A Pleistocene ice core record of atmospheric O2 concentrations.

The history of atmospheric O2 partial pressures (Po2) is inextricably linked to the coevolution of life and Earth's biogeochemical cycles. Reconstructions of past Po2 rely on models and proxies but often markedly disagree. We present a record of Po2 reconstructed using O2/N2 ratios from ancient air trapped in ice. This record indicates that Po2 declined by 7 per mil (0.7%) over the past 800,000 years, requiring that O2 sinks were ~2% larger than sources. This decline is consistent with changes in burial and weathering fluxes of organic carbon and pyrite driven by either Neogene cooling or increasing Pleistocene erosion rates. The 800,000-year record of steady average carbon dioxide partial pressures (Pco2) but declining Po2 provides distinctive evidence that a silicate weathering feedback stabilizes Pco2 on million-year time scales.

Epoch-based Entropy for Early Screening of Alzheimer's Disease.

In this paper, we introduce a novel entropy measure, termed epoch-based entropy. This measure quantifies disorder of EEG signals both at the time level and spatial level, using local density estimation by a Hidden Markov Model on inter-channel stationary epochs. The investigation is led on a multi-centric EEG database recorded from patients at an early stage of Alzheimer's disease (AD) and age-matched healthy subjects. We investigate the classification performances of this method, its robustness to noise, and its sensitivity to sampling frequency and to variations of hyperparameters. The measure is compared to two alternative complexity measures, Shannon's entropy and correlation dimension. The classification accuracies for the discrimination of AD patients from healthy subjects were estimated using a linear classifier designed on a development dataset, and subsequently tested on an independent test set. Epoch-based entropy reached a classification accuracy of 83% on the test dataset (specificity = 83.3%, sensitivity = 82.3%), outperforming the two other complexity measures. Furthermore, it was shown to be more stable to hyperparameter variations, and less sensitive to noise and sampling frequency disturbances than the other two complexity measures.

Abrupt change of Antarctic moisture origin at the end of Termination II.

The deuterium excess of polar ice cores documents past changes in evaporation conditions and moisture origin. New data obtained from the European Project for Ice Coring in Antarctica Dome C East Antarctic ice core provide new insights on the sequence of events involved in Termination II, the transition between the penultimate glacial and interglacial periods. This termination is marked by a north-south seesaw behavior, with first a slow methane concentration rise associated with a strong Antarctic temperature warming and a slow deuterium excess rise. This first step is followed by an abrupt north Atlantic warming, an abrupt resumption of the East Asian summer monsoon, a sharp methane rise, and a CO(2) overshoot, which coincide within dating uncertainties with the end of Antarctic optimum. Here, we show that this second phase is marked by a very sharp Dome C centennial deuterium excess rise, revealing abrupt reorganization of atmospheric circulation in the southern Indian Ocean sector.

Identification of the binding site of the {sigma}54 hetero-oligomeric FleQ/FleT activator in the flagellar promoters of Rhodobacter sphaeroides.

Expression of the flagellar genes in Rhodobacter sphaeroides is dependent on one of the four sigma-54 factors present in this bacterium and on the enhancer binding proteins (EBPs) FleQ and FleT. These proteins, in contrast to other well-characterized EBPs, carry out activation as a hetero-oligomeric complex. To further characterize the molecular properties of this complex we mapped the binding sites or upstream activation sequences (UASs) of six different flagellar promoters. In most cases the UASs were identified at approximately 100 bp upstream from the promoter. However, the activity of the divergent promoters flhAp-flgAp, which are separated by only 53 bp, is mainly dependent on a UAS located approximately 200 bp downstream from each promoter. Interestingly, a significant amount of activation mediated by the upstream or contralateral UAS was also detected, suggesting that the architecture of this region is important for the correct regulation of these promoters. Sequence analysis of the regions carrying the potential FleQ/FleT binding sites revealed a conserved motif. In vivo footprinting experiments with the motAp promoter allowed us to identify a protected region that overlaps with this motif. These results allow us to propose a consensus sequence that represents the binding site of the FleQ/FleT activating complex.

A machine-learning approach to the prediction of oxidative stress in chronic inflammatory disease.

Oxidative stress is implicated in the development of a wide range of chronic human diseases, ranging from cardiovascular to neurodegenerative and inflammatory disorders. As oxidative stress results from a complex cascade of biochemical reactions, its quantitative prediction remains incomplete. Here, we describe a machine-learning approach to the prediction of levels of oxidative stress in human subjects. From a database of biochemical analyses of oxidative stress biomarkers in blood, plasma and urine, non-linear models have been designed, with a statistical methodology that includes variable selection, model training and model selection. Our data demonstrate that, despite a large inter- and intra-individual variability, levels of biomarkers of oxidative damage in biological fluids can be predicted quantitatively from measured concentrations of a limited number of exogenous and endogenous antioxidants.

Orbital and millennial Antarctic climate variability over the past 800,000 years.

A high-resolution deuterium profile is now available along the entire European Project for Ice Coring in Antarctica Dome C ice core, extending this climate record back to marine isotope stage 20.2, approximately 800,000 years ago. Experiments performed with an atmospheric general circulation model including water isotopes support its temperature interpretation. We assessed the general correspondence between Dansgaard-Oeschger events and their smoothed Antarctic counterparts for this Dome C record, which reveals the presence of such features with similar amplitudes during previous glacial periods. We suggest that the interplay between obliquity and precession accounts for the variable intensity of interglacial periods in ice core records.

Predicting activities without computing descriptors: graph machines for QSAR.

We describe graph machines, an alternative approach to traditional machine-learning-based QSAR, which circumvents the problem of designing, computing and selecting molecular descriptors. In that approach, which is similar in spirit to recursive networks, molecules are considered as structured data, represented as graphs. For each example of the data set, a mathematical function (graph machine) is built, whose structure reflects the structure of the molecule under consideration; it is the combination of identical parameterised functions, called "node functions" (e.g. a feedforward neural network). The parameters of the node functions, shared both within and across the graph machines, are adjusted during training with the "shared weights" technique. Model selection is then performed by traditional cross-validation. Therefore, the designer's main task consists in finding the optimal complexity for the node function. The efficiency of this new approach has been demonstrated in many QSAR or QSPR tasks, as well as in modelling the activities of complex chemicals (e.g. the toxicity of a family of phenols or the anti-HIV activities of HEPT derivatives). It generally outperforms traditional techniques without requiring the selection and computation of descriptors.

Clinical performance with the Levitronix Centrimag short-term ventricular assist device.

BACKGROUND: The Levitronix ventricular assist device (VAD) is a centrifugal pump designed for extracorporeal support and that operates without mechanical bearings or seals. The rotor is magnetically levitated so that rotation is achieved without friction or wear, which seems to minimize blood trauma and mechanical failure. The aim of this study is to report our early results with the Levitronix Centrimag device. METHODS: Between June 2003 and April 2005, 18 patients (pts) were supported using the Levitronix at our institution. Fourteen were male. Mean age was 40.3 +/- 18.3 (range 8 to 64) years. Indications for support at implantation were: post-cardiotomy cardiogenic shock in 12 cases (Group A), and bridge to decision regarding long-term ventricular support in 6 cases (Group B). RESULTS: Mean support time was 14.2 +/- 15.2 days for all patients (range 1 to 64 days). Operative (30-day) mortality was 50% (9 pts). Six pts were in Group A and 3 pts were in Group B. Overall, 6 pts (33%) were discharged home and are presently alive and well (mean follow-up 13 months, range 5 to 17 months). Bleeding requiring re-operation occurred in 8 cases (44%), cerebral thromboembolism in 1 and pulmonary embolism in 1. There were no device failures. CONCLUSIONS: The Levitronix functioned well and proved to be useful in patients with extremely poor prognosis previously considered non-suitable for a long-term assist device. The device was technically easy to implant and manage. There was no device dysfunction and complications were acceptable or consistent with other devices. Survival to explant or a definitive procedure (VAD or transplantation) was encouraging.

[Pleuro-pulmonary paragonimiasis]. / La paragonimose pleuropulmonaire.

Paragonimiasis is a food borne zoonosis due to a trematode belonging to the genus Paragonimus. Although present throughout the world, about 90% of the cases occur in Asia where around 20 million people are infected. The parasitic cycle is complex with two different intermediate hosts. Man is infected by ingesting the raw or undercooked flesh of the second host - a freshwater crab or prawn - or possibly of a paratenic mammal host (wild boar), which contains the infective larval stage metacercariae that reaches the lung which is the main target organ. Epidemiological, pathological, and clinical aspects are reviewed. The main symptoms are protracted cough, and recurrent "benign" hemoptysis. Abnormal pleuro-pulmonary imaging features are constant, but protean and non-specific, leading to frequent confusion with tuberculosis. Diagnosis is easily achieved by ova search in the sputum or pleural fluid, or by serology. Evolution is usually considered benign, although not well known. Finally, praziquantel is the effective first choice treatment. Some paradoxical aspects of this disease are underlined such as: underdiagnosis despite a very simple diagnostic procedure, or opposite tendencies according to location, either extinction or re-emergence.

Probable allergic reaction to cyclosporin and early formation of thrombi on a pulmonary artery catheter: two unusual complications during bilateral lung transplantation.

We describe a patient who had two rare complications (a probable allergic reaction to cyclosporin and the early formation of a right atrial thrombus) during bilateral sequential single lung transplantation performed under the one anaesthetic. The thrombus, discovered at the end of the procedure, was then removed under cardiopulmonary bypass. Peroperative transoesophageal echocardiography was useful in providing critical diagnostic and therapeutic information.

How to be a gray box: dynamic semi-physical modeling.

A general methodology for gray-box, or semi-physical, modeling is presented. This technique is intended to combine the best of two worlds: knowledge-based modeling, whereby mathematical equations are derived in order to describe a process, based on a physical (or chemical, biological, etc.) analysis, and black-box modeling, whereby a parameterized model is designed, whose parameters are estimated solely from measurements made on the process. The gray-box modeling technique is very valuable whenever a knowledge-based model exists, but is not fully satisfactory and cannot be improved by further analysis (or can only be improved at a very large computational cost). We describe the design methodology of a gray-box model, and illustrate it on a didactic example. We emphasize the importance of the choice of the discretization scheme used for transforming the differential equations of the knowledge-based model into a set of discrete-time recurrent equations. Finally, an application to a real, complex industrial process is presented.

Repair of anterior leaflet prolapse by papillary muscle repositioning: a new surgical option.

BACKGROUND: Although mitral valve repair is considered the gold standard for treating mitral regurgitation, anterior leaflet prolapse may still remain a challenging problem. This challenge is even greater for posterior commissural prolapse. We have used papillary muscle repositioning to treat anterior leaflet prolapse and suggest it as an alternative technique for all other methods previously described. METHODS: From 1989 to 1999 we performed 253 mitral valve repairs, among which 132 involved anterior leaflet prolapse. In this population there were two groups: group I (n = 92) treated with papillary muscle repositioning and group II (n = 40) treated with chordal shortening. There was no statistical difference between the two groups concerning age, functional class, and left ventricular function. Etiology was similar in both groups, a degenerative process being predominant. At echocardiography, regurgitation was graded 3.4/4 in both groups. There was no statistical difference concerning preoperative ejection fraction, end-systolic and end-diastolic left ventricular diameter. RESULTS: There were one in-hospital death in group I and two deaths in group II not related to mitral valve repair. Mean follow up is 36.4 +/- 29.2 months in group I and 70.5 +/- 9.5 months in group II. No patient was lost to follow-up. Mean regurgitation at follow-up was 0.75 +/- 0.67 in group I and 0.8 +/- 0.8 in group II (p = not significant). There was no statistical difference between the two groups concerning postoperative ejection fraction, end-systolic and end-diastolic left ventricular diameter. There was no late cardiac death in either group and there were no thromboembolic events. Actuarial survival rate is 98.9% and 96.3% in group I and 92.5% and 88.1% in group II at 3 and 8 years, respectively. CONCLUSIONS: Therefore, we conclude that papillary muscle repositioning is a safe technique that provides excellent results at mid-term follow-up and facilitates treatment of anterior leaflet prolapse.

The N terminus of FliM is essential to promote flagellar rotation in Rhodobacter sphaeroides.

FliM is part of the flagellar switch complex. Interaction of this protein with phospho-CheY (CheY-P) through its N terminus constitutes the main information relay point between the chemotactic system and the flagellum. In this work, we evaluated the role of the N terminus of FliM in the swimming behavior of Rhodobacter sphaeroides. Strains expressing the FliM protein with substitutions in residues previously reported in Escherichia coli as being important for interaction with CheY showed an increased stop frequency compared with wild-type cells. In accordance, we observed that R. sphaeroides cells expressing FliM lacking either the first 13 or 20 amino acids from the N terminus showed a stopped phenotype. We show evidence that FliMDelta13 and FliMDelta20 are stable proteins and that cells expressing them allow flagellin export at levels indistinguishable from those detected for the wild-type strain. These results suggest that the N-terminal region of FliM is required to promote swimming in this bacterium. The role of CheY in controlling flagellar rotation in this organism is discussed.

The hook gene (flgE) is expressed from the flgBCDEF operon in Rhodobacter sphaeroides: study of an flgE mutant.

In this work we identified the flgE gene encoding the flagellar hook protein from Rhodobacter sphaeroides. Our results show that this gene is part of a flagellar cluster that includes the genes flgB, flgC, flgD, flgE, and flgF. Two different types of mutants in the flgE gene were isolated, and both showed a Fla(-) phenotype, indicating the functionality of this sequence. Complementation studies of these mutant strains suggest that flgE is included in a single transcriptional unit that starts in flgB and ends in flgF. In agreement with this possibility, a specific transcript of approximately 3.5 kb was identified by Northern blot. This mRNA is large enough to represent the complete flgBCDEF operon. FlgE showed a relatively high proline content; in particular, a region of 12 amino acids near the N terminus, in which four prolines were identified. Cells expressing a mutant FlgE protein lacking this region showed abnormal swimming behavior, and their hooks were curved. These results suggest that this region is involved in the characteristic quaternary structure of the hook of R. sphaeroides and also imply that a straight hook, or perhaps the rigidity associated with this feature, is important for an efficient swimming behavior in this bacterium.

[Surgery of heart insufficiency]. / Chirurgie de l'insuffisance cardiaque.

Apart from heart transplantation for heart failure, the problem arises of which surgical approach should be adopted to treat this disorder. Ischemic heart disease can be surgically managed in three ways: via bypass, the Dor procedure, or by isolated or associated mitral plasty; however, cases of enlarged heart disease can only be surgically treated in two ways: i.e., by mitral plasty, or by the Batista procedure. In cases of ischemic heart disease, the following conditions must be present for coronary bypass: the patients should have an adequate contractile myocardial reserve, that is to say the left ventricle should not be greatly enlarged (< 80 mm in telediastole) or a cardiac output reserve, and there should not be any sign of over-high pulmonary hypertension (an index of > 1.6 or a pulmonary pressure of < 45); an assessment of myocardial viability should then be carried out, mainly based on a thallium fixation at rest and on echographically determined doubtamine-associated stress. In the present study, the mortality rate in a series of 260 patients was 6.3% for subjects aged under 70 years old, with an actuarial survival rate of 82% at one year post-surgery, and of 70% at five years. The Dor procedure can be used in the treatment of dyskinesia, which is now practically non-existent, but also in cases of acute akinesia with resulting left ventricular dysfunction. The aim of this technique is to alter the form of a cavity that has become ovoid to an elliptical form via the insertion of a circular endoventricular patch. The results reported for this technique show an improvement in functional class and ejection fraction. Finally, the technique for repairing mitral failure is more complicated than the two previous methods, as it requires a dynamic assessment of mitral failure, which is best carried out by an evaluation of echographically determined stress. Any mitral failure of ischemic origin of > grade 2 can be corrected during bypass surgery by ring insertion, thereby effecting a simple annuloplasty. On the other hand, the assessment of cases of enlarged heart disease is more complicated, and it is more difficult to carry out palliative surgery. The mitral plasty procedure proposed by Bolling is the technique of choice for patients with severe mitral failure, in general when the ventricle is not too enlarged. However, surgery involving the reduction in size of the left ventricle (the Batista procedure) always includes mitral plasty, and may be performed in patients with a very enlarged ventricle (> 70 mm), in general with moderate mitral failure. These two techniques have been critically assessed both as regards results and when they should be adopted, and their limitations have also been discussed. In conclusion, there are valid surgical alternatives to heart transplantation in cases of heart failure that does not respond to medical treatment, and they should probably be seriously considered before any decision is made to perform heart transplantation. These results appear encouraging, particularly in terms of functional class and left ventricular function, but there are conflicting results for hemodynamic improvement. As regards survival, it is not yet possible to propose prospective randomized trials to compare medical treatment with these surgical techniques. However, further development of these techniques is bound to occur, and an ever-widening gap will exist between the limited number of cases requiring transplantation and the more complex surgical approaches adopted in future, such as permanent circulatory backup or xenografts.

Surgery of acute type A dissection: what have we learned during the past 25 years?

Every acute dissection involving the ascending aorta (Stanford type A) must undergo emergency surgical repair. However, the surgical techniques must vary according to the clinical presentation of the patients or the anatomical patterns observed. Furthermore, surgery is generally difficult because of the poor condition of the aortic tissues. To reduce those difficulties many technical artifacts have been described. In 1977, we proposed the use of gelatin-resorcin-formalin (GRF) biological glue to reinforce the suture areas. From January 1977 to July 1999, 212 patients (pts) (152 males and 60 females) aged from 15 to 80 years (mean age: 54 +/- 11 years) underwent an emergency operation for type A aortic dissection. One-hundred-seventy-eight pts (84%) were operated on within 4 hours after being referred to the hospital. Twenty-eight pts (13.2%) had Marfan's syndrome. In 44 patients (20.7%), the aortic valve was replaced either independently (6 cases--2.8%) or by means of a composite graft (38 cases--17.9%). Because of the location of the intimal tear, the aortic replacement was extended to the transverse arch in 61 pts (28.7%). Hospital mortality amounts to 21.6% (46 pts), 25% in pts with arch replacement and 19.4% in pts without arch replacement (n.s). Analysis of hospital mortality demonstrates that the main causes of death were cardiac tamponade, neurologic disorders and visceral malperfusion. One-hundred-sixty-six pts were discharged and surveyed from 5 months to 22 years postoperatively (mean follow-up: 85 +/- 66 months). During this period of time, 25 pts (15%) had to be reoperated for a total of 33 reoperations. Seven pts (28%) died at reoperation. Using univariate analysis, the presence of Marfan's syndrome (p < 0.05) and absence of arch replacement (p < 0.02) were determinant risk factors for reoperation. Emergency (p < 0.01) and thoraco-abdominal replacement (p < 0.04) were determinant riskfactors for death at reoperation. The freedom from reoperation (Kaplan-Meier, CI: 95%) is 96% (90-98), 87% (79-92), 80% (70-88), 66% (51-78) at 1, 5, 10 and 15 years respectively. A total of 39 pts (24.3%) died during follow-up. The presence of Marfan's syndrome (p < 0.01), reoperation (p < 0.02), stroke (p < 0.05), and cardiac failure (p < 0.05) were determinant risk factors of late mortality. The late survival rate (K-M. C.I.: 95%), including hospital mortality, is 71% (64-77), 66% (58-73), 56% (47-64), 46% (36-56), 37% (28-44) at 1, 10, 15 and 20 years, respectively. From our experience extending over more than 23 years, GRF glue has proved to be extremely useful, making the procedure much easier and safer. Nevertheless, many factors are of importance in the pre-, intra- and postoperative management of the patients. Cardiac tamponade and visceral malperfusion must be properly diagnosed and treated. During aortic repair, the main intimal tear must be resected. The transverse arch must be checked and replaced whenever necessary. The aortic valve should be preserved whenever possible. During CPB, perfusing the aorta in the regular antegrade manner seems to dramatically reduce the rate of malperfusion. The quality of the first emergency operation seems to have a major influence on the late results, especially concerning the rate of late reoperations and aortic ruptures. However, those late results depend also on the patient's basic condition, particularly in Marfan patients.