple steps, and which type of model they used (area or set). Based on their wide range of pictorial strategies, we discuss potential benefits of PSTs’ construction of their own representations for a word problem in developing problem solving skills
A kinetic model explains why shorter and less affine enzyme-recruiting oligonucleotides can be more potent
Antisense oligonucleotides complementary to RNA targets promise generality and ease of drug design. The first systemically administered antisense drug was recently approved for treatment and others are in clinical development. Chemical modifications that increase the hybridization affinity of oligonucleotides are reasoned to confer higher potency, i.e., modified oligonucleotides can be dosed at lower concentrations to achieve the same effect. Surprisingly, shorter and less affine oligonucleotides sometimes display increased potency. To explain this apparent contradiction, increased uptake or decreased propensity to form structures have been suggested as possible mechanisms. Here, we provide an alternative explanation that invokes only the kinetics behind oligonucleotide-mediated cleavage of RNA targets. A model based on the law of mass action predicts, and experiments support, the existence of an optimal binding affinity. Exaggerated affinity, and not length per se, is detrimental to potency. This finding clarifies how to optimally apply high-affinity modifications in the discovery of potent antisense oligonucleotide drugs
Crural Index and extensive atherosclerosis of crural vessels are associated with long-term cardiovascular mortality in patients with symptomatic peripheral artery disease
Background and aims: Limited data exist on the association of the anatomical distribution of atherosclerotic lesions and the extent of atherosclerosis at defined arterial segments with life expectancy. We recently presented a new classification of the extent of atherosclerosis in crural vessels and showed that Crural Index (CIx) was associated with mid-term survival of symptomatic peripheral artery disease (PAD) patients. This study evaluates the significance of the extent of crural atherosclerosis on long-term cardiovascular mortality. Methods: 887 consecutive patients with PAD, admitted for digital subtraction angiography (DSA) at Turku University Hospital Department of Vascular Surgery (Turku, Finland) between January 1st, 2009 and July 30th, 2011, were retrospectively analysed. Each crural angiographic image was graded according to CIx criteria. Aorto-iliac and femoro-popliteal arterial segments were similarly graded according to modified TASC II criteria. CIx was used as the categorical variable for the extent of atherosclerosis in crural vessels for survival analysis. Survival was also evaluated with respect to which arterial segment was most severely affected. Causes of death were provided by the Cause of Death Registry of Statistics Finland, updated on January 23rd, 2017. Results: Altogether, 408 (46%) patients died during follow-up. The majority of deaths were due to cardiovascular causes (n = 246, 60%). Cardiovascular mortality was strongly associated with a high CIx (CIx III (Hazard ratio (HR) 2.16, Confidence interval (CI) 95% 1.23-3.80, p = 0.007)) and CIx IV (HR 3.513, 95% CI 1.93-4.565, p <0.001), as compared to CIx 0. In patients having the crural segment as the most severely affected arterial segment, cardiovascular mortality was significantly increased (HR 2.321, 95% CI 1.45-3.73, p <0.001), as was overall mortality (HR 2.177, 95% CI 1.53-3.10, p <0.001). Conclusions: High Crural Index and extensive crural vessel atherosclerosis are associated with long-term cardiovascular mortality, and both may serve as useful indicators of survival among patients with symptomatic PAD. (c) 2017 Elsevier B.V. All rights reserved.Peer reviewe
Meconium in the Amniotic Fluid of Pregnancies Complicated by Preterm Premature Rupture of Membranes Is Associated With Early Onset Neonatal Sepsis
Objective: This study was to determine the significance of meconium in the amniotic fluid of pregnancies complicated by preterm premature rupture of membranes (PPROM) without labor
Toe Pressure and Toe Brachial Index are Predictive of Cardiovascular Mortality, Overall Mortality, and Amputation Free Survival in Patients with Peripheral Artery Disease
Objective/Background: Peripheral haemodynamic parameters are used to assess the presence and severity of peripheral artery disease (PAD). The prognostic value of ankle brachial index (ABI) has been thoroughly delineated. Nonetheless, the relative usefulness of ankle pressure (AP), ABI, toe pressure (TP), and toe brachial index (TBI) in assessing patient outcome has not been investigated in a concurrent study setting. This study aimed to resolve the association of all four non-invasive haemodynamic parameters in clinically symptomatic patients with PAD with cardiovascular mortality, overall mortality, and amputation free survival (AFS). Methods: In total, 732 symptomatic patients with PAD admitted to the Department of Vascular Surgery for conventional angiography at Turku University Hospital, Turku, Finland, between January 2009 and August 2011 were reviewed retrospectively. Demographic factors, cardiovascular mortality, all-cause mortality, and above foot level amputations were obtained and assessed in relation to AP, ABI, TP, and TBI by means of Kaplan-Meier life tables and a multivariate Cox regression model. Results: The haemodynamic parameter that was associated with poor 36 month general outcome was TP <30 mmHg. Univariate Cox regression analysis of stratified values showed that TP and TBI associated significantly with mortality. In multivariate analysis both TP and TBI were associated with a significant risk of death. For TP <30 mmHg and TBI <0.25 the risk of cardiovascular mortality was hazard ratio [HR] 2.84, 95% confidence interval [CI] 1.75-4.61 [p Conclusion: Among non-invasive haemodynamic measurements and pressure indices both TP and TBI appear to be associated with cardiovascular and overall mortality and AFS for patients with PAD presenting symptoms of the disease. (C) 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.Peer reviewe
Stratigraphy, structure, and production history of the Trenton limestone (Ordovician) and adjacent strata in northwestern Ohio
Stencil Printing-A Novel Manufacturing Platform for Orodispersible Discs
Stencil printing is a commonly used printing method, but it has not previously been used for production of pharmaceuticals. The aim of this study was to explore whether stencil printing of drug containing polymer inks could be used to manufacture flexible dosage forms with acceptable mass and content uniformity. Formulation development was supported by physicochemical characterization of the inks and final dosage forms. The printing of haloperidol (HAL) discs was performed using a prototype stencil printer. Ink development comprised of investigations of ink rheology in combination with printability assessment. The results show that stencil printing can be used to manufacture HAL doses in the therapeutic treatment range for 6-17 year-old children. The therapeutic HAL dose was achieved for the discs consisting of 16% of hydroxypropyl methylcellulose (HPMC) and 1% of lactic acid (LA). The formulation pH remained above pH 4 and the results imply that the drug was amorphous. Linear dose escalation was achieved by an increase in aperture area of the print pattern, while keeping the stencil thickness fixed. Disintegration times of the orodispersible discs printed with 250 and 500 mu m thick stencils were below 30 s. In conclusion, stencil printing shows potential as a manufacturing method of pharmaceuticals
Are Canadian General Internal Medicine training program graduates well prepared for their future careers?
BACKGROUND: At a time of increased need and demand for general internists in Canada, the attractiveness of generalist careers (including general internal medicine, GIM) has been falling as evidenced by the low number of residents choosing this specialty. One hypothesis for the lack of interest in a generalist career is lack of comfort with the skills needed to practice after training, and the mismatch between the tertiary care, inpatient training environment and "real life". This project was designed to determine perceived effectiveness of training for 10 years of graduates of Canadian GIM programs to assist in the development of curriculum and objectives for general internists that will meet the needs of graduates and ultimately society. METHODS: Mailed survey designed to explore perceived importance of training for and preparation for various aspects of Canadian GIM practice. After extensive piloting of the survey, including a pilot survey of two universities to improve the questionnaire, all graduates of the 16 universities over the previous ten years were surveyed. RESULTS: Gaps (difference between importance and preparation) were demonstrated in many of the CanMEDS 2000/2005(® )competencies. Medical problems of pregnancy, perioperative care, pain management, chronic care, ambulatory care and community GIM rotations were the medical expert areas with the largest gaps. Exposure to procedural skills was perceived to be lacking. Some procedural skills valued as important for current GIM trainees and performed frequently (example ambulatory ECG interpretation) had low preparation ratings by trainees. Other areas of perceived discrepancy between training and practice included: manager role (set up of an office), health advocate (counseling for prevention, for example smoking cessation), and professional (end of life issues, ethics). CONCLUSION: Graduates of Canadian GIM training programs over the last ten years have identified perceived gaps between training and important areas for practice. They have identified competencies that should be emphasized in Canadian GIM programs. Ongoing review of graduate's perceptions of training programs as it applies to their current practice is important to ensure ongoing appropriateness of training programs. This information will be used to strengthen GIM training programs in Canada
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