Total Ionizing Dose Effects on TiN/Ti/HfO2/TiN Resistive Random-Access Memory Studied via Electrically Detected Magnetic Resonance.

We observe a gamma-irradiation induced change in electrically detected magnetic resonance (EDMR) in TiN/Ti/HfO2/TiN resistive random access memory (RRAM). EDMR measurements exclusively detect electrically active defects which are directly involved in the transport mechanisms within these devices. The EDMR response has an isotropic g-value of 2.001 ± 0.0003. The response increases dramatically with increased gamma-irradiation. We tentatively associate this EDMR response with spin dependent trap assisted tunneling (SDTAT) events at O 2 - centers coupled to hafnium ions. Although our study cannot fully identify the role of these defects in electronic transport, the study does unambiguously identify changes in transport defects caused by the ionizing radiation on defects involved in electronic transport in RRAM devices. This work also contributes more broadly to the RRAM field by providing direct, though incomplete, information about atomic scale defects involved in electronic transport in leading RRAM systems.

Systematic review of CT and MR perfusion imaging for assessment of acute cerebrovascular disease.

BACKGROUND AND PURPOSE: Perfusion imaging sequences are an important part of imaging studies designed to provide information to guide therapy for treatment of cerebrovascular disease. The purpose of this study was to perform a meta-analysis of the medical literature on perfusion imaging to determine its role in clinical decision making for patients with acute cerebral ischemia. MATERIALS AND METHODS: We searched MEDLINE by using a strategy that combined terms related to perfusion imaging with terms related to acute cerebral ischemia and brain tumors. We identified 658 perfusion imaging articles and classified them according to the clinical usefulness criteria of Thornbury and Fryback. We found 59 articles with promise of indicating usefulness in clinical decision making. We devised and implemented a clinical decision making scoring scale more appropriate to the topic of acute cerebral ischemia. RESULTS: Several articles provided important insights into the physiologic processes underlying acute cerebral ischemia by correlation of initial perfusion imaging deficits with clinical outcome or ultimate size of the infarct. However, most articles showed relatively low relevance to influencing decisions in implementing treatment. CONCLUSION: Most perfusion imaging articles are oriented toward important topics such as optimization of imaging parameters, determination of ischemia penumbra, and prediction of outcome. However, information as to the role of perfusion imaging in clinical decision making is lacking. Studies are needed to demonstrate that use of perfusion imaging changes outcome of patients with acute cerebral ischemia.

Oxygen for relief of dyspnoea in mildly- or non-hypoxaemic patients with cancer: a systematic review and meta-analysis.

The aim of this study was to determine the efficacy of palliative oxygen for relief of dyspnoea in cancer patients. MEDLINE and EMBASE were searched for randomised controlled trials, comparing oxygen and medical air in cancer patients not qualifying for home oxygen therapy. Abstracts were reviewed and studies were selected using Cochrane methodology. The included studies provided oxygen at rest or during a 6-min walk. The primary outcome was dyspnoea. Standardised mean differences (SMDs) were used to combine scores. Five studies were identified; one was excluded from meta-analysis due to data presentation. Individual patient data were obtained from the authors of the three of the four remaining studies (one each from England, Australia, and the United States). A total of 134 patients were included in the meta-analysis. Oxygen failed to improve dyspnoea in mildly- or non-hypoxaemic cancer patients (SMD=-0.09, 95% confidence interval -0.22 to 0.04; P=0.16). Results were stable to a sensitivity analysis, excluding studies requiring the use of imputed quantities. In this small meta-analysis, oxygen did not provide symptomatic benefit for cancer patients with refractory dyspnoea, who would not normally qualify for home oxygen therapy. Further study of the use of oxygen in this population is warranted given its widespread use.

Validation of feed and manure data collected on Wisconsin dairy farms.

An on-farm study of 54 representative Wisconsin dairy farms was conducted to evaluate the influence of biophysical and socioeconomic factors on overall feed, fertilizer, and manure nutrient use. This report validates 1) how well data on cow diets, feed analyses, and milk production reflected established feed-milk-manure relationships; and 2) how well farmer-recorded data on manure land application reflected literature values of manure N and P excretion, collection, and loss. Calculated feed N and P use efficiencies (18 to 33% and 18 to 35%, respectively) fell within ranges expected for dairy farms. This suggested that our on-farm methods of data collection provided reliable information on relationships among feed N and P intake, secretions in milk, and excretion in manure. On stanchion farms, there were no differences between farmer estimates (kg/farm) of manure P collected (1,140) and land-applied (1,210) and what would be calculated from the literature (1,340). On freestall farms, there were no differences in amounts (kg/farm) of manure P collected (2,889), land-applied (2,350), or literature estimates (2,675). Manure P applications (kg/ha) to tilled cropland would be similar using either farmer estimates of manure collected and land-applied, or literature estimates. The data provided a snapshot of Wisconsin industry practices, as well as information on the range of feed and manure management practices on individual dairy farms. Improvements to data collection methods would require increased skill and training of both farmers and those responsible for assisting farmers in on-farm data collection and analyses.

An audit of pre-operative skin preparative methods.

INTRODUCTION: A study into how pre-operative skin preparation varies between surgical units and surgeons. MATERIALS AND METHODS: A postal audit of general, vascular and thoracic surgeons in Northern Ireland was conducted together with a literature review to establish best practice. RESULTS: Overall, 73 surgeons were contacted, and 63 (86.3%) responded. There was marked variation in shaving of the operative site. A wide range of solutions was used, and 14 different sequences were employed. All surgeons used a swab or sponge to apply the solutions. Several drying methods were employed. CONCLUSIONS: There is variation in the method of skin preparation employed between surgical units and surgeons. There is limited evidence-based research on this topic. Recommendations are made as to best practice.

A survey of selected heavy metal concentrations in Wisconsin dairy feeds.

Heavy metals such as zinc (Zn), copper (Cu), chromium (Cr), arsenic (As), cadmium (Cd), and lead (Pb) are potential bioaccumulative toxins of the dairy production system. The heavy metal content of dairy feeds, however, remains poorly documented, particularly in the United States. This survey determined the heavy metal content of 203 typical dairy ration components sampled from 54 dairy farms in Wisconsin. Lowest heavy metal concentrations were found in homegrown alfalfa (Medicago sativa L.) hay and haylage, and corn (Zea mays L.) grain and silage. Highest metal concentrations were found in purchased feeds, particularly mineral supplements, and to a lesser extent corn- or soybean-based concentrates. Zinc and Cu were found at the highest concentration in complete dairy (total mixed and aggregated component) rations and reflected the deliberate addition of these metals to meet animal nutrient requirements although more than half the farms fed Cu and Zn above US recommended levels. Concentrations of Cr, As, Cd, and Pb were present in much lower concentrations and decreased in the order Cr > As > Pb > Cd. No complete Wisconsin dairy ration contained heavy metal concentrations above US maximum acceptable concentrations and would be unlikely to induce any toxic effects in dairy cattle. Concentrations of Cd in complete dairy rations were closest to US maximum acceptable concentrations, suggesting the greatest potential long-term risk to exceed US maximum acceptable concentrations if whole farm levels of Cd were to increase in the future. With the exception of Pb, the main sources of Zn, Cu, Cr, As, and Cd in the complete dairy feed ration originated from imported feed. The continued importation of heavy metals in dairy feed is likely to be associated with accumulation of these metals in soils where manure is applied. Although the cycling of many heavy metals through the dairy food chain will be limited by factors such as a soil's cation exchange capacity, pH, salinity, and phytotoxicity of the metal, these may be less limiting for Cd. It is important that sources of Cd in the dairy system are identified and minimized to prevent problems associated with Cd accumulation in the dairy soil system arising over the long-term.

How treatment priorities influence triptan preferences in clinical practice: perspectives of migraine sufferers, neurologists, and primary care physicians.

BACKGROUND: In treating migraine sufferers, physicians can choose from among seven triptans with different attributes. OBJECTIVE: To develop a system for selecting an oral triptan based on treatment priorities of migraine sufferers, neurologists, and primary care physicians (PCPs) in the United States, and evidence-based performance of triptans in clinical trials. METHODS: The TRIPSTAR project combines data on the treatment preferences of migraineurs and physicians with results from a meta-analysis of individual triptans, which evaluated their effectiveness on various clinical endpoints. Telephone interviews with migraine sufferers, neurol ogists, and PCPs were conducted to elicit individual views on the relative importance of a prespecified set of acute treatment outcomes. Four hundred and fifteen migraine sufferers, both triptan-experienced and triptan-naive, were interviewed. Also, 200 board-certified neurologists and 200 PCPs provided information on migraine patients from their clinical practice. A multiattribute decision model for selecting an oral triptan was constructed using attribute importance weights collected at telephone interview and the meta-analysis data, which were drawn from 53 clinical trials of 6 oral triptans. RESULTS: Efficacy attributes were rated significantly more important than tolerability or consistency in selecting an oral triptan, according to migraine sufferers and physicians. Freedom from cardiovascular adverse events was the most important tolerability attribute, according to migraine sufferers and physicians alike. Pain free at 1 h was the most important lower-level efficacy attribute for migraine sufferers, while sustained pain free was most important for physicians. When weighted treatment attributes were combined with meta-analysis data in a multi-attribute decision model, almotriptan 12.5 mg, eletriptan 80 mg, and rizatriptan 10 mg were significantly closer to the hypothetical ideal triptan than was suma triptan 100 mg. Triptans selected by the model were generally closer to the patient-specific ideal triptan than were the triptans prescribed by physicians. CONCLUSIONS: Almotriptan, eletriptan, and rizatriptan were the three triptans closest to the ideal, from the perspectives of migraine sufferers, PCPs, and neurologists alike. The TRIPSTAR model may be a potentially useful decision-support tool to help physicians select the triptan most likely to produce a successful outcome in migraine sufferers.

Cost of multiple sclerosis by level of disability: a review of literature.

We performed a review of the economic literature to identify what is known about the relationship between Expanded Disability Status Scale (EDSS) categories and cost of multiple sclerosis (MS). We sought cohort studies of patients with multiple sclerosis that described the costs attributed to each EDSS score and utilized specific inclusion criteria for the selection of 10 studies. We found that both direct and indirect costs rise continuously with increasing EDSS category, and this rise is qualitatively exponential. The rise in indirect costs appears at lower EDSS scores. The cost of a relapse occurring in any given EDSS category exceeds that associated with that particular EDSS category. Few studies comprehensively assessed the entire spectrum of the costs, and much of the literature is based on EDSS categories in coarse groupings. In spite of several variations between studies, one important conclusion that we can draw is that rise in cost is positively correlated to scores on the EDSS categories, and therefore agents with a capacity to prevent or arrest the rate of MS progression may affect the overall cost of MS.

The use of multiattribute decision models in evaluating triptan treatment options in migraine.

BACKGROUND: The physician treating patients with migraine is now able to choose from among seven triptans-almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan. These differ, to greater or lesser degrees, on a range of clinical attributes important for treatment selection. OBJECTIVE: To outline the basic principles of Multiattribute Decision Making (MADM) and describe how one such method-TOPSIS (Technique for Order Preference by Similarity to the Ideal Solution)-can be applied to evaluate the currently available triptans. METHODS: In an example application, summary data from a recent meta-analysis of 53 published and unpublished placebo-controlled trials of the oral triptans were combined in TOPSIS models with computer-generated attribute importance weights representing the entire range of possible values, That is, the relative performance of the triptans was explored across all logically possible combinations of relative importance of the treatment attributes available from the meta-analysis, and uncertainty was assessed based on the confidence intervals from the meta-analysis. RESULTS: When compared across the entire range of values for relative attribute importance, almotriptan, eletriptan and rizatriptan were more similar to a hypothetical ideal triptan and were more likely to appear in the top three closest to the hypothetical ideal, than were naratriptan, sumatriptan, and zolmitriptan. CONCLUSION: Using the TOPSIS model, almotriptan, eletriptan and rizatriptan were more likely to appear in the top three closest to the hypothetical ideal triptan.

TRIPSTAR: prioritizing oral triptan treatment attributes in migraine management.

Migraine can be associated with severe pain and is often very disabling. Optimal treatment should provide rapid and sustained, complete pain relief, be well tolerated and restore normal function. The seven commercially available triptans show differences in performance on individual treatment attributes. The TRIPSTAR multiattribute decision model compares the profiles of the oral triptans, using efficacy and tolerability data weighted for importance, to identify if measurable differences are clinically relevant. Application of the TRIPSTAR model was demonstrated at the Migraine Trust International Symposium 2002, where delegates collectively prioritized treatment attributes according to the needs of a specific patient case history. The TRIPSTAR model identified the preferred triptans for this patient. These three triptans, almotriptan 12.5 mg, eletriptan 80 mg and rizatriptan 10 mg, standout in a triptan meta-analysis, three TRIPSTAR surveys and in a demonstration of the TRIPSTAR model at a symposium in the USA. Taken together the findings suggest that some differences amongst triptans may be relevant in clinical practice.

Oral sumatriptan for acute migraine.

BACKGROUND: Migraine is a common neurovascular disorder characterized by recurrent episodes of disabling headache, autonomic nervous system dysfunction, and, in some patients, neurological aura symptoms. Sumatriptan is one of a class of selective serotonin 5-hydroxytryptamine (5-HT1B/1D) agonists (triptans) thought to relieve migraine attacks by several mechanisms, including cranial vasoconstriction and peripheral and central neural inhibition. OBJECTIVES: To describe and assess the evidence from randomized controlled trials (RCTs) concerning the efficacy and tolerability of oral sumatriptan for the treatment of a single acute attack of migraine in adults. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Cochrane Library, Issue 4, 2001), MEDLINE (1966 through November 2001), and reference lists of articles and books. SELECTION CRITERIA: We included double-blind RCTs comparing oral sumatriptan (100 mg, 50 mg, 25 mg) with placebo, no intervention, other drug treatments, behavioral therapy, or physical therapy for the treatment of an acute attack of migraine in adults. Trials comparing different doses of sumatriptan or dosing regimens were also included. Outcomes considered were: 2-hour pain-free response, headache relief/headache intensity, and functional disability; headache recurrence; and adverse events. DATA COLLECTION AND ANALYSIS: Data were abstracted by one reviewer and over-read by the other. The two reviewers independently assessed trial quality. Information on adverse events was collected from trial reports. MAIN RESULTS: Twenty-five trials involving 16,200 participants were included. Methodological quality was generally good. Sixteen trials were placebo comparisons and showed that sumatriptan in doses of 100 mg (14 trials), 50 mg (five trials), and 25 mg (three trials) provided significantly better pain-free response (100 mg and 25 mg only), headache relief, and relief of disability at 2 hours. Numbers-needed-to-treat (NNTs) for pain-free response at 2 hours were 5.1 (3.9 to 7.1) for the 100-mg dose (n = 2221) and 7.5 (2.7 to 142) for the 25-mg dose (n = 131); there was no significant difference between the 50-mg dose and placebo for this outcome (n = 127). For headache relief at 2 hours, NNTs were 3.4 (3.0 to 4.0), 3.2 (2.4 to 5.1), and 3.4 (2.3 to 6.6) for sumatriptan 100 mg (n = 2940), 50 mg (n = 420), and 25 mg (n = 226), respectively. Precise estimates of the efficacy of the 50- and 25-mg doses relative to the 100-mg dose could not be obtained. Adverse events were more common with sumatriptan 100 mg than with placebo (risk difference [RD] = 0.14 [0.09 to 0.20]; number-needed-to-harm [NNH] = 7.1 [5.0 to 11.1]; n = 3172). RDs for the 50- and 25-mg vs. placebo comparisons were not statistically significant. REVIEWER'S CONCLUSIONS: Oral sumatriptan has been shown to be an effective drug for the treatment of a single acute attack of migraine. It is well tolerated, though minor adverse events were not uncommon in the included trials. Other triptans were generally similar in efficacy and adverse events. Among non-triptan drugs, ergotamine + caffeine was significantly less effective than sumatriptan, and other drugs have been insufficiently studied to draw firm conclusions.

Host immune responses and intestinal permeability in patients with jaundice.

BACKGROUND: Systemic endotoxaemia is implicated in the development of complications associated with obstructive jaundice. The aims of these studies were to assess the systemic immune response to intervention in patients with jaundice and to compare the effects of surgical and non-surgical biliary drainage on host immune function and gut barrier function. METHODS: In the first study, 18 jaundiced and 12 control patients were studied to assess systemic immune responses before and after intervention. In the second study, immune responses and gut barrier function were assessed following surgical and non-operative biliary decompression in 45 patients with jaundice. RESULTS: Endotoxin antibody concentrations fell significantly in patients with jaundice immediately after surgical intervention, but not after non-operative biliary drainage. This decrease was associated with a significant increase in serum P(55) soluble tumour necrosis factor (sTNF) receptor concentration (5.3 versus 10.5 ng/ml; P < 0.001), urinary excretion of P(55) TNF receptors (21.4 versus 78.8 ng/ml; P = 0.002) and intestinal permeability (lactulose : mannitol ratio 0.032 versus 0.082; P = 0.048). Intestinal permeability was significantly increased in patients with jaundice compared with controls (0.033 versus 0.015; P = 0.002). CONCLUSION: These data suggest that obstructive jaundice is associated with impaired gut barrier function and activation of host immune function that is exacerbated by intervention. Surgery causes an exaggerated pathophysiological disturbance not seen with non-operative biliary drainage procedures.

Anti-cholinergic bronchodilators versus beta2-sympathomimetic agents for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Inhaled bronchodilators form the mainstay of treatment for acute exacerbations of COPD. Two types of agent are used routinely, either singly or in combination: anticholinergic agents and beta2-sympathomimetic agonists. OBJECTIVES: To assess the effect of anti-cholinergic agents on lung function and dyspnea in patients with acute exacerbations of COPD, compared with placebo or short-acting beta-2 agonists. SEARCH STRATEGY: A comprehensive search of the literature was carried out on MEDLINE, EMBASE, CINAHL and the Cochrane COPD Trials Register, using the terms: bronchodilator* OR ipratropium OR oxitropium. References listed in each included trial were searched for additional trial reports. SELECTION CRITERIA: Studies were included if the participants were adult patients with a known diagnosis of COPD and had symptoms consistent with criteria for acute exacerbation of COPD. All randomized controlled trials that compared inhaled ipratropium bromide or oxitropium bromide to appropriate controls were considered. Appropriate control treatments included placebo, other bronchodilating agents, or combination therapies. Studies of acute asthma or ventilated patients were excluded. DATA COLLECTION AND ANALYSIS: All trials that appeared to be relevant were assessed by two reviewers who independently selected trials for inclusion. Differences were resolved by consensus. MAIN RESULTS: Four trials compared the short-term effects of ipratropium bromide vs. a beta2-agonist. Short-term changes in FEV1 (up to 90 minutes) showed no significant difference between beta2-agonist and ipratropium bromide treated patients. The differences were similar among the studies and when combined: Weighted Mean Difference (WMD) 0.0 liters (95% Confidence Interval (95% CI) -0.19, 0.19). There was no significant additional increase in change in FEV1 on adding ipratropium to beta2-agonist: WMD 0.02 liter (95% CI -0.08, 0.12). Long-term effects (24 hours) of the ipratropium bromide and beta2-agonist treatment combination were similar: WMD 0.05 liters (95%CI -0.14, 0.05). Neither of two studies found significant changes in PaO2, either short- or long-term, with ipratropium vs. beta-agonist, although one showed an increase in PaO2 in subjects receiving ipratropium bromide at 60 minutes. Adverse drug reactions included dry mouth and tremor. REVIEWER'S CONCLUSIONS: There was no evidence that the degree of bronchodilation achieved with ipratropium bromide was greater than that using a short-acting beta2-agonist. The combination of a beta2-agonist and ipratropium did not appear to increase the effect on FEV1 more than either used alone.

Inhaled short-acting beta2-agonists versus ipratropium for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Inhaled short acting beta2 adrenergic agonists and ipratropium bromide are both used in the treatment of acute exacerbations of chronic obstructive pulmonary disease. OBJECTIVES: In patients with acute exacerbations of COPD to: 1. To assess the efficacy of short-acting beta-2 agonists against placebo; 2. Compare the efficacy of short-acting beta-2 agonists and ipratropium. SEARCH STRATEGY: A comprehensive search of the literature was carried out of EMBASE, MEDLINE, CINAHL and the Cochrane COPD trials register was carried out using the terms: bronchodilator* OR albuterol OR metaproterenol OR terbutaline OR isoetharine OR pirbuterol OR salbutamol OR beta-2 agonist. SELECTION CRITERIA: All trials that appeared to be relevant were assessed by two reviewers who independently selected trials for inclusion. Differences were resolved by consensus. DATA COLLECTION AND ANALYSIS: All trials that appeared to be relevant were assessed by two reviewers who independently selected trials for inclusion. Differences were resolved by consensus. References listed in each included trial were searched for additional trial reports. Trials were combined using Review Manager using a fixed effects model. The size of the treatment effects were tested for heterogeneity. MAIN RESULTS: We identified no placebo-controlled comparisons of beta-2 agonists. Three studies permitted comparison of ipratropium to an inhaled beta-2 agonist. These studies included a total of 103 patients. The beta2-agonists used were: fenoterol and metaproterenol. One study was a parallel group trial of regular therapy for seven days. The other two were cross over studies of single dose treatments, with efficacy measured 90 min post dose. There was no washout period between treatments. Both treatments produced an improvement in forced expiratory volume (FEV1) after 90 min in the range 150-250 ml. The was no difference between treatments, mean difference in FEV1 10 ml; 95% CI -220, 230 ml. In one small crossover study (n=10) there was a significant improvement in arterial PaO2 after 30 minutes with ipratropium (+5.8 mm Hg +/- 3.0 (SEM)) compared to metaproterenol (-6.2 +/- 1.2 mm Hg), but this was not significant at 90 min. There were no data concerning respiratory symptoms. The crossover studies showed no evidence of an additive effect of the two treatments, although they were not designed specifically to test this. REVIEWER'S CONCLUSIONS: There are few controlled trial data concerning the use of inhaled beta2-agonist agents in acute exacerbations of COPD and none that have compared these agents directly with placebo. None of the studies used the more modern beta2-agonists used most widely in this setting (salbutamol and terbutaline). Beta2-agonists and ipratropium both produce small improvements in FEV1, but beta2-agonists may worsen PaO2 for a period. We could not draw conclusions concerning possible additive effects.