FEMS MICROBIOLOGY LETTERS, Issue 1 2010
Jivko V. Stoyanov
Abstract Intracellular copper routing in Enterococcus hirae is accomplished by the CopZ copper chaperone. Under copper stress, CopZ donates Cu+ to the CopY repressor, thereby releasing its bound zinc and abolishing repressor,DNA interaction. This in turn induces the expression of the cop operon, which encodes CopY and CopZ, in addition to two copper ATPases, CopA and CopB. To gain further insight into the function of CopZ, the yeast two-hybrid system was used to screen for proteins interacting with the copper chaperone. This led to the identification of Gls24, a member of a family of stress response proteins. Gls24 is part of an operon containing eight genes. The operon was induced by a range of stress conditions, but most notably by copper. Gls24 was overexpressed and purified, and was shown by surface plasmon resonance analysis to also interact with CopZ in vitro. Circular dichroism measurements revealed that Gls24 is partially unstructured. The current findings establish a novel link between Gls24 and copper homeostasis. [source]

Characteristics of spousal homicide perpetrators: a study of all cases of spousal homicide in Sweden 1990,1999

CRIMINAL BEHAVIOUR AND MENTAL HEALTH, Issue 2 2004
Professor Henrik Belfrage PhD
Background In Sweden 20 000 cases of assault against women are reported to the police every year. Method All data on the perpetrators of spousal homicide in Sweden between 1990 and 1999 were investigated (n = 164). A control group of all other perpetrators of homicide in Sweden during the same period, i.e. cases of homicide not committed in the context of spouse violence (n = 690) was used. All verdicts, as well as all material in the police investigations, including interviews with all of the police investigators, were analysed. Copies of police examinations of the suspects, and forensic reports from the autopsies, were also examined. Data on all registered criminality were collected from the National Police Register, and in cases where the perpetrators had been subject to forensic psychiatric examinations, those reports were obtained from the Swedish National Board of Forensic Medicine. In addition, the Psychopathy Checklist: Screening Version scores were rated from the forensic psychiatric examinations. Results There was a four times higher suicide rate among the spousal homicide perpetrators (24%, n = 40) compared with the perpetrators in the control-group (6%, n = 39, chi-squared = 55,42df = 1 , p < 0.001). Consequently, suicidal ideation must be considered as an important risk factor for spousal homicide. In 79% of the cases the spousal homicide perpetrators were subject to forensic psychiatric examinations. All except 5% were diagnosed with at least one psychiatric diagnosis, and 34% were sentenced to forensic psychiatric treatment. If it is assumed that the psychiatric morbidity was high in the 24% of the perpetrators who committed suicide, then 80% of all perpetrators of spouse homicide during the study period can be characterized as mentally disordered. ,Psychopathic' perpetrators, who generally are over-represented in most violent criminality, were comparatively uncommon. Only seven (4%) in the study group met the diagnostic criteria for psychopathy as measured with the PCL:SV. Discussion The group of spouse killers studied here fits the dysphoric/borderline group of spouse assaulters. This is a group that may benefit from treatment. Perhaps police officers could help identify this kind of spouse assaulter before a fatality occurs. Copyright © 2004 Whurr Publishers Ltd. [source]

Peer Review Emergency Medicine Australasia

EMERGENCY MEDICINE AUSTRALASIA, Issue 4 2005
Article first published online: 2 AUG 200
Fellows of the Australasian College for Emergency Medicine and members of the Australasian Society for Emergency Medicine are invited to forward to the journal, details of their publications which have appeared in journals other than Emergency Medicine Australasia during the period September-October 2005. Commentary on these papers will appear in the April 2006 issue of the journal. Copies of the papers are to be forwarded by mail or fax to journal headquarters (34 Jeffcott Street, West Melbourne, Victoria 3003, Australia; fax: +61 3 9320 0400) by 15 November 2005. Alternatively, an electronic copy in PDF format may be e-mailed to journal@acem.org.au. The next call will be for papers published in the period November-December 2005. [source]

Email Copies in Workplace Interaction

JOURNAL OF COMPUTER-MEDIATED COMMUNICATION, Issue 1 2006
Karianne Skovholt
This study examines how employees in a distributed work group use email copies in networks of collaboration. It studies the audience design of messages with multiple recipients, analyzing explicit and implicit addressing devices used to appoint recipients as primary and secondary participants in the interaction. Copying in recipients serves to share knowledge of ongoing projects and to build up a common information pool. Furthermore, it is used to facilitate multi-party interaction and to build personal identity and alliances. Copies to third parties may also be used for reasons of social control, for instance in order to gain compliance or to put pressure on the addressee to conform to social norms of conduct. [source]

The contribution of MD,PhD training to academic orthopaedic faculties

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2001
John M. Clark
Little is known about the distribution of research-trained physicians across the various specialties. To document the extent to which MD,PhD programs are a source of research-trained faculty for orthopaedic departments, this study examined the specialty choices of graduates of the Medical Scientist Training Program (MSTP) from 1964 to 1994. The MSTP, a combined MD,PhD program supported by the National Institute of General Medical Sciences, (NIGMS), produces roughly 25% of all MD,PhDs in the US. Methods. Copies of the appendices from training grant applications containing information on MSTP graduates were obtained from the NIGMS. Also, a questionnaire was mailed to 116 university-affiliated orthopaedic surgery departments asking how many faculty were MD's, PhDs or MD,PhDs. Results. Records were obtained for all MST programs. Information on postdoctoral training and/or a current position was reported for 1615 graduates who earned both MD and PhD. Of these graduates, 277 chose non-clinical paths. The other 1338 entered a residency or internship. Of these, 593 were still in residency training, 566 were academic faculty members and 130 were in private practice. In the records, 12 (0.9%) were listed as orthopaedic surgical residents (6) or faculty (6). At this time, all 12 have completed training, and 11 are in academic practice. Eighty-three departments replied to the questionnaire. In that sample of 1761 faculty positions, 1478 were MDs, 217 were PhDs and 36 (2.0%) were MD-PhDs. Conclusion. Despite robust support of MD,PhD programs, the number of dual degree recipients on orthopaedic faculties is small when compared to the relative size of the specialty. Other sources of research-trained staff should perhaps be developed. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source]

Latest news and product developments

PRESCRIBER, Issue 3 2008
Article first published online: 26 FEB 200
Higher risk of CV events in aspirin resistance More than one in four patients may have aspirin resistance, a new metaanalysis shows, and they face a four-to sixfold increased risk of a major cardiovascular event or death compared with aspirin-sensitive patients taking low-dose aspirin (BMJ online: 17 Jan 2008; doi:10. 1136/bmj.39430.529549.BE). The analysis included 20 studies involving a total of 2930 patients with cardiovascular disease. Of these, 28 per cent were defined as having aspirin resistance (according to the various definitions in each study). Compared with aspirin-sensitive patients, the odds ratio of any cardiovascular event or acute coronary syndrome was about 4 and the odds ratio of death was 6. Aspirin-resistant patients did not benefit from other antiplatelet treatment. ADOPT: rosiglitazone fracture risk in women A new analysis of the ADOPT trial (N Engl J Med 2006;355: 2427-43) has found that the risk of fractures during treatment with rosiglitazone (Avandia) is approximately twice as high as with metformin or glibenclamide, but mainly in women (Diabetes Care online: 25 Jan 2008; doi: 10.2337/dc07-2270). The study found a significant difference in risk between the drugs only for women, with a cumulative incidence of 15.1 per cent with rosiglitazone, 7.3 per cent with metformin and 7.7 per cent with glibenclamide after five years. No risk factors were identified although the incidence of fractures was higher among postmenopausal than premenopausal women. New from NICE Infliximab for the treatment of adults with psoriasis. Technology Appraisal Guidance No. 134, Jan 2008 Infliximab (Remicade), a monoclonal antibody against TNF-alpha, should be an option for treating very severe plaque psoriasis in adults, NICE recommends. Using its fast-track single technology appraisal procedure, NICE concluded that infliximab should be considered when standard therapies,methotrexate or ciclosporin (Neoral), or PUVA , have failed or are unsuitable. The criteria for disease severity are defined by the Psoriasis Area Severity Index (PASI) score (,20) and the Dermatology Life Quality Index (DLQI) score (>18). Treatment response is also defined by these measures and infliximab should be continued for longer than 10 weeks only when predefined thresholds are met. Infliximab costs an average of £11 750 annually. In 2006, NICE recommended etanercept (Enbrel) and efalizumab (Raptiva) for patients with severe psoriasis (PASI ,10 and DLQI >10). Commons committee wants tougher targets Most GPs get full QOF points for medicines management even though there is inexplicably large variation in good prescribing practice between PCTs, the Public Accounts Select Committee points out in its latest report, Prescribing Costs in Primary Care. The Committee wants to see tougher QOF targets among several initiatives to reduce prescribing costs. Although most publicity centred on its endorsement of the National Audit Office claim that GPs could save £200 million by prescribing lower-cost drugs, the report contains some more far-reaching proposals. GPs should prescribe generic alternatives within a therapeutic category, so when a brand is not available generically, eg Lipitor, a different drug that is, eg simvastatin, should be used when clinically appropriate. Further, this form of substitution should be rewarded via QOF targets. There should be greater uniformity in the appearance, labelling and packaging of generic and branded equivalents. The Department of Health should consider raising awareness of the value of medicines by printing the cost on packaging, and to reduce the £100 million wasted annually in dumped medicines, it should investigate which drugs aren't used and why patients won't take them. Strategic health authorities should work with the National Prescribing Centre to develop more prescribing indicators with which to measure PCT performance and support PCTs to promulgate best practice. They should also collaborate on promoting joint primary-secondary care formularies and increase the consistency of prescribing, not only between hospital specialists and GPs but also between PCTs. To monitor the influence of the pharmaceutical industry, PCTs should keep a record of gifts and hospitality and publish a register. Questions to ask about mental health treatment The Department of Health has published a booklet designed to raise awareness of medicines management issues affecting people using mental health services and their carers, and professionals in the health and social services. Although one aim of Medicines Management: Everybody's Business is to empower people with mental health problems to ask about their medication, its formal style is better suited to staff who need to improve their person-centred approach to care. It covers what information people should expect and what questions to ask when drug treatment is being considered, what to expect at review and issues to consider when contemplating stopping treatment. Copies can be downloaded at www.dh.gov.uk. Consider statins for all patients with diabetes Treatment with a statin should be considered for all patients with diabetes unless their risk is low, say the authors of a new study (Lancet 2008;371:117-25). Their meta-analysis of 14 randomised trials involving 18 686 people with diabetes and an average follow-up of 4.3 years found that statins reduced vascular events and vascular mortality as much as in nondiabetic populations. The overall benefit was 42 fewer major events per 1000 people treated for five years. This was independent of a history of vascular disease or other baseline characteristics. No evidence for OTC cough medicines There is no evidence that over-the-counter cough medicines for adults and children are effective in relieving acute cough, a new Cochrane review has concluded (Cochrane Database of Systematic Reviews 2008, Issue 1). The review of 17 randomised trials involving 2876 adults and eight involving 616 children reported conflicting findings of uncertain clinical relevance. The trials were heterogeneous and of low quality. Copyright © 2008 Wiley Interface Ltd [source]

Latest news and product developments

PRESCRIBER, Issue 22 2007
Article first published online: 28 DEC 200
Glitazones: benefits outweigh the risks Following a review of the safety of rosiglitazone and pioglitazone, the European Medicines Agency (EMEA) has concluded that their benefits outweigh their risks in the approved indications. The review was prompted by reports of an increased risk of fractures in women and, in patients taking rosiglitazone, ischaemic heart disease. The EMEA concluded that prescribing information for rosiglitazone should now include a warning that, in patients with ischaemic heart disease, it should only be used after careful evaluation of each patient's individual risk, and the combination of rosiglitazone and insulin should only be used in exceptional cases and under close supervision. No change was considered necessary to the prescribing information for pioglitazone. Modern dressings no better? A systematic review has found only weak evidence that modern dressings are better than saline gauze or paraffin gauze for healing acute and chronic wounds (Arch Dermatol 2007;143: 1297-304). The analysis, which included 99 studies, found that only hydrocolloids were demonstrably better than older dressings for healing chronic wounds, and alginates were superior to other modern dressings for debriding necrotic wounds. There was no evidence that modern dressings offered superior overall performance to the older alternatives. Hospital inflation twice primary care level The cost of drugs prescribed in secondary care but dispensed in the community increased by 6.4 per cent in 2006 - twice the rate of inflation in primary care - according to the latest statistics on hospital prescribing in England. The increase follows a reduction in costs in 2005 after the introduction of the new PPRS scheme. Data from The Information Centre (www.ic.nhs.uk) show that hospital medicines make up about 24 per cent of the NHS drugs budget. Secondary care has a consistently better record than primary care in prescribing lower-cost alternatives within therapeutic categories, eg simvastatin and pravastatin among the statins, omeprazole and lansoprazole among PPIs, and ACE inhibitors among drugs acting on the renin angiotensin system. The most expensive drug prescribed by hospital specialists and dispensed in the community is interferon beta. MHRA limits the use of fibrates The Medicines and Healthcare products Regulatory Agency (MHRA) has advised that fibrates should now be reserved for the treatment of isolated severe hypertriglyceridaemia. They should be considered for hypercholesterolaemia only when a statin or other treatment is contraindicated or not tolerated. In the latest Drug Safety Update, the MHRA says there is insufficient evidence of long-term benefits from fibrates, and first-line use is no longer justified because the evidence for the benefits of statins is robust. The MHRA also warns that some breastfeeding infants have increased susceptibility to the adverse effects of codeine taken by their mother, and that St John's wort may affect the hepatic metabolism of any anticonvulsant. Annual zoledronic acid infusion cuts mortality after hip fracture Once-yearly infusion of zoledronic acid (Aclasta) after hip fracture reduces deaths over a two-year period by 28 per cent compared with placebo, US investigators say (N Engl J Med 2007;357:1799-809). The HORIZON Recurrent Fracture Trial randomised 2127 men and women (mean age 75) within 90 days of surgery for hip fracture to zoledronic acid 5mg yearly or placebo. Mortality over 1.9 years of follow-up was 9.6 per cent with zoledronic acid and 13.3 per cent with placebo. Zoledronic acid also significantly reduced the rate of any new clinical fractures (by 35 per cent) and new clinical vertebral fractures(by 45 per cent),but the lower rate of hip fracture (2.0 vs 3.5 per cent with placebo) was not statistically significant. Rivastigmine patch for mild to moderate AD Rivastigmine (Exelon) is now available as a transdermal patch for the treatment of mild to moderate Alzheimer's disease. Applied once daily, the patch delivers 9.5mg per 24 hours and, says manufacturer Novartis, is associated with a lower incidence of nausea and vomiting than a comparable oral dose. The patch is available in two strengths: 4.6mg per 24hr is equivalent to oral doses of 3 or 6mg per day, and the 9.5mg per 24hr patch is equivalent to 9 or 12mg per day orally. The recommended dose of the patch is 9.5mg per day; both strengths cost £83.84 for 30 patches. Women more aspirin resistant than men? The cardioprotective effect of low-dose aspirin may be lower in women than men, say Canadian investigators (BMC Medicine 2007;5:29 doi: 10.1186/1741-70155-29). Their meta-analysis of 23 randomised trials involving a total of 113 494 participants found that aspirin significantly reduced the risk of nonfatal but not fatal myocardial infarction (MI). About one-quarter of the variation in its effects on nonfatal MI was accounted for by the sex mix of the trial population. Separating the results by sex showed the reduction in risk with aspirin use was statistically significant in men (relative risk, RR, 0.62) but not in women (RR 0.87). Look after physical health of mentally ill GPs and other primary care workers should take more responsibility for the physical health of their mentally ill patients, say advocacy groups. Mind and Body: Preventing and Improving Physical Health Problems in Patients With Schizophrenia points out that the mental health needs of patients with schizophrenia are met in secondary care, but their physical health needs should be met in primary care. In particular, the metabolic effects of antipsychotics may lead to obesity, diabetes and cardiovascular disease, and weight gain in particular is a frequent reason for nonadherence to treatment. The Mind and Body Manifesto was developed by SANE, The Mental Health Nurses Association, The National Obesity Forum and The Disability Rights Commission and sponsored by Bristol-Myers Squibb Pharmaceuticals Limited and Otsuka Pharmaceuticals (UK) Ltd. Copies are available from elizabeth.green@ ogilvyhealthworld.com. Health eCard costs Some costs quoted in our article on the Health eCard (The Health eCard: the way ahead for medical records?,5 October issue, pages 28-9) have been revised: the card and initial download will cost patients £39.50, and GPs will be entitled to charge patients £10 per annum for subsequent downloads. NICE appraisals of cytokine inhibitors in RA NICE has endorsed the use of the anti-TNF agents adalimumab (Humira), etanercept (Enbrel) and infliximab (Remicade), normally in conjunction with methotrexate, for the treatment of active RA when methotrexate and another DMARD have failed (also see New from NICE below). NICE has provisionally concluded, subject to consultation, that abatacept (Orencia) should not be recommended for the treatment of RA. Boots and BMJ launch health advice site www.askbootshealth.com is a new website providing information about health and medicines for the public produced by Boots using information provided by the BMJ Publishing Group. The website covers many of the topics already available from NHSDirect, with perhaps more information about available treatments. Diabetes care shows small improvement The third National Diabetes Audit in England and Wales has found that more people with diabetes were achieving the targets set by NICE for cholesterol levels, glycaemic control and blood pressure in 2005/06 - but younger patients were doing less well. Overall, the HbA1C target of ,7.5 per cent was achieved in 60 per cent of people with diabetes compared with 58 per cent in 2004/05. However, HbA1C was >9.5 per cent in 30 per cent of children and young people, of whom 9 per cent experienced at least one episode of ketoacidosis. More topics for NICE New topics referred to NICE include clinical guidelines on ovarian cancer, coeliac disease and stable angina, public health guidance on preventing cardiovascular disease, and technology appraisals on insulin detemir (Levemir) for type 1 diabetes, several treatments for cancer and hepatic and haematological disorders, and biological therapies for juvenile arthritis. New from NICE NICE appraisal on anti-TNFs for RA Since NICE published its first appraisal of agents acting against tumour necrosis factor-alpha (anti-TNFs) for the treatment of RA in 2002, the product licences for etanercept (Enbrel) and infliximab (Remicade) have changed and a new agent, adalimumab (Humira), has been introduced. The anti-TNFs act in different ways. Infliximab is a chimeric monoclonal antibody that binds to TNF-alpha, neutralising its activity. Etanercept, a recombinant human TNF-alpha receptor fusion protein, and adalimumab, a human-sequence antibody, both bind to TNF-alpha and block its interaction with cell surface receptors. Adalimumab also modulates some biological responses induced or regulated by TNF-alpha. These agents are recommended for adults with severe active RA (defined as a disease activity score - DAS28 - greater than 5.1) who have already tried two disease-modifying drugs, including methotrexate (if not contraindicated). Prior treatment should have been of at least six months' duration, including two months at the standard dose (unless limited by toxicity). Anti-TNFs should normally be prescribed with methotrexate; when this is not appropriate, etanercept and adalimumab may be prescribed as monotherapy. Treatment with an anti-TNF should be continued beyond six months only if there is an adequate response (defined as an improvement in DAS28 of at least 1.2). Data from the British Rheumatology Society Biologics register show that, after six months, 67 per cent of patients met NICE criteria for an adequate response; this declined to 55 per cent at 18 months. The basic annual cost of treatment is £9295 for adalimumab 40mg on alternate weeks or etanercept 25mg twice weekly; infliximab costs £3777 for a loading dose, then £7553-£8812 depending on dose. Assuming no progression of disability, the incremental costs per QALY (compared with sequential DMARDs) were £30 200 for adalimumab, £24 600 for etanercept and £39 400 for infliximab. There are no direct comparative trials of the anti-TNFs, and their clinical trial findings are not directly comparable. Unless other factors determine treatment choice, NICE therefore recommends the least expensive. If the first anti-TNF is withdrawn within six months due to an adverse event, a second may be tried. [source]

Latest news and product developments

PRESCRIBER, Issue 20 2007
Article first published online: 26 NOV 200
GPs and pharmacists to work more closely Closer working between GPs and community and primary-care pharmacists ,could further improve prescribing quality and therapeutic outcomes for patients', according to a report by the London School of Pharmacy and Alliance Boots. The report suggests that the expansion of primary-care centres and the increasing complexity of care they offer mean that community pharmacists will increasingly need to take on some GP roles. It foresees an increase in shared premises and calls for closer interdisciplinary working between GPs, pharmacists and nurses. Variation in PCT commissioning of enhanced services from pharmacies has resulted in ,a fragmented system of postcode pharmaceutical care rationing'. Full read-write access to patients' records will be essential if the benefits of electronic prescribing are to be realised. How pharmacists can support commissioners The NHS Alliance and Primary Care Pharmacists' Association have published a guide for practice-based commissioners on making the most of primary-care pharmacists. Prescribing Support and Prescribing Advice for Practice Based Commissioners , A Guide for Commissioning Groups and GPs illustrates how pharmacists can support commissioners at all levels of medicines use. Copies are free to NHS Alliance members and cost £10 for others. Directory website aids diabetes management The National Diabetes Support Team is developing a website that brings together different datasets and tools for diabetes management. The Diabetes Data Directory (www.yhpho.org.uk/diabetesdatadirectory/introddd.asp) summarises what other online databases can provide and lists the tools that can be used to answer specific questions. The first edition is now online, providing direct links to the appropriate sites. Flu vaccine efficacy in older people challenged US reviewers have questioned the effectiveness of flu vaccine in older people (Lancet Infect Dis online: 24 September; doi: 10.1016/ S1473-3099(07)70236-0). They were unable to confirm a reduction in flu mortality since 1980, concluding that biased patient selection and nonspecific end-points such as all-cause mortality may have exaggerated the benefits of vaccination in clinical trials. The Department of Health is encouraging younger people in at-risk groups to be vaccinated against flu this winter; last year, 58 per cent of under-65s at risk were not vaccinated. OC cervical cancer risk probably overestimated Recent evidence that oral contraceptives may be associated with a small increase in the incidence of cervical cancer probably overestimates the risk, says the Clinical Effectiveness Unit of the Faculty of Family Planning and Reproductive Health Care (www.ffprhc.org.uk). A recent study in the BMJ reported a 12 per cent reduced overall risk of cancer associated with oral contraceptives but an increased risk of cervical cancer of 38 per 100 000 woman-years after at least eight years' use. The FFPRHC says this study was conducted before the UK cervical screening programme was established, and at a time when the average Inhaled insulin ,unlikely to be cost effective' Inhaled insulin (Exubera) is safe and effective but costs so much more than injected insulin that it is unlikely to be cost effective, according to a new Health Technology Assessment (2007;11:No.33.www.hta.nhsweb.nhs.uk). The review included nine trials (seven of Exubera), in which the only significant difference between inhaled and injected soluble insulin was in patient preference. However, most of the trials used syringes for insulin injection rather than pens. The extra cost of inhaled insulin is put at between £600 and £1000 per year. New topics for NICE The Secretary of State for Health has referred the novel antihypertensive aliskiren (Rasilez) for appraisal by NICE; aliskiren is the first direct renin inhibitor to be introduced. Other referrals to NICE include five clinical guidelines (multiple pregnancy, transient loss of consciousness, lower UTI in men, post-ITU rehabilitation and colorectal and anal cancer). Topics for technology appraisals include cetuximab (Erbitux) for colorectal and head and neck cancers. QOF statistics for 06/07 GPs in England averaged 96.3 per cent of the maximum points available for the clinical domain of the Quality and Outcomes Framework in 2006/07 compared with 97.1 per cent previously, official statistics show. Mean practice scores for most clinical areas were in the mid-90 per cent range, but highest for obesity (100 per cent) and lowest for depression (81 per cent), palliative care (90 per cent), mental health and epilepsy (<95 per cent). NICE consulting on type 2 diabetes guideline NICE is consulting on its draft clinical guideline for the management of type 2 diabetes. Comments should be submitted online by 22 November; publication is scheduled for April 2008. The drug of first choice for glycaemic control is metformin, which should be considered even for patients who are not overweight; a sulphonylurea is an alternative or adjunctive agent if glycaemic control is not achieved with metformin alone. If these regimens fail, a glitazone may be added. Exenatide (Byetta) is recommended only for obese patients for whom other oral treatments have failed. The guidance will update and replace clinical guidelines E, F, G and H, and technology appraisals 53, 60 and 63. Glitazones increase risk of HF but not CV death A new meta-analysis , this time of seven trials involving a total of 20 191 patients with type 2 diabetes or impaired glucose tolerance treated with a glitazone , has concluded that these agents are associated with an increased risk of heart failure but not cardiovascular death (Lancet 2007;370:1129,36). Compared with comparator drugs, glitazones were associated with an increased risk of congestive heart failure (2.3 vs 1.4 per cent; relative risk, RR, 1.72; number needed to harm over 30 months, 107). There was no heterogeneity between studies, showing that this is a class effect. However, the risk of cardiovascular death was not increased for either rosiglitazone (Avandia) or pioglitazone (Actos). Copyright © 2007 Wiley Interface Ltd [source]

Latest news and product developments

PRESCRIBER, Issue 10 2007
Article first published online: 13 SEP 200
Sitagliptin: novel drug for type 2 diabetes Sitagliptin (Januvia), the first dipeptidyl peptidase-4 (DPP-4) inhibitor, has been introduced for the treatment of type 2 diabetes in combination with metformin or a glitazone when either agent plus exercise and diet fail to control blood glucose. Inhibition of DPP-4 prevents the breakdown of incretin hormones that promote insulin release from pancreatic beta cells. In trials lasting up to 24 weeks, adding sitagliptin to established therapy reduced HbA1C by 0.67-0.90 per cent. It is contraindicated in patients with moderate or more severe renal impairment. At the recommended dose of 100mg per day, a month's treatment with sitagliptin costs £33.36. Guide to treating mentalillness in primary care A new guide from the Centre for Clinical and Academic Workforce Innovation aims to help health professionals and others treating people with mental illness. A Complete Guide to Primary Care Mental Health, a toolkit presented as a reference book and CD, covers aspects of treatment, the law and working with the voluntary sector and includes training materials compatible with evidence-based guidance. Copies are available from amazon.co.uk. Follow-up improves statin adherence Patients may take long holidays from statin treatment but a visit to the doctor is among the most effective ways to improve adherence, a US study shows (Arch Intern Med 2007;167:847,52). Observation of 239 911 patients who began statin treatment during a seven-year period showed that 54 per cent stopped their treatment for at least 90 days. Of these, 48 per cent restarted within one year and 60 per cent within two years. Factors associated with restarting treatment were a visit to the doctor who prescribed the statin (odds ratio, OR, 6.1) or a visit to a different doctor (OR 2.9). A cholesterol test and hospital admission for a cardiovascular event were also significant factors. Pharmacist MUR does not reduce heart failure deaths Medication review by trained community pharmacists does not reduce admissions or deaths among patients with heart failure, according to a study from East Anglia (BMJ online: 23 April 2007; doi:10.1136/bmj.39164.568183.AE). Patients admitted as emergencies with heart failure were randomised to usual care or two home visits by a community pharmacist within two and eight weeks after discharge. Pharmacists reviewed medication and advised on self-management of symptoms and lifestyle. There were no significant differences in hospital admissions over the next six months (rate ratio 1.15 for pharmacist vs control) or deaths (rate ratio 1.18); quality of life scores were similar in the two groups. The authors speculate that the interventions may have been too brief or too late (lifestyle changes having been made already), or disadvantaged by not adjusting beta-blocker doses. A Cardiff study of pharmacist medication reviews for elderly patients (BMJ online: 20 April 2007; doi:10.1136/bmj.39171. 577106.55), found that their advice had the potential to undermine patients' ,confidence, integrity and self-governanc'. The study found that pharmacists gave advice unnecessarily and uninvited. CHD targets met early The national programme to tackle heart disease has made substantial progress towards it targets, the Department of Health says in a 10-year report, and a 40 per cent cut in mortality will be achieved ahead of the deadline of 2010. Coronary Heart Disease Ten Years On: Improving Heart Care, a report by Professor Roger Boyle, National Director for Heart Disease and Stroke, states that 7 per cent of the population is now taking statins, resulting in 9700 deaths avoided annually. The prevalence of untreated hypertension fell from 32 to 24 per cent between 1998 and 2003. The report also summarises changes in service delivery, nutrition and smoking cessation. HRT: ovarian cancer risk The MHRA has not altered its advice on the use of HRT following news that five years' use increases ovarian cancer risk in women over 50. The Million Women Study revealed an approximately 20 per cent increased risk of ovarian cancer or death among women still using HRT after five or more years. There was no difference in risk between oestrogen-only and combined formulations. The MHRA says HRT is still indicated for relieving symptoms of the menopause for short-term use; as an alternative for women over 50 who cannot take other treatments to prevent osteoporosis, or when such options fail; and in women under 50 who experience a premature menopause. Poor angina treatment Over half of patients with angina continue to experience attacks despite treatment, according to a survey by the British Cardiac Patients Association. The survey of 600 patients with angina also found that twot-hirds of respondents reported that angina had a moderate to severe impact on their lives. Half said that the adverse effects of their treatment negatively affected their work, two-thirds reported an adverse impact on sex, and almost three-quarters of patients taking beta-blockers reported fatigue. A second survey of 2000 adults revealed widespread ignorance about the prevalence and symptoms of angina. The surveys were sponsored by Servier Laboratories Limited and conducted in collaboration with Research Quorum. Cabergoline restriction Indications for the dopamine agonist cabergoline (Cabaser) are being restricted to match those of pergolide (Celance), the MHRA has announced. Pergolide was recently withdrawn in the United States and its use in the EU is limited because of the risk of cardiac valvular damage. Similar toxicity has been reported with cabergolide, which is now restricted to second-line use when a nonergot treatment for Parkinson's disease has failed. It is contraindicated in patients with valvular damage or a history of fibrotic disorders and requires patient monitoring. Sodium reduction cuts CV events Long-term reduction in dietary sodium may reduce cardiovascular events by 25 per cent, US epidemiologists say (BMJ online: 20 April 2007; doi:10.1136/bmj.39147.604896.55). Participants in the two Trials of Hypertension Prevention (TOHP I and II) reduced their sodium intake by 44 and 33mmol per 24hr. After 10,15 years' follow-up of 2415 participants, the adjusted relative risk of cardiovascular events was 0.75 compared with controls. There was a nonsignificant 20 per cent reduction in mortality. Copyright © 2007 Wiley Interface Ltd [source]

Latest news and product developments

PRESCRIBER, Issue 4 2007
Article first published online: 3 APR 200
Low-dose aspirin may reduce asthma risk Low-dose aspirin may reduce the risk of new-onset asthma, according to a US analysis (Am J Respir Crit Care Med 2007;175:120-5). Prompted by speculation of such a link, the authors conducted a post-hoc analysis of the Physicians' Health Study, a placebo-controlled study of aspirin 325mg on alternate days involving 22 071 men aged 40-84. The risk of developing a new diagnosis of asthma during the five-year study was reduced by 22 per cent (p=0.045) among those taking aspirin. However, the number of cases was low: 113 among aspirin recipients and 145 with placebo. The clinical importance of this finding is therefore uncertain, though it received wide coverage in the lay media. Lifestyle changevsdrugs in type 2 diabetes Modifying lifestyle is at least as effective as drugs in delaying the onset of type 2 diabetes in people with impaired glucose tolerance, according to a study from Leicester (BMJ online. doi: 10.1136/bmj.39063.689375.55). The meta-analysis of 17 trials involving 8084 participants found that lifestyle change or orlistat approximately halved the risk of progressing to diabetes, whereas oral hypoglycaemic agents reduced the risk by 30 per cent. A Chinese herb, jiang tang bushen, reduced the risk by two-thirds. The analysis was conducted before the findings of major trials of rosiglitazone (Avandia) , DREAM and ADOPT , were published. Optician prescribing The diagnosis and treatment of disorders such as conjunctivitis by opticians is to be an enhanced service that PCTs can commission according to local need, a Department of Health review has concluded. The General Ophthalmic Services Review considered new arrangements to support PCTs provide ophthalmic services. Professional representatives proposed that the diagnosis and treatment of some eye conditions should be classed as ,additional services' that PCTs should be obliged to commission. While the Department agreed that opticians can play an important role, it found a lack of evidence of benefits and concluded that PCTs should be able to determine their level of services. A commissioning toolkit has been produced to help implement the review's findings. Warfarin stroke risk A four-fold increase in warfarin use has been linked with an increased incidence of intracerebral haemorrhage in a US study (Neurology 2007;68:116-21). Reviewing all first admissions for haemorrhagic stroke in the Cincinnati area, the study found that the proportion of cases associated with warfarin or heparin increased from 5 per cent in 1988 to 9 per cent in 1993/94 and 17 per cent in 1999. The annual incidence among patients aged 80 or older increased from 2.5 to 46 per 100 000 from 1988 to 1999. During the same period, warfarin distribution increased four-fold and there was no change in the incidence of thromboembolic strokes. Co-proxamol will go, MHRA reaffirms The MHRA has confirmed that it still intends to withdraw co-proxamol from the market despite protestations from MPs. The issue was raised by two MPs , one a member of the Health Select Committee , in a House of Commons debate. Both called for the withdrawal process to be abandoned, arguing that GPs should have the right to prescribe a drug for which there may be no alternative. The MHRA has restated its view that the risk from overdose with co-proxamol outweighs its benefits, adding: ,The avoidable death toll from co-proxamol overdose cannot be ignored. Sometimes regulation has to balance the needs of the individual against the benefits at a population level. In this case the removal of marketing authorisations with continued use possible in exceptional circumstances is the best balance that could be achieved. The public health gain is already becoming apparent.' Co-proxamol may still be prescribed as an unlicensed drug after its product licence is withdrawn at the end of this year. Guide to pharmacy services A guide to community pharmacy services has been published for patients, carers and members of patient organisations. Developed by the South East Local Pharmaceutical Committee Forum, Understanding and Making the Best Use of Community Pharmacy explains what pharmacies offer and the services available under the 2005 pharmacy contract. Copies can be downloaded from www.psnc.org.uk/resources. Little benefit from opioids for back pain There is little evidence that opioids relieve chronic back pain but the risk of abuse is high, according to a US analysis (Ann Intern Med 2007;146:116-27). The systematic review of trials of oral, topical and transdermal opioids in the treatment of chronic back pain found no trials lasting more than 16 weeks. There was no significant reduction in pain in placebo-controlled trials and limited, nonsignificant pain reductions in comparative trials. By contrast, estimates of prevalence of current substance misuse were as high as 43 per cent and that of ,aberrant medication-taking behaviours' ranged from 5 to 24 per cent. Dual antiplatelet therapy with drug-eluting stents Patients with drug-eluting stents should not stop dual antiplatelet therapy prematurely (Circulation 2007; published online 15 January; DOI: 10.1161/CIRCUL ATIONAHA.106.180944). Although 12 months' treatment with low-dose aspirin plus a thienopyri- dine, eg clopidogrel (Plavix) and ticlopidine, has been shown to reduce cardiac events after implanting a drug-eluting stent, it is not uncommon for the thienopyridine to be discontinued. Health professionals must do more to educate patients about their treatment and the risks associated with stopping. Scottish approval The SMC (www.scottishmedicines.org.uk) has approved varenicline (Champix) for use within NHS Scotland as part of a smoking cessation programme; it notes that the benefits of extending a course of treatment beyond the initial 12 weeks are modest. Controversially, the SMC has not approved omalizumab (Xolair) as add-on therapy for severe persistent allergic asthma on the grounds that an economic case had not been made. Asthma UK criticised the decision as unjust and inhumane. NICE is due to publish an appraisal of omalizumab later this year. No decline with anti- psychotics Treatment with anti- psychotics does not hasten cognitive decline in patients with Alzheimer's disease, say investigators from London (J Neurol Neurosurg Psychiatry 2007;78:25-9). Their prospective study of 224 patients found no difference in the rate of cognitive decline in those treated with antipsychotics (atypical or otherwise) for at least six months. Label translation online Health IT consultancy Rxinfo has developed a website offering translations of the most common types of labelling. The site (www.translabel.co.uk) offers translations into 13 Asian and European languages for 15 standard labelling phrases covering oral medicines and ENT formulations. A free application can be downloaded to allow direct-to-printer printing. Copyright © 2007 Wiley Interface Ltd [source]

The state of residential care for people with mental illness; insights from an audit of the screening tool for entry to licensed residential facilities

AUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 2 2009
Lauren J. Bailey
Abstract Objective: To describe the medical and psychiatric profile of people assessed with the ,Screening Tool for Entry to Licensed Residential Centres' (Boarding House Screening Tool), examine the impact on their accommodation and the screening process. Methods: Copies of all of the Boarding House Screening Tools completed by the Camperdown Aged Care Assessment Team in 2003 and 2004 were examined. Accommodation status in 2006 was obtained from the Boarding House Team, GP or hospital database. A structured telephone survey of Aged Care Assessment Team staff was performed. Results: Thirty-nine Boarding House Screening Tools were reviewed. The mean age of the screened population was 43 yrs (range 22-76 yrs), most were men (36M: 3F). Eighty-two per cent had a listed psychiatric diagnosis, 23% a recent history of substance abuse, 10% a diagnosis of intellectual disability/cognitive impairment and 28% had more than two listed medical diagnoses. Seven people (18%), diagnosed with Schizophrenia, were not approved by the Boarding House Screening Tool because of high care needs and/or violent behaviour, however, only one remained in a high care facility in 2006. Forty-two per cent of people approved by the Boarding House Screening Tool were living in Licensed Boarding Houses in 2006. Conclusion and implications: People being assessed for entry to Licensed Boarding Houses are young with high levels of psychiatric illness, medical co-morbidity and drug and alcohol use. The Boarding House Screening Tool is effective in keeping people who are not approved out of Licensed Boarding Houses; however, even if approved this accommodation is short-term in the majority of cases. [source]

An investigation of Detect, Practice, and Repair to remedy math-fact deficits in a group of third-grade students

PSYCHOLOGY IN THE SCHOOLS, Issue 4 2010
Brian C. Poncy
A multiple-probe-across-problem-sets (tasks) design was used to evaluate the effects of the Detect, Practice, and Repair (DPR) on multiplication-fact fluency development in seven third-grade students nominated by their teacher as needing remediation. DPR is a multicomponent intervention and begins with a group-administered, metronome-paced assessment used to identify specific facts in need of repair. Next, Cover, Copy, and Compare (CCC) procedures are used to enhance automaticity with those specific facts. Lastly, students complete a 1-min speed drill and self-graph their fluency performance. Results showed large level and trend increases in fact fluency after DPR was applied across all three sets of multiplication problems. Discussion focuses on the importance of developing effective and efficient basic-skill-remediation procedures and directions for future research. © 2010 Wiley Periodicals, Inc. [source]

Fair Copy: Protecting Access to Scientific Information in Post-War Britain

THE MODERN LAW REVIEW, Issue 2 2010
Brad Sherman
This paper extends recent discussions about copyright and the public domain by looking at attempts in post-war Britain to promote access to scientific information. More specifically, it concentrates on the Royal Society's Fair Copy Declaration (1950) and the related library copying provisions introduced in the Copyright Act 1956, which were designed to protect access to information. While the UK library copying provisions were presented as an expanded version of the Fair Copy Declaration recast in a statutory format, we show that the library copying provisions reflected a specific way of thinking about creation, production and distribution that differed markedly from those that underpinned the Fair Copy Declaration. We also argue that the logic of creation reflected in the library copying provisions shaped copyright law over the course of the twentieth century and beyond. [source]

Sapphire: copying garbage collection without stopping the world

CONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 3-5 2003
Richard L. Hudson
Abstract The growing use in concurrent systems of languages that require garbage collection (GC), such as Java, is raising practical interest in concurrent GC. Sapphire is a new algorithm for concurrent copying GC for Java. It stresses minimizing the amount of time any given application thread may need to block to support the collector. In particular, Sapphire is intended to work well in the presence of a large number of application threads, on small- to medium-scale shared memory multiprocessors. Sapphire extends previous concurrent copying algorithms, and is most closely related to replicating copying collection, a GC technique in which application threads observe and update primarily the old copies of objects. The key innovations of Sapphire are: (1) the ability to ,flip' one thread at a time (changing the thread's view from the old copies of objects to the new copies), as opposed to needing to stop all threads and flip them at the same time; (2) exploiting Java semantics and assuming any data races occur on volatile fields, to avoid a barrier on reads of non-volatile fields; and (3) working in concert with virtually any underlying (non-concurrent) copying collection algorithm. Copyright © 2003 John Wiley & Sons, Ltd. [source]

Efficient communication using message prediction for clusters of multiprocessors

CONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 10 2002
Ahmad Afsahi
Abstract With the increasing uniprocessor and symmetric multiprocessor computational power available today, interprocessor communication has become an important factor that limits the performance of clusters of workstations/multiprocessors. Many factors including communication hardware overhead, communication software overhead, and the user environment overhead (multithreading, multiuser) affect the performance of the communication subsystems in such systems. A significant portion of the software communication overhead belongs to a number of message copying operations. Ideally, it is desirable to have a true zero-copy protocol where the message is moved directly from the send buffer in its user space to the receive buffer in the destination without any intermediate buffering. However, due to the fact that message-passing applications at the send side do not know the final receive buffer addresses, early arrival messages have to be buffered at a temporary area. In this paper, we show that there is a message reception communication locality in message-passing applications. We have utilized this communication locality and devised different message predictors at the receiver sides of communications. In essence, these message predictors can be efficiently used to drain the network and cache the incoming messages even if the corresponding receive calls have not yet been posted. The performance of these predictors, in terms of hit ratio, on some parallel applications are quite promising and suggest that prediction has the potential to eliminate most of the remaining message copies. We also show that the proposed predictors do not have sensitivity to the starting message reception call, and that they perform better than (or at least equal to) our previously proposed predictors. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Enhancer detection in the ascidian Ciona intestinalis with transposase-expressing lines of Minos

DEVELOPMENTAL DYNAMICS, Issue 1 2008
Yasunori Sasakura
Abstract Germline transgenesis with a Tc1/mariner superfamily Minos transposon was achieved in the ascidian Ciona intestinalis. Transgenic lines that express transposases in germ cells are very useful for remobilizing transposon copies. In the present study, we created transposase-expressing lines of Minos in Ciona. A Ciona gene encoding protamine (Ci - prm) is expressed in the testes and sperm. Transgenic lines expressing Minos transposase in the testes and sperm were created with a cis -element of Ci - prm, and used for enhancer detection. Double-transgenic animals between transposase lines and a transgenic line with an enhancer detection vector passed on several independent enhancer detection events to subsequent progeny. This technique allowed us to isolate transgenic lines that express GFP in restricted tissues. This system provides an easy and efficient method for large-scale enhancer detection in Ciona intestinalis. Developmental Dynamics 237:39,50, 2008. © 2007 Wiley-Liss, Inc. [source]

Calculating credibility: print culture, trust and economic figures in early eighteenth-century England1

ECONOMIC HISTORY REVIEW, Issue 4 2007
NATASHA GLAISYER
Credit in early modern England has been studied by both social historians of the market and historians of the book. The intersection of these literatures is explored by asking the question: how did producers of books about interest (which was closely connected to credit) convince readers that their books could be trusted? One particular book is considered: a palm-sized book of interest calculations by John Castaing. Most importantly, and unusually, many copies of this book contain his signature, which, it is argued, must be interpreted in the context of the particular role that signatures played in guaranteeing financial transactions. [source]

Economic aspects of human cloning and reprogenetics

ECONOMIC POLICY, Issue 36 2003
Gilles Saint-Paul
SUMMARY While most discussions of human cloning start and end with ethics, this paper analyses the economics of human cloning. I analyse the incentives for cloning and its implications for the long-run distribution of skills and income. I discuss models of human cloning for different motives, focusing on those that tend to produce new human beings with improved ability. I distinguish three cases: cloning as a means of assisted reproduction for infertile couples, cloning by fertile couples aimed at producing high ability offspring and, finally, financially motivated cloning. The third case supposes that the creator of a clone can appropriate some fraction of the clone's future income. Even if this fraction is small, the possibility of producing exceptionally talented clones with correspondingly high incomes might make it profitable, and thus turn cloning into a form of financial investment. An important consequence of these models is that to the extent that ability is genetically determined and cloners prefer to make high-ability clones, cloning will act as a form of what might be called ,unnatural selection'. Following standard Darwinian logic, such selection will tend to increase the proportion of high ability people in society. Indeed, under some assumptions the distribution of ability eventually converges to a mass point at the highest possible ability level. Under weaker assumptions, it is shown that ability-reducing genes are eventually eliminated. These results do not depend on cloning displacing sexual reproduction or even being widespread; they hold even if a small, or even negligible number of top ability workers are cloned at a small (but not negligible) number of copies. The paper discusses the plausibility of the models and their results in light on the evidence on marriage markets, child selection, human assisted reproduction and animal husbandry. Finally, it is shown how the analysis can be used to help formulate policies toward cloning, whether they aim at preventing it or managing its external effects. , Gilles Saint-Paul [source]

Dynamics of the SAR11 bacterioplankton lineage in relation to environmental conditions in the oligotrophic North Pacific subtropical gyre

ENVIRONMENTAL MICROBIOLOGY, Issue 9 2009
Alexander Eiler
Summary A quantitative PCR assay for the SAR11 clade of marine Alphaproteobacteria was applied to nucleic acids extracted from monthly depth profiles sampled over a 3-year period (2004,2007) at the open-ocean Station ALOHA (A Long-term Oligotrophic Habitat Assessment; 22°45,N, 158°00,W) in the oligotrophic North Pacific Ocean. This analysis revealed a high contribution (averaging 36% of 16S rRNA gene copies) of SAR11 to the total detected 16S rRNA gene copies over depths ranging from the surface layer to 4000 m, and revealed consistent spatial and temporal variation in the relative abundance of SAR11 16S rRNA gene copies. On average, a higher proportion of SAR11 rRNA gene copies were detected in the photic zone (< 175 m depth; mean = 38%) compared with aphotic (> 175 m depth; mean = 30%), and in the winter months compared with the summer (mean = 44% versus 33%, integrated over 175 m depth). Partial least square to latent structure projections identified environmental variables that correlate with variation in the absolute abundance of SAR11, and provided tools for developing a predictive model to explain time and depth-dependent variations in SAR11. Moreover, this information was used to hindcast temporal dynamics of the SAR11 clade between 1997 and 2006 using the existing HOT data set, which suggested that interannual variations in upper ocean SAR11 abundances were related to ocean-climate variability such as the El Niño Southern Oscillation. [source]

Molecular analysis of the phosphorus starvation response in Trichodesmium spp.

ENVIRONMENTAL MICROBIOLOGY, Issue 9 2009
Elizabeth D. Orchard
Summary The marine diazotroph Trichodesmium is a major contributor to primary production and nitrogen fixation in the tropical and subtropical oceans. These regions are often characterized by low phosphorus (P) concentrations, and P starvation of Trichodesmium could limit growth, and potentially constrain nitrogen fixation. To better understand how this genus responds to P starvation we examined four genes involved in P acquisition: two copies of a high-affinity phosphate binding protein (pstS and sphX) and two putative alkaline phosphatases (phoA and phoX). Sequence analysis of these genes among cultured species of Trichodesmium (T. tenue, T. erythraeum, T. thiebautii and T. spiralis) showed that they all are present and conserved within the genus. In T. erythraeum IMS101, the expression of sphX, phoA and phoX were sensitive to P supply whereas pstS was not. The induction of alkaline phosphatase activity corresponded with phoA and phoX expression, but enzyme activity persisted after the expression of these genes returned to basal levels. Additionally, nifH (nitrogenase reductase; involved in nitrogen fixation) expression was downregulated under P starvation conditions. These data highlight molecular level responses to low P and lay a foundation for better understanding the dynamics of Trichodesmium P physiology in low-P environments. [source]

Isolation and gene quantification of heterotrophic N2 -fixing bacterioplankton in the Baltic Sea

ENVIRONMENTAL MICROBIOLOGY, Issue 1 2007
Kjärstin H. Boström
Summary Cyanobacteria are regarded as the main N2 -fixing organisms in marine waters. However, recent clone libraries from various oceans show a wide distribution of the dinitrogenase reductase gene (nifH) originating from heterotrophic bacterioplankton. We isolated heterotrophic N2 -fixing bacteria from Baltic Sea bacterioplankton using low-nitrogen plates and semi-solid diazotroph medium (SSDM) tubes. Isolates were analysed for the nitrogenase (nifH) gene and active N2 fixation by nested polymerase chain reaction (PCR) and acetylene reduction respectively. A primer-probe set targeting the nifH gene from a , - proteobacterial isolate, 97% 16S rDNA similarity to Pseudomonas stutzeri, was designed for measuring in situ dynamics using quantitative real-time PCR. This nifH gene sequence was detected at two of 11 stations in a Baltic Proper transect at abundances of 3 × 104 and 0.8 × 103 copies per litre seawater respectively. Oxygen requirements of isolates were examined by cultivation in SSDM tubes where oxygen gradients were determined with microelectrodes. Growth, and thereby N2 fixation, was observed as horizontal bands formed at oxygen levels of 0,6% air saturation. The apparent microaerophilic or facultative anaerobic nature of the isolates explains why the SSDM approach is the most appropriate isolation method. Our study illustrates how combined isolation, functional analyses and in situ quantification yielded insights into the oxygen requirements of heterotrophic N2 -fixing bacterioplankton isolates, which were confirmed to be present in situ. [source]

Multiple displacement amplification as a pre-polymerase chain reaction (pre-PCR) to process difficult to amplify samples and low copy number sequences from natural environments

ENVIRONMENTAL MICROBIOLOGY, Issue 7 2005
Juan M. Gonzalez
Summary Microbial assessment of natural biodiversity is usually achieved through polymerase chain reaction (PCR) amplification. Deoxyribonucleic acid (DNA) sequences from natural samples are often difficult to amplify because of the presence of PCR inhibitors or to the low number of copies of specific sequences. In this study, we propose a non-specific preamplification procedure to overcome the presence of inhibitors and to increase the number of copies prior to carrying out standard amplification by PCR. The pre-PCR step is carried out through a multiple displacement amplification (MDA) technique using random hexamers as priming oligonucleotides and ,29 DNA polymerase in an isothermal, whole-genome amplification reaction. Polymerase chain reaction amplification using specific priming oligonucleotides allows the selection of the sequences of interest after a preamplification reaction from complex environmental samples. The procedure (MDA-PCR) has been tested on a natural microbial community from a hypogean environment and laboratory assemblages of known bacterial species, in both cases targeting the small subunit ribosomal RNA gene sequences. Results from the natural community showed successful amplifications using the two steps protocol proposed in this study while standard, direct PCR amplification resulted in no amplification product. Amplifications from a laboratory assemblage by the two-step proposed protocol were successful at bacterial concentrations ,,10-fold lower than standard PCR. Amplifications carried out in the presence of different concentrations of fulvic acids (a soil humic fraction) by the MDA-PCR protocol generated PCR products at concentrations of fulvic acids over 10-fold higher than standard PCR amplifications. The proposed procedure (MDA-PCR) opens the possibility of detecting sequences represented at very low copy numbers, to work with minute samples, as well as to reduce the negative effects on PCR amplifications of some inhibitory substances commonly found in environmental samples. [source]

Isolation and characterization of Tn -Dha1, a transposon containing the tetrachloroethene reductive dehalogenase of Desulfitobacterium hafniense strain TCE1

ENVIRONMENTAL MICROBIOLOGY, Issue 1 2005
Julien Maillard
Summary A new 9.9 kb catabolic transposon, Tn -Dha1, containing the gene responsible for tetrachloroethene (PCE) reductive dechlorination activity, was isolated from Desulfitobacterium hafniense strain TCE1. Two fully identical copies of the insertion sequence ISDha1, a new member of the IS256 family, surround the gene cluster pceABCT, a truncated gene for another transposase and a short open reading frame with homology to a member of the twin-arginine transport system (tatA). Evidence was obtained by Southern blot for an alternative form of the transposon element as a circular molecule containing only one copy of ISDha1. This latter structure most probably represents a dead-end product of the transposition of Tn -Dha1. Strong indications for the transposition activity of ISDha1 were given by polymerase chain reaction (PCR) amplification and sequencing of the intervening sequence located between both inverted repeats (IR) of ISDha1 (IR junction). A stable genomic ISDha1 tandem was excluded by quantitative real-time PCR. Promoter mapping of the pceA gene, encoding the reductive dehalogenase, revealed the presence of a strong promoter partially encoded in the right inverted repeat of ISDha1. A sequence comparison with pce gene clusters from Desulfitobacterium sp. strains PCE-S and Y51 and from Dehalobacter restrictus, all of which show 100% identity for the pceAB genes, indicated that both Desulfitobacterium strains seem to possess the same transposon structure, whereas only the pceABCT gene cluster is conserved in D. restrictus. [source]

Stable augmentation of activated sludge with foreign catabolic genes harboured by an indigenous dominant bacterium

ENVIRONMENTAL MICROBIOLOGY, Issue 10 2002
Kazuya Watanabe
Summary Comamonas sp. rN7 is a phenol-degrading bacterium that represents the dominant catabolic population in activated sludge. The present study examined the utility of this bacterium for establishing foreign catabolic genes in phenol-digesting activated sludge. The phc genes coding for phenol hydroxylase and its transcriptional regulators of C. testosteroni R5 were integrated into the chromosome of strain rN7. The specific phenol-oxygenating activity of a resultant transformant designated rN7(R503) was three times higher than the activity of strain rN7, and the phc genes were stably inherited by rN7(R503) grown in a non-selective laboratory medium. Inoculation of phenol-acclimatized activated sludge with rN7(R503) resulted in a high phenol-oxygenating activity and improved resistance to phenol-shock loading compared to sludge inoculated with either no cells, rN7 or R5. Quantitative competitive polymerase chain reaction (PCR) showed that the phc genes were retained in the rN7(R503)-inoculated sludge at a density of more than 108 copies per ml of mixed liquor for more than 35 days, whereas those in the R5-inoculated sludge disappeared rapidly. No transfer of the phc genes to other indigenous populations was apparent in the rN7(R503)-harbouring sludge. From these results, we concluded that the phenol treatment of the activated sludge was enhanced by the phc genes harboured by the rN7(R503) population. This study suggests a possible bioaugmentation strategy for stably utilizing foreign catabolic genes in natural ecosystems. [source]

Intralesional bovine papillomavirus DNA loads reflect severity of equine sarcoid disease

EQUINE VETERINARY JOURNAL, Issue 4 2010
R. HARALAMBUS
Summary Reasons for performing study: Sarcoids are nonmetastasising, yet locally aggressive skin tumours that constitute the most frequent neoplasm in equids. Infection by bovine papillomaviruses types 1 and 2 (BPV-1, BPV-2) has been recognised as major causative factor in sarcoid pathogenesis, but a possible correlation of intralesional virus load with disease severity has not been established thus far. Hypothesis: Given the pathogenic role of BPV-1 and BPV-2 in sarcoid disease, we suggest that intralesional viral DNA concentration may reflect the degree of affection. Methods: Severity of disease was addressed by recording the tumour growth kinetics, lesion number and tumour type for 37 sarcoid-bearing horses and one donkey. Viral load was estimated via quantitative real-time PCR (qPCR) of the E2, E5, L1 and L2 genes from the BPV-1/-2 genome for one randomly selected lesion per horse and correlated with disease severity. Results: Quantitative PCR against E2 identified viral DNA concentrations ranging from 0,556 copies/tumour cell. Of 16 horses affected by quiescent, slowly growing single tumours or multiple mild-type lesions, 15 showed a viral load up to 1.4 copies per cell. In stark contrast, all equids (22/22) bearing rapidly growing and/or multiple aggressive sarcoids had a viral load between 3 and 569 copies per cell. Consistent results were obtained with qPCR against E5, L1 and L2. Conclusions: While tumours of the same clinical type carried variable virus load, confirming that viral titre does not determine clinical appearance, we identified a highly significant correlation between intralesional viral load and disease severity. Potential relevance: The rapid determination of BPV viral load will give a reliable marker for disease severity and may also be considered when establishing a therapeutic strategy. [source]

High epitope density in a single protein molecule significantly enhances antigenicity as well as immunogenicity: a novel strategy for modern vaccine development and a preliminary investigation about B,cell discrimination of monomeric proteins

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2005
Wanli Liu
Abstract Although early studies have shown a close correlation between epitope density and epitope-specific humoral immune responses, few attempts have been made to quantitatively compare the antigenic and immunogenic differences between protein molecules bearing low or high degrees of epitope density, nor have studies quantitatively investigated the mechanism of B,cell discrimination of monomeric antigens. In this study, we prepared glutathione S-transferase (GST) fusion proteins bearing various copies of the M2e epitope from the influenza virus M2,protein [GST-(M2e)8, GST-(M2e)4 and GST-(M2e)1], which were used to detect and compare the real-time kinetic binding with M2e-specific mAb by surface plasma resonance. Our data show clearly that fusion proteins bearing higher M2e epitope density resulted in higher average avidity for M2e-specific mAb. Furthermore, it was observed that fusion proteins bearing high M2e epitope density could induce polyclonal antibodies (pAb) with enhanced an average affinity constant (KA) for M2e epitope peptide compared to fusion proteins bearing low epitope density. The average KA of pAb induced by GST-(M2e)8 (3.08 × 108,M,1 or 9.96 × 108,M,1) was up to two orders of magnitude greater than the average KA of pAb induced by GST-(M2e)1 (2.00 × 106,M,1 or 3.43 × 106,M,1). Thus, the data presented here demonstrate that high epitope density in a single protein molecule significantly enhances antigenicity and immunogenicity. These findings enrich our knowledge of how epitope density might relate to the recognition, activation and antibody production processes of epitope-specific immature B,cells. [source]

Polymorphisms located in the region containing BHMT and BHMT2 genes as maternal protective factors for orofacial clefts

EUROPEAN JOURNAL OF ORAL SCIENCES, Issue 4 2010
Adrianna Mostowska
Mostowska A, Hozyasz KK, Biedziak B, Misiak J, Jagodzinski PP. Polymorphisms located in the region containingBHMTandBHMT2genes as maternal protective factors for orofacial clefts. Eur J Oral Sci 2010; 118: 325,332. © 2010 The Authors. Journal compilation © 2010 Eur J Oral Sci Nonsyndromic cleft lip with or without cleft palate (NCL/P) is one of the most common craniofacial malformations; however, its aetiology is still unclear. Because the effects of maternal nutrition on fetal development are well known, we decided to pursue the question of whether polymorphic variants of genes encoding enzymes involved in choline metabolism might be associated with the maternal risk of having a baby with NCL/P. Analysis of 18 single nucleotide polymorphisms (SNPs) of betaine-homocysteine methyltransferase (BHMT), betaine-homocysteine methyltransferase-2 (BHMT2), choline dehydrogenase (CHDH), choline kinase (CHKA), dimethylglycine dehydrogenase (DMGDH), choline-phosphate cytidylyltransferase A (PCYT1A), and phosphatidylethanolamine N -methyltransferase (PEMT) provided evidence that polymorphisms located in the region containing BHMT and BHMT2 were protective factors against NCL/P affected pregnancies in our population. The strongest signal was found for the SNP located in the intronic sequence of BHMT2. Women carrying two copies of the rs625879 T allele had a significantly decreased risk of having offspring with orofacial clefts. These results were significant, even after correction for multiple comparisons. Moreover, the gene,gene interaction analysis revealed a significant epistatic interaction of BHMT2 (rs673752), PEMT (rs12325817), and PCYT1A (rs712012) with maternal NCL/P susceptibility. Altogether, our study identified a novel gene, the nucleotide variants of which were be associated with a decreased risk of having a baby with NCL/P. [source]

Glycerol and Glycerol Glycol Glycodendrimers

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 22 2003
Mike M. K. Boysen
Abstract Non-covalent interactions between structural parts of complex oligosaccharides and saccharide-recognising proteins are of crucial importance for many cell communication phenomena. Specificity of such interactions and stability of these ligand-receptor complexes are achieved through multivalent interactions between multiple copies of a saccharide ligand and a corresponding number of protein receptors. Substances presenting multiple copies of the saccharide ligand on easily accessible scaffold molecules therefore appear to be promising tools for study of multivalent interactions and their possible inhibition. Such multivalent glycomimetics can be prepared by attachment of saccharide residues to the surface functional groups of dendrimers. In the course of our work, we have prepared novel glycodendrimers with glycerol and glycerol glycol polyether scaffolds. Isopropylidene-protected hydroxyethyl mannoside was chosen as the carbohydrate component, with the construction of the dendritic structures proceeding by a convergent approach featuring iterative Williamson etherification and ozonolysis/hydride reduction steps. Deprotected representatives of such structures are potential inhibitors of mannose-binding lectins of E. coli. Three representative compounds were deprotected and their anti-adhesive properties were examined. The route to these glycodendrimers was also evaluated in terms of synthetic chemistry. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source]

FMRFamide gene and peptide expression during central nervous system development of the cephalopod mollusk, Idiosepius notoides

EVOLUTION AND DEVELOPMENT, Issue 2 2010
Tim Wollesen
SUMMARY Mollusks are a showcase of brain evolution represented by several classes with a varying degree of nervous system centralization. Cellular and molecular processes involved in the evolution of the highly complex cephalopod brain from a simple, monoplacophoran-like ancestor are still obscure and homologies on the cellular level are poorly established. FMRFamide (Phe-Ile-Arg-Phe-NH2)-related peptides (FaRPs) constitute an evolutionarily conserved and diverse group of neuropeptides in the central nervous system (CNS) of many metazoans. Herein, we provide a detailed description of the developing FMRFamide-like immunoreactive (Fa-lir) CNS of the pygmy squid Idiosepius notoides using gene expression analyses and immunocytochemistry. The open reading frame of the I. notoides FMRFamide gene InFMRF predicts one copy each of FIRFamide, FLRFamide (Phe-Leu-Arg-Phe-NH2), ALSGDAFLRFamide (Ala-Leu-Ser-Gly-Asp-Ala-Phe-Leu-Arg-Phe-NH2), and 11 copies of FMRFamide. Applying matrix-assisted laser desorption/ionization time-of-flight (ToF) mass spectrometry-based peptide profiling, we characterized all predicted FaRPs except ALSGDAFLRFamide. Two cell clusters express InFMRF and show FMRFamide-like-immunoreactivity within the palliovisceral ganglia, that is, the future posterior subesophageal mass, during the lobe differentiation phase. They project neurites via ventral axonal tracts, which form the scaffold of the future subesophageal mass. In the supraesophageal mass, InFMRF is first expressed during mid-embryogenesis in the superior and inferior buccal lobes. A neurite of the peduncle commissure represents the first Fa-lir element. Later, the sub- and supraesophageal mass interconnect via Fa-lir neurites and more brain lobes express InFMRF and FMRFamide-like peptides. InFMRF expression was observed in fewer brain lobes than Fa-lir elements. The early expression of InFMRF and FMRFamide-lir peptides in the visceral system and not the remaining CNS of the cephalopod I. notoides resembles the condition found in the majority of investigated gastropods. [source]

On the origin of the chordate central nervous system: expression of onecut in the sea urchin embryo

EVOLUTION AND DEVELOPMENT, Issue 4 2004
Albert J. Poustka
Summary We identified a transcription factor of the onecut class in the sea urchin Strongylocentrotus purpuratus that represents an ortholog of the mammalian gene HNF6, the founding member of the onecut class of proteins. The isolated sea urchin gene, named SpOnecut, encodes a protein of 483 amino acids with one cut domain and a homeodomain. Phylogenetic analysis clearly places the sea urchin gene into this family, most closely related to the ascidian onecut gene HNF-6. Nevertheless, phylogenetic analysis reveals a difficult phylogeny indicating that certain members of the family evolve more rapidly than others and also that the cut domain and homeodomain evolve at a different pace. In fly, worm, ascidian, and teleost fish, the onecut genes isolated so far are exclusively expressed in cells of the central nervous system (CNS), whereas in mammals the two copies of the gene have acquired additional functions in liver and pancreas development. In the sea urchin embryo, expression is first detected in the emerging ciliary band at the late blastula stage. During the gastrula stage, expression is limited to the ciliary band. In the early pluteus stage, SpOnecut is expressed at the apical organ and the elongating arms but continues most prominently in the ciliary band. This is the first gene known that exclusively marks the ciliary band and therein the apical organ in a pluteus larva, whereas chordate orthologs execute essential functions in dorsal CNS development. The significance of this finding for the hypothesis that the ciliary bands and apical organs of the hypothetical "dipleurula"-like chordate ancestor and the chordate/vertebrate CNS are of common origin is discussed. [source]