bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical significance of low‐grade renal artery stenosis
Authors: Dechering D. G. , Kruis H. M. E. , Adiyaman A. , Thien Th. , Postma C. T. 
Published: June 2009

Abstract.  Dechering DG, Kruis HME, Adiyaman A, Thien Th, Postma CT (Radboud University, Nijmegen, The Netherlands, and University Hospital Münster, Münster, Germany). Clinical significance of low‐grade renal artery stenosis. J Intern Med 2010; 267: 305–315.Background.  Patients with a renal artery stenosis (RAS) >50% carry an increased risk for future cardiovascular (CV) events. Experimental literature on this topic suggests that this might as well be true for subjects with lower‐grade RAS.Methods.  Recruitment in this longitudinal cohort study was conducted from 1982 to 2002 in a Dutch University Hospital. Included in this study were 301 hypertensive patients clinically suspected of having RAS. Study participants were radiologically classified as having no, a low‐grade (<50% lumen narrowing) or high‐grade (≥50%) RAS. A predetermined composite CV end‐point was defined as one of the following: myocardial infarction or ‘objectified’ angina pectoris, ischaemic stroke or death from any CV cause. Other end‐points were the occurrence of CV complications, all‐cause plus CV mortality and decline in renal function.Results.  During a median follow‐up of 8.2 years, the incidence of the composite end‐point totalled 79 events. After full adjustment in Cox models, a significant risk increase in high‐grade [hazard ratio (HR) 2.81; P = 0.002] and low‐grade RAS (HR 2.32; P = 0.038) was observed. Other end‐points did not differ significantly between study groups.Conclusion.  Hypertensive subjects with RAS of any extent, compared with hypertensives without RAS, carry a substantially increased risk for future CV events. Therefore, even in patients with low‐grade RAS, aggressive pharmacological treatment strategies should be adopted as a preventive measure.
Self‐pressurized rapid freezing (SPRF): a novel cryofixation method for specimen preparation in electron microscopy
Authors: LEUNISSEN J.L.M. , YI H. 
Published: June 2009

SummaryA method is described for the cryofixation of biological specimens for ultrastructural analysis and immunocytochemical detection studies. The method employs plunge freezing of specimens in a sealed capillary tube into a cryogen such as liquid propane or liquid nitrogen. Using this method a number of single‐cell test specimens were well preserved. Also multicellular organisms, such as Caenorhabditis elegans, could be frozen adequately in low ionic strength media or even in water. The preservation of these unprotected specimens is comparable to that achieved with high‐pressure freezing in the presence of cryoprotectant. The results are explained by the fact that cooling of water in a confined space below the melting point gives rise to pressure build‐up, which may originate from the conversion of a fraction of the water content into low‐density hexagonal ice and/or expansion of water during supercooling. Calculations indicate the pressure may be similar in magnitude to that applied in high‐pressure freezing. Because the specimens are plunge cooled, suitable cryogens are not limited to liquid nitrogen. It is shown that a range of cryogens and cryogen temperatures can be used successfully. Because the pressure is generated inside the specimen holders as a result of the cooling rather than applied from an external source as in high‐pressure freezing, the technique has been referred to as self‐pressurized rapid freezing.
Statistical analysis of labelling patterns of mammary carcinoma cell nuclei on histological sections
Authors: MATTFELDT T. , ECKEL S. , FLEISCHER F. , SCHMIDT V. 
Published: June 2009

SummaryIt is of central interest for tumour biology to explore the mechanisms of tumour cell proliferation. In this study, methods of spatial statistics were used to study the spatial distribution of proliferating cells within tumour tissue quantitatively and objectively. Mammary cancer tissue was studied as an example. It was attempted to clarify whether cell division occurs entirely at random (random labelling), i.e. the process of division occurs at random, independently from the state of the neighbouring nuclei, or whether the spatial distribution of proliferation is more complex, e.g. in the form of actively proliferating clusters alternating with relatively silent zones. In the case of random labelling, the reduced second moment functions K(r) of the labelled and the unlabelled nuclei would be identical. The same would hold for the pair correlation functions g(r). The alternative hypothesis is that the second‐order properties of the processes of the labelled and the unlabelled nuclei are different. Twenty cases of invasive ductal mammary carcinomas were studied. The nuclei of proliferating cells were stained immunohistochemically with the monoclonal antibody MIB‐1, which detects specifically the proliferation‐associated nuclear antigen Ki 67. The planar coordinates of the tumor cell nucleus profiles from two rectangular visual fields per case were recorded. For each visual field, the following investigations were performed: estimation of the explorative summary characteristics K(r) and g(r), fitting of the parameters of a stationary Strauss hard‐core model to the observed point patterns, estimation of two distance‐dependent Simpson indices and Monte Carlo tests of all individual patterns on the null hypothesis of random labelling. Significant differences between the mean K‐functions and the mean g‐functions of the labelled and the unlabelled nuclei were found. Moreover, the mean interaction parameter γ of the stationary Strauss hard‐core model was significantly higher for the labelled nuclei than for the unlabelled nuclei. The estimates of the two distance‐dependent Simpson indices showed a tendency of points with the same label towards a positive spatial correlation. In the Monte Carlo tests, the null hypothesis of random labelling was rejected for the majority of the visual fields. These four lines of investigation led to the concordant conclusion that the labelling of mammary carcinoma nuclei by MIB‐1 is not simply random. The data suggest that the second‐order properties of the point process of the labelled nuclei are significantly different from those of the unlabelled nuclei. In particular, the process of the labelled nuclei shows a higher degree of clustering (increased strength of interaction) than the process of the unlabelled points.
Redistribution of slow wave activity of sleep during pharmacological treatment of depression with paroxetine but not with nefazodone
Authors: ARGYROPOULOS SPILIOS V. , HICKS JANE A. , NASH JOHN R. , BELL CAROLINE J. , RICH ANNE S. , NUTT DAVID J. , WILSON SUE 
Published: June 2009

SummaryIt has been suggested that increase in delta sleep ratio (DSR), a marker for the relative distribution of slow wave activity (SWA) over night time, is associated with clinical response to antidepressant treatment. We examined this index and its relationship to rapid eye movement (REM) suppression before and during long‐term treatment with nefazodone, which does not suppress REM sleep, and paroxetine which does. The effect of serotonin (5‐HT2A) receptor blockade on the evolution of SWA during treatment was also investigated. In a double‐blind, randomised, parallel group, 8‐week study in 29 depressed patients, sleep electroencephalograms were performed at home at baseline, on night 3 and 10, and at 8 weeks of treatment with either paroxetine or nefazodone. SWA was automatically analysed and a modified DSR (mDSR) was derived, being the ratio of amount of SWA in the first 90 min of sleep to that in the second plus third 90‐min periods. At baseline, the pattern of SWA over night time was similar to other reports of depressed patients. mDSR improved over the course of treatment; there was no difference between remitters and non‐remitters but there was a significant drug effect and a significant drug × time effect with paroxetine patients having a much higher mDSR after treatment, regardless of clinical status. SWA and REM during antidepressant treatment appear to be interdependent and neither of them alone is likely to predict response to treatment. Higher mDSR did not predict therapeutic response. 5‐HT2A blockade by nefazodone does not increase SWA above normal levels.
Sleep and sleep homeostasis in constant darkness in the rat
Authors: DEBOER TOM 
Published: June 2009

SummaryAccording to the two‐process model of sleep regulation, a homeostatic Process S increases during waking and decreases during sleep. The time course of Process S can be derived on the basis of changes in vigilance states and changes in electroencephalogram slow‐wave activity (SWA, activity below 4 Hz) during non‐rapid eye movement (NREM) sleep. In most mouse strains, an optimal fit between S and SWA was achieved with one increasing (active during waking and REM sleep) and one decreasing time constant (active during NREM sleep) for Process S. However, in the rat, systematic deviations in the light and dark periods were observed, which were resolved by introducing different decreasing time constants between the light and dark periods. The present study shows that this difference between the rest (light) and active (dark) phases remains, and may even be larger, after animals are adapted to constant dark conditions for at least a week. In addition, the data show that the build‐up rate of SWA at the onset of a NREM sleep episode is slow compared with the increase rate under light–dark conditions, and that this build‐up rate changes with the circadian phase. The slow build‐up rate introduces a systematic error between the simulation of Process S and SWA in NREM sleep. The circadian modulation of the build‐up rate may, together with circadian changes in NREM sleep episode duration, be the source of the necessity of introducing a difference in the decreasing time constant between the rest and active phases.
CNS arousal and neurobehavioral performance in a short‐term sleep restriction paradigm
Authors: COTE KIMBERLY A. , MILNER CATHERINE E. , SMITH BRIAN A. , AUBIN ADAM J. , GREASON TAMARA A. , CUTHBERT BRIELLE P. , WIEBE STEPHANIE , DUFFUS SHANNON E. G. 
Published: June 2009

SummaryFew studies have investigated waking electrophysiological measures of arousal during sleep restriction. This study examined electroencephalogram (EEG) activity and performance during a 96‐hour laboratory protocol where participants slept a baseline night (8 h), were randomly assigned to 3‐, 5‐, or 8‐hour sleep groups for the next two nights sleep restriction (SR1, SR2), and then slept a recovery night (8 h). There were dose‐dependent deficits on measures of mood, sleepiness, and reaction time that were apparent during this short‐term bout of sleep restriction. The ratio of alpha to theta EEG recorded at rest indicated dose‐dependent changes in CNS arousal. At 9:00 hours, both the 3‐ and 5‐hour groups showed EEG slowing (sleepiness) during restriction, with the 3‐hour group exhibiting greater deficits. Later in the day at 13:00 hours, the 5‐hour group no longer exhibited EEG slowing, but the extent of slowing was more widespread across the scalp for the 3‐hour group. High‐frequency EEG, a measure of effort, was greater on the mornings following sleep restriction. The 5‐hour group had increased beta EEG at central‐parietal sites following both nights of restriction, whereas the 3‐hour group had increased beta and gamma EEG at occipital regions following the first night only. Short‐term sleep restriction leads to deficits in performance as well as EEG slowing that correspond to the amount and duration of sleep loss. High‐frequency EEG may be a marker of effort or compensation.
Information processing during sleep: the effect of olfactory stimuli on dream content and dream emotions
Authors: SCHREDL MICHAEL , ATANASOVA DESISLAVA , HÖRMANN KARL , MAURER JOACHIM T. , HUMMEL THOMAS , STUCK BORIS A. 
Published: June 2009

SummaryResearch has shown that external stimuli presented during sleep can affect dream content, thus reflecting information processing of the sleeping brain. Olfactory stimuli should have a stronger effect on dream emotions because their processing is linked directly to the limbic system. Because selective olfactory stimulation does not increase arousal activity, intense olfactory stimulation is therefore a prime paradigm for studying information processing during sleep. Fifteen healthy, normosmic volunteers were studied by intranasal chemosensory stimulation during rapid eye movement sleep based on air‐dilution olfactometry. For olfactory stimulation, hydrogen sulphide (smell of rotten eggs) and phenyl ethyl alcohol (smell of roses) was used and compared with a control condition without stimulation. The olfactory stimuli affected significantly the emotional content of dreams: the positively toned stimulus yielded more positively toned dreams, whereas the negative stimulus was followed by more negatively toned dreams. Direct incorporations, i.e. the dreamer is smelling something, were not found. The findings indicate that information processing of olfactory stimuli is present in sleep and that the emotional tone of dreams can be influenced significantly depending upon the hedonic characteristic of the stimulus used. It would be interesting to conduct learning experiments (associating specific odours with declarative material) to study whether this declarative material is incorporated into subsequent dreams if the corresponding odour cue is presented during sleep. It would also be interesting to study the effect of positively toned olfactory stimuli on nightmares.
A landscape genetics approach for quantifying the relative influence of historic and contemporary habitat heterogeneity on the genetic connectivity of a rainforest bird
Authors: PAVLACKY JR DAVID C. , GOLDIZEN ANNE W. , PRENTIS PETER J. , NICHOLLS JAMES A. , LOWE ANDREW J. 
Published: June 2009

AbstractLandscape genetics is an important framework for investigating the influence of spatial pattern on ecological process. Nevertheless, the standard analytic frameworks in landscape genetics have difficulty evaluating hypotheses about spatial processes in dynamic landscapes. We use a predictive hypothesis‐driven approach to quantify the relative contribution of historic and contemporary processes to genetic connectivity. By confronting genetic data with models of historic and contemporary landscapes, we identify dispersal processes operating in naturally heterogeneous and human‐altered systems. We demonstrate the approach using a case study of microsatellite polymorphism and indirect estimates of gene flow for a rainforest bird, the logrunner (Orthonyx temminckii). Of particular interest was how much information in the genetic data was attributable to processes occurring in the reconstructed historic landscape and contemporary human‐modified landscape. A linear mixed model was used to estimate appropriate sampling variance from nonindependent data and information‐theoretic model selection provided strength of evidence for alternative hypotheses. The contemporary landscape explained slightly more information in the genetic differentiation data than the historic landscape, and there was considerable evidence for a temporal shift in dispersal pattern. In contrast, migration rates estimated from genealogical information were primarily influenced by contemporary landscape change. We discovered that landscape heterogeneity facilitated gene flow before European settlement, but contemporary deforestation is rapidly becoming the most important barrier to logrunner dispersal.
Bathymetric barriers promoting genetic structure in the deepwater demersal fish tusk (Brosme brosme)
Authors: KNUTSEN HALVOR , JORDE PER ERIK , SANNÆS HANNE , RUS HOELZEL A. , BERGSTAD ODD AKSEL , STEFANNI SERGIO , JOHANSEN TORILD , STENSETH NILS CHR. 
Published: June 2009

AbstractPopulation structuring in the North Atlantic deepwater demersal fish tusk (Brosme brosme) was studied with microsatellite DNA analyses. Screening eight samples from across the range of the species for seven loci revealed low but significant genetic heterogeneity (FST = 0.0014). Spatial genetic variability was only weakly related to geographical (Euclidean) distance between study sites or separation of study sites along the path of major ocean currents. Instead, we found a significant effect of habitat, indicated by significant differentiation between relatively closely spaced sites: Rockall, which is surrounded by very deep water (>1000 m), and the Mid‐Atlantic Ridge, which is separated from the European slope by a deep ocean basin, were differentiated from relatively homogeneous sites across the Nordic Seas. Limited adult migration across bathymetric barriers in combination with limited intersite exchange of pelagic eggs and larvae due to site‐specific circulatory retention or poor survival during drift phases across deep basins may be reducing gene flow. We regard these limitations to gene flow as the most likely mechanisms for the observed population structure in this demersal species. The results underscore the importance of habitat boundaries in marine species.
Comparison of quantitative and molecular genetic variation of native vs. invasive populations of purple loosestrife (Lythrum salicaria L., Lythraceae)
Authors: CHUN YOUNG JIN , NASON JOHN D. , MOLONEY KIRK A. 
Published: June 2009

AbstractStudy of adaptive evolutionary changes in populations of invasive species can be advanced through the joint application of quantitative and population genetic methods. Using purple loosestrife as a model system, we investigated the relative roles of natural selection, genetic drift and gene flow in the invasive process by contrasting phenotypical and neutral genetic differentiation among native European and invasive North American populations (QST − FST analysis). Our results indicate that invasive and native populations harbour comparable levels of amplified fragment length polymorphism variation, a pattern consistent with multiple independent introductions from a diverse European gene pool. However, it was observed that the genetic variation reduced during subsequent invasion, perhaps by founder effects and genetic drift. Comparison of genetically based quantitative trait differentiation (QST) with its expectation under neutrality (FST) revealed no evidence of disruptive selection (QST > FST) or stabilizing selection (QST < FST). One exception was found for only one trait (the number of stems) showing significant sign of stabilizing selection across all populations. This suggests that there are difficulties in distinguishing the effects of nonadaptive population processes and natural selection. Multiple introductions of purple loosestrife may have created a genetic mixture from diverse source populations and increased population genetic diversity, but its link to the adaptive differentiation of invasive North American populations needs further research.
Antigens for pre‐erythrocytic malaria vaccines: building on success
Authors: SPEAKE C. , DUFFY P. E. 
Published: June 2009

SummaryImmunization with attenuated pre‐erythrocytic malaria parasites can confer sterile protection against malaria in humans and rodents, and a single pre‐erythrocytic antigen incorporated in a subunit vaccine has substantially reduced clinical Plasmodium falciparum malaria episodes in African infants during phase 2 trials. Building upon this success has been hindered by technical obstacles that limit research on pre‐erythrocytic parasites, especially the liver stage (LS) parasites, and by an incomplete understanding of the immune mechanisms that confer protection in humans. Recent improvements in growing and isolating LS parasites have allowed progress in defining the transcriptome and proteome of the LS parasite, although more work remains to be done particularly for the early LS parasite of P. falciparum. Next generation pre‐erythrocytic antigens can be assessed and prioritized based on immunization studies in animals, and on models of immunity such as attenuated parasite vaccines that confer sterile protection or naturally acquired LS‐specific immune responses that correlate with protection in endemic areas. Although mechanisms of protection in humans remain poorly understood, the availability of a human malaria challenge model for early clinical testing of candidate vaccines is a valuable tool to confirm which immunogens should move forward to larger field trials.
Do we still need a malaria vaccine?
Authors: GREENWOOD B. , TARGETT G. 
Published: June 2009

SummaryAn unexpectedly large reduction in the burden of malaria has recently been achieved in a number of malaria endemic countries following the scaling up of effective treatment and simple vector control programmes. These achievements question the need for a partially effective malaria vaccine targeted at disease prevention. If an anti‐disease vaccine is to replace or supplement existing control measures a high level of efficacy, sustained over a number of years, will be required. Recent successes in malaria control have re‐awakened interest in the possibility of malaria elimination in areas where this was not previously considered to be a feasible objective. Malaria vaccines with transmission‐blocking properties could play a key role in future elimination programmes.
Adjuvants for malaria vaccines
Authors: COLER R. N. , CARTER D. , FRIEDE M. , REED S. G. 
Published: June 2009

SummaryThere is a renewed enthusiasm about subunit vaccines for malaria coincident with the formation of new alliances and partnerships raising international public awareness, attracting increased resources and the re‐focusing of research programs on adjuvant development for infectious disease vaccines. It is generally accepted that subunit vaccines for malaria will require adjuvants to induce protective immune responses, and availability of suitable adjuvants has in the past been a barrier to the development of malaria vaccines. Several novel adjuvants are now in licensed products or in late stage clinical development, while several others are in the earlier development pipeline. Successful vaccine development requires knowing which adjuvants to use and knowing how to formulate adjuvants and antigens to achieve stable, safe, and immunogenic vaccines. For the majority of vaccine researchers this information is not readily available, nor is access to well‐characterized adjuvants. In this minireview, we outline the current state of adjuvant research and development as it pertains to effective malaria vaccines.