Radiation effects on silver and zinc battery electrodes, III Interim report, Oct. 1965 - Jan. 1966

Radiation effects on silver-zinc battery electrode

Chemical-genetic attenuation of focal neocortical seizures.

Focal epilepsy is commonly pharmacoresistant, and resective surgery is often contraindicated by proximity to eloquent cortex. Many patients have no effective treatment options. Gene therapy allows cell-type specific inhibition of neuronal excitability, but on-demand seizure suppression has only been achieved with optogenetics, which requires invasive light delivery. Here we test a combined chemical-genetic approach to achieve localized suppression of neuronal excitability in a seizure focus, using viral expression of the modified muscarinic receptor hM4Di. hM4Di has no effect in the absence of its selective, normally inactive and orally bioavailable agonist clozapine-N-oxide (CNO). Systemic administration of CNO suppresses focal seizures evoked by two different chemoconvulsants, pilocarpine and picrotoxin. CNO also has a robust anti-seizure effect in a chronic model of focal neocortical epilepsy. Chemical-genetic seizure attenuation holds promise as a novel approach to treat intractable focal epilepsy while minimizing disruption of normal circuit function in untransduced brain regions or in the absence of the specific ligand

The 'four principles of bioethics' as found in 13(th) century Muslim scholar Mawlana's teachings

BACKGROUND: There have been different ethical approaches to the issues in the history of philosophy. Two American philosophers Beachump and Childress formulated some ethical principles namely 'respect to autonomy', 'justice', 'beneficence' and 'non-maleficence'. These 'Four Principles' were presented by the authors as universal and applicable to any culture and society. Mawlana, a great figure in Sufi tradition, had written many books which not only guide people how to worship God to be close to Him, but also advise people how to lead a good life to enrich their personality, as well as to create a harmonious society and a peaceful world. METHODS: In this study we examined the major works of Mawlana to find out which of these 'Four Principles of Bioethics' exist in Mawlana's ethical understanding. RESULTS: We have found in our study that all these principles exist in Mawlana's writings and philosophy in one form or another. CONCLUSIONS: We have concluded that, further to Beachump and Childress' claim that these principles are universal and applicable to any culture and society, these principles have always existed in different moral traditions in different ways, of which Mawlana's teaching might be presented as a good example

Development of an invasively monitored porcine model of acetaminophen-induced acute liver failure

Background: The development of effective therapies for acute liver failure (ALF) is limited by our knowledge of the pathophysiology of this condition, and the lack of suitable large animal models of acetaminophen toxicity. Our aim was to develop a reproducible invasively-monitored porcine model of acetaminophen-induced ALF. Method: 35kg pigs were maintained under general anaesthesia and invasively monitored. Control pigs received a saline infusion, whereas ALF pigs received acetaminophen intravenously for 12 hours to maintain blood concentrations between 200-300 mg/l. Animals surviving 28 hours were euthanased. Results: Cytochrome p450 levels in phenobarbital pre-treated animals were significantly higher than non pre-treated animals (300 vs 100 pmol/mg protein). Control pigs (n=4) survived 28-hour anaesthesia without incident. Of nine pigs that received acetaminophen, four survived 20 hours and two survived 28 hours. Injured animals developed hypotension (mean arterial pressure; 40.8+/-5.9 vs 59+/-2.0 mmHg), increased cardiac output (7.26+/-1.86 vs 3.30+/-0.40 l/min) and decreased systemic vascular resistance (8.48+/-2.75 vs 16.2+/-1.76 mPa/s/m3). Dyspnoea developed as liver injury progressed and the increased pulmonary vascular resistance (636+/-95 vs 301+/-26.9 mPa/s/m3) observed may reflect the development of respiratory distress syndrome. Liver damage was confirmed by deterioration in pH (7.23+/-0.05 vs 7.45+/-0.02) and prothrombin time (36+/-2 vs 8.9+/-0.3 seconds) compared with controls. Factor V and VII levels were reduced to 9.3 and 15.5% of starting values in injured animals. A marked increase in serum AST (471.5+/-210 vs 42+/-8.14) coincided with a marked reduction in serum albumin (11.5+/-1.71 vs 25+/-1 g/dL) in injured animals. Animals displayed evidence of renal impairment; mean creatinine levels 280.2+/-36.5 vs 131.6+/-9.33 mumol/l. Liver histology revealed evidence of severe centrilobular necrosis with coagulative necrosis. Marked renal tubular necrosis was also seen. Methaemoglobin levels did not rise >5%. Intracranial hypertension was not seen (ICP monitoring), but there was biochemical evidence of encephalopathy by the reduction of Fischer's ratio from 5.6 +/- 1.1 to 0.45 +/- 0.06. Conclusion: We have developed a reproducible large animal model of acetaminophen-induced liver failure, which allows in-depth investigation of the pathophysiological basis of this condition. Furthermore, this represents an important large animal model for testing artificial liver support systems

Optimising use of electronic health records to describe the presentation of rheumatoid arthritis in primary care: a strategy for developing code lists

Background Research using electronic health records (EHRs) relies heavily on coded clinical data. Due to variation in coding practices, it can be difficult to aggregate the codes for a condition in order to define cases. This paper describes a methodology to develop ‘indicator markers’ found in patients with early rheumatoid arthritis (RA); these are a broader range of codes which may allow a probabilistic case definition to use in cases where no diagnostic code is yet recorded. Methods We examined EHRs of 5,843 patients in the General Practice Research Database, aged ≥30y, with a first coded diagnosis of RA between 2005 and 2008. Lists of indicator markers for RA were developed initially by panels of clinicians drawing up code-lists and then modified based on scrutiny of available data. The prevalence of indicator markers, and their temporal relationship to RA codes, was examined in patients from 3y before to 14d after recorded RA diagnosis. Findings Indicator markers were common throughout EHRs of RA patients, with 83.5% having 2 or more markers. 34% of patients received a disease-specific prescription before RA was coded; 42% had a referral to rheumatology, and 63% had a test for rheumatoid factor. 65% had at least one joint symptom or sign recorded and in 44% this was at least 6-months before recorded RA diagnosis. Conclusion Indicator markers of RA may be valuable for case definition in cases which do not yet have a diagnostic code. The clinical diagnosis of RA is likely to occur some months before it is coded, shown by markers frequently occurring ≥6 months before recorded diagnosis. It is difficult to differentiate delay in diagnosis from delay in recording. Information concealed in free text may be required for the accurate identification of patients and to assess the quality of care in general practice

A minimally invasive technique for closing an iatrogenic subclavian artery cannulation using the Angio-Seal closure device: two case reports

<p>Abstract</p> <p>Introduction</p> <p>In the two cases described here, the subclavian artery was inadvertently cannulated during unsuccessful access to the internal jugular vein. The puncture was successfully closed using a closure device based on a collagen plug (Angio-Seal, St Jude Medical, St Paul, MN, USA). This technique is relatively simple and inexpensive. It can provide clinicians, such as intensive care physicians and anesthesiologists, with a safe and straightforward alternative to major surgery and can be a life-saving procedure.</p> <p>Case presentation</p> <p>In the first case, an anesthetist attempted ultrasound-guided access to the right internal jugular vein during the preoperative preparation of a 66-year-old Caucasian man. A 7-French (Fr) triple-lumen catheter was inadvertently placed into his arterial system. In the second case, an emergency physician inadvertently placed a 7-Fr catheter into the subclavian artery of a 77-year-old Caucasian woman whilst attempting access to her right internal jugular vein. Both arterial punctures were successfully closed by means of a percutaneous closure device (Angio-Seal). No complications were observed.</p> <p>Conclusions</p> <p>Inadvertent subclavian arterial puncture can be successfully managed with no adverse clinical sequelae by using a percutaneous vascular closure device. This minimally invasive technique may be an option for patients with non-compressible arterial punctures. This report demonstrates two practical points that may help clinicians in decision-making during daily practice. First, it provides a practical solution to a well-known vascular complication. Second, it emphasizes a role for proper vascular ultrasound training for the non-radiologist.</p

Impact of EMA regulatory label changes on systemic diclofenac initiation, discontinuation, and switching to other pain medicines in Scotland, England, Denmark, and The Netherlands

PURPOSE: In June 2013 a European Medicines Agency referral procedure concluded that diclofenac was associated with an elevated risk of acute cardiovascular events and contraindications, warnings, and changes to the product information were implemented across the European Union. This study measured the impact of the regulatory action on the prescribing of systemic diclofenac in Denmark, The Netherlands, England, and Scotland. METHODS: Quarterly time series analyses measuring diclofenac prescription initiation, discontinuation and switching to other systemic nonsteroidal anti‐inflammatory (NSAIDs), topical NSAIDs, paracetamol, opioids, and other chronic pain medication in those who discontinued diclofenac. Absolute effects were estimated using interrupted time series regression. RESULTS: Overall, diclofenac prescription initiations fell during the observation periods of all countries. Compared with Denmark where there appeared to be a more limited effect, the regulatory action was associated with significant immediate reductions in diclofenac initiation in The Netherlands (−0.42%, 95% CI, −0.66% to −0.18%), England (−0.09%, 95% CI, −0.11% to −0.08%), and Scotland (−0.67%, 95% CI, −0.79% to −0.55%); and falling trends in diclofenac initiation in the Netherlands (−0.03%, 95% CI, −0.06% to −0.01% per quarter) and Scotland (−0.04%, 95% CI, −0.05% to −0.02% per quarter). There was no significant impact on diclofenac discontinuation in any country. The regulatory action was associated with modest differences in switching to other pain medicines following diclofenac discontinuation. CONCLUSIONS: The regulatory action was associated with significant reductions in overall diclofenac initiation which varied by country and type of exposure. There was no impact on discontinuation and variable impact on switching

Evolutionary relationships between Rhynchosporium lolii sp. nov. and other Rhynchosporium species on grass.

Copyright: 2013 King et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThe fungal genus Rhynchosporium (causative agent of leaf blotch) contains several host-specialised species, including R. commune (colonising barley and brome-grass), R. agropyri (couch-grass), R. secalis (rye and triticale) and the more distantly related R. orthosporum (cocksfoot). This study used molecular fingerprinting, multilocus DNA sequence data, conidial morphology, host range tests and scanning electron microscopy to investigate the relationship between Rhynchosporium species on ryegrasses, both economically important forage grasses and common wild grasses in many cereal growing areas, and other plant species. Two different types of Rhynchosporium were found on ryegrasses in the UK. Firstly, there were isolates of R. commune that were pathogenic to both barley and Italian ryegrass. Secondly, there were isolates of a new species, here named R. lolii, that were pathogenic only to ryegrass species. R. lolii was most closely related to R. orthosporum, but exhibited clear molecular, morphological and host range differences. The species was estimated to have diverged from R. orthosporum ca. 5735 years before the present. The colonisation strategy of all of the different Rhynchosporium species involved extensive hyphal growth in the sub-cuticular regions of the leaves. Finally, new species-specific PCR diagnostic tests were developed that could distinguish between these five closely related Rhynchosporium species.Peer reviewedFinal Published versio

The relative contribution of shape and colour to object memory

The current studies examined the relative contribution of shape and colour in object representations in memory. A great deal of evidence points to the significance of shape in object recognition, with the role of colour being instrumental under certain circumstances. A key but yet unanswered question concerns the contribution of colour relative to shape in mediating retrieval of object representations from memory. Two experiments (N=80) used a new method to probe episodic memory for objects and revealed the relative contribution of colour and shape in recognition memory. Participants viewed pictures of objects from different categories, presented one at a time. During a practice phase, participants performed yes/no recognition with some of the studied objects and their distractors. Unpractised objects shared shape only (Rp–Shape), colour only (Rp–Colour), shape and colour (Rp–Both), or neither shape nor colour (Rp–Neither), with the practised objects. Interference effects in memory between practised and unpractised items were revealed in the forgetting of related unpractised items – retrieval-induced forgetting. Retrieval-induced forgetting was consistently significant for Rp–Shape and Rp–Colour objects. These findings provide converging evidence that colour is an automatically encoded object property, and present new evidence that both shape and colour act simultaneously and effectively to drive retrieval of objects from long-term memory