Agriculture specialization influence on nutrient use efficiency and fluxes in the St. Lawrence Basin over the 20th century.

Increasing the overall use efficiency of nitrogen (N) and phosphorus (P) resources in food production while minimizing losses to the environment are required to meet the dual challenge of food security and sustainability. Yet studies quantifying the overall performance of different agro-system types and how these have changed over time remain rare, although they are essential to propose solution pathways. Here, we reconstructed fluxes of N and P within 78 watersheds of the St. Lawrence Basin (SLB) of eastern Canada between 1901 and 2011, using the Generalized Representation of Agro-Food System model (GRAFS). This analysis allowed us to classify different agro-food system types and to evaluate how agricultural specialization influenced nutrient efficiencies and potential losses to the environment over time. Using a cluster analysis, we identified four agro-food system types with different overall outcomes in efficiencies and losses. We show that agricultural practices in the SLB were similar until the 1950's and deemed unsustainable in several watersheds by depleting agricultural soils of their nutrients (particularly N). With the advent of manufactured fertilizers and the intensification of livestock farming, the SLB then rapidly shifted through the 1970s and 1980s to more intensified and highly unsustainable agro-food system types, where, in 2011, ~77 % of N and ~ 94 % of P inputs were lost to the environment. We also show that nutrient pollution continued to increase despite gains in the nutrient use efficiency of animal farming due to higher nutrient throughput from intensive production. The increased proportion of confined animals, disconnected from croplands, indeed resulted in inefficient nutrient recycling. While nutrient use efficiency may mitigate nutrient pollution, reducing the absolute nutrient flux through agro-food systems should be a priority, likely through a reconnection of crop and animal farming and an overall reduction of meat production, specifically from concentrated, intensive livestock systems.

[Normal childbirth: physiologic labor support and medical procedures. Guidelines of the French National Authority for Health (HAS) with the collaboration of the French College of Gynaecologists and Obstetricians (CNGOF) and the French College of Midwives (CNSF) -- Text of the Guidelines (short text)]. / Accouchement normal : accompagnement de la physiologie et interventions médicales. Recommandations de la Haute Autorité de Santé (HAS) avec la collaboration du Collège National des Gynécologues Obstétriciens Français (CNGOF) et du Collège National des Sages-Femmes de France (CNSF) ­ Texte des recommandations (texte court).

OBJECTIVE: The objective of these guidelines is to define for women at low obstetric risk modalities that respect the physiology of delivery and guarantee the quality and safety of maternal and newborn care. METHODS: These guidelines were made by a consensus of experts based on an analysis of the scientific literature and the French and international recommendations available on the subject. RESULTS: It is recommended to conduct a complete initial examination of the woman in labor at admission (consensus agreement). The labor will be monitored using a partogram that is a useful traceability tool (consensus agreement). A transvaginal examination may be offered every two to four hours during the first stage of labor and every hour during the second stage of labor or before if the patient requests it, or in case of a warning sign. It is recommended that if anesthesia is required, epidural or spinal anesthesia should be used to prevent bronchial inhalation (grade A). The consumption of clear fluids is permitted throughout labor in patients with a low risk of general anesthesia (grade B). It is recommended to carry out a "low dose" epidural analgesia that respects the experience of delivery (grade A). It is recommended to maintain the epidural analgesia through a woman's self-administration pump (grade A). It is recommended to give the woman the choice of continuous (by cardiotocography) or discontinuous (by cardiotocography or intermittent auscultation) monitoring if the conditions of maternity organization and the permanent availability of staff allow it and, after having informed the woman of the benefits and risks of each technique (consensus agreement). In the active phase of the first stage of labor, the dilation rate is considered abnormal if it is less than 1cm/4h between 5 and 7cm or less than 1cm/2h above 7cm (level of Evidence 2). It is then recommended to propose an amniotomy if the membranes are intact or an oxytocin administration if the membranes are already ruptured, and the uterine contractions considered insufficient (consensus agreement). It is recommended not to start expulsive efforts as soon as complete dilation is identified, but to let the presentation of the fetus drop (grade A). It is recommended to inform the gynecologist-obstetrician in case of nonprogression of the fetus after two hours of complete dilation with sufficient uterine dynamics (consensus agreement). It is recommended not to use abdominal expression (grade B). It is recommended to carry out preventive administration of oxytocin at 5 or 10 IU to prevent PPH after vaginal delivery (grade A). In the case of placental retention, it is recommended to perform a manual removal of the placenta (grade A). In the absence of bleeding, it should be performed 30minutes but not more than 60minutes after delivery (consensus agreement). It is recommended to assess at birth the breathing or screaming, and tone of the newborn to quickly determine if resuscitation is required (consensus agreement). If the parameters are satisfactory (breathing present, screaming frankly, and normal tonicity), it is recommended to propose to the mother that she immediately place the newborn skin-to-skin with her mother if she wishes, with a monitoring protocol (grade B). Delayed cord clamping is recommended beyond the first 30seconds in neonates, not requiring resuscitation (grade C). It is recommended that the first oral dose (2mg) of vitamin K (consensus agreement) be given systematically within two hours of birth. CONCLUSION: These guidelines allow women at low obstetric risk to benefit from a better quality of care and optimal safety conditions while respecting the physiology of delivery.

[Impact of sonography simulation in the training of midwifery students]. / Impact de l'intégration de la simulation en échographie obstétricale dans le cursus des étudiants sages-femmes.

OBJECTIVE: During their studies, French midwives need to acquire basic ultrasound skills to measure the amniotic fluid index, fetal biometry and identify fetal lie and placental positions. They have a clinical ultrasound training during their curriculum to acquire these skills. Assess the contribution that a training on an obstetrical ultrasound simulator (OUS) could make to the competence of midwives and to evaluate the best time to integrate it into their curriculum. METHODS: Forty students in their 4th and final year in midwifery were randomized into 2 groups. Group A learned with the traditional academic course, with a clinical ultrasound training which was followed by an evaluation on an OUS (E1A). Group B was evaluated on a simulator before the clinical ultrasound training (E1B). After these initial assessments, both groups were provided with learning and training sessions on OUS, and re-evaluated in the same exercise (E2A and E2B). Group B then completed its clinical ultrasound training and was evaluated one month later on the simulator (E3B). The evaluation consisted of scoring the biometry images according to previously published quality criteria, and of assessing their competence based on a published objective and structured assessment score of ultrasound skills (OSAUS). RESULTS: Evaluation 1 found comparable OSAUS scores (2.375/5 vs. 2.24/5 P=0.52) between the two groups (E1A vs. E1B) but a significantly higher image quality score for Group A (P=0.02). In Evaluation 2, an improvement was noted for both groups with comparable OSAUS averages between the two groups (P=0.76). After the clinical training of Group B, their OSAUS score (E3B) was significantly better than that of Group A (E1A) after their clinical training (3.45/5 vs. 2.375/5 [P=0.00017]). The same was true for the quality of their images (12.67/16 vs. 9.95/16 [P=0.003]). CONCLUSION: Ultrasound simulation-based training, as an adjunct to ultrasound clinical training, significantly improves obstetrical ultrasound skills. The best time to train on simulators seems to be prior to clinical training on real patients.

[Human Resources for Unplanned Activities in Obstetrics and Gynecology. Consensus statements by the CNGOF, CARO, CNSF, FFRSP, SFAR, SFMP and SFN]. / Ressources humaines pour les activités non programmées en gynécologie-obstétrique. Propositions élaborées par le CNGOF, le CARO, le CNSF, la FFRSP, la SFAR, la SFMP et la SFN.

OBJECTIVE: To determine a minimum threshold of human resources (midwives, obstetricians and gynecologists, anesthesiology and intensive care units, pediatricians) to ensure the safety and quality of unplanned activities in Obstetrics and Gynecology. MATERIALS AND METHODS: Consultation of the MedLine database, the Cochrane Library and the recommendations of authorities. Meetings of representative members in different modes of practice (university, hospital, liberal) under the aegis of and belonging to the French College of Obstetricians and Gynecologists (CNGOF), the French Society of Anesthesia and Resuscitation (SFAR), the French Society of Neonatalogy (SFN), the French Society of Perinatal Medicine (SFMP), the French College of Midwives (CNSF), the French Federation of Perinatal Care Networks (FFRSP) with elaboration of a re-read text by external experts, in particular by the members of the Boards of Directors of these authorities and of Club of Anesthesiology-Intensive Care Medicine in Obstetrics (CARO). RESULTS: Different minimum thresholds for each category of caregivers were proposed based on the number of births/year. These proposed minimum thresholds can be modulated upwards according to the types (level I, IIA, IIB or III) or the activity (existence of an emergency reception service, maternal-fetal and/or surgical activity of resort or referral). Due to peak activity and the possibility of unpredictable concomitance of urgent medical procedures, it is necessary that organizations plan to use resource persons. The occupancy rate of the target beds of a maternity ward must be 85%. CONCLUSION: These proposed minimum thresholds are intended to help caregivers providing non-scheduled perinatal as well as Obstetrics and Gynecology care to make the most of the human resources allocated to institutional bodies to ensure their safety and quality.

Reducing marine eutrophication may require a paradigmatic change.

Marine eutrophication in the North-East Atlantic (NEA) strongly relies on nutrient enrichment at the river outlets, which is linked to human activities and land use in the watersheds. The question is whether human society can reduce its nutrient emissions by changing land use without compromising food security. A new version of Riverstrahler model (pyNuts-Riverstrahler) was designed to estimate the point and diffuse nutrient emissions (N, P, Si) to the rivers depending on land use in the watersheds across a large domain (Western Europe agro-food systems, waste water treatment). The loads from the river model have been used as inputs to three marine ecological models (PCOMS, ECO-MARS3D, MIRO&CO) covering together a large part of the NEA from the Iberian shelf to the Southern North Sea. The modelling of the land-ocean continuum allowed quantifying the impact of changes in land use on marine eutrophication. Pristine conditions were tested to scale the current eutrophication with respect to a "natural background" (sensu WFD), i.e. forested watersheds without any anthropogenic impact. Three scenarios representing potential management options were also tested to propose future perspectives in mitigating eutrophication. This study shows that a significant decrease in nitrogen fluxes from land to sea is possible by adapting human activities in the watersheds, preventing part of the eutrophication symptoms in the NEA rivers and adjacent coastal zones. It is also shown that any significant achievement in that direction would very likely require paradigmatic changes at social, economic and agricultural levels. This requires reshaping the connections between crop production and livestock farming, and between agriculture and local human food consumption. It also involves cultural changes such as less waste production and a shift towards lower-impact and healthier diets where half of the animal products consumption is replaced by vegetal proteins consumption, known as a demitarian diet (http://www.nine-esf.org/node/281/index.html).

A long-term view of nutrient transfers through the Seine river continuum.

A model (the Riverstrahler model) is used to describe nutrient transfer and transformation at the scale of the whole drainage network of the Seine based on information concerning the basic mechanisms governing N, P and Si inputs to the drainage network and in-stream transformation and retention. It was used to calculate the budget of these nutrients through the whole river continuum from land to sea. With the help of historical documents, the constraints used as forcing function in this model were reconstructed to express the changing conditions of land-use and urban population over the last five hundred years. The corresponding scenarios were run for different hydrological regimes including dry, mean and wet conditions. The results were validated on the long-term series of nutrient measurements spanning more than a century available at some stations on the Seine, upstream and downstream of the city of Paris. The model was also used to explore past and future trends in nutrient loading, retention and delivery to the coastal zone, in response to human management of the terrestrial watershed. Beside the initial pristine state, used as an idealized reference state (with N, P and Si delivered fluxes of about 45-110 kg N km(-2) yr(-1), 2-5 kg P km(-2) yr(-1), 510-1325 kg Si km(-2) yr(-1)), four periods were distinguished. The first one is that of the traditional cottage economy which prevailed, with quite a constant total population, until the end of the 18th century. N, P and Si fluxes were about 235-750 kg N km(-2) yr(-1), 15-60 kg P km(-2) yr(-1) and 425-1280 kg Si km(-2) yr(-1), depending on hydrological conditions. The second period, from the beginning of the 19th century to about the 1950's, corresponded to rapid increase in the total and urban population with a corresponding increase of point sources of N and P. From 1950 onwards, modern farming practices resulted in a dramatic increase in diffuse sources of nitrogen and to a lesser extent phosphorus: riverine N and P export reached 1320-2800 kg N km(-2) yr(-1), and 310-340 kg P km(-2) yr(-1): silica export remained fairly constant at around 410-1260 kg Si km(-2) yr(-1) depending on the hydrological conditions. In the 1990's, the fourth period is represented by a stabilized population and improved wastewater treatment, when the export of phosphorus is reduced to values as low as 40-60 kg P km(-2) yr(-1), but without as effective a reduction of nitrogen export. This represents an unprecedented situation for the marine coastal system, i.e. a shift from nitrogen to phosphorus limitation, as nitrogen is still delivered far in excess of the amount of silica available for diatom blooms.

[Management of cutaneous leishmaniasis in adults and children]. / Traitement des leishmanioses cutanées de l'adulte et de l'enfant.

Cutaneous leishmaniasis can present a variety of clinical features and courses. The causative Leishmania species is an important prognostic factor in immunocompetent patients. Local treatment modalities including topical paromomycin, cryotherapy, localized controlled heat, carbon dioxide laser therapy, or intralesional meglumine antimoniate can be effective against Leishmania major or Leishmania tropica. Oral fluconazole may be a second-line treatment. Parenteral antimonials are useful for persistent or recurrent Old World leishmaniasis. For New World leishmaniasis, parenteral antimonials represent the first-line treatment in all forms except those caused by Leishmania guyanensis in which pentamidine is preferable. Liposomal amphotericin B appears to be effective for treatment of cutaneous leishmaniasis but further study will be needed. Results using oral Miltefosine are promising against Indian kala-azar (Leishmania donovani) but disappointing against South American leishmaniasis.

Tryptophan missense mutation in the ligand-binding domain of the vitamin D receptor causes severe resistance to 1,25-dihydroxyvitamin D.

In this study, two related young children, brother and sister, exhibited severe vitamin D-resistant rickets without alopecia. Sequence analysis of the total vitamin D receptor (VDR) cDNA from skin fibroblasts revealed a substitution of the unique tryptophan of the VDR by arginine at amino acid 286 (W286R). Cultured skin fibroblasts of the two patients expressed normal-size VDR protein (immunocytochemistry and Western blotting) and normal length VDR mRNA (Northern blotting). But, these fibroblasts, as well as COS-7 cells transfected with the W286R mutant, failed to bind 3H 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The tryptophan substitution did not affect VDR trafficking toward the nucleus but abolished the 24-hydroxylase gene response to 1,25(OH)2D3, even at 10(-6) M concentrations. In conclusion, this case report of a new family with hereditary vitamin D-resistant rickets (HVDRR) emphasizes the crucial role of the VDR tryptophan for ligand binding and for transactivation of 1,25(OH)2D3 target genes. It clearly shows the clinical significance of this VDR amino acid for calcium homeostasis and bone mineralization. This observation suggests further that the presence of a stable VDR-bound ligand may not be obligatory for normal hair follicle development.

Efficient cloning of cDNAs of retinoic acid-responsive genes in P19 embryonal carcinoma cells and characterization of a novel mouse gene, Stra1 (mouse LERK-2/Eplg2).

Pluripotent mouse P19 embryonal carcinoma (EC) cells have been extensively used as a developmental model system because they can differentiate in the presence of retinoic acid (RA) into derivatives of all three germ layers depending on RA dosage and culture conditions. The expression of several genes has been shown to be induced in RA-treated P19 EC cells and, interestingly, some of these genes may play important roles during mouse embryogenesis. In view of the increasing evidence that RA is a crucial signaling molecule during vertebrate development, we have initiated a study aimed at the systematic isolation of genes whose expression is induced in P19 cells at various times after exposure to RA. We describe here an efficient differential subtractive hybridization cloning strategy which was used to identify additional RA-responsive genes in P19 cells. Fifty different cDNA fragments corresponding to RA-induced genes were isolated. Ten cDNAs represent known genes, 4 of which have already been described as RA-inducible, while the remaining 40 correspond to novel genes. Many of these cDNA sequences represent low-abundance mRNAs. Kinetic analysis of mRNA accumulation following RA treatment allowed us to characterize four classes of RA-responsive genes. We also report the sequence and expression pattern in mouse embryos and adult tissues of one of these novel RA-inducible genes, Stra1, and show that it corresponds to the mouse ligand for the Cek5 receptor protein-tyrosine kinase.

The N-terminal part of TIF1, a putative mediator of the ligand-dependent activation function (AF-2) of nuclear receptors, is fused to B-raf in the oncogenic protein T18.

Nuclear receptors (NRs) bound to response elements mediate the effects of cognate ligands on gene expression. Their ligand-dependent activation function, AF-2, presumably acts on the basal transcription machinery through intermediary proteins/mediators. We have isolated a mouse nuclear protein, TIF1, which enhances RXR and RAR AF-2 in yeast and interacts in a ligand-dependent manner with several NRs in yeast and mammalian cells, as well as in vitro. Remarkably, these interactions require the amino acids constituting the AF-2 activating domain conserved in all active NRs. Moreover, the oestrogen receptor (ER) AF-2 antagonist hydroxytamoxifen cannot promote ER-TIF1 interaction. We propose that TIF1, which contains several conserved domains found in transcriptional regulatory proteins, is a mediator of ligand-dependent AF-2. Interestingly, the TIF1 N-terminal moiety is fused to B-raf in the mouse oncoprotein T18.

Characterization of cDNAs encoding the chick retinoic acid receptor gamma 2 and preferential distribution of retinoic acid receptor gamma transcripts during chick skin development.

Retinoic acid receptors alpha, beta and gamma (RAR alpha, beta and gamma) are ligand-inductible transcriptional activators which belong to the steroid/thyroid hormone receptor superfamily. At least two major isoforms (1 and 2) of each RAR arise by differential use of two promoters and alternative splicing. In mouse, the three RAR genes are expressed in stage- and tissue-specific patterns during embryonic development. In order to understand the role of the different RARs in chick, RAR gamma 2 cDNAs were isolated from an 8.5-day (stage 35 of Hamburger and Hamilton) chick embryo skin library. The deduced chick RAR gamma 2 amino acid sequence displays uncommon features such as 21 specific amino acid replacements, 12 of them being clustered in the amino-terminal region (domains A2 and B), and a truncated acidic carboxy-terminal region (F domain). However, the pattern of RAR gamma expression in chick embryo resembles that reported in mouse, particularly in skin where RAR gamma expression occurs in both the dermal and epidermal layers at the beginning of feather formation, and is subsequently restricted to the differentiating epidermal cells. Northern blot analysis suggests that different RAR gamma isoforms could be successively required during chick development.

[Endoscopic bronchial exploration under local anesthesia in children]. / L'endoscopie bronchique au tube souple sous anesthésie locale chez l'enfant.

One hundred and forty-two flexible fiberoptic bronchoscopies were carried out in 1 year, under local anaesthesia, in 123 children aged between 15 days and 17 years. Indications were tuberculosis (n = 26), persistent pneumonia (n = 20), suspected foreign body or control after extraction (n = 18), asthma (n = 17), atelectasis (n = 14), recurrent pneumonia (n = 13), opportunistic pneumonia (n = 11), permanent bronchial obstruction (n = 10), miscellaneous disease (n = 13). Fiberoptic bronchoscopy was abnormal in 101 patients (80%) and led to a change in the treatment in 84 cases (68%). True complications (n = 5) were all transient and were followed by complete recovery. Flexible fiberoptic bronchoscopy under local anaesthesia is a simple and safe procedure. It is an essential diagnostic and therapeutic tool in the management of pediatric respiratory disorders.

Development of an extended simulated annealing method: application to the modeling of complementary determining regions of immunoglobulins.

An extended simulated annealing process (ESAP) has been developed in order to obtain an ensemble of conformations of a peptide segment from a protein fluctuating at a given temperature. The annealing process was performed with a fast Monte Carlo method using the scaled collective variables developed by Noguti and Go. The system was divided into two parts: one consists of one or more peptide segments and is flexible around the main-chain and side-chain torsional angles; the other represents the rest of the molecule and was maintained fixed at the atomic positions determined by x-ray experiments. The target function included the nonbonding atomic interactions and a distance function to anchor the N and C terminal ends of each segment to the fixed part. Three systems of complementary determining regions (CDR) of antibodies were tested and compared to x-ray data: L2 loop (7 residues) of the light chain of lambda-type Bence-Jones protein, H1 and the H2 loops (14 residues) of McPC603, and H1 and H2 loops (12 residues) of HyHEL-5. Each state of CDR conformations was characterized at room temperature by the average of their coordinates (average conformation) and the internal energy. With a limited number of annealing processes (10), starting from the extended conformation, we have obtained states with conformations close to the observed x-ray structures, from 1.1 to 1.7 A root mean square deviation (rmsd) of main-chain atoms depending on the system. These states were identical or within 0.25 A rmsd of those of lowest internal energy. For unknown CDR structures the criteria of lowest internal energies from ESAP can be used to predict hypervariable loop structures in antibodies with an accuracy comparable to other methods.

[Endolymphatic curietherapy by lymphography with labelled lipiodol in Hodgkin's disease. A report on 408 cases (author's transl)]. / La curiethérapie endolymphatique par lymphographie au lipiodol marqué dans la maladie de Hodgkin. 408 observations.

The results of 373 lymphography examinations with radioactive lipiodol, conducted in 408 patients with Hodgkin's disease for diagnostic and prophylactic therapeutic purposes, during investigations carried out from 1966 to 1973 are analyzed. Tolerance was always excellent, especially from the hematological point of view. The efficacy of the procedure can be assessed by the fact that there were only 6% of failures (21/373) in glandular regions irradiated in this way for prophylactic purposes. Relapses occur more frequently in the inguino-iliac and lumbo-aortic regions than in the pelvic chains which were perfectly protected. This technique also enables both pelvic irradiation and ovarian protection in young women without any risk of failure. The procedure is particularly indicated in the following cases: supradiaphragmatic stages I and II, whatever the sex, and stage III especially in women. In sub-diaphragmatic stages I and II, it allows, in favourable cases, the ovarian function in women to remain intact by limiting external irradiation to invaded regions only.