Showing papers by "Aarhus University published in 2003"

Multifactorial Intervention and Cardiovascular Disease in Patients with Type 2 Diabetes

Abstract: From the Steno Diabetes Center, Copenhagen (P.G., P.V., N.L., H.-H.P., O.P.); Herlev County Hospital, Herlev (N.L.); Amtssygehuset Roskilde, Roskilde (G.V.H.J.); and the Faculty of Health Science, Aarhus University, Aarhus (H.-H.P., O.P.) — all in Denmark. Address reprint requests to Dr. Pedersen at the Steno Diabetes Center, Niels Steensens Vej 2, 2820 Gentofte, Denmark, or at oluf@steno.dk. N Engl J Med 2003;348:383-93. Copyright © 2003 Massachusetts Medical Society. background Cardiovascular morbidity is a major burden in patients with type 2 diabetes. In the Steno-2 Study, we compared the effect of a targeted, intensified, multifactorial intervention with that of conventional treatment on modifiable risk factors for cardiovascular disease in patients with type 2 diabetes and microalbuminuria. methods The primary end point of this open, parallel trial was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, revascularization, and amputation. Eighty patients were randomly assigned to receive conventional treatment in accordance with national guidelines and 80 to receive intensive treatment, with a stepwise implementation of behavior modification and pharmacologic therapy that targeted hyperglycemia, hypertension, dyslipidemia, and microalbuminuria, along with secondary prevention of cardiovascular disease with aspirin. results The mean age of the patients was 55.1 years, and the mean follow-up was 7.8 years. The decline in glycosylated hemoglobin values, systolic and diastolic blood pressure, serum cholesterol and triglyceride levels measured after an overnight fast, and urinary albumin excretion rate were all significantly greater in the intensive-therapy group than in the conventional-therapy group. Patients receiving intensive therapy also had a significantly lower risk of cardiovascular disease (hazard ratio, 0.47; 95 percent confidence interval, 0.24 to 0.73), nephropathy (hazard ratio, 0.39; 95 percent confidence interval, 0.17 to 0.87), retinopathy (hazard ratio, 0.42; 95 percent confidence interval, 0.21 to 0.86), and autonomic neuropathy (hazard ratio, 0.37; 95 percent confidence interval, 0.18 to 0.79). conclusions A target-driven, long-term, intensified intervention aimed at multiple risk factors in patients with type 2 diabetes and microalbuminuria reduces the risk of cardiovascular and microvascular events by about 50 percent.

Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia

Abstract: Background Imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase, produces high response rates in patients with chronic-phase chronic myeloid leukemia (CML) who have had no response to interferon alfa. We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML. Methods We randomly assigned 1106 patients to receive imatinib (553 patients) or interferon alfa plus low-dose cytarabine (553 patients). Crossover to the alternative group was allowed if stringent criteria defining treatment failure or intolerance were met. Patients were evaluated for hematologic and cytogenetic responses, toxic effects, and rates of progression. Results After a median follow-up of 19 months, the estimated rate of a major cytogenetic response (0 to 35 percent of cells in metaphase positive for the Philadelphia chromosome) at 18 months was 87.1 percent (95 percent confidence interval, 84.1 to 90.0) in the imatinib group and 34.7 percent (95 perce...

From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II.

Abstract: Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document focuses on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.

European guidelines on cardiovascular disease prevention in clinical practice. Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice.

Abstract: Guidelines aim to present all the relevant evidence on a particular issue in order to help physicians to weigh the benefits and risks of a particular diagnostic or therapeutic procedure. They should be helpful in everyday clinical decision-making. A great number of guidelines have been issued in recent years by different organizations-European Society of Cardiology (ESC), American Heart Association (AHA), American College of Cardiology (ACC), and other related societies. By means of links to web sites of National Societies several hundred guidelines are available. This profusion can put at stake the authority and validity of guidelines, which can only be guaranteed if they have been developed by an unquestionable decision-making process. This is one of the reasons why the ESC and others have issued recommendations for formulating and issuing guidelines. In spite of the fact that standards for issuing good quality guidelines are well defined, recent surveys of guidelines published in peer-reviewed journals between 1985 and 1998 have shown that methodological standards were not complied with in the vast majority of cases. It is therefore of great importance that guidelines and recommendations are presented in formats that are easily interpreted. Subsequently, their implementation programmes must also be well conducted. Attempts have been made to determine whether guidelines improve the quality of clinical practice and the utilization of health resources. In addition, the legal implications of medical guidelines have been discussed and examined, resulting in position documents, which have been published by a specific Task Force. The ESC Committee for Practice Guidelines (CPG) supervises and coordinates the preparation of new Guidelines and Expert Consensus Documents produced by Task Forces, expert groups or consensus panels. The Committee is also responsible for the endorsement of these guidelines or statements. The rationale for an active approach to the prevention of cardiovascular diseases (CVD) is …

Bone healing and soft tissue contour changes following single-tooth extraction: a clinical and radiographic 12-month prospective study.

Abstract: Preservation of alveolar bone volume following tooth extraction facilitates subsequent placement of dental implants and leads to an improved esthetic and functional prosthodontic result. The aim of the present study was to assess bone formation in the alveolus and the contour changes of the alveolar process following tooth extraction. The tissue changes after removal of a premolar or molar in 46 patients were evaluated in a 12-month period by means of measurements on study casts, linear radiographic analyses, and subtraction radiography. The results demonstrated that major changes of an extraction site occurred during 1 year after tooth extraction.

A very energetic supernova associated with the |[gamma]|-ray burst of 29 March 2003

Abstract: Over the past five years evidence has mounted that long-duration (greater than 2s) gamma-ray bursts (GRBs), the most brilliant of all astronomical explosions, signal the collapse of massive stars in our Universe. This evidence, originally based on the probable association of one unusual GRB with a supernova, now includes the association of GRBs with regions of massive star-formation in distant galaxies, tantalizing evidence of supernova-like light-curve 'bumps' in the optical afterglows of several bursts, and lines of freshly synthesized elements in the spectra of a few X-ray afterglows. These observations support, but do not yet conclusively validate, models based upon the deaths of massive stars, presumably associated with core collapse. Here we report evidence for a very energetic supernova (a hypernova), temporally and spatially coincident with a GRB at redshift z=0.1685. The timing of the supernova indicates that it exploded within a few days of the GRB, strongly suggesting that core-collapse events can give rise to GRBs. Amongst the GRB central engine models proposed to-date, the properties of this supernova thus favour the collapsar model.

A Comparison of Coronary Angioplasty with Fibrinolytic Therapy in Acute Myocardial Infarction

Abstract: Among patients who underwent randomization at referral hospitals, the primary end point was reached in 8.5 percent of the patients in the angioplasty group, as compared with 14.2 percent of those in the fibrinolysis group (P=0.002). The results were similar among patients who were enrolled at invasive-treatment centers: 6.7 percent of the patients in the angioplasty group reached the primary end point, as compared with 12.3 percent in the fibrinolysis group (P=0.05). Among all patients, the better outcome after angioplasty was driven primarily by a reduction in the rate of reinfarction (1.6 percent in the angioplasty group vs. 6.3 percent in the fibrinolysis group, P<0.001); no significant differences were observed in the rate of death (6.6 percent vs. 7.8 percent, P=0.35) or the rate of stroke (1.1 percent vs. 2.0 percent, P=0.15). Ninety-six percent of patients were transferred from referral hospitals to an invasive-treatment center within two hours. conclusions A strategy for reperfusion involving the transfer of patients to an invasive-treatment center for primary angioplasty is superior to on-site fibrinolysis, provided that the transfer takes two hours or less.

The evolutionary and ecological role of heat shock proteins

Abstract: Most heat shock proteins (Hsp) function as molecular chaperones that help organisms to cope with stress of both an internal and external nature. Here, we review the recent evidence of the relationship between stress resistance and inducible Hsp expression, including a characterization of factors that induce the heat shock response and a discussion of the associated costs. We report on studies of stress resistance including mild stress, effects of high larval densities, inbreeding and age on Hsp expression, as well as on natural variation in the expression of Hsps. The relationship between Hsps and life history traits is discussed with special emphasis on the ecological and evolutionary relevance of Hsps. It is known that up-regulation of the Hsps is a common cellular response to increased levels of non-native proteins that facilitates correct protein folding/refolding or degradation of non-functional proteins. However, we also suggest that the expression level of Hsp in each species and population is a balance between benefits and costs, i.e. a negative impact on growth, development rate and fertility as a result of overexpression of Hsps. To date, investigations have focused primarily on the Hsp70 family. There is evidence that representatives of this Hsp family and other molecular chaperones play significant roles in relation to stress resistance. Future studies including genomic and proteonomic analyses will increase our understanding of molecular chaperones in stress research.

Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients.

Abstract: Background Everolimus, a novel proliferation inhibitor and immunosuppressive agent, may suppress cardiac-allograft vasculopathy. We conducted a randomized, double-blind, clinical trial comparing everolimus with azathioprine in recipients of a first heart transplant. Methods A total of 634 patients were randomly assigned to receive 1.5 mg of everolimus per day (209 patients), 3.0 mg of everolimus per day (211 patients), or 1.0 to 3.0 mg of azathioprine per kilogram of body weight per day (214 patients), in combination with cyclosporine, corticosteroids, and statins. The primary efficacy end point was a composite of death, graft loss or retransplantation, loss to follow-up, biopsy-proved acute rejection of grade 3A, or rejection with hemodynamic compromise. Results At six months, the percentage of patients who had reached the primary efficacy end point was significantly smaller in the group given 3.0 mg of everolimus (27.0 percent, P<0.001) and the group given 1.5 mg of everolimus (36.4 percent, P=0.03) tha...

Plant recognition of symbiotic bacteria requires two LysM receptor-like kinases

Abstract: Although most higher plants establish a symbiosis with arbuscular mycorrhizal fungi, symbiotic nitrogen fixation with rhizobia is a salient feature of legumes. Despite this host range difference, mycorrhizal and rhizobial invasion shares a common plant-specified genetic programme controlling the early host interaction. One feature distinguishing legumes is their ability to perceive rhizobial-specific signal molecules. We describe here two LysM-type serine/threonine receptor kinase genes, NFR1 and NFR5, enabling the model legume Lotus japonicus to recognize its bacterial microsymbiont Mesorhizobium loti. The extracellular domains of the two transmembrane kinases resemble LysM domains of peptidoglycan- and chitin-binding proteins, suggesting that they may be involved directly in perception of the rhizobial lipochitin-oligosaccharide signal. We show that NFR1 and NFR5 are required for the earliest physiological and cellular responses to this lipochitin-oligosaccharide signal, and demonstrate their role in the mechanism establishing susceptibility of the legume root for bacterial infection.

Defining and classifying clinical indicators for quality improvement

Abstract: Objective. This paper provides a brief review of deWnitions, characteristics, and categories of clinical indicators for quality improvement in health care. Analysis. Clinical indicators assess particular health structures, processes, and outcomes. They can be rate- or mean-based, providing a quantitative basis for quality improvement, or sentinel, identifying incidents of care that trigger further investigation. They can assess aspects of the structure, process, or outcome of health care. Furthermore, indicators can be generic measures that are relevant for most patients or disease-speciWc, expressing the quality of care for patients with speciWc diagnoses. Conclusions. Monitoring health care quality is impossible without the use of clinical indicators. They create the basis for quality improvement and prioritization in the health care system. To ensure that reliable and valid clinical indicators are used, they must be designed, deWned, and implemented with scientiWc rigour.

A receptor kinase gene of the LysM type is involved in legume perception of rhizobial signals.

Abstract: Plants belonging to the legume family develop nitrogen-fixing root nodules in symbiosis with bacteria commonly known as rhizobia. The legume host encodes all of the functions necessary to build the specialized symbiotic organ, the nodule, but the process is elicited by the bacteria. Molecular communication initiates the interaction, and signals, usually flavones, secreted by the legume root induce the bacteria to produce a lipochitin-oligosaccharide signal molecule (Nod-factor), which in turn triggers the plant organogenic process. An important determinant of bacterial host specificity is the structure of the Nod-factor, suggesting that a plant receptor is involved in signal perception and signal transduction initiating the plant developmental response. Here we describe the cloning of a putative Nod-factor receptor kinase gene (NFR5) from Lotus japonicus. NFR5 is essential for Nod-factor perception and encodes an unusual transmembrane serine/threonine receptor-like kinase required for the earliest detectable plant responses to bacteria and Nod-factor. The extracellular domain of the putative receptor has three modules with similarity to LysM domains known from peptidoglycan-binding proteins and chitinases. Together with an atypical kinase domain structure this characterizes an unusual receptor-like kinase.

Suicide risk in relation to socioeconomic, demographic, psychiatric, and familial factors: a national register-based study of all suicides in Denmark, 1981-1997.

Abstract: OBJECTIVE: Suicide risk was addressed in relation to the joint effect of factors regarding family structure, socioeconomics, demographics, mental illness, and family history of suicide and mental illness, as well as gender differences in risk factors. METHOD: Data were drawn from four national Danish longitudinal registers. Subjects were all 21,169 persons who committed suicide in 1981–1997 and 423,128 live comparison subjects matched for age, gender, and calendar time of suicide by using a nested case-control design. The effect of risk factors was estimated through conditional logistic regression. The interaction of gender with the risk factors was examined by using the log likelihood ratio test. The population attributable risk was calculated. RESULTS: Of the risk factors examined in the study, a history of hospitalization for psychiatric disorder was associated with the highest odds ratio and the highest attributable risk for suicide. Cohabiting or single marital status, unemployment, low income, retir...

Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study.

Abstract: The objective of this study was to describe the prevalence of Klinefelter syndrome (KS) prenatally and postnatally in Denmark and determine the influence of maternal age. All chromosomal examinations in Denmark are registered in the Danish Cytogenetic Central Registry. Individuals with KS diagnosed prenatally or postnatally were extracted from the registry with information about age at the time of diagnosis and mother's age. In the period 1970-2000, 76,526 prenatal examinations on male fetuses resulted in the diagnosis of 163 fetuses with KS karyotype, corresponding to a prevalence of 213 per 100,000 male fetuses. Standardization according to maternal age resulted in a prevalence of 153 per 100,000 males. Postnatally, 696 males of 2,480,858 live born were diagnosed with KS, corresponding to a prevalence among adult men of approximately 40 per 100,000. Less than 10% of the expected number was diagnosed before puberty. Advanced maternal age had a significant impact on the prevalence. KS is severely underdiagnosed in Denmark. Only approximately one fourth of adult males with KS are diagnosed. There is a marked delay in diagnosis of the syndrome. A delay in treatment with testosterone may lead to decreased muscle and bone mass with subsequent risk of osteoporosis.

The Balanced Scorecard: what is the score? A rhetorical analysis of the Balanced Scorecard

Abstract: The Balanced Scorecard currently receives much attention. This article analyses the means by which the authors of The Balanced Scorecard have created that attention. Is it the result of a new and convincing theory,or is it merely the result of persuasive rhetoric,where convincing theory differs from solely persuasive rhetoric in that concepts and claims are based on sound argumentation? The article concludes that the text is not so convincing as persuasive—a feature characteristic of the genre of management guru texts; and,at the end,the article discusses the reasons for and appropriateness of such a genre and the consequences that should follow from the results of the analysis. # 2003 Elsevier Ltd. All rights reserved.

From Greenland to green lakes: Cultural eutrophication and the loss of benthic pathways in lakes

Abstract: Benthic community responses to lake eutrophication are poorly understood relative to pelagic responses. We compared phytoplankton and periphyton productivity along a eutrophication gradient in Greenland, U.S., and Danish lakes. Phytoplankton productivity increased along the phosphorus gradient (total phosphorus [TP] 5 2‐430 mg m 23 ), but whole-lake benthic algal productivity decreased, substantially depressing increases in primary productivity at the whole-lake scale. In shallow, oligotrophic Greenland lakes, periphyton was responsible for 80‐98% of primary production, whereas in Danish lakes with TP . 100 mg m 23 , phytoplankton were responsible for nearly 100% of primary production. Benthic contributions ranged from 5 to 80% depending on morphometry and littoral habitat composition in lakes with intermediate phosphorus concentrations. Thus, eutrophication was characterized by a switch from benthic to pelagic dominance of primary productivity. Carbon stable isotope analysis showed that the redistribution of primary production entailed a similar shift from periphyton to phytoplankton in the diets of zoobenthos. Benthic and pelagic habitats were energetically linked through food web interactions, but eutrophication eroded the benthic primary production pathway.

Marked loss of myelinated nerve fibers in the human brain with age.

Abstract: The white matter is the structure of the brain that declines most with age—almost 30%, but little is known about the age-effect on the fibers that constitute the white matter. In the present study, the total length of myelinated fibers was measured with a newly developed stereologic method. Specimens came from 36 normal Danes (18 males and 18 females) with an age ranging between 18 and 93 years. Samples were taken systematically and randomly from the white matter, and the biopsy specimens were randomly rotated before sectioning to avoid bias due to the anisotropic nature of nerve fibers. The fibers were counted at light microscopic level at approximately 10,000× magnification, and the diameter of each counted fiber was measured to get the diameter distribution. Males were found to have a total myelinated fiber length of 176,000 km at the age of 20 and 97,200 km at the age of 80, whereas the total length in females was 149,000 km at the age of 20 and 82,000 km at the age of 80. This finding corresponds to a 10% decrease per decade or a total decrease of 45% from the age of 20 to 80 years, and a sex difference of 16%. The fiber diameter distribution showed that primarily the thinner fibers were lost with a relative preservation of the thicker ones. The marked loss of myelinated nerve fibers with age could explain some of the cognitive decline seen in the elderly. J. Comp. Neurol. 462:144–152, 2003. © 2003 Wiley-Liss, Inc.

Na+-K+ Pump Regulation and Skeletal Muscle Contractility

Abstract: In skeletal muscle, excitation may cause loss of K+, increased extracellular K+ ([K+]o), intracellular Na+ ([Na+]i), and depolarization. Since these events interfere with excitability, the processes of excitation can be self-limiting. During work, therefore, the impending loss of excitability has to be counterbalanced by prompt restoration of Na+-K+ gradients. Since this is the major function of the Na+-K+ pumps, it is crucial that their activity and capacity are adequate. This is achieved in two ways: 1) by acute activation of the Na+-K+ pumps and 2) by long-term regulation of Na+-K+ pump content or capacity. 1) Depending on frequency of stimulation, excitation may activate up to all of the Na+-K+ pumps available within 10 s, causing up to 22-fold increase in Na+ efflux. Activation of the Na+-K+ pumps by hormones is slower and less pronounced. When muscles are inhibited by high [K+]o or low [Na+]o, acute hormone- or excitation-induced activation of the Na+-K+ pumps can restore excitability and contractile force in 10-20 min. Conversely, inhibition of the Na+-K+ pumps by ouabain leads to progressive loss of contractility and endurance. 2) Na+-K+ pump content is upregulated by training, thyroid hormones, insulin, glucocorticoids, and K+ overload. Downregulation is seen during immobilization, K+ deficiency, hypoxia, heart failure, hypothyroidism, starvation, diabetes, alcoholism, myotonic dystrophy, and McArdle disease. Reduced Na+-K+ pump content leads to loss of contractility and endurance, possibly contributing to the fatigue associated with several of these conditions. Increasing excitation-induced Na+ influx by augmenting the open-time or the content of Na+ channels reduces contractile endurance. Excitability and contractility depend on the ratio between passive Na+-K+ leaks and Na+-K+ pump activity, the passive leaks often playing a dominant role. The Na+-K+ pump is a central target for regulation of Na+-K+ distribution and excitability, essential for second-to-second ongoing maintenance of excitability during work.

Belief and recollection of autobiographical memories

Abstract: In three experiments, undergraduates rated autobiographical memories on scales derived from existing theories of memory. In multiple regression analyses, ratings of the degree to which subjects recollected (i.e., relived) their memories were predicted by visual imagery, auditory imagery, and emotions, whereas ratings of belief in the accuracy of their memories were predicted by knowledge of the setting. Recollection was predicted equally well in between- and within-subjects analyses, but belief consistently had smaller correlations and multiple regression predictions between subjects; individual differences in the cognitive scales that we measured could not account well for individual differences in belief. In contrast, measures of mood (Beck Depression Index) and dissociation (Dissociative Experience Scale) added predictive value for belief, but not for recollection. We also found that highly relived memories almost always had strong visual images and thatremember/know judgments made on autobiographical memories were more closely related to belief than to recollection.

Intensive Insulin Therapy Exerts Antiinflammatory Effects in Critically Ill Patients and Counteracts the Adverse Effect of Low Mannose-Binding Lectin Levels

Abstract: Adverse outcome of critical illness is often caused by systemic inflammation and sepsis. A recent study showed that mortality is significantly reduced by maintenance of normoglycemia using intensive insulin therapy. We examined whether the beneficial effects of intensive insulin therapy involve modulations of mannose-binding lectin (MBL) and C-reactive protein (CRP) levels. From a study of 1548 patients randomly assigned to either conventional treatment or intensive insulin therapy at an intensive care unit (ICU) we included all 451 patients who needed prolonged intensive care (>5 d). CRP and MBL concentrations were measured on admission, d 5, d 15, and the last day in the ICU. In all patients, serum MBL concentrations increased with time in the ICU (P < 0.0001). This acute phase response was suppressed by intensive insulin therapy at all time points studied (P < 0.02). Selectively in patients receiving conventional therapy, MBL concentrations at baseline were almost 3 times higher in survivors than in nonsurvivors (P = 0.04). Baseline CRP concentrations were elevated, but decreased with time in ICU (P < 0.0001). The decrease in CRP was significantly more pronounced in the intensive insulin-treated patients compared with the conventionally treated patients (P

Geographical isolation in hot spring cyanobacteria

Abstract: Summary It has been proposed that free-living microorganisms exhibit ubiquitous dispersal, do not form geographically isolated populations and rarely (if ever) speciate via allopatry. We studied island-like hot spring cyanobacterial communities in which geographical isolation should be prominent and detectable if it influences the evolution of bacteria. The genetic diversity of cyanobacteria indigenous to North American, Japanese, New Zealand and Italian springs was surveyed by (i) amplification and cloning of 16S rRNA and 16S−23S internal transcribed spacer regions; (ii) lineage-specific oligonucleotide probing (used to verify the predominance of cloned sequences); and (iii) lineage-specific polymerase chain reaction (PCR) (used to search for possible rare genotypes). Phylogenetic and distribution patterns were found to be consistent with the occurrence of geographical isolation at both global and local spatial scales, although different cyanobacterial lineages were found to vary in their distribution. A lack of correspondence between biological patterning and the chemical character of springs sampled suggested that the geographical distribution of thermophilic cyanobacteria cannot be explained by the 20 potential niche-determining chemical parameters that we assayed. Thus, geographical isolation (i.e. genetic drift) must in part be responsible for driving the observed evolutionary divergences. Geographical isolation may be an important underestimated aspect of microbial evolution.

Pfold: RNA secondary structure prediction using stochastic context-free grammars

Abstract: RNA secondary structures are important in many biological processes and efficient structure prediction can give vital directions for experimental investigations. Many available programs for RNA secondary structure prediction only use a single sequence at a time. This may be sufficient in some applications, but often it is possible to obtain related RNA sequences with conserved secondary structure. These should be included in structural analyses to give improved results. This work presents a practical way of predicting RNA secondary structure that is especially useful when related sequences can be obtained. The method improves a previous algorithm based on an explicit evolutionary model and a probabilistic model of structures. Predictions can be done on a web server at http://www.daimi.au.dk/~compbio/pfold.

Translation of symptoms and signs into mechanisms in neuropathic pain

Abstract: 1. IntroductionFor centuries, clinicians have been taught to examine andclassify patients on the basis of topographical lesion and theunderlying pathology. In most clinical specialities, such anapproach has been a key element in understanding thepathophysiology of diseases and has led to progress interms of finding disease modifying or even disease curingtherapies. Examples are multiple including bacterial menin-gitis, painful neuroborrelosis, osteoarthrosis, cancer, rheu-matoid arthritis, ischaemic heart disease etc. In most ofthese disorders, pain can be a major complaint, whichthen rapidly disappears after the relevant therapy has beengiven.But what happens when the symptom itself becomes adisease? When pain persists and becomes a chronic problemand when the underlying diseases such as diabetes, cancer,vasculitis are known, or cannot be cured? Are we thenhelped by the classical ‘Sherlock Holmes’ approach, first,to look for the ‘crime site’ (topography of lesion) andsecond, for the ‘criminal’ (the disease) that caused thispain? The short answer is: no. Clinical experience anddecades of rather discouraging systematic research mainlyrelated to therapy in chronic pain have shown that a strategydirected at examining, classifying and treating pain on basisof anatomy or underlying disease is of limited help to thesepatients and their pain. These observations have then raisedthe question whether an entirely different strategy in whichpain is analysed on the basis of underlying mechanismscould be an alternative approach to examine and classifypatients to obtain a better outcome. Our increasing under-standing of mechanisms underlying chronic pain togetherwith the discovery of new molecular targets for modifyingpain has strengthened the demand for other ways to treatpain. Woolf and other authors (Woolf et al., 1998; Woolfand Decosterd, 1999; Sindrup and Jensen, 1999) haveemphasised the rational for a treatment approach directedat mechanism(s) rather than at diseases because new treat-ments are being developed on basis of the biologicalmechanisms that underlie the pain. One area that needssuch a new approach is neuropathic pain.2. Neuropathic pain classification problemsAccording to the current International Association forthe Study of Pain (IASP) definition of neuropathic pain,these disorders are characterised by lesions or dysfunctionof the system(s) that under normal conditions transmitnoxious information to the central nervous system. Thusin theory, neuropathic pain should be easy to distinguishfrom other conditions, but in practise, they are both diffi-cult to identify and to treat and there are several reasonwhy this is the case:† There is rarely one diagnostic test that can confirm orrefute the hypothesis of nerve lesion/dysfunction.† The perception of neuropathic (and other types of) painis a pure subjective phenomenon, which despite use ofthe most sophisticated equipment can’t be measured;only correlates to the perceived content can be obtained.† The borderland between definite, probable, possible andunlikely diagnoses is not clear. Prevalent disorders suchas cancer, low back pain, traumatic injuries may containa considerable (although as yet undetermined) neuro-pathic component.† In contrast to other sensory systems, the pain system isnot static, but changes in a dynamic and somewhatunpredictable fashion whenever the system has beenactivated.

Reducing the run-time complexity of multiobjective EAs: The NSGA-II and other algorithms

Abstract: The last decade has seen a surge of research activity on multiobjective optimization using evolutionary computation and a number of well performing algorithms have been published. The majority of these algorithms use fitness assignment based on Pareto-domination: Nondominated sorting, dominance counting, or identification of the nondominated solutions. The success of these algorithms indicates that this type of fitness is suitable for multiobjective problems, but so far the use of Pareto-based fitness has lead to program run times in O(GMN/sup 2/), where G is the number of generations, M is the number of objectives, and N is the population size. The N/sup 2/ factor should be reduced if possible, since it leads to long processing times for large population sizes. This paper presents a new and efficient algorithm for nondominated sorting, which can speed up the processing time of some multiobjective evolutionary algorithms (MOEAs) substantially. The new algorithm is incorporated into the nondominated sorting genetic algorithm II (NSGA-II) and reduces the overall run-time complexity of this algorithm to O(GN log/sup M-1/N), much faster than the O(GMN/sup 2/) complexity published by Deb et al. (2002). Experiments demonstrate that the improved version of the algorithm is indeed much faster than the previous one. The paper also points out that multiobjective EAs using fitness based on dominance counting and identification of nondominated solutions can be improved significantly in terms of running time by using efficient algorithms known from computer science instead of inefficient O(MN/sup 2/) algorithms.

Long-distance teleportation of qubits at telecommunication wavelengths

Abstract: Matter and energy cannot be teleported (that is, transferred from one place to another without passing through intermediate locations). However, teleportation of quantum states (the ultimate structure of objects) is possible1: only the structure is teleported—the matter stays at the source side and must be already present at the final location. Several table-top experiments have used qubits2,3,4,5,6,7 (two-dimensional quantum systems) or continuous variables8,9,10 to demonstrate the principle over short distances. Here we report a long-distance experimental demonstration of probabilistic quantum teleportation. Qubits carried by photons of 1.3 µm wavelength are teleported onto photons of 1.55 µm wavelength from one laboratory to another, separated by 55 m but connected by 2 km of standard telecommunications fibre. The first (and, with foreseeable technologies, the only) application of quantum teleportation is in quantum communication, where it could help to extend quantum cryptography to larger distances11,12,13.