bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Bradford Hill considerations on causality: a counterfactual perspective
Authors: Höfler Michael 
Published: November 2005

AbstractBradford Hill's considerations published in 1965 had an enormous influence on attempts to separate causal from non-causal explanations of observed associations. These considerations were often applied as a checklist of criteria, although they were by no means intended to be used in this way by Hill himself. Hill, however, avoided defining explicitly what he meant by "causal effect".This paper provides a fresh point of view on Hill's considerations from the perspective of counterfactual causality. I argue that counterfactual arguments strongly contribute to the question of when to apply the Hill considerations. Some of the considerations, however, involve many counterfactuals in a broader causal system, and their heuristic value decreases as the complexity of a system increases; the danger of misapplying them can be high. The impacts of these insights for study design and data analysis are discussed. The key analysis tool to assess the applicability of Hill's considerations is multiple bias modelling (Bayesian methods and Monte Carlo sensitivity analysis); these methods should be used much more frequently.
Pulse contour analysis after normothermic cardiopulmonary bypass in cardiac surgery patients
Authors: Sander Michael , von Heymann Christian , Foer Achim , von Dossow Vera , Grosse Joachim , Dushe Simon , Konertz Wolfgang F , Spies Claudia D 
Published: November 2005

Abstract
Introduction
Monitoring of the cardiac output by continuous arterial pulse contour (COPiCCOpulse) analysis is a clinically validated procedure proved to be an alternative to the pulmonary artery catheter thermodilution cardiac output (COPACtherm) in cardiac surgical patients. There is ongoing debate, however, of whether the COPiCCOpulse is accurate after profound hemodynamic changes. The aim of this study was therefore to compare the COPiCCOpulse after cardiopulmonary bypass (CPB) with a simultaneous measurement of the COPACtherm.

Methods
After ethical approval and written informed consent, data of 45 patients were analyzed during this prospective study. During coronary artery bypass graft surgery, the aortic transpulmonary thermodilution cardiac output (COPiCCOtherm) and the COPACtherm were determined in all patients. Prior to surgery, the COPiCCOpulse was calibrated by triple transpulmonary thermodilution measurement of the COPiCCOtherm. After termination of CPB, the COPiCCOpulse was documented. Both COPACtherm and COPiCCOtherm were also simultaneously determined and documented.

Results
Regression analysis between COPACtherm and COPiCCOtherm prior to CPB showed a correlation coefficient of 0.95 (P < 0.001), and after CPB showed a correlation coefficient of 0.82 (P < 0.001). Bland-Altman analysis showed a mean bias and limits of agreement of 0.0 l/minute and -1.4 to +1.4 l/minute prior to CPB and of 0.3 l/minute and -1.9 to +2.5 l/minute after CPB, respectively. Regression analysis of COPiCCOpulse versus COPiCCOtherm and of COPiCCOpulse versus COPACtherm after CPB showed a correlation coefficient of 0.67 (P < 0.001) and 0.63 (P < 0.001), respectively. Bland-Altman analysis showed a mean bias and limits of agreement of -1.1 l/minute and -1.9 to +4.1 l/minute versus -1.4 l/minute and -4.8 to +2.0 l/minute, respectively.

Conclusion
We observed an excellent correlation of COPiCCOtherm and COPACtherm measurement prior to CPB. Pulse contour analysis did not yield reliable results with acceptable accuracy and limits of agreement under difficult conditions after weaning from CPB in cardiac surgical patients. The pulse contour analysis thus should be re-calibrated as soon as possible, to prevent false therapeutic consequences.
Year-round recordings of behavioural and physiological parameters reveal the survival strategy of a poorly insulated diving endotherm during the Arctic winter
Authors: Grémillet David , Kuntz Grégoire , Woakes Anthony J. , Gilbert Caroline , Robin Jean-Patrice , Le Maho Yvon , Butler Patrick J. 
Published: November 2005

SUMMARY
Warm-blooded diving animals wintering in polar regions are expected to show a high degree of morphological adaptation allowing efficient thermal insulation. In stark contrast to other marine mammals and seabirds living at high latitudes, Arctic great cormorants Phalacrocorax carbo have very limited thermal insulation because of their partly permeable plumage. They nonetheless winter in Greenland, where they are exposed to very low air and water temperatures. To understand how poorly insulated diving endotherms survive the Arctic winter, we performed year-round recordings of heart rate,dive depth and abdominal temperature in male great cormorants using miniature data loggers. We also examined the body composition of individuals in the spring. Abdominal temperatures and heart rates of birds resting on land and diving showed substantial variability. However, neither hypothermia nor significantly lower heart rate levels were recorded during the winter months. Thus our data show no indication of general metabolic depression in great cormorants wintering in Greenland. Furthermore, great cormorants did not reduce their daily swimming time during the coldest months of the year to save energy; they continued to forage in sub-zero waters for over an hour every day. As birds spent extended periods in cold water and showed no signs of metabolic depression during the Arctic winter, their theoretical energy requirements were substantial. Using our field data and a published algorithm we estimated the daily food requirement of great cormorants wintering in Greenland to be 1170±110 g day-1. This is twice the estimated food requirement of great cormorants wintering in Europe. Great cormorants survive the Arctic winter but we also show that they come close to starvation during the spring, with body reserves sufficient to fast for less than 3 days. Lack of body fuels was associated with drastically reduced body temperatures and heart rates in April and May. Concurrent, intense feeding activity probably allowed birds to restore body reserves. Our study is the first to record ecophysiological parameters in a polar animal on a year-round basis. It challenges the paradigm that efficient thermal insulation is a prerequisite to the colonization of polar habitats by endotherms.
Thermally induced changes in lipid composition of raft and non-raft regions of hepatocyte plasma membranes of rainbow trout
Authors: Zehmer John K. , Hazel Jeffrey R. 
Published: November 2005

SUMMARY
In poikilotherms, increases in plasma membrane (PM) cholesterol and an increase in the degree of lipid acyl chain saturation commonly accompany an increase in growth temperature. This has typically been interpreted in terms of membrane fluidity/order homeostasis, but these changes would also be expected to stabilize the structure of PM rafts against thermal perturbation. Rafts are microdomains that organize the molecules of many signaling cascades and are formed as a result of interactions between lipids with saturated acyl chains and cholesterol. No study to date has examined the thermally induced compositional changes of raft and non-raft regions of the PM separately. In this study we have measured the phospholipid class composition and fatty acid composition of raft-enriched (raft) and raft-depleted PM (RDPM) of hepatocytes from trout Oncorhynchus mykiss acclimated to 5°C and 20°C. In the raft, warm acclimation was associated with a reduction in the proportion of phosphatidylcholine from 56% to 30% while phosphatidylserine and phosphatidylinositol each increased from 8% to approximately 20% of the total phospholipid. Additionally, there were significantly fewer unsaturated fatty acids in the raft lipids from warm-acclimated (61%) than from the cold-acclimated trout (68%). In contrast, there were no significant changes in phospholipid class or acyl chain unsaturation in the RDPM. These data suggest that changes in raft lipid composition, rather than the PM as a whole, are particularly important during thermal acclimation.
Time course of osmoregulatory and metabolic changes during osmotic acclimation in Sparus auratus
Authors: Sangiao-Alvarellos Susana , Arjona Francisco J. , del Río María P. Martín , Míguez Jesús M. , Mancera Juan M. , Soengas José L. 
Published: November 2005

SUMMARY
Changes in different osmoregulatory and metabolic parameters over time were assessed in gills, kidney, liver and brain of gilthead sea bream Sparus auratus transferred either from seawater (SW, 38 p.p.t.) to hypersaline water (HSW, 55 p.p.t.) or from SW to low salinity water (LSW, 6 p.p.t.) for 14 days. Changes displayed by osmoregulatory parameters revealed two stages during hyperosmotic and hypo-osmotic acclimation: (i) an adaptive period during the first days of acclimation (1–3 days), with important changes in these parameters, and (ii) a chronic regulatory period (after 3 days of transfer) where osmotic parameters reached homeostasis. From a metabolic point of view, two clear phases can also be distinguished during acclimation to hyperosmotic or hypo-osmotic conditions. The first one coincides with the adaptive period and is characterized by enhanced levels of plasma metabolites(glucose, lactate, triglycerides and protein), and use of these metabolites by different tissues in processes directly or indirectly involved in osmoregulatory work. The second stage coincides with the chronic regulatory period observed for the osmoregulatory parameters and is metabolically characterized in HSW-transferred fish by lower energy expenditure and a readjustment of metabolic parameters to levels returning to normality,indicative of reduced osmoregulatory work in this stage. In LSW-transferred fish, major changes in the second stage include: (i) decreased glycolytic potential, capacity for exporting glucose and potential for amino acid catabolism in liver; (ii) enhanced use of exogenous glucose through glycolysis, pentose phosphate and glycogenesis in gills; (iii) increased glycolytic potential in kidney; and (iv) increased glycogenolytic potential and capacity for use of exogenous glucose in brain.
Desert ants compensate for navigation uncertainty
Authors: Wolf Harald , Wehner Rüdiger 
Published: November 2005

SUMMARY
During foraging trips, desert ants Cataglyphis fortis do not rely only on their well-studied path integration system, they also use olfactory cues when approaching a familiar food source. When a wind is blowing from a constant direction, as is characteristic of their desert habitat, the ants do not approach the feeder directly. They rather steer some distance downwind of the food source to pick up odour filaments emanating from the food. They follow this odour trail upwind, and find the source quickly and reliably.
This approach behaviour was examined in more detail in order to identify the underlying orientation strategy. First, the ants may employ a `goal expansion strategy', using odour spread as a spatially limited indicator for the presence of food. In that case, the distance steered downwind of the feeder should be determined by the range of the odour plume (and, for instance, wind speed). It should be independent of the distance between nest and feeder. Second, the ants may apply an `error compensation strategy', using odour filaments as a guideline towards the food source. Steering downwind by a margin just exceeding their maximum navigation error will lead the ants safely across the odour guide. In that case, the distance steered downwind of the feeder should increase more or less linearly with the nest-feeder distance.
Our results unambiguously support the second strategy. When feeders were established at distances of 5-75 m from the nest, the distances steered downwind of the food increased from 0.7 m to 3.4 m in a linear fashion. This result was independent of wind speed or wind direction. It translates into an ant's estimate of its navigation error within a range of 3° to 8°.
Neural plasticity of mushroom body-extrinsic neurons in the honeybee brain
Authors: Menzel Randolf , Manz Gisela 
Published: November 2005

SUMMARYCentral interneurons exiting the alpha lobe of the mushroom bodies were studied with respect to their plasticity by electrically stimulating their presynaptic inputs, the Kenyon cells. Special attention was given to the analysis of a single, identified neuron, the PE1. Three stimulation protocols were tested: double pulses, tetanus (100 Hz for 1 s), and tetanus paired with intracellular de- or hyper-polarization of the recorded cell. Double-pulse stimulations revealed short-term facilitation and depression, tuning the responses of these interneurons to frequencies in the range of 20–40 Hz. The tetanus may lead to augmentation of responses to test stimuli lasting for several minutes, or to depression followed by augmentation. Associative long-term potentiation (LTP) was induced in the PE1 neuron by pairing a presynaptic tetanus with depolarization. This is the first time that associative LTP has been found in an interneuron of the insect nervous system. These data are discussed in the context of spike tuning in the output of the mushroom body, and the potential role of associative LTP in olfactory learning. It is concluded that the honeybee mushroom body output neurons are likely to contribute to the formation of olfactory memory.
Dissolution of uranium dioxide in simulated Boom clay water
Authors: Guilbert S. , Guittet M.J. , Barré N. , Trocellier P. , Gautier-Soyer M. , Andriambololona Z. 
Published: November 2005

SummaryThe solubility behavior of uranium dioxide was studied under oxidizing and reducing conditions in simulated Belgian Boom clay water at 25 °C, on unirradiated fuel pellets. For a comparable period (1 month), the uranium concentration and the dissolution rate (10−12mol m−2s−1) in reduced medium were ∼30 times smaller than in oxidizing conditions (3 × 10−11mol m−2s−1). X-ray photoelectron spectroscopy analyses revealed that U(VI) and U(IV) oxidation states were present in the altered layer in both cases. In the case of the experiments performed in oxidizing conditions, this technique also revealed the formation of U-OH bonds. Although steady state was not reached, geochemical calculations allowed us to suggest a class of secondary phases able to control the uranium solubility in the long term.
Synthesis and investigation of Pu-doped single crystal zircon, (Zr, Pu)SiO4
Authors: Burakov B. E. , Hanchar J. M. , Zamoryanskaya M. V. , Garbuzov V. M. , Zirlin V. A. 
Published: November 2005

Summary
Single crystals of zircon doped with 239Pu, up to 2 mm in size, were grown for the first time ever, using a Li-Mo flux. The crystals were transparent and free of inclusions of separated Pu phases. The zircon crystals were studied using optical and scanning electron microscopy, the electron microprobe, and cathodoluminescence imaging and spectroscopy. The incorporation of 239Pu ranged from 0.1 to 1.4 wt.% el. The intensity of the CL emission in the Pu-doped crystals is correlated with the Pu content.
Old Bone Marrow Cells Inhibit Skin Wound Vascularization
Authors: Schatteman Gina C. , Ma Ning 
Published: November 2005

Abstract
Local injection of hematopoietic stem cell–enriched cells, including mouse lin− cells, accelerates vascularization in animal injury models, apparently by release of angiogenic factors. Locally injected lin− cells from nondiabetic mice dramatically improve, but those from obese diabetic mice inhibit vascular growth in obese diabetic mouse skin wounds. Because of similarities between diabetes and aging and because autologous bone marrow–derived cells are currently being tested in clinical trials involving older patients, we investigated the effects of old lin− cells on skin wound vascularization in nondiabetic and obese diabetic mice. Treatment with old lin− bone marrow cells resulted in decreased vessel size and numerical density, leading to profoundly reduced vascular volume density in wounds of non-diabetic and diabetic mice. Our data suggest that bone marrow–derived cells may be poor candidates for therapeutic use in older patients and could actually harm them.
How Today's Developments in the Treatment of Non-Small Cell Lung Cancer Will Change Tomorrow's Standards of Care
Authors: Kris Mark G. 
Published: November 2005

AbstractLearning ObjectivesAfter completing this course, the reader will be able to: Discuss the current status of adjuvant therapy in NSCLC.Articulate the developing rate of targeted agents in the treatment of NSCLC.Describe how tumor molecular biology may impact response to novel treatment.Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.comCisplatin (Platinol®; Bristol-Myers Squibb, Princeton, NJ, http://www.bms.com) and carboplatin (Paraplatin®; Bristol-Myers Squibb), together with newer chemotherapies, such as docetaxel (Taxotere®; Aventis Pharmaceuticals Inc., Bridgewater, NJ, http://www.aventispharma-us.com), paclitaxel (Taxol®; Bristol-Myers Squibb), vinorelbine (Navelbine®; GlaxoSmith-Kline, Philadelphia, http://www.gsk.com), pemetrexed (Alimta®; Eli Lilly and Company, Indianapolis, http://www.lilly.com), and gemcitabine (Gemzar®; Eli Lilly and Company), have improved treatment outcomes in both advanced non-small cell lung cancer (NSCLC) and in the adjuvant/neoadjuvant setting. Newer systemic treatments for NSCLC, used in advanced stage IV management, are beginning to be studied in earlier stages of the disease, when treatment is better tolerated and potentially curative. Hopefully, newer agents with proven efficacies in advanced disease will enhance curability. Following the successful addition of bevacizumab (Avastin®; Genentech, Inc., South San Francisco, CA, http://www.gene.com) to carboplatin/paclitaxel in advanced disease, bevacizumab is now being incorporated into adjuvant and neoadjuvant trials. Trials in stage IB–IIIA patients will study neoadjuvant docetaxel/cisplatin/bevacizumab. The discovery that patients with exon 19 and 21 mutations in the epidermal growth factor receptor gene EGFR have around an 80% response rate to gefitinib (Iressa®; AstraZeneca Pharmaceuticals, Wilmington, DE, http:// www.astrazeneca-us.com) and that this response confers survival benefit indicates its potential utility for mutation-positive patients with advanced- and earlier-stage disease. Clinical characteristics, such as never smoking status and adenocarcinoma, and especially bronchioloalveolar carcinoma histological features, can also identify individuals likely to respond to EGFR tyrosine kinase inhibitors. Studies of neoadjuvant erlotinib (Tarceva®; OSI Pharmaceuticals, Inc., Melville, NY, http://www.osip.com) in operable NSCLC are planned. One such study includes cisplatin and docetaxel. Effective development of active agents and disease management based on molecular profiling of lung tumors will change tomorrow's standard of care.
Rapid Evolution in Colorectal Cancer: Therapy Now and Over the Next Five Years
Authors: Gramont Aimery 
Published: November 2005

Abstract

Learning Objectives
After completing this course, the reader will be able to:Discuss the public health importance and natural history of colorectal cancer.Describe how treatments developed in the context of clinical trials have changed the prognosis of this disease.Explain the potential impact of clinical trials on future treatment guidelines.
Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com
A large number of patients with colorectal cancer have relatively early disease, and thus, adjuvant therapy has the potential to save lives. In stage III patients, there has been a steady improvement in 3-year disease-free survival with the use of 5-fluorouracil/leucovorin (5-FU/LV) regimens and capecitabine (Xeloda®; Hoffmann-La Roche Inc., Nutley, NJ, http://www.rocheusa.com) regimens. A median survival longer than 20 months was observed in patients with metastatic disease when treated with combination chemotherapy containing oxaliplatin (Eloxatin®; Sanofi-Synthelabo Inc., New York, http://www.sanofi-synthelabo.us) or irinotecan (Camptosar®; Pfizer Pharmaceuticals, New York, http://www.pfizer.com). This has led to 5-FU/LV/oxaliplatin becoming standard therapy, along with 5-FU/LV/irinotecan. New data confirm the beneficial effect on disease-free survival of adding oxaliplatin to adjuvant colorectal cancer regimens based on 5-FU. These regimens show an effect when given in bolus as well as in infusional schedules. Interest in future adjuvant regimens focuses on the potential additional benefit of molecularly targeted agents, such as bevacizumab (Avastin®; Genentech, Inc., South San Francisco, CA, http://www.gene.com), and on the ability of applied genomics to distinguish between high- and low-risk populations.
Significance of Auditory Brain Stem Response and Gadolinium‐Enhanced Magnetic Resonance Imaging for Idiopathic Sudden Sensorineural Hearing Loss
Authors: Busaba Nicolas Y. , Rauch Steven D. 
Published: November 2005

Previous studies tried to correlate prognosis and response to oral corticosteroids in patients with idiopathic sudden sensorineural hearing loss to such factors as the age of the patient, presence of vertigo, shape of the audiogram, or severity of the hearing loss. However, temporal bone histopathologic evidence shows that idiopathic sudden sensorineural hearing loss may be caused by cochleitis or cochlear nerve neuritis. Herein we report results of a retrospective study of 96 consecutive patients with idiopathic sudden sensorineural hearing loss who were evaluated with auditory brain stem responses and gadolinium‐enhanced magnetic resonance imaging. Results of the auditory brain stem response and magnetic resonance imaging were correlated with hearing outcome. Follow‐up was available for 65 patients: 14 with abnormal and 51 with normal auditory brain stem responses. The overall rate of hearing recovery or improvement was 65% in the normal auditory brain stem response group compared with 43% in the abnormal auditory brain stem response group (p = 0.07). Among the 38 patients treated with a tapering course of oral corticosteroids, the recovery or improvement rate was 83% for those with normal auditory brain stem responses and 56% for those with abnormal auditory brain stem responses (p < 0.05). Of the 27 patients who did not receive steroid therapy, the improvement rate was 41% in those with normal auditory brain stem responses and 20% in those with abnormal auditory brain stem responses (p = 0.09). Magnetic resonance imaging with gadolinium was obtained on all 14 patients with abnormal auditory brain stem responses but on none with normal auditory brain stem responses. Only 1 magnetic resonance image of 14 demonstrated an abnormality, showing a high signal intensity in the distal internal auditory canal; this resolved 6 weeks later on a follow‐up magnetic resonance image. We conclude that idiopathic sudden sensorineural hearing loss patients with abnormal auditory brain stem responses have poorer hearing prognoses compared with those patients with normal auditory brain stem responses, irrespective of treatment. Idiopathic sudden sensorineural hearing loss patients with abnormal auditory brain stem responses may have cochlear neuritis causing their hearing loss or may have a more extensive involvement of their auditory system, and this “lesion” may have a lower spontaneous recovery rate and less response to therapy. Magnetic resonance imaging with gadolinium may show abnormal signal intensities along the course of the eighth nerve in patients with idiopathic sudden sensorineural hearing loss, but this is infrequent, and its prognostic implications are not clear.