Showing papers by "University of Bern published in 2001"
TL;DR: In this paper, five test runs were performed to assess possible bias when performing the loss on ignition (LOI) method to estimate organic matter and carbonate content of lake sediments.
Abstract: Five test runs were performed to assess possible bias when performing the loss on ignition (LOI) method to estimate organic matter and carbonate content of lake sediments. An accurate and stable weight loss was achieved after 2 h of burning pure CaCO3 at 950 °C, whereas LOI of pure graphite at 530 °C showed a direct relation to sample size and exposure time, with only 40-70% of the possible weight loss reached after 2 h of exposure and smaller samples losing weight faster than larger ones. Experiments with a standardised lake sediment revealed a strong initial weight loss at 550 °C, but samples continued to lose weight at a slow rate at exposure of up to 64 h, which was likely the effect of loss of volatile salts, structural water of clay minerals or metal oxides, or of inorganic carbon after the initial burning of organic matter. A further test-run revealed that at 550 °C samples in the centre of the furnace lost more weight than marginal samples. At 950 °C this pattern was still apparent but the differences became negligible. Again, LOI was dependent on sample size. An analytical LOI quality control experiment including ten different laboratories was carried out using each laboratory's own LOI procedure as well as a standardised LOI procedure to analyse three different sediments. The range of LOI values between laboratories measured at 550 °C was generally larger when each laboratory used its own method than when using the standard method. This was similar for 950 °C, although the range of values tended to be smaller. The within-laboratory range of LOI measurements for a given sediment was generally small. Comparisons of the results of the individual and the standardised method suggest that there is a laboratory-specific pattern in the results, probably due to differences in laboratory equipment and/or handling that could not be eliminated by standardising the LOI procedure. Factors such as sample size, exposure time, position of samples in the furnace and the laboratory measuring affected LOI results, with LOI at 550 °C being more susceptible to these factors than LOI at 950 °C. We, therefore, recommend analysts to be consistent in the LOI method used in relation to the ignition temperatures, exposure times, and the sample size and to include information on these three parameters when referring to the method.
4,163 citations
TL;DR: The concept of study quality and the methods used to assess quality are discussed and the methodology for both the assessment of quality and its incorporation into systematic reviews and meta-analysis is discussed.
Abstract: This is the first in a series of four articles
The quality of controlled trials is of obvious relevance to systematic reviews. If the “raw material” is flawed then the conclusions of systematic reviews cannot be trusted. Many reviewers formally assess the quality of primary trials by following the recommendations of the Cochrane Collaboration and other experts. 1 2 However, the methodology for both the assessment of quality and its incorporation into systematic reviews and meta-analysis are a matter of ongoing debate.3-5 In this article we discuss the concept of study quality and the methods used to assess quality.
#### Components of internal and external validity of controlled clinical trials
Internal validity —extent to which systematic error (bias) is minimised in clinical trials
Quality is a multidimensional concept, which could relate to the design, conduct, and analysis of a trial, its clinical relevance, or quality of reporting.6 The validity of the findings generated by a study clearly is an important dimension of quality. In the 1950s the social scientist Campbell proposed a useful distinction between internal and external validity (see box below). 7 8 Internal validity implies that the differences observed between groups of patients allocated to different …
2,746 citations
TL;DR: The previously reported benefits of carvedilol with regard to morbidity and mortality in patients with mild-to-moderate heart failure were also apparent in the patients with severe heart failure who were evaluated in this trial.
Abstract: Background: Beta-blocking agents reduce the risk of hospitalization and death in patients with mild-to-moderate heart failure, but little is known about their effects in severe heart failure.
Methods: We evaluated 2289 patients who had symptoms of heart failure at rest or on minimal exertion, who were clinically euvolemic, and who had an ejection fraction of less than 25 percent. In a double-blind fashion, we randomly assigned 1133 patients to placebo and 1156 patients to treatment with carvedilol for a mean period of 10.4 months, during which standard therapy for heart failure was continued. Patients who required intensive care, had marked fluid retention, or were receiving intravenous vasodilators or positive inotropic drugs were excluded.
Results: There were 190 deaths in the placebo group and 130 deaths in the carvedilol group. This difference reflected a 35 percent decrease in the risk of death with carvedilol (95 percent confidence interval, 19 to 48 percent; P=0.00013, unadjusted; P=0.0014, adjusted for interim analyses). A total of 507 patients died or were hospitalized in the placebo group, as compared with 425 in the carvedilol group. This difference reflected a 24 percent decrease in the combined risk of death or hospitalization with carvedilol (95 percent confidence interval, 13 to 33 percent; P<0.001). The favorable effects on both end points were seen consistently in all the subgroups we examined, including patients with a history of recent or recurrent cardiac decompensation. Fewer patients in the carvedilol group than in the placebo group withdrew because of adverse effects or for other reasons (P=0.02).
Conclusions: The previously reported benefits of carvedilol with regard to morbidity and mortality in patients with mild-to-moderate heart failure were also apparent in the patients with severe heart failure who were evaluated in this trial.
2,566 citations
TL;DR: In this article, the authors describe a technique for operative dislocation of the hip, based on detailed anatomical studies of the blood supply, which combines aspects of approaches which have been reported previously and consists of an anterior dislocation through a posterior approach with a 'trochanteric flip' osteotomy.
Abstract: Surgical dislocation of the hip is rarely undertaken. The potential danger to the vascularity of the femoral head has been emphasised, but there is little information as to how this danger can be avoided. We describe a technique for operative dislocation of the hip, based on detailed anatomical studies of the blood supply. It combines aspects of approaches which have been reported previously and consists of an anterior dislocation through a posterior approach with a 'trochanteric flip' osteotomy. The external rotator muscles are not divided and the medial femoral circumflex artery is protected by the intact obturator externus. We report our experience using this approach in 213 hips over a period of seven years and include 19 patients who underwent simultaneous intertrochanteric osteotomy. The perfusion of the femoral head was verified intraoperatively and, to date, none has subsequently developed avascular necrosis. There is little morbidity associated with the technique and it allows the treatment of a variety of conditions, which may not respond well to other methods including arthroscopy. Surgical dislocation gives new insight into the pathogenesis of some hip disorders and the possibility of preserving the hip with techniques such as transplantation of cartilage.
1,223 citations
TL;DR: Recent developments in this area justify the hypothesis that the distinct migration patterns of lymphocytes throughout their life cycle are finely tuned by changing sets of chemokines that are selective for developmentally regulated chemokine receptors.
Abstract: In contrast to the remarkable chemokine responses of phagocytes and monocytes that were documented early on, lymphocytes have been considered for a long time to be poor targets for chemokine action. This view has changed dramatically with the discovery that peripheral blood T cells need to be activated before they can migrate in response to inflammatory chemokines. These chemokines do not act on the bulk of resting T cells that are in circulation. The identification of a new group of chemokines that selects resting, as opposed to effector, T and B cells was very exciting. These inflammation-unrelated chemokines affect transendothelial migration and localization of progenitor and mature lymphocytes in lymphoid and nonlymphoid tissues. Here, we summarize the current view of chemokine-mediated lymphocyte traffic and focus on the molecular mechanisms by which T cell responses to chemokines are modulated. Recent developments in this area justify the hypothesis that the distinct migration patterns of lymphocytes throughout their life cycle--that is, during lymphopoiesis, antigen-dependent priming, inflammation and immune surveillance--are finely tuned by changing sets of chemokines that are selective for developmentally regulated chemokine receptors. Thus, the chemokine system assures that cell traffic during inflammatory responses occurs in the proper spatial and temporal fashion and disturbance of this system, therefore, can lead to inflammatory disease.
1,212 citations
TL;DR: The Cluster Ion Spectrometry (CIS) experiment as discussed by the authors measured the full, three-dimensional ion distribution of the major magnetospheric ions (H+, He+, He++, and O+) from the thermal energies to about 40 keV/e.
Abstract: . On board the four Cluster spacecraft, the Cluster Ion Spectrometry (CIS) experiment measures the full, three-dimensional ion distribution of the major magnetospheric ions (H+, He+, He++, and O+) from the thermal energies to about 40 keV/e. The experiment consists of two different instruments: a COmposition and DIstribution Function analyser (CIS1/CODIF), giving the mass per charge composition with medium (22.5°) angular resolution, and a Hot Ion Analyser (CIS2/HIA), which does not offer mass resolution but has a better angular resolution (5.6°) that is adequate for ion beam and solar wind measurements. Each analyser has two different sensitivities in order to increase the dynamic range. First tests of the instruments (commissioning activities) were achieved from early September 2000 to mid January 2001, and the operation phase began on 1 February 2001. In this paper, first results of the CIS instruments are presented showing the high level performances and capabilities of the instruments. Good examples of data were obtained in the central plasma sheet, magnetopause crossings, magnetosheath, solar wind and cusp measurements. Observations in the auroral regions could also be obtained with the Cluster spacecraft at radial distances of 4–6 Earth radii. These results show the tremendous interest of multispacecraft measurements with identical instruments and open a new area in magnetospheric and solar wind-magnetosphere interaction physics. Key words. Magnetospheric physics (magnetopause, cusp and boundary layers; magnetopheric configuration and dynamics; solar wind - magnetosphere interactions)
1,209 citations
TL;DR: The similarity of changes in CO2 concentration and variations of atmospheric methane concentration suggests that processes in the tropics and in the Northern Hemisphere, where the main sources for methane are located, also had substantial effects on atmospheric CO2 concentrations.
Abstract: A record of atmospheric carbon dioxide (CO2) concentration during the transition from the Last Glacial Maximum to the Holocene, obtained from the Dome Concordia, Antarctica, ice core, reveals that an increase of 76 parts per million by volume occurred over a period of 6000 years in four clearly distinguishable intervals The close correlation between CO2 concentration and Antarctic temperature indicates that the Southern Ocean played an important role in causing the CO2 increase However, the similarity of changes in CO2 concentration and variations of atmospheric methane concentration suggests that processes in the tropics and in the Northern Hemisphere, where the main sources for methane are located, also had substantial effects on atmospheric CO2 concentrations
1,200 citations
TL;DR: A precise relative chronology for Greenland and West Antarctic paleotemperature is extended to 90,000 years ago, based on correlation of atmospheric methane records from the Greenland Ice Sheet Project 2 and Byrd ice cores, to provide further evidence for the operation of a "bipolar see-saw" in air temperatures and an oceanic teleconnection between the hemispheres on millennial time scales.
Abstract: A precise relative chronology for Greenland and West Antarctic paleotemperature is extended to 90,000 years ago, based on correlation of atmospheric methane records from the Greenland Ice Sheet Project 2 and Byrd ice cores. Over this period, the onset of seven major millennial-scale warmings in Antarctica preceded the onset of Greenland warmings by 1500 to 3000 years. In general, Antarctic temperatures increased gradually while Greenland temperatures were decreasing or constant, and the termination of Antarctic warming was apparently coincident with the onset of rapid warming in Greenland. This pattern provides further evidence for the operation of a “bipolar see-saw” in air temperatures and an oceanic teleconnection between the hemispheres on millennial time scales.
1,158 citations
TL;DR: This study showed no survival benefit for chemoradiotherapy but revealed a potential benefit for adjuvant chemotherapy, justifying further randomised controlled trials of adjUvant chemotherapy in pancreatic cancer.
990 citations
TL;DR: In this paper, the concurrent effects of increasing atmospheric CO2 concentration, climate variability, and cropland establishment and abandonment on terrestrial carbon storage between 1920 and 1992 were assessed using a standard simulation protocol with four process-based terrestrial biosphere models.
Abstract: The concurrent effects of increasing atmospheric CO2 concentration, climate variability, and cropland establishment and abandonment on terrestrial carbon storage between 1920 and 1992 were assessed using a standard simulation protocol with four process-based terrestrial biosphere models. Over the long-term (1920-1992), the simulations yielded a time history of terrestrial uptake that is consistent (within the uncertainty) with a long-term analysis based on ice core and atmospheric CO2 data. Up to 1958, three of four analyses indicated a net release of carbon from terrestrial ecosystems to the atmosphere caused by cropland establishment. After 1958, all analyses indicate a net uptake of carbon by terrestrial ecosystems, primarily because of the physiological effects of rapidly rising atmospheric CO2. During the 1980s the simulations indicate that terrestrial ecosystems stored between 0.3 and 1.5 Pg C yr(-1), which is within the uncertainty of analysis based on CO2 and O-2 budgets. Three of the four models indicated tin accordance with O-2 evidence) that the tropics were approximately neutral while a net sink existed in ecosystems north of the tropics. Although all of the models agree that the long-term effect of climate on carbon storage has been small relative to the effects of increasing atmospheric CO2 and land use, the models disagree as to whether climate variability and change in the twentieth century has promoted carbon storage or release. Simulated interannual variability from 1958 generally reproduced the El Nino/Southern Oscillation (ENSO)-scale variability in the atmospheric CO2 increase, but there were substantial differences in the magnitude of interannual variability simulated by the models. The analysis of the ability of the models to simulate the changing amplitude of the seasonal cycle of atmospheric CO2 suggested that the observed trend may be a consequence of CO2 effects, climate variability, land use changes, or a combination of these effects. The next steps for improving the process-based simulation of historical terrestrial carbon include (1) the transfer of insight gained from stand-level process studies to improve the sensitivity of simulated carbon storage responses to changes in CO2 and climate, (2) improvements in the data sets used to drive the models so that they incorporate the timing, extent, and types of major disturbances, (3) the enhancement of the models so that they consider major crop types and management schemes, (4) development of data sets that identify the spatial extent of major crop types and management schemes through time, and (5) the consideration of the effects of anthropogenic nitrogen deposition. The evaluation of the performance of the models in the context of a more complete consideration of the factors influencing historical terrestrial carbon dynamics is important for reducing uncertainties in representing the role of terrestrial ecosystems in future projections of the Earth system.
743 citations
TL;DR: In this article, the authors measured the femoral neck and the offset of the head at various circumferential positions, using MRI data from volunteers with no osteoarthritic changes on standard radiographs.
Abstract: We have observed damage to the labrum as a result of repetitive acetabular impingement in non-dysplastic hips, in which the femoral neck appears to abut against the acetabular labrum and a non-spherical femoral head to press against the labrum and adjacent cartilage. In both mechanisms anatomical variations of the proximal femur may be a factor. We have measured the orientation of the femoral neck and the offset of the head at various circumferential positions, using MRI data from volunteers with no osteoarthritic changes on standard radiographs. Compared with the control subjects, paired for gender and age, patients showed a significant reduction in mean femoral anteversion and mean head-neck offset on the anterior aspect of the neck. This was consistent with the site of symptomatic impingement in flexion and internal rotation, and with lesions of the adjacent rim. Furthermore, when stratified for gender and age, and compared with the control group, the mean femoral head-neck offset was significantly reduced in the lateral-to-anterior aspect of the neck for young men, and in the anterolateral-to-anterior aspect of the neck for older women. For patients suspected of having impingement of the rim, anatomical variations in the proximal femur should be considered as a possible cause.
TL;DR: A high-resolution record of oxygen isotope variations, for the period from 9.6 to 6.1 kyr before present, in a Th–U-dated stalagmite from Oman suggests that one of the primary controls on centennial- to decadal-scale changes in tropical rainfall and monsoon intensity during this time are variations in solar radiation.
Abstract: Variations in the amount of solar radiation reaching the Earth are thought to influence climate, but the extent of this influence on timescales of millennia to decades is unclear. A number of climate records show correlations between solar cycles and climate1, but the absolute changes in solar intensity over the range of decades to millennia are small2 and the influence of solar flux on climate is not well established. The formation of stalagmites in northern Oman has recorded past northward shifts of the intertropical convergence zone3, whose northward migration stops near the southern shoreline of Arabia in the present climate4. Here we present a high-resolution record of oxygen isotope variations, for the period from 9.6 to 6.1 kyr before present, in a Th–U-dated stalagmite from Oman. The δ18O record from the stalagmite, which serves as a proxy for variations in the tropical circulation and monsoon rainfall, allows us to make a direct comparison of the δ18O record with the Δ14C record from tree rings5, which largely reflects changes in solar activity6,7. The excellent correlation between the two records suggests that one of the primary controls on centennial- to decadal-scale changes in tropical rainfall and monsoon intensity during this time are variations in solar radiation.
TL;DR: Atrial fibrillation is a ubiquitous yet diverse cardiac arrhythmia whose incidence increases with age; with most forms of cardiac and some pulmonary diseases; and with a number of metabolic, toxic, endocrine, or genetic abnormalities.
Abstract: Atrial fibrillation (AF) is a ubiquitous yet diverse cardiac arrhythmia whose incidence increases with age; with most forms of cardiac and some pulmonary diseases; and with a number of metabolic, toxic, endocrine, or genetic abnormalities.1 2 Classification of clinical AF subtypes can be achieved on the basis of the ease by which episodes of the arrhythmia terminate as follows3 : “Paroxysmal” AF refers to episodes that generally stop spontaneously after no more than a few days. “Persistent” AF occurs less frequently than paroxysmal AF and, rather than self-terminating, requires cardioversion to restore sinus rhythm. “Permanent” AF cannot be converted to sinus rhythm. These terms apply strictly to chronic AF, because a single episode of the arrhythmia cannot be fully categorized. Although there are some mixed patterns, they generally derive from physician impatience for early cardioversion or from pragmatic clinical considerations (eg, to avoid thrombus formation or hemodynamic decompensation).
Patients initially presenting with paroxysmal AF often progress to longer, non–self-terminating bouts. An exception may be paroxysmal AF during intense vagotonia. Moreover, AF initially responsive to pharmacological or electrical cardioversion tends to become resistant and cannot then be converted to sinus rhythm. To some extent, the failure of the physician to suggest or the patient to accept further cardioversion attempts may lead to diagnosis of “permanent” AF. Thus, the “point of no return” may be determined by true pathophysiological abnormalities or may merely be an artifact of clinical pragmatism.
Effective prevention is essential in managing this arrhythmia whose occurrence is widespread, progression is relentless, and morbidity and mortality are significant. To focus on means for prevention necessitates considering both clinical risk factors and pathophysiology.
AF derives from a complex continuum predisposing factors, summarized in Table 1⇓. In the West, about 5% of the population >65 years of age …
TL;DR: The Kessler Institute for Biomedicine and Institute for Research in Biomedicaine in Bellinzona, Switzerland, and Theodor Kocher Institute, University of Bern, are using nanofiltration membranes for the first time to study the role of phosphorous in the immune response to chemotherapy.
Abstract: About 50 human chemokines and nearly 20 receptors have been identified and characterized in little more than a decade since the discovery of interleukin 8 (IL-8), the first chemotactic cytokine. Research in this field has dramatically changed our understanding of leucocyte traffic in inflammation and immunity. This paper has been written for scientists and practitioners in the field of medicine. It reviews in concise and intelligible form information that I consider useful for understanding the role of chemokines in human pathophysiology. The main areas covered are: (i) the basics of chemokine structures, mode of action, activities and selectivity; (ii) newer aspects of the broad involvement of chemokines in the regulation of immune defence and the housekeeping of the immune system; (iii) the role of chemokines in pathology as illustrated by animal models and studies of human diseases; and (iv) novel therapeutic approaches for a variety of inflammatory conditions, which are based on modulation of chemokine activity.
Journal Article•
TL;DR: It is concluded that HIF-1alpha is overexpressed in the vast majority of patients with squamous cell cancer of the oropharynx and that the degree of expression has predictive and prognostic significance in individuals undergoing curative radiation therapy.
Abstract: Hypoxia has long been recognized as detrimental to the successful treatment of malignant tumors with ionizing radiation. Because hypoxia-inducible factor (HIF)-1α plays an essential role in oxygen homeostasis in vitro, we explored the predictive potential of this factor in a cohort of 98 patients with squamous cell cancer of the oropharynx, who were treated by curative radiation therapy. Ninety-four % of the primary tumors showed overexpression of HIF-1α, relative to the surrounding tissue, as determined by immunohistochemistry. The degree of HIF-1α immunoreactivity correlated inversely with both the rate of complete remission of the primary tumor (odds ratio, 0.33; P = 0.03) and lymph node metastases (odds ratio, 0.34; P = 0.02) as well as with local failure-free survival (risk ratio, 2.15; P = 0.006), disease-free survival (risk ratio, 2.01; P = 0.008), and overall survival (risk ratio, 2.17; P = 0.002). The multivariate analysis revealed the predictive power of HIF-1α to be independent of other covariables. We conclude that HIF-1α is overexpressed in the vast majority of patients with squamous cell cancer of the oropharynx and that the degree of expression has predictive and prognostic significance in individuals undergoing curative radiation therapy.
TL;DR: A comprehensive review of previous studies and concepts concerning the North Atlantic Oscillation can be found in this paper, where the authors provide a comprehensive review and analysis of the NAO teleconnection.
Abstract: This paper aims to provide a comprehensive review of previous studies and concepts concerning the North Atlantic Oscillation. The North Atlantic Oscillation (NAO) and its recent homologue, the Arctic Oscillation/Northern Hemisphere annular mode (AO/NAM), are the most prominent modes of variability in the Northern Hemisphere winter climate. The NAO teleconnection is characterised by a meridional displacement of atmospheric mass over the North Atlantic area. Its state is usually expressed by the standardised air pressure difference between the Azores High and the Iceland Low. This NAO index is a measure of the strength of the westerly flow (positive with strong westerlies, and vice versa). Together with the El Nino/Southern Oscillation (ENSO) phenomenon, the NAO is a major source of seasonal to interdecadal variability in the global atmosphere. On interannual and shorter time scales, the NAO dynamics can be explained as a purely internal mode of variability of the atmospheric circulation. Interdecadal variability may be influenced, however, by ocean and sea-ice processes.
TL;DR: In this article, the authors review the radiometric ages of the 16 currently known Martian meteorites, classified as 11 shergottites (8 basaltic and 3 lherzolitic), 3 nakhlites (clinopyroxenites), Chassigny (a dunite), and the orthopyroxensite ALH84001.
Abstract: We review the radiometric ages of the 16 currently known Martian meteorites, classified as 11 shergottites (8 basaltic and 3 lherzolitic), 3 nakhlites (clinopyroxenites), Chassigny (a dunite), and the orthopyroxenite ALH84001. The basaltic shergottites represent surface lava flows, the others magmas that solidified at depth. Shock effects correlate with these compositional types, and, in each case, they can be attributed to a single shock event, most likely the meteorite’s ejection from Mars. Peak pressures in the range 15 – 45 GPa appear to be a “launch window”: shergottites experienced ~ 30 – 45 GPa, nakhlites ~ 20 ± 5 GPa, Chassigny ~35 GPa, and ALH84001 ~35 – 40 GPa. Two meteorites, lherzolitic shergottite Y-793605 and orthopyroxenite ALH84001, are monomict breccias, indicating a two-phase shock history in toto: monomict brecciation at depth in a first impact and later shock metamorphism in a second impact, probably the ejection event.
TL;DR: It is concluded that sst2, with high affinity for current radiopharmaceuticals such as Octreoscan, is predominantly expressed in a majority of tumours and suggests the existence of an as yet unknown subtype in selected tumours.
Abstract: Somatostatin receptors are known to be expressed in a large number of human tumours and represent the basis for in vivo tumour targeting. Stable somatostatin derivatives such as octreotide or lanreotide are the most frequently used radiopharmaceuticals acting through specific binding to somatostatin receptors; however, they do not bind with high affinity to all five receptor subtypes. Whereas the mRNAs for most receptor subtypes have been detected in tumours, it is in most cases unclear which of the receptor subtype proteins are expressed. Since in vitro receptor binding methods are close correlates and predictors of in vivo peptide receptor targeting, we took advantage of the recently developed subtype-selective analogues and evaluated approximately 200 tumours for their receptor subtype protein expression in specific binding assays using autoradiography with 125I-[Leu8, D-Trp22, Tyr25]-somatostatin-28 and displacement by subtype-selective analogues. The majority of the tested neuroblastomas, meningiomas, medulloblastomas, breast carcinomas, lymphomas, renal cell carcinomas, paragangliomas, small cell lung carcinomas and hepatocellular carcinomas predominantly expressed sst2. The prostate carcinomas and sarcomas preferentially expressed sst1, while a majority of inactive pituitary adenomas displayed sst3 and, to a lesser extent, sst2. Growth hormone-secreting pituitary adenomas preferentially expressed sst2 and sst5; gastroenteropancreatic tumours and phaeochromocytomas frequently displayed sst2 and/or sst1. Non-neoplastic human tissues such as vessels, nerve plexus, pancreatic islets, prostatic stroma, adrenal medulla, spleen and germinal centres of the lymphoid tissues preferentially expressed sst2. However, the human gastric mucosa predominantly expressed sst1 while colonic mucosa displayed sst2. Interestingly, a minority of tumours showed a strong 125I-[Leu8, D-Trp22, Tyr25]-somatostatin-28 binding, of which less than 50% could be displaced by the sum of the five subtype-selective analogues. This observation suggests the existence of an as yet unknown subtype in selected tumours. This study is the first report to analyse the somatostatin receptor subtype expression in tumours with binding methods. We conclude that sst2, with high affinity for current radiopharmaceuticals such as Octreoscan, is predominantly expressed in a majority of tumours. Fewer tumour types (sarcomas, prostate cancers, inactive pituitary adenomas) preferentially express another subtype. This information is of importance with regard to the clinical applications and development of somatostatin analogues with distinct receptor subtype selectivities.
TL;DR: The phenotype of the beta1-deficient mice resembles pathological changes observed in human cortical dysplasias, suggesting that defective integrin-mediated signal transduction contributes to the development of some of these diseases.
TL;DR: Treatment with a combination of folic acid, vitamin B12, and pyridoxine significantly reduces homocysteine levels and decreases the rate of restenosis and the need for revascularization of the target lesion after coronary angioplasty.
Abstract: Background We have previously demonstrated an association between elevated total plasma homocysteine levels and restenosis after percutaneous coronary angioplasty. We designed this study to evaluate the effect of lowering plasma homocysteine levels on restenosis after coronary angioplasty. Methods A combination of folic acid (1 mg), vitamin B12 (400 μg), and pyridoxine (10 mg) — referred to as folate treatment — or placebo was administered to 205 patients (mean [±SD] age, 61±11 years) for six months after successful coronary angioplasty in a prospective, double-blind, randomized trial. The primary end point was restenosis within six months as assessed by quantitative coronary angiography. The secondary end point was a composite of major adverse cardiac events. Results Base-line characteristics and initial angiographic results after coronary angioplasty were similar in the two study groups. Folate treatment significantly lowered plasma homocysteine levels from 11.1±4.3 to 7.2±2.4 μmol per liter (P<0.001). ...
TL;DR: These findings demonstrate, as evaluated by non-decalcified histology under unloaded conditions in the canine mandible, that crestal bone changes around 2-piece, non-submerged titanium implants are significantly influenced by possible movements between implants and abutments, but not by the size of the microgap (interface).
Abstract: Background: Endosseous implants can be placed according to a non-submerged or submerged approach and in 1- or 2-piece configurations. Recently, it was shown that peri-implant crestal bone changes differ significantly under such conditions and are dependent on a rough/smooth implant border in 1-piece implants and on the location of an interface (microgap) between the implant and abutment/restoration in 2-piece configurations. Several factors may influence the resultant level of the crestal bone under these conditions, including movements between implant components and the size of the microgap (interface) between the implant and abutment. However, no data are available on the impact of possible movements between these components or the impact of the size of the microgap (interface). The purpose of this study was to histometrically evaluate crestal bone changes around unloaded, 2-piece non-submerged titanium implants with 3 different microgap (interface) dimensions and between implants with components welded...
TL;DR: In this study, inhibition of the hepatocanalicular bile salt export pump (rodents, Bsep; humans, BSEP ABCB11) could account for bosentan‐induced liver injury.
Abstract: BACKGROUND: During clinical trials bosentan, the first orally active endothelin receptor antagonist, caused asymptomatic transaminase elevations in some patients. In this study we investigated whether inhibition of the hepatocanalicular bile salt export pump (rodents, Bsep; humans, BSEP ABCB11) could account for bosentan-induced liver injury. METHODS: We reanalyzed the safety database of the bosentan trials for cholestatic liver injury, determined the cholestatic potency of bosentan in the rat, and studied the effects of bosentan and its metabolites on Bsep-mediated taurocholate transport in vitro. RESULTS: Bosentan caused dose-dependent and reversible liver injury in 2% to 18% of patients and caused a significant increase of serum bile salt levels (P RESULTS: Bosentan caused dose-dependent and reversible liver injury in 2% to 18% of patients and caused a significant increase of serum bile salt levels (P >.01). Concomitant administration of glyburide (INN, glibenclamide) enhanced the cholestatic potency of bosentan. Similar effects were seen in rats, in which serum bile salt levels were increased by glyburide less than by bosentan, which increased the levels less than a combination of bosentan and glyburide. In vitro, Bsep-mediated taurocholate transport was inhibited by bosentan (inhibition constant, approximately 12 micromol/L) and metabolites (inhibition constant, approximately 8.5 micromol/L for metabolite Ro 47-8634). CONCLUSIONS: These results indicate that bosentan-induced liver injury is mediated, at least in part, by inhibition of Bsep/BSEP-causing intracellular accumulation of cytotoxic bile salts and bile salt induced liver cell damage. The data further emphasize the pathophysiologic importance of drug-Bsep interactions in acquired forms of cholestatic liver injury.
TL;DR: In this paper, the authors focus on the quality dimension of wellness services, which is increasingly becoming the decisive competitive factor for the wellness industry and the importance of quality management plays an important role.
Abstract: The term ‘wellness’ is widely used in European tourism. The principal observations regarding the wellness industry concern an expanding supply of and an insufficiently researched demand for wellness programmes. The quality dimension of wellness services is increasingly becoming the decisive competitive factor. For this reason quality management plays an important role. Market research shows that average three- to five-star hotels provide fairly comprehensive wellness facilities. Wellness hotels should therefore specialise in health information, individual care and a wide range of cultural and relaxation programmes. Although the same hotel can host cure and wellness guests at the same time, these two segments have to be considered separately when deciding on the marketing strategy. It is therefore assumed that wellness is pursued solely by ‘healthy’ people, the prime aim being prevention. ‘Normal cure’ guests aim to heal their illness.
TL;DR: A novel feature of the system is that the HMM is applied in such a way that the difficult problem of segmenting a line of text into individual words is avoided and linguistic knowledge beyond the lexicon level is incorporated in the recognition process.
Abstract: In this paper, a system for the reading of totally unconstrained handwritten text is presented. The kernel of the system is a hidden Markov model (HMM) for handwriting recognition. The HMM is enhanced by a statistical language model. Thus linguistic knowledge beyond the lexicon level is incorporated in the recognition process. Another novel feature of the system is that the HMM is applied in such a way that the difficult problem of segmenting a line of text into individual words is avoided. A number of experiments with various language models and large vocabularies have been conducted. The language models used in the system were also analytically compared based on their perplexity.
TL;DR: In this article, the presence of the virus and the integrity of the viral E2 gene in tumors of patients who have undergone curative irradiation was determined. But, the authors did not identify the specific subgroup of oropharyngeal squamous cell carcinoma of the opharynx that arise preferentially among individuals with no consumption of tobacco and alcohol and that have an increased sensitivity toward radiotherapy.
Abstract: BACKGROUND
Epidemiologic evidence points to a connection between viral infection by the human papillomavirus (HPV) and a subgroup of squamous cell carcinoma of the oropharynx. To assess the impact of HPV infection on the response of these tumors toward radiotherapy, the authors retrospectively determined the presence of the virus and the integrity of the viral E2 gene in tumors of patients who have undergone curative irradiation.
METHODS
Paraffin embedded biopsies from 99 patients were analyzed for HPV infection and E2 gene integrity by multiplex PCR. The experimental findings were correlated with clinical characteristics, known risk factors, and treatment outcome.
RESULTS
Fourteen of 99 tumors were HPV positive (11 HPV16, 1 HPV33, 1 HPV35, and 1 HPV45). Human papillomavirus positivity was closely linked to female gender (odds ratio [OR], 5.75; P = 0.004), age older than 56 years (OR, 7.42; P = 0.012), nonsmokers (OR, 21.33; P = 0.00001), and alcohol abstainers (OR, 5.35; P = 0.012). There was an inverse association with p53 nuclear immunoreactivity (OR, 0.06; P = 0.008). The Kaplan–Meier survival estimates showed a better local control (P = 0.050, log-rank) and a better overall survival (P = 0.046, log-rank) for patients with HPV positive tumors. In the multivariate analysis, HPV positivity remained to be associated with a lower risk of local failure (risk ratio [RR], 0.31; P = 0.048). Four of 11 HPV16 positive tumors had a disrupted E2 gene. Only tumors with a disrupted E2 gene manifested local treatment failure.
CONCLUSIONS
Human papillomavirus positivity designates a specific subgroup of oropharyngeal squamous cell carcinomas of the oropharynx that arise preferentially among individuals with no consumption of tobacco and alcohol and that have a favorable outcome attributable to an increased sensitivity toward radiotherapy. Cancer 2001;92:805–13. © 2001 American Cancer Society.
TL;DR: Findings, as evaluated by nondecalcified histology under unloaded conditions in the canine mandible, suggest that the gingival margin (GM) is located more coronally and Biologic Width (BW) dimensions are more similar to natural teeth around one-piece nonsubmerged implants compared to either two- piece nonsubMERged or two-piece submerged implants.
Abstract: Gingival esthetics around natural teeth is based upon a constant vertical dimension of healthy periodontal soft tissues, the Biologic Width. When placing endosseous implants, however, several factors influence periimplant soft and crestal hard tissue reactions, which are not well understood as of today. Therefore, the purpose of this study was to histometrically examine periimplant soft tissue dimensions dependent on varying locations of a rough/smooth implant border in one-piece implants or a microgap (interface) in two-piece implants in relation to the crest of the bone, with two-piece implants being placed according to either a submerged or a nonsubmerged technique. Thus, 59 implants were placed in edentulous mandibular areas of five foxhounds in a side-by-side comparison. At the time of sacrifice, six months after implant placement, the Biologic Width dimension for one-piece implants, with the rough/smooth border located at the bone crest level, was significantly smaller (P<0.05) compared to two-piece implants with a microgap (interface) located at or below the crest of the bone. In addition, for one-piece implants, the tip of the gingival margin (GM) was located significantly more coronally (P<0.005) compared to two-piece implants. These findings, as evaluated by nondecalcified histology under unloaded conditions in the canine mandible, suggest that the gingival margin (GM) is located more coronally and Biologic Width (BW) dimensions are more similar to natural teeth around one-piece nonsubmerged implants compared to either two-piece nonsubmerged or two-piece submerged implants.
TL;DR: There appears to be some relationships between aspects of physical and social environment and physical activity participation, however, future research is needed to refine and clarify this.
TL;DR: The findings suggest that HIF-1 is specifically involved in the regulation of muscle adaptations after hypoxia training, and fine-tuning of the training response is recognized at the molecular level, and with less sensitivity also at the structural level, but not at global functional responses like maximal O(2) uptake or maximal power output.
Abstract: This study was performed to explore changes in gene expression as a consequence of exercise training at two levels of intensity under normoxic and normobaric hypoxic conditions (corresponding to an altitude of 3,850 m). Four groups of human subjects trained five times a week for a total of 6 wk on a bicycle ergometer. Muscle biopsies were taken, and performance tests were carried out before and after the training period. Similar increases in maximal O2 uptake (8.3–13.1%) and maximal power output (11.4–20.8%) were found in all groups. RT-PCR revealed elevated mRNA concentrations of the α-subunit of hypoxia-inducible factor 1 (HIF-1) after both high- (+82.4%) and low (+78.4%)-intensity training under hypoxic conditions. The mRNA of HIF-1α736, a splice variant of HIF-1α newly detected in human skeletal muscle, was shown to be changed in a similar pattern as HIF-1α. Increased mRNA contents of myoglobin (+72.2%) and vascular endothelial growth factor (+52.4%) were evoked only after high-intensity training in h...
TL;DR: It is recommended that the laser device is used in the decision-making process in relation to the diagnosis of occlusal caries as a second opinion in cases of doubt after visual inspection.
Abstract: Children and adolescents must be examined often for occlusal caries. Diagnosis of fissure caries is difficult especially when the tooth surface appears seemingly intact. It has been shown that using traditional clinical methods, as little as 20% of teeth with fissure caries under intact surfaces were correctly recognised as such. Therefore, new methods for increasing the accuracy of diagnosis have been sought for years. Recently, a new device, based on fluorescence measurements, was introduced. The purpose of this study was to test the device under in vivo conditions in order to provide recommendations for its use in the dental office. Seven general dental practitioners examined a total of 332 occlusal surfaces in 240 patients. Caries extent was determined for each site after operative intervention (='gold standard'). Clinical inspection and analysis of bitewing radiographs exhibited statistically significant lower sensitivities (31-63%) than did the DIAGNOdent device (sensitivity > or = 92%). It is recommended that the laser device is used in the decision-making process in relation to the diagnosis of occlusal caries as a second opinion in cases of doubt after visual inspection.
TL;DR: Favourable clinical conditions were found at tooth and implant abutments after 4-5 years of function and bruxism as well as extensions were associated with more technical failures.
Abstract: The aim of this study was to compare the frequency of biological and technical complications with fixed partial dentures (FPDs) on implants, teeth and as mixed tooth-implant supported FPDs over 4 to 5 years of function. All implants belonged to the ITI Dental Implant System. Group I-I (implant FPD) included 33 patients with 40 FPDs, group T-T (tooth FPDs) 40 patients with 58 FPDs, group I-T (mixed tooth-implant FPDs) 15 with 18 FPD. Of the bridge abutments 144 were teeth and 105 were implants. The median number of units replaced by the FPDs was 3 (range 2-14). The mean age of the patients was 55.7 years (range 23-83). Complete failures resulted in the loss of one FPD in each group. Two implants were lost due to fracture secondarily to development of a bone defect. One tooth had a vertical fracture and 1 tooth was lost due to periodontitis. Biological complications (peri-implantitis, PPD > or = 5 mm and BOP+) occurred at 9.6% (10) of the implants. This number was, however, reduced to 5% if the threshold for definition of peri-implantitis was set at PPD > or = 6 mm and BOP+. Biological complications occurred in 11.8% (17) of the abutment teeth (NS compared to implants); 2.8% (4) had secondary caries, 4.9% (7) endodontic problems and 4.1% (6) had periodontitis (PPD > or = 5 mm, BOP+). Ten out of 32 patients with a general health problem indicated a biological complication, whereas 9 out of 53 patients with no general health problem had a biological complication (chi 2: NS). Statistically significantly more technical complications were found in FPDs on implants (chi 2, P < or = 0.05). The technical complications were associated with bruxism. Out of 10 bruxers 6 had a technical complication whereas 13 out of 75 non-bruxers had such a complication (chi 2 < or = 0.01). Extensions were associated with more technical complications (13 out of 35 with extensions versus 9 out of 81 without). In conclusion, favourable clinical conditions were found at tooth and implant abutments after 4-5 years of function. Loss of FPD over 4-5 years occurred at a similar rate with mixed, implant or tooth supported reconstructions. Significantly more porcelain fractures were found in FPDs on implants. Impaired general health status was not significantly associated with more biological failures but bruxism as well as extensions were associated with more technical failures.