Mapping drug calculation skills in an undergraduate nursing curriculum

The ability to calculate drug dosages correctly is an essential skill for registered nurses to possess. Performing drug calculations accurately is not a skill that new graduates have the luxury of developing over time. Drug errors are in many instances directly related to either the administration of an incorrect dose or incorrect infusion rate (Gladstone, 1995) caused by calculation errors. A strategy for implementing drug calculation skills into our new under graduate nursing curriculum was initiated to assist students in developing proficiency in drug calculations. The aim of this program is to promote the development of calculation skills in undergraduate nursing students, rather than simply assessing their skills.

Alteration of GSH level, gene expression and cell transformation in NIH3T3 cells by chronic exposure to low dose of arsenic

It is well established that arsenic toxicity is postulated to be primarily due to the binding of As(III) to sulfhydryl-containing enzymes. However, the mechanism of carcinogenesis induced by arsenic is still unclear. The interaction of arsenic with GSH and related enzymes seems a very important issue regarding mechanism of arsenical induced toxicity or carcinogenesis. The purpose of this work is to investigate the effect of chronic exposure to low dose of As(III) on GSH level, gene expression and cell transformation in NIH3T3 cells. The results showed that long-term, low dose arsenic treatment makes 3T3 cell more resistant to acute arsenic treatment. There were morphology changes after long-term arsenic treatment. First, partially immortalized 3T3 cell became immortalized. In addition, the cells were doubling more quickly than the control cells and attained higher density than the control cells at confluence. Second, cells treated with 0.1 µ.M As(III) exhibited anchorage-independent growth. Arsenic could enhance GSH level at 0.5 -10 µM dose of arsenic in 24 h treatment and decrease it at 25 µM and above. In long-term treatment with low dose of arsenic, GSH levels were decreased. As(I1I) can increase both glutathione S-transferase (GST) and glutathione reductase (GR) activities at low dose (0.5-10 M), but decreased GST and GR activities at 25 M and higher dose of arsenic, while in long-term As(III) treatment, GST and GR activities are increased. Both long-term and short-term treatments with As(III) can induce GR gene expression. GPx mRNA levels were decreased both in acute and chronic arsenic treated cells. Chronic treatment with As(III) also decreased the p53 mRNA level. Taken together, our results suggest that As(III) can alter GST, GR enzyme activities as well as GSH level and related gene expression both in long-term and short-term treatment but in a different manner in different doses. Alteration of cellular GSH level by As(III) might play all important role in gene expression and arsenic induced cell transformation.

Regulation of redox and DNA repair genes by arsenic : low dose protection against oxidative stress?

We have evaluated the molecular responses of human epithelial cells to low dose arsenic to ascertain how target cells may respond to physiologically relevant concentrations of arsenic. Data gathered in numerous experiments in different cell types all point to the same conclusion: low dose arsenic induces what appears to be a protective response against subsequent exposure to oxidative stress or DNA damage, whereas higher doses often provoke synergistic toxicity. In particular, exposure to low, sub-toxic doses of arsenite, As(III), causes coordinate up-regulation of multiple redox and redox-related genes including thioredoxin (Trx) and glutathione reductase (GR). Glutathione peroxidase (GPx) is down-regulated in fibroblasts, but up-regulated in keratinocytes, as is glutathione S-transferase (GST). The maximum effect on these redox genes occurs after 24 h exposure to 5–10 mM As(III). This is 10-fold higher than the maximum As(III) concentrations required for induction of DNA repair genes, but within the dose region where DNA repair genes are co-ordinately down-regulated. These changes in gene regulation are brought about in part by changes in DNA binding activity of the transcription factors activating protein-1 (AP-1), nuclear factor kappa-B, and cAMP response element binding protein (CREB). Although sub-acute exposure to micromolar As(III) up-regulates transcription factor binding, chronic exposure to submicromolar As(III) causes persistent down-regulation of this response. Similar long-term exposure to micromolar concentrations of arsenate in drinking water results in a decrease in skin tumour formation in dimethylbenzanthracene (DMBA)/phorbol 12-tetradecanoate 13-acetate (TPA) treated mice. Altered response patterns after long exposure to As(III) may play a significant role in As(III) toxicology in ways that may not be predicted by experimental protocols using short-term exposures.

Cycling at 120 when compared to 80 rev/min increases the accumulated oxygen deficit but does not affect the precision of its calculation

The aim of the present study was to determine the influence of pedal rate on the precision and quantification of the accumulated oxygen deficit (AOD). Eight trained male triathletes completed a lactate threshold test, VO2 peak test, 10 x 3 min submaximal exercise bouts and a high-intensity exercise bout, all performed at 80 and 120 rev/min. For both pedal rates the intensities for the sub-maximal and high-intensity tests were relative to the lactate threshold and VO2 peak work rates. The VO2-power regressions were calculated using 5 intensities from above the lactate threshold combined with a y intercept value with VO2 measured after 3 min of exercise. For the 120 compared to the 80 rev/min tests, the lactate threshold work rate (255±13 versus 276±47 Watts) (p<0.01) and VO2 peak work rate (352±17 versus 382±20, Watts) (p<0.05) were lower at 120 rev/m. Conversely, the VO2 peak and the VO2 measured during the exhaustive exercise were the same for both pedal rates (p>0.05). Using linear regression modelling the slope of the VO2-power regression (0.0112 versus 0.010 L/Watt) (p<0.01), the estimated total energy demand (ETED) (5.13±0.75 versus 4.89±0.88 L/min) and the AOD (4.27±0.94 versus 3.66±1.25 L) (p<0.05) were greater at 120 rev/m. However, the 95% confidence interval for the ETED and the standard error of the predicted value were the same for both pedal rates (p>0.05). Our results demonstrate that pedal rate effects the size but not the precision of the calculated AOD and should therefore be considered when developing an AOD protocol.

Arsenic, mode of action at biologically plausible low doses : what are the implications for low dose cancer risk?

Arsenic is an established human carcinogen. However, there has been much controversy about the shape of the arsenic response curve, particularly at low doses. This controversy has been exacerbated by the fact that the  mechanism(s) of arsenic carcinogenesis are still unclear and because there are few satisfactory animal models for arsenic-induced carcinogenesis. Recent epidemiological studies have shown that the relative risk for cancer among populations exposed to ≤60 ppb As in their drinking water is often lower than the risk for the unexposed control population. We have found that treatment of human keratinocyte and fibroblast cells with 0.1 to 1 μM arsenite (As^III) also produces a low dose protective effect against oxidative stress and DNA damage. This response includes increased transcription, protein levels and enzyme activity of several base excision repair genes, including DNA polymerase β and DNA ligase I. At higher concentrations (> 10 μM), As induces down-regulation of DNA repair, oxidative DNA damage and apoptosis. This low dose adaptive (protective) response by a toxic agent is known as hormesis and is characteristic of many agents that induce oxidative stress. A mechanistic model for arsenic carcinogenesis based on these data would predict that the low dose risk for carcinogenesis should be sub-linear. The threshold dose where toxicity outweighs protection is hard to predict based on in vitro dose response data, but might be estimated if one could determine the form (metabolite) and concentration of arsenic responsible for changes in gene regulation in the target tissues.

Injecting early years teaching with a strong dose of multiliteracies

Tech-savvy children elaborately dance through a myriad of informal and formal school and out-of-school literacy practices, sometimes leaving the adults who teach and care for them feeling like relics of yesterday. How can we harness what students bring to learning and reconcile that with what we have traditionally taught this age group? How do we leave our comfort zones and design meaningful experiences which transform learners (both young and not so young)?

Effect of low-dose mobile versus traditional epidural techniques on mode of delivery: a randomised controlled trial

Background

Epidural analgesia is the most effective labour pain relief but is associated with increased rates of instrumental vaginal delivery and other effects, which might be related to the poor motor function associated with traditional epidural. New techniques that preserve motor function could reduce obstetric intervention. We did a randomised controlled trial to compare low-dose combined spinal epidural and low-dose infusion (mobile) techniques with traditional epidural technique.
Methods

Between Feb 1, 1999, and April 30, 2000, we randomly assigned 1054 nulliparous women requesting epidural pain relief to traditional (n=353), low-dose combined spinal epidural (n=351), or low-dose infusion epidural (n=350). Primary outcome was mode of delivery, and secondary outcomes were progress of labour, efficacy of procedure, and effect on neonates. We obtained data during labour and interviewed women postnatally.
Findings

The normal vaginal delivery rate was 35·1% in the traditional epidural group, 42·7% in the low-dose combined spinal group (odds ratio 1·38 [95% CI 1·01–1·89]; p=0·04); and 42·9% in the low-dose infusion group (1·39 [1·01–1·90]; p=0·04). These differences were accounted for by a reduction in instrumental vaginal delivery. Overall, 5 min APGAR scores of 7 or less were more frequent with low-dose technique. High-level resuscitation was more frequent in the low-dose infusion group.

Simultaneous estimation of optical flow and object state: A modified approach to optical flow calculation

Differential optical flow methods are widely used within the computer vision community. They are classified as being either local, as in the Lucas-Kanade method, or global, as in the Horn-Schunck technique. As the physical dynamics of an object is inherently coupled into the behavior of its image in the video stream, in this paper, we use such dynamic parameter information in calculating optical flow when tracking a moving object using a video stream. Indeed, we use a modified error function in the minimization that contains physical parameter information. Further, the refined estimates of optical flow is used for better estimation of the physical parameters of the object in the simultaneous estimation of optical flow and object state(SEOS).

Feasibility study of partial recrystallisation in multi-pass hot deformation process and application to calculation of mean flow stress

A feasibility study for handling the partial recrystallisation in multi-pass hot deformation where the heterogeneity of microstructure of deformed austenite is inherently accompanied is presented. The proposed model is based on modification of the conventional model in which the microstructure of deformed austenite at each pass is simply taken as being homogeneous during the multi-pass deformation. The usefulness of the modified model has been demonstrated by applying it to a four-pass oval–round (or round–oval) rod rolling sequence. The recrystallised fraction, austenite grain size (AGS) and mean flow stress at each pass computed from the modified model has been compared with those from the conventional model. The result showed that the recrystallisation behaviour and evolution of AGS at a given pass were dependent on the modelling method of the partial recrystallisation in the multi-pass rolling for the case studied. As the rolling speed increased, the difference between the mean flow stresses calculated by the conventional model and the proposed model was gradually larger in accordance with the contribution of partial recrystallisation.

Impact of in vivo fatty acid oxidation blockade on glucose turnover and muscle glucose metabolism during low-dose AICAR infusion

AMPK plays a central role in influencing fuel usage and selection. The aim of this study was to analyze the impact of low-dose AMP analog 5-aminoimidazole-4-carboxamide-1-ß-D-ribosyl monophosphate (ZMP) on whole body glucose turnover and skeletal muscle (SkM) glucose metabolism. Dogs were restudied after prior 48-h fatty acid oxidation (FAOX) blockade by methylpalmoxirate (MP; 5 x 12 hourly 10 mg/kg doses). During the basal equilibrium period (0–150 min), fasting dogs (n = 8) were infused with [3-³H]glucose followed by either 2-h saline or AICAR (1.5–2.0 mg·kg^–1·min^–1) infusions. SkM was biopsied at completion of each study. On a separate day, the same protocol was undertaken after 48-h in vivo FAOX blockade. The AICAR and AICAR + MP studies were repeated in three chronic alloxan-diabetic dogs. AICAR produced a transient fall in plasma glucose and increase in insulin and a small decline in free fatty acid (FFA). Parallel increases in hepatic glucose production (HGP), glucose disappearance (Rd tissue), and glycolytic flux (GF) occurred, whereas metabolic clearance rate of glucose (MCR_g) did not change significantly. Intracellular SkM glucose, glucose 6-phosphate, and glycogen were unchanged. Acetyl-CoA carboxylase (ACC~pSer²²¹) increased by 50%. In the AICAR + MP studies, the metabolic responses were modified: the glucose was lower over 120 min, only minor changes occurred with insulin and FFA, and HGP and Rd tissue responses were markedly attenuated, but MCR_g and GF increased significantly. SkM substrates were unchanged, but ACC~pSer²²¹ rose by 80%. Thus low-dose AICAR leads to increases in HGP and SkM glucose uptake, which are modified by prior FA_ox blockade.

Low dose supplementation with two different marine oils does not reduce pro-inflammatory eicosanoids and cytokines in vivo

In view of the reported potential anti-inflammatory activity of the New Zealand green lipped mussel (NZGLM), we aimed to compare the effect of low dose marine oil supplementation, from mussels and fish, in reducing blood markers of inflammation. Thirty apparently healthy males and females were recruited from the general public in Melbourne, Australia to participate in a double blind, randomised, parallel intervention study. Subjects were consuming approximately 73 mg of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) daily in their background diet prior to the commencement of the intervention. Subjects were randomly assigned to consume either 2 mL/day of the NZGLM oil preparation (mixed with olive oil and dl-alpha-tocopherol) or fish oil preparation (also mixed with olive oil and dl-alpha-tocopherol) for six weeks. Two mL of the oils contained 241 mg and 181 mg of n-3 LCPUFA, respectively. Neutrophil phospholipid fatty acids, serum thromboxane B2 (TXB2), stimulated monocyte production of prostaglandin E2 (PGE2), interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNFalpha) were measured. During the intervention, the total intakes of n-3 LCPUFA from the background diet and the supplements were 199 mg/d and 173 mg/day for the NZGLM and FO groups, respectively. Following six weeks of supplementation, both groups showed a small, but significant increase in neutrophil phospholipid proportion of eicosapentaenoic acid. The NZGLM group also showed a significant increase in docosahexaenoic acid levels. There were no significant changes with time or treatment for TXB2, PGE2, IL-1 beta or TNFalpha. This study showed that low dose supplementation with n-3 LCPUFA from two different marine oil preparations showed no difference in inflammatory markers in this group of healthy individuals. Further studies are warranted including dose response trials and studies in populations with inflammatory conditions.

1-14C-Linoleic Acid distrubution in various tissue lipids of guinea pigs following an oral dose

A recent study on the metabolism of 1-¹⁴C-α-linolenic acid in the guinea pig revealed that the fur had the highest specific activity of all tissues examined, 48 h after dosing. The present study investigated the pattern of tissue lipid labeling following an oral dose of 1-¹⁴C-linoleic acid after the animals had been dosed for the same time as above. Guinea pigs were fed one of two diets with a constant linoleic acid content (18% total fatty acids) and a different content of α-linolenic acid (0.3 or 17.3%) from weaning for 3 wk and 1-¹⁴C-linoleic acid was given orally to each animal for 48 h prior to sacrifice. The most highly labeled tissues (dpm/mg of linoleic acid) were liver, followed by brain, lung and spleen, heart, kidney and adrenal and intestines, in both diet groups. The liver had almost a three-fold higher specific activity than skin and fur which was more extensively labeled than the adipose and carcass. Approximately two-thirds of the label in skin plus fur was found in the fur which, because of a low lipid mass, would indicate that the fur was highly labeled. All tissues derived from animals on the diet with the low α-linolenic acid level were significantly more labeled than the tissues from the animals on the high α-linolenic acid diet, by a factor of 1.5 to 3. The phospholipid fraction was the most highly labeled fraction in the liver, free fatty acids were the most labeled fraction in skin & fur, while triacyglycerols were the most labeled in the carcass and adipose tissue. In these tissues, more than 90% of the radioactivity was found in fatty acids with 2-double bonds in the tissue lipids. These data indicate that the majority of label found in guinea pig tissues 48 h after dosing was still associated with a fatty acid fraction with 2-double bonds, which suggests there was little metabolism of linoleic acid to more highly unsaturated fatty acids in this time frame. In this study, the labeling of guinea pig tissues with linoleic acid, 48 h after dosing, was quite different from the labeling with α-linolenic acid reported previously. The retention of the administered radioactivity from ¹⁴C-linoleic acid in the whole body lipids was 1.6 times higher in the group fed the low α-linolenic acid diet (diet contained a total of 1.8 g PUFA/100 g diet)compared with the group fed the high α-linolenic acid diet (diet contained 3.6 g PUFA/100 g diet). The lack of retention of ¹⁴C-labeled lipids in the whole body would be consistent with an increased rate of β-oxidation of the labeled fatty acid on the diet rich in PUFA, a result supported by other studies using direct measurement of labeled carbon dioxide.

Cost-effectiveness analysis of screening for lung cancer with low dose spiral CT (computed tomography) in the Australian setting

Introduction:
Low dose spiral computed tomography (CT) is a sensitive screening tool for lung cancer that is currently being evaluated in both non-randomised studies and randomised controlled trials.
Methods:
We conducted a quantitative decision analysis using a Markov model to determine whether, in the Australian setting, offering spiral CT screening for lung cancer to high risk individuals would be cost-effective compared with current practice. This exploratory analysis was undertaken predominantly from the perspective of the government as third-party funder. In the base-case analysis, the costs and health outcomes (life-years saved and quality-adjusted life years) were calculated in a hypothetical cohort of 10,000 male current smokers for two alternatives: (1) screen for lung cancer with annual CT for 5 years starting at age 60 year and treat those diagnosed with cancer or (2) no screening and treat only those who present with symptomatic cancer.
Results:
For male smokers aged 60–64 years, with an annual incidence of lung cancer of 552 per 100,000, the incremental cost-effectiveness ratio was $57,325 per life-year saved and $105,090 per QALY saved. For females aged 60–64 years with the same annual incidence of lung cancer, the cost-effectiveness ratio was $51,001 per life-year saved and $88,583 per QALY saved. The model was used to examine the relationship between efficacy in terms of the expected reduction in lung cancer mortality at 7 years and cost-effectiveness. In the base-case analysis lung cancer mortality was reduced by 27% and all cause mortality by 2.1%. Changes in the estimated proportion of stage I cancers detected by screening had the greatest impact on the efficacy of the intervention and the cost-effectiveness. The results were also sensitive to assumptions about the test performance characteristics of CT scanning, the proportion of lung cancer cases overdiagnosed by screening, intervention rates for benign disease, the discount rate, the cost of CT, the quality of life in individuals with early stage screen-detected cancer and disutility associated with false positive diagnoses. Given current knowledge and practice, even under favourable assumptions, reductions in lung cancer mortality of less than 20% are unlikely to be cost-effective, using a value of $50,000 per life-year saved as the threshold to define a “cost-effective” intervention.
Conclusion:
The most feasible scenario under which CT screening for lung cancer could be cost-effective would be if very high-risk individuals are targeted and screening is either highly effective or CT screening costs fall substantially.

Interlink decision making index (IDMI) : a simple tool/concept to assist decision making for sustainability part 2 : calculation and examples of IDMI

There is an apparent gap between the LCA or other assessment's outcomes and its effective application in the decision making process. It is needed to provide to the decision makers a simple, less human interfered mechanism that integrates all the key criteria (environmental, economic, technical and safety etc.). The proposed index: Interlink Decision Making Index (IDMI) has all these features: simple, interlink (all criteria) and automatically and quantified influence of critical criteria (ie. no human weighting needed) and is able to assist the multi-criteria decision making for sustainability based on the outcomes of specific assessments (eg. LCA, BIA etc.). The index represents a pure numerical value and does not necessarily have any physical meanings, but it reflects the total merits of a particular option once the normal decision making criteria and (up to two) critical criteria (Ce) have been chosen. Then, without arbitrarily weighting process, the comparison and selection of the best possible option, ie. decision can be made based on the derived IDMI results. Two hypothetical examples are presented in the part 2 of the paper to demonstrate the application of the IDMI concept and it's differences with the traditional "tabular method" in the decision making process.