Author Correction: Nearly all the sky is covered by Lyman-α emission around high-redshift galaxies.

Change history: In this Letter, author M. Akhlaghi should be associated with affiliation (2) rather than (3). This error has been corrected online.

Nearly all the sky is covered by Lyman-α emission around high-redshift galaxies.

Galaxies are surrounded by large reservoirs of gas, mostly hydrogen, that are fed by inflows from the intergalactic medium and by outflows from galactic winds. Absorption-line measurements along the lines of sight to bright and rare background quasars indicate that this circumgalactic medium extends far beyond the starlight seen in galaxies, but very little is known about its spatial distribution. The Lyman-α transition of atomic hydrogen at a wavelength of 121.6 nanometres is an important tracer of warm (about 104 kelvin) gas in and around galaxies, especially at cosmological redshifts greater than about 1.6 at which the spectral line becomes observable from the ground. Tracing cosmic hydrogen through its Lyman-α emission has been a long-standing goal of observational astrophysics1-3, but the extremely low surface brightness of the spatially extended emission is a formidable obstacle. A new window into circumgalactic environments was recently opened by the discovery of ubiquitous extended Lyman-α emission from hydrogen around high-redshift galaxies4,5. Such measurements were previously limited to especially favourable systems6-8 or to the use of massive statistical averaging9,10 because of the faintness of this emission. Here we report observations of low-surface-brightness Lyman-α emission surrounding faint galaxies at redshifts between 3 and 6. We find that the projected sky coverage approaches 100 per cent. The corresponding rate of incidence (the mean number of Lyman-α emitters penetrated by any arbitrary line of sight) is well above unity and similar to the incidence rate of high-column-density absorbers frequently detected in the spectra of distant quasars11-14. This similarity suggests that most circumgalactic atomic hydrogen at these redshifts has now been detected in emission.

Sub-micrometer focusing setup for high-pressure crystallography at the Extreme Conditions beamline at PETRA†III.

Scientific tasks aimed at decoding and characterizing complex systems and processes at high pressures set new challenges for modern X-ray diffraction instrumentation in terms of X-ray flux, focal spot size and sample positioning. Presented here are new developments at the Extreme Conditions beamline (P02.2, PETRA III, DESY, Germany) that enable considerable improvements in data collection at very high pressures and small scattering volumes. In particular, the focusing of the X-ray beam to the sub-micrometer level is described, and control of the aberrations of the focusing compound refractive lenses is made possible with the implementation of a correcting phase plate. This device provides a significant enhancement of the signal-to-noise ratio by conditioning the beam shape profile at the focal spot. A new sample alignment system with a small sphere of confusion enables single-crystal data collection from grains of micrometer to sub-micrometer dimensions subjected to pressures as high as 200 GPa. The combination of the technical development of the optical path and the sample alignment system contributes to research and gives benefits on various levels, including rapid and accurate diffraction mapping of samples with sub-micrometer resolution at multimegabar pressures.

Can hypothermic oxygenated perfusion (HOPE) rescue futile DCD liver grafts?

BACKGROUND: The new UK-DCD-Risk-Score has been recently developed to predict graft loss in DCD liver transplantation. Donor-recipient combinations with a cumulative risk of >10 points were classified as futile and achieved an impaired one-year graft survival of <40%. The aim of this study was to show, if hypothermic oxygenated perfusion (HOPE) can rescue such extended DCD livers and improve outcomes. METHODS: "Futile"-classified donor-recipient combinations were selected from our HOPE-treated human DCD liver cohort (01/2012-5/2017), with a minimum follow-up of one year. Main risk factors, which contribute to the classification "futile" include: elderly donors>60years, prolonged functional donor warm ischemia time (fDWIT > 30min), long cold ischemia time>6hrs, donor BMI>25 kg/m2, advanced recipient age (>60years), MELD-score>25points and retransplantation status. Endpoints included all outcome measures during and after DCD LT. RESULTS: Twenty-one donor-recipient combinations were classified futile (median UK-DCD-Risk-Score:11 points). The median donor age and fDWIT were 62 years and 36 min, respectively. After cold storage, livers underwent routine HOPE-treatment for 120 min. All grafts showed immediate function. One-year and 5-year tumor death censored graft survival was 86%. CONCLUSION: HOPE-treatment achieved excellent outcomes, despite high-risk donor and recipient combinations. Such easy, endischemic perfusion approach may open the door for an increased utilization of futile DCD livers in other countries.

The Extreme Conditions Beamline P02.2 and the Extreme Conditions Science Infrastructure at PETRA III.

A detailed description is presented of the Extreme Conditions Beamline P02.2 for micro X-ray diffraction studies of matter at simultaneous high pressure and high/low temperatures at PETRA III, in Hamburg, Germany. This includes performance of the X-ray optics and instrumental resolution as well as an overview of the different sample environments available for high-pressure studies in the diamond anvil cell. Particularly emphasized are the high-brilliance and high-energy X-ray diffraction capabilities of the beamline in conjunction with the use of fast area detectors to conduct time-resolved compression studies in the millisecond time regime. Finally, the current capability of the Extreme Conditions Science Infrastructure to support high-pressure research at the Extreme Conditions Beamline and other PETRA III beamlines is described.

New dynamic diamond anvil cell for time-resolved radial x-ray diffraction.

The dynamic diamond anvil cell (dDAC) is a recently developed experimental platform that has shown promise for studying the behavior of materials at strain rates ranging from intermediate to quasi-static and shock compression regimes. Combining dDAC with time-resolved x-ray diffraction (XRD) in the radial geometry (i.e., with incident x-rays perpendicular to the axis of compression) enables the study of material properties such as strength, texture evolution, and deformation mechanisms. This work describes a radial XRD dDAC setup at beamline P02.2 (Extreme Conditions Beamline) at DESY's PETRA III synchrotron. Time-resolved radial XRD data are collected for titanium, zirconium, and zircon samples, demonstrating the ability to study the strength and texture of materials at compression rates above 300 GPa/s. In addition, the simultaneous optical imaging of the DAC sample chamber is demonstrated. The ability to conduct simultaneous radial XRD and optical imaging provides the opportunity to characterize plastic strain and deviatoric strain rates in the DAC at intermediate rates, exploring the strength and deformation mechanisms of materials in this regime.

Implementation of the quality management system improves postoperative pain treatment: a prospective pre-/post-interventional questionnaire study.

BACKGROUND: An organizational approach is proposed as an immediate solution for improving postoperative pain (POP) management. The aim was to evaluate the clinical effectiveness of a quality management system (QMS), based on procedure-specific, multimodal analgesic protocols, modified to meet the individual patients' requirements. METHODS: Patients from the orthopaedic, gynaecological, visceral, and trauma surgery departments of the university hospital were involved in two prospective surveys. Survey 1 was performed at baseline and survey 2 was performed after the implementation of QMS within an interval of 1 year. The patients were asked to report pain intensity on the visual rating scale, incidence of analgesia-related side-effects, and incidence of pain interference with the items of life quality and their satisfaction with the treatment of POP. RESULTS: Patients from Survey 2 (n=251) reported 25-30% less pain than those from Survey 1 (n=269) (P<0.0001). Nausea was reported by 40% of the patients from Survey 1 vs 17% from Survey 2, vomiting by 25 vs 11% and fatigue by 76% in Survey 1 vs 30% in Survey 2 (P<0.0001). Life quality and patients' satisfaction improved in Survey 2 vs Survey 1 (P<0.001). CONCLUSIONS: The implementation of QMS allowed the reduction in POP intensity with a simultaneous decrease in analgesia-related side-effects. This has led to an increased quality of life and patient satisfaction.

Are biters sick? Health status of tail biters in comparison to control pigs.

BACKGROUND: Tail biting is a multifactorial problem. As the health status is one of the factors commonly linked to tail biting, this study focuses on the health of identified biters. 30 (obsessive) biters are compared to 30 control animals by clinical and pathological examination as well as blood and cerebrospinal fluid samples. In that way, altogether 174 variables are compared between the groups. Moreover, connections between the variables are analysed. RESULTS: In the clinical examination, 6 biters, but only 2 controls (P = 0.019) were noticeably agitated in the evaluation of general behaviour, while 8 controls were noticeably calmer (2 biters, P = 0.02). Biters had a lower body weight (P = 0.0007) and 13 biters had overlong bristles (4 controls, P = 0.008). In the pathological examination, 5 biters, but none of the controls had a hyperceratosis or inflammation of the pars proventricularis of the stomach (P = 0.018). However, 7 controls and only 3 biters were affected by gut inflammation (P = 0.03). In the blood sample, protein and albumin levels were below normal range for biters (protein: 51.6 g/l, albumin: 25.4 g/l), but not for controls (protein: 53.7 g/l, albumin: 27.4 g/l), (protein: P = 0.05, albumin: P = 0.02). Moreover, 14 biters, but only 8 controls had poikilocytosis (P = 0.05). Although not statistically different between groups, many animals (36/60) were affected by hypoproteinemia and hyponatremia as well as by hypokalemia (53/60) and almost all animals (58/60) had hypomagnesemia. For hypomagnesemia, significant connections with variables linked to tail damage and ear necrosis were detected (rs/V/ρ ≥ 0.4, P ≤ 0.05). CONCLUSION: The results suggest that behavioural tests might be helpful in identifying biters. Moreover, cornification and inflammation of the pars proventricularis is linked to becoming a biter. Furthermore, the results highlight the need for appropriate and adjusted nutrient and mineral supply, especially with regard to magnesium.

Rituximab in relapsing or refractory ANCA-associated vasculitis: a case series of 16 patients.

OBJECTIVES: Cyclophosphamide (CYC) and corticosteroids are generally considered standard induction therapy for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, a subset of patients are refractory or intolerant to this treatment. Rituximab, a chimeric anti-CD20 antibody, has emerged as a second-line therapy, although controlled studies are scarce in patients with relapsing or refractory disease. METHODS: We report 16 patients with AAV who received rituximab for refractory or relapsing vasculitis having previously received CYC. The treatment protocols were 375 mg/m(2) × IV in five patients, 1000 mg × II in six patients, and 500 mg × II in five patients, all in combination with corticosteroids. A majority of patients used other concurrent immunosuppression, most commonly mycophenolate mofetil. Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS 2003) at baseline and during follow-up together with C-reactive protein (CRP) and ANCA. Complete remission was defined as a BVAS score of 0 and partial remission as a reduction in BVAS of at least 50%. RESULTS: Twelve patients achieved complete remission, three patients partial remission, and one patient died during follow-up (median of 20 months, range 3-48 months). Six patients relapsed and received rituximab again. Four of these were positive for capture proteinase 3 (PR-3) ANCA but negative with conventional PR-3 ANCA upon retreatment. Seven patients had an adverse event, including two hepatitis B reactivations and one fatal sepsis. CONCLUSION: Treatment with rituximab in AAV was associated with prolonged remission in a subset of patients otherwise difficult to manage.

Development of a new grading system to assess the foster performance of lactating sows.

Increasing litter size has created the need for more sophisticated, accurate, and welfare-oriented systems for assessing the foster performance of lactating sows. The estimation of milk yield alone is not sufficient for meeting these requirements. Therefore, the aim of the current study was to develop a grading system for assessing the foster performance of lactating sows that can be easily applied in commercial farm practice. Data were collected in two German conventional farrow-to-feeder farms with a total sample size of 639 sows (4.05 ± 2.86 parities) and 1 728 litters. Besides general performance data, the piglets were weighed individually within the first 24 hours after birth and at the peak of lactation (day 18.22 ± 2.48). Based on these data, we proposed a new score referring to the milk score (MS). This score was compared with the commonly used formula for estimating milk yield (est. MY), which solely involves litter weight gain and litter size. The improvement of the developed MS allowed us to distinguish between the birth and foster performances of the lactating sows through considering cross-fostering, litter size, individual piglet weights, and piglet mortality during lactation. Both scores showed a similar progression across parities. It was found that litter size had a significant impact on the performance of lactating sows. A high est. MY was found to be associated with a significantly higher number of piglets per litter (15.79 ± 2.20), lower weight gain per piglet, and increased piglet mortality during lactation compared with sows with high MS, which showed a smaller litter size (13.51 ± 2.18) (P < 0.05). The focus on smaller litter size indicates a performance limitation, which seems to be related to the average teat number of 13-15 teats per sow. We recommend the consideration of the number of functional teats, because a litter size above it will not result in a sow having higher foster performance. In conclusion, as an extension of the common est. MY calculation, the MS considers cross-fostering as current farm-management practice when dealing with larger litters. Our recommendations emphasise the importance of an MS which indicates smaller litter size, higher piglet weight gain, and lower piglet mortality during lactation; these factors are related to an improvement in animal welfare for sows and piglets. Moreover, the presented MS could be used to develop a management tool for farmers to assess the foster performance of lactating sows, considering individual farm-management practices.

Differences in human and minipig platelet number, volume and activation induced by borosilicate glass beads in a modified chandler loop-system.

The pig is the most widely used large animal model in Europe, with cardiovascular research being one of the main areas of application. Adequate refinement of interventional studies in this field, meeting the requirements of Russel and Burchs' 3 R concept, can only be performed if blood-contacting medical devices are hemocompatible. Because most medical devices for cardiovascular interventional procedures are developed for humans they are tested mostly for compatibility with human blood. The aim of this study was therefore to determine whether there are differences in behavior of porcine and human platelets when they come into contact with glass, which was used as an exemplary thrombogenic material. For this purpose changes of platelet count, platelet volume and platelet expression of the activation markers CD61, CD62P and CD63 were measured using a modified chandler loop-system simulating the fluidic effects of the blood flow. Minipig and human platelets showed significant differences in number and volume, but not in activation after 4-8 min exposure to glass.

[Prevention of infections under anesthetic breathing with breathing filters: concerted recommendations of the Deutsche Gesellschaft für Krankenhaushygiene e.V. (DGKH) and the Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin e.V. (DGAI)]. / Infektionsprävention bei der Narkosebeatmung durch Einsatz von Atemsystemfiltern: Gemeinsame Empfehlung der Deutschen Gesellschaft für Krankenhaushygiene e.V. (DGKH) und der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin e.V. (DGAI).

An interdisciplinary working group from the German Society of Hospital Hygiene (DGKH) and the German Society for Anesthesiology and Intensive Care (DGAI) worked out the following recommendations for infection prevention during anesthesia by using breathing system filters (BSF). The BSF shall be changed after each patient. The filter retention efficiency for airborne particles is recommended to be >99% (II). The retention performance of BSF for liquids is recommended to be at pressures of at least 60 hPa (=60 mbar) or 20 hPa above the selected maximum ventilation pressure in the anesthetic system.The anesthesia breathing system may be used for a period of up to 7 days provided that the functional requirements of the system remain unchanged and the manufacturer states this in the instructions for use. The breathing system and the manual ventilation bag are changed immediately after the respective anesthesia if the following situation has occurred or it is suspected to have occurred: Notifiable infectious disease involving the risk of transmission via the breathing system and the manual bag, e.g. tuberculosis, acute viral hepatitis, measles, influenza virus, infection and/or colonization with a multi-resistant pathogen or upper or lower respiratory tract infections. In case of visible contamination e.g. by blood or in case of defect, it is required that the BSF and also the anesthesia breathing system is changed and the breathing gas conducting parts of the anesthesia ventilator are hygienically reprocessed.Observing of the appropriate hand disinfection is very important. All surfaces of the anesthesia equipment exposed to hand contact must be disinfected after each case.

Mycophenolate mofetil as second line immunosuppressant in Myasthenia gravis--a long-term prospective open-label study.

BACKGROUND: The preferred immunosuppressive drug for long term treatment of myasthenia gravis (MG) is azathioprine (AZA). Mycophenolate mofetil (MMF) was suggested as an effective and safe second line alternative to AZA. METHODS: In a prospective open-label study, 11 patients with acetylcholine receptor antibody (AChR-ab) positive MG (n=4 ocular MG, n=7 generalized MG) were treated with MMF which replaced AZA. Reasons for the change of immunosuppressant therapy were side effects (n=9) or unresponsiveness under AZA (n=3). RESULTS: Mean duration of MMF treatment was 16.9 months (6-46 months). During MMF treatment AZA side effects resolved in 8/9 patients, concomitant therapy could be discontinued in 4 patients and reduced in 5 patients, and 5 patients remitted and 3 remained in remission. One MMF-refractory patient required add-on IVIG therapy and another with ocular MG showed signs of generalization after 20 months of MG treatment. One patient was diagnosed with bronchial carcinoma after 10 months of MMF treatment. CONCLUSION: Due to its favourable spectrum of side effects compared to AZA MMF might serve as a second-line immunosuppressant in those MG patients who have not tolerated AZA.

4G versus 3G-enabled telemedicine in prehospital acute stroke care.

BACKGROUND: Time to reperfusion treatment is closely related to outcome in ischemic stroke. Prehospital stroke work-up in CT-equipped mobile stroke units is effective in reducing time to thrombolytic treatment. Current evidence predominantly comes from mobile stroke units staffed with neurologists but telemedicine-guided management may be acceptable for providing neurological expertise in ambulances. With unsatisfactory experiences in third-generation (3G)-based approaches, fourth-generation (4G) networks may provide adequate audio-visual quality but systematic comparisons of technological parameters and decision-making are lacking. METHODS: Trained actors presented stroke symptoms and paramedics assisted the remotely guided extended National Institutes of Health Stroke Scale (eNIHSS) assessment on the mobile stroke unit in Berlin, Germany. We compared technical parameters of 4G and 3G connections, assessed audio-visual quality of examination, and analyzed reliability of neurological assessment and treatment decisions made by the remote neurologist versus the mobile stroke unit neurologist. RESULTS: 4G and 3G connections were evaluated in 40 scenarios each. Connectivity was not available in 17% of 4G- and 15% of 3G-attempts with 6% simultaneous unavailability of both networks. The remote examiners graded audio and video quality in 4G better than in 3G with slightly shorter assessment duration in 4G (mean: 9 (SD:5) vs. mean 11 (SD:3) min, p = 0.10). Reliability of the eNIHSS sum scores was high with intraclass correlation coefficients of 0.99 (95% CI: 0.987-1.00) for 4G and 0.98 (95% CI: 0.96-0.99) for 3G. None of the remote treatment decisions differed from onsite decisions. CONCLUSIONS: 4G mobile communications provided higher quality of video-examination and allowed reliable remote assessment of stroke symptoms but coverage was still incomplete in both networks.

New dynamic diamond anvil cells for tera-pascal per second fast compression x-ray diffraction experiments.

Fast compression experiments performed using dynamic diamond anvil cells (dDACs) employing piezoactuators offer the opportunity to study compression-rate dependent phenomena. In this paper, we describe an experimental setup which allows us to perform time-resolved x-ray diffraction during the fast compression of materials using improved dDACs. The combination of the high flux available using a 25.6 keV x-ray beam focused with a linear array of compound refractive lenses and the two fast GaAs LAMBDA detectors available at the Extreme Conditions Beamline (P02.2) at PETRA III enables the collection of x-ray diffraction patterns at an effective repetition rate of up to 4 kHz. Compression rates of up to 160 TPa/s have been achieved during the compression of gold in a 2.5 ms fast compression using improved dDAC configurations with more powerful piezoactuators. The application of this setup to low-Z compounds at lower compression rates is described, and the high temporal resolution of the setup is demonstrated. The possibility of applying finely tuned pressure profiles opens opportunities for future research, such as using oscillations of the piezoactuator to mimic propagation of seismic waves in the Earth.

Response of the rat intestinal microcirculation to experimental endotoxemia is attenuated by ampicillin but not by its derivative KKP723.

KKP723 (KKP), a derivative of ampicillin, is a newly developed beta-lactam antibiotic. Using an experimental endotoxemia model, the intestinal microcirculation in four groups of animals were evaluated using intravital microscopy (IVM). The groups included were a control group, an endotoxemic group (15 mg/kg i.v. LPS from E. coli), an ampicillin (50 mg/kg i.v.) treated endotoxemic group and an endotoxemic group treated with KKP (67.4 mg/kg i.v.). Ampicillin treatment resulted in a significant reduced number of firmly adhering leukocytes in intestinal submucosal venules. KKP treatment did not show this effect on leukocyte activation. We found no changes of the functional capillary density (FCD) of the intestinal wall by treatment with ampicillin or its derivative KKP. The increased leukocyte adherence in the KKP treated LPS animals may be explained by a loss of a possible ampicillin-related anti-inflammatory effect by the biotransformation process. The endotoxemia IVM model is useful to detect effects of antibiotics in an impaired microcirculation.

Ordnung muss sein: heteroelement order and disorder in polyoxovanadates.

The first mixed antimonato-germanato polyoxovanadates were synthesized using two different strategies, highlighting the critical role of the precursors. Following the traditional route using multiple single sources as precursors the polyanions [V15Sb2Ge4O42(OH)4(H2O)]6- (1) and [V15Sb3Ge3O42(OH)3(H2O)]6- (2) are obtained, which display disorder of their Sb/Ge positions, indicating that clusters of different compositions are in equilibrium in solution. In contrast, if the water-soluble single-source precursor {Ni(en)3}3[V15Sb6O42(H2O)]·ca. 15H2O is reacted with GeO2, {Ni(en)3}3[V15Sb3Ge3O42(OH)3(H2O)]·≈9H2O (3) forms, in which Sb and Ge occupy distinct positions that might have been formed via partial substitution reactions in the {V15Sb6} precursor.

Silencing of epithelial CXCL12 expression by DNA hypermethylation promotes colonic carcinoma metastasis.

Cellular metastasis is the most detrimental step in carcinoma disease progression, yet the mechanisms that regulate this process are poorly understood. CXCL12 and its receptor CXCR4 are co-expressed in several tissues and cell types throughout the body and play essential roles in development. Disruption of either gene causes embryonic lethality due to similar defects. Post-natally, CXCL12 signaling has a wide range of effects on CXCR4-expressing cells, including the directed migration of leukocytes, lymphocytes and hematopoietic stem cells. Recently, this signaling axis has also been described as an important regulator of directed carcinoma cell metastasis. We show herein that while CXCR4 expression remains consistent, constitutive colonic epithelial expression of CXCL12 is silenced by DNA hypermethylation in primary colorectal carcinomas as well as colorectal carcinoma-derived cell lines. Inhibition of DNA methyltransferase (Dnmt) enzymes with 5-aza-2'-deoxycytidine or genetic ablation of both Dnmt1 and Dnmt3b prevented promoter methylation and restored CXCL12 expression. Re-expression of functional, endogenous CXCL12 in colorectal carcinoma cells dramatically reduced metastatic tumor formation in mice, as well as foci formation in soft agar. Decreased metastasis was correlated with increased caspase activity in cells re-expressing CXCL12. These data constitute the unique observation that silencing CXCL12 within colonic carcinoma cells greatly enhances their metastatic potential.

Ketamine does not affect intestinal microcirculation in pentobarbital-anaesthetized rats during experimental endotoxaemia.

The objective of the study was to evaluate the effects of ketamine on intestinal microcirculation in pentobarbital-anaesthetized rats during experimental endotoxaemia. A prospective, randomized, controlled study was carried out using 32 male Lewis rats. The animals were divided into four groups (n = 8 each). All animals were initially anaesthetized with 60 mg/kg pentobarbital (i.p.). Group 1 served as a control (18.5 mg/kg/h pentobarbital i.v.). Groups 2 and 4 received an endotoxin intravenous infusion of 15 mg/kg lipopolysaccharide (LPS) from Escherichia coli. Groups 3 and 4 also received 10 mg/kg/h ketamine (i.v.). After 2 h of observation, the animals were examined for intestinal functional capillary density (FCD) and leukocyte adherence to the venular endothelium by means of intravital fluorescence microscopy (IVM). Subsequent to this examination, blood samples were collected to determine release of the cytokines tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and IL-10. Endotoxaemia tended to decrease intestinal FCD (mucosa: -10.1%, muscularis longitudinalis: -2%, muscularis circularis: -9.8%) and significantly increase leukocyte adherence within submucosal venules (collecting venules: +133%, postcapillary venules: +207%; P<0.05). TNF-alpha, IL-1beta, IL-6 and IL-10 levels were significantly elevated following endotoxin challenge. The addition of ketamine to pentobarbital anaesthesia did not significantly affect FCD, leukocyte behaviour or cytokine levels. In conclusion, intravenous pentobarbital anaesthesia with the additional administration of ketamine did not cause alterations within the microcirculation or changes in cytokine release during endotoxaemia. In rats, the combination of pentobarbital and ketamine is suitable for use during the study of intestinal microcirculation in experimental endotoxaemia.