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Abstract Background Intravenous recombinant tissue plasminogen activator (rtPA) is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit. Design International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rtPA in acute ischaemic stroke. Suitable patients had to be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracranial haemorrhage and stroke mimics. Results The initial pilot phase was double blind and then, on 01/08/2003, changed to an open design. Recruitment began on 05/05/2000 and closed on 31/07/2011, by which time 3035 patients had been included, only 61 (2%) of whom met the criteria for the 2003 European approval for thrombolysis. 1617 patients were aged over 80 years at trial entry. The analysis plan will be finalised, without reference to the unblinded data, and published before the trial data are unblinded in early 2012. The main trial results will be presented at the European Stroke Conference in Lisbon in May 2012 with the aim to publish simultaneously in a peer-reviewed journal. The trial result will be presented in the context of an updated Cochrane systematic review. We also intend to include the trial data in an individual patient data meta-analysis of all the relevant randomised trials. Conclusion The data from the trial will: improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of iv rtPA in acute ischaemic stroke; provide: new evidence on the balance of risk and benefit of intravenous rtPA among types of patients who do not clearly meet the terms of the current EU approval; and, provide the first large-scale randomised evidence on effects in patients over 80, an age group which had largely been excluded from previous acute stroke trials. Trial registration ISRCTN25765518

Abstract Background Clostridium sticklandii belongs to a cluster of non-pathogenic proteolytic clostridia which utilize amino acids as carbon and energy sources. Isolated by T.C. Stadtman in 1954, it has been generally regarded as a "gold mine" for novel biochemical reactions and is used as a model organism for studying metabolic aspects such as the Stickland reaction, coenzyme-B12- and selenium-dependent reactions of amino acids. With the goal of revisiting its carbon, nitrogen, and energy metabolism, and comparing studies with other clostridia, its genome has been sequenced and analyzed. Results C. sticklandii is one of the best biochemically studied proteolytic clostridial species. Useful additional information has been obtained from the sequencing and annotation of its genome, which is presented in this paper. Besides, experimental procedures reveal that C. sticklandii degrades amino acids in a preferential and sequential way. The organism prefers threonine, arginine, serine, cysteine, proline, and glycine, whereas glutamate, aspartate and alanine are excreted. Energy conservation is primarily obtained by substrate-level phosphorylation in fermentative pathways. The reactions catalyzed by different ferredoxin oxidoreductases and the exergonic NADH-dependent reduction of crotonyl-CoA point to a possible chemiosmotic energy conservation via the Rnf complex. C. sticklandii possesses both the F-type and V-type ATPases. The discovery of an as yet unrecognized selenoprotein in the D-proline reductase operon suggests a more detailed mechanism for NADH-dependent D-proline reduction. A rather unusual metabolic feature is the presence of genes for all the enzymes involved in two different CO2-fixation pathways: C. sticklandii harbours both the glycine synthase/glycine reductase and the Wood-Ljungdahl pathways. This unusual pathway combination has retrospectively been observed in only four other sequenced microorganisms. Conclusions Analysis of the C. sticklandii genome and additional experimental procedures have improved our understanding of anaerobic amino acid degradation. Several specific metabolic features have been detected, some of which are very unusual for anaerobic fermenting bacteria. Comparative genomics has provided the opportunity to study the lifestyle of pathogenic and non-pathogenic clostridial species as well as to elucidate the difference in metabolic features between clostridia and other anaerobes.

Abstract Background Before the widespread use of primary percutaneous coronary intervention (PCI) and glycoprotein IIb/IIIa inhibitors (GP IIb/IIIa) left ventricular (LV) thrombus formation had been reported to complicate up to 20% of acute myocardial infarctions (AMI). The incidence of LV thrombus formation with these treatment modalities is not well known. Methods 92 consecutive patients with ST-elevation AMI treated with PCI and GP IIb/IIIa inhibitors underwent 2-D echocardiograms, with and without echo contrast agent, within 24–72 hours. Results Only 4/92 (4.3%) had an LV thrombus, representing a significantly lower incidence than that reported in the pre-PCI era. Use of contrast agents did not improve detection of LV thrombi in our study. Conclusion The incidence of LV thrombus formation after acute MI, in the current era of rapid reperfusion, is lower than what has been historically reported.

Objective: To describe the research publication outputs from intervention research funded by Australia's National Health and Medical Research Council (NHMRC)., Design and Setting: Analysis of descriptive data and data on publication outputs collected between 23 July 2012 and 10 December 2013 relating to health intervention research project grants funded between 1 January 2003 and 31 December 2007., Main Outcome Measures: Stages of development of intervention studies (efficacy, effectiveness, replication, adaptation or dissemination of intervention); types of interventions studied; publication output per NHMRC grant; and whether interventions produced statistically significant changes in primary outcome variables., Results: Most of the identified studies tested intervention efficacy or effectiveness in clinical or community settings, with few testing the later stages of intervention development, such as replication, adaptation or dissemination. Studies focused largely on chronic disease treatment and management, and encompassed various medical and allied health disciplines. Equal numbers of studies had interventions that produced statistically significant results on primary outcomes, (27) and those that did not (27). The mean number of total published articles per grant was 3.3, with 2.0 articles per grant focusing on results, and the remainder covering descriptive, exploratory or methodological aspects of intervention research., Conclusions: Our study provides a benchmark for the publication outputs of NHMRC-funded health intervention research in Australia. Research productivity is particularly important for intervention research, where findings are likely to have more immediate and direct applicability to health policy and practice. Tracking research outputs in this way provides information on whether current research investment patterns match the need for evidence about health care interventions.

We compare the power output from a year of electricity generation data from one solar thermal plant, two solar photovoltaic (PV) arrays, and twenty Electric Reliability Council of Texas (ERCOT) wind farms. The analysis shows that solar PV electricity generation is approximately one hundred times more variable at frequencies on the order of 10(-3) Hz than solar thermal electricity generation, and the variability of wind generation lies between that of solar PV and solar thermal. We calculate the cost of variability of the different solar power sources and wind by using the costs of ancillary services and the energy required to compensate for its variability and intermittency, and the cost of variability per unit of displaced CO(2) emissions. We show the costs of variability are highly dependent on both technology type and capacity factor. California emissions data were used to calculate the cost of variability per unit of displaced CO(2) emissions. Variability cost is greatest for solar PV generation at $8-11 per MWh. The cost of variability for solar thermal generation is $5 per MWh, while that of wind generation in ERCOT was found to be on average $4 per MWh. Variability adds ~$15/tonne CO(2) to the cost of abatement for solar thermal power, $25 for wind, and $33-$40 for PV.

A medical record review was conducted to determine the clinical outcome and average time to resolution of verruca plantaris in 20 patients treated with twice-daily applications of either 0.5% or 5.0% topical fluorouracil combined with topical 17% and 40% salicylic acid. Seven patients used 0.5% fluorouracil, and 13 used 5.0% fluorouracil. All of the lesions were sharply debrided at regular 1- or 2-week intervals. All 20 patients achieved full clinical resolution in a mean +/- SD of 82.5 +/- 56.6 days. Three patients (15%) had recurrent lesions, which subsequently resolved with repeated treatment. Two patients (10%) developed local dermatitis, which resolved with temporary discontinuation of the medication and the addition of a topical corticosteroid. It was observed that the twice-daily application of topical fluorouracil and salicylic acid is a safe and effective treatment for verruca plantaris.

Endoscopic sphincterotomy has been used for the treatment of many biliary disorders, including extraction of obstructing common bile duct stones. Manometric studies of the sphincter of Oddi and the common bile duct have shown a marked decrease in biliary tract pressures after sphincterotomy. A prospective study of 12 patients with intact gallbladders using hepatobiliary imaging before and after sphincterotomy was performed to assess changes in bile dynamics. Nonfilling of the gallbladder occurred in 9 of the 12 patients after sphincterotomy, indicating significant alteration of bile flow. Such changes in bile dynamics may have serious implications in patients selected for medical dissolution of gallstones. It may also adversely affect specificity of cholescintigraphy in diagnosing acute cholecystitis.

We studied 56 cases of disseminated sclerosis, all during an attack of the disease and all presenting with symptoms of incoordination. The diagnosis was certain both clinically and biochemically. Out of this population, 64% of the patients had unprovoked nystagmus; of these patients 48% had central type nystagmus (multiple, vertical superior or vertical inferior, or bilateral "gaze nystagmus"). We investigated particularly abnormalities in the bithermic tests (vestibular hypovalency, directional preponderance of nystagmus, thermic preponderance) and in particular we studied an index which to the best of our knowledge has never been seriously and statistically investigated. We called this the bithermic reflexogenic index or BRI. We express abnormalities in this index in terms of a disharmony in the bithermic response of one or both vestibules. This index is expressed by the formula o cold + o hot/o cold-o hot x 10 which is the relative difference in the cold and hot test for the same vestibule. The normal index based on research in 180 normal vestibules, is always less than 20. The response is measured in frequency. The results of this study on bithermic tests allowed us to divide our DS population into two main groups: -- the first group comprised 36% of our cases. All the parametric indices are normal (directional preponderance of the nystagmus, thermic preponderance and bithermic reflexogenic index) but the presence of unprovoked nystagmus (88% of the group) is always associated with bilateral vestibular hypereflectivity; -- the second group comprised 64% of the DS patients studied. Unprovoked nystagmus was seen in 50%. All had normal vestibular reflexes or subnormal reflexes without clear cut hypovalency, associated with an abnormality either of directional preponderance of the nystagmus (30%) or of thermic preponderance (25%), or both combined (22%). But in all cases there was an abnormality of the bithermic reflexogenic index greater than 20. This abnormality seems to us to be the most frequent and the most typical. The specificity of this index is under study at the present time. One or another of these syndromes appearing in a young subject who does not have a past medical history of head injury or vascular accidents is strongly in favour of an attack of disseminated sclerosis.