Precision Determination of Pion-Nucleon Coupling Constants Using Effective Field Theory.

The pion-nucleon coupling constants determine the strength of the long-range nuclear forces and play a fundamental part in our understanding of nuclear physics. While the charged- and neutral-pion couplings to protons and neutrons are expected to be very similar, owing to the approximate isospin symmetry of the strong interaction, the different masses of the up and down quarks and electromagnetic effects may result in their slightly different values. Despite previous attempts to extract these coupling constants from different systems, our knowledge of their values is still deficient. In this Letter, we present a precision determination of these fundamental observables with fully controlled uncertainties from neutron-proton and proton-proton scattering data using chiral effective field theory. To achieve this goal, we use a novel methodology based on the Bayesian approach and perform, for the first time, a full-fledged partial-wave analysis of nucleon-nucleon scattering up to the pion production threshold in the framework of chiral effective field theory, including a complete treatment of isospin-breaking effects and our own determination of mutually consistent data. The resulting values of the pion-nucleon coupling constants are accurate at the percent level and show no significant charge dependence. These results mark an important step toward developing a precision theory of nuclear forces and structure.

Extraction of the Neutron Charge Radius from a Precision Calculation of the Deuteron Structure Radius.

We present a high-accuracy calculation of the deuteron structure radius in chiral effective field theory. Our analysis employs the state-of-the-art semilocal two-nucleon potentials and takes into account two-body contributions to the charge density operators up to fifth order in the chiral expansion. The strength of the fifth-order short-range two-body contribution to the charge density operator is adjusted to the experimental data on the deuteron charge form factor. A detailed error analysis is performed by propagating the statistical uncertainties of the low-energy constants entering the two-nucleon potentials and by estimating errors from the truncation of the chiral expansion as well as from uncertainties in the nucleon form factors. Using the predicted value for the deuteron structure radius together with the very accurate atomic data for the difference of the deuteron and proton charge radii we, for the first time, extract the charge radius of the neutron from light nuclei. The extracted value reads r_{n}^{2}=-0.106_{-0.005}^{+0.007} fm^{2} and its magnitude is about 1.7σ smaller than the current value given by the Particle Data Group. In addition, given the high accuracy of the calculated deuteron charge form factor and its careful and systematic error analysis, our results open the way for an accurate determination of the nucleon form factors from elastic electron-deuteron scattering data measured at the Mainz Microtron and other experimental facilities.

Correction to: In vitro prediction of stop-codon suppression by intravenous gentamicin in patients with cystic fibrosis: a pilot study.

The original article [1] contains errors in Table 1 affecting some of the presented oligonucleotide sequences and readthrough values in Table 1.

[Vaccine prevention in perinatal health care: parents, children and professionals]. / Vaccination en périnatalité : parents, enfants, professionnels.

Recent legislative texts have changed vaccinal policy and reinforced the role of midwives in vaccine prevention in perinatal healthcare. Quite as paediatricians and obstetricians-gynecologists, midwives can now prescribe and carry out, for the mothers, vaccines against rubella, tetanus, poliomyelitis, diphtheria, hepatitis B, influenza and whooping-cough and for the newborns vaccines against hepatitis B and tuberculosis. Concerning vaccinations, practitioners have to respect the vaccination calendar and a collaborative action is useful and necessary. These national guidelines are regularly updated when new vaccines and new recommendations come to light, for example for children (papillomavirus, tuberculosis, pneumococcus...), young adults (varicella, whooping-cough) and health professions in contact with very young children (varicella, measles, influenza and whooping-cough). The recent changes in tuberculosis prevention from routine vaccination of all newborn infants to selective vaccination lead to reinforce measures to detect the infants at higher risk, for them to be vaccinated before discharge at home. Midwives and nurses occupy a central place in family policy and become, with obstetricians-gynecologists and pediatricians, key actors for the effectiveness and the success of vaccine strategies in perinatal health.

[Immunogenicity and reactogenicity of DTPa-IPV-HBV/Hib and DTPa-IPV/Hib vaccines coadministered with 7-valent pneumococcal conjugate vaccine as primary vaccination and booster in healthy infants, according to the French vaccination calendar]. / Immunogénicité et réactogénicité des vaccins DTCa-P-HepB/Hib et DTCa-P/Hib coadministrés avec le vaccin pneumococcique osidique conjugué, adsorbé, chez des nourrissons en primovaccination et en rappel selon le calendrier vaccinal français.

OBJECTIVE: Assessment of immunogenicity and reactogenicity of DTPa-IPV/Hib (Infanrixquinta) and DTPa-IPV-HBV/Hib (Infanrixhexa) combined vaccines coadministered in healthy infants with 7-valent pneumococcal conjugate vaccine (Prevenar), according to the current French vaccine recommendations. METHOD: Multicenter, open label, non-controlled study performed in France. Each subject received 1 dose of DTPa-IPV-HBV/Hib combined vaccine at 2, 4 and 16-18 months of age, coadministered with conjugated pneumococcal vaccine and 1 dose of DTPa-IPV/Hib vaccine at 3 months of age coadministered with conjugated pneumococcal vaccine. RESULTS: Among the 102 enrolled infants, 64 were analysed (10.09 weeks+/-1.22 of age; boys: 58%) in the According-To-Protocol (ATP) immunogenicity cohort. One month after the administration of the booster dose of DTPa-IPV-HBV/Hib vaccine, 93.8% of subjects had protective titres for anti-HBs antibody superior or equal to 10 mIU/ml (primary objective). Seroprotection rate against Haemophilus influenzae type b component (anti-PRP antibody >or=0.15 microg/ml) was 98.4% and the immune response for the 7-valent pneumococcal serotypes (antipneumococcal antibody >or=0,05 microg/ml) was between 98.4 and 100%. Local reactogenicity increased with the number of doses administered, but was comparable between combined vaccines and conjugated pneumococcal vaccine. The incidence of fever increased between the primary vaccination and the booster. CONCLUSION: The immunogenicity and reactogenicity profile of DTPa-IPV-HBV/Hib and DTPa-IPV/Hib combined vaccines coadministered with conjugated pneumococcal vaccine according to the schedule recommended in the French vaccine calendar is acceptable and similar to previous reports.

[Distribution of neutralizing measles serum antibodies according to age in women of childbearing age in France in 2005-2006]. / Distribution en fonction de l'âge de la concentration sérique des anticorps neutralisants antirougeole chez les femmes en âge de procréer en France en 2005-2006.

UNLABELLED: Measles-vaccine coverage (MVC) increased significantly only beginning in 1983 based on the official recommendations. The majority of women born after 1983 should have vaccine-acquired rather than naturally derived immunity. Passively transferred measles antibodies (Mab) are expected to provide protection to offsprings during their 1st few months of life. OBJECTIVE: Compare neutralizing Mab titers according to age in women aged 12-40 years, i.e., born before and after 1983. METHODS: A multicenter seroepidemiological study was conducted in France in 2005-2006; 210 outpatient or hospitalized women were enrolled and classified into 4 age groups (12-18, 19-22, 23-30, and 31-40 years). Mab titers were assessed using a reference plaque reduction neutralization assay (protection threshold > 120 mIU/ml). RESULTS: Ninety-four percent of subjects had a Mabs titer greater than 120 mIU/ml. Women born before 1983 had significantly higher geometric mean titers (GMTs) of Mabs than those born after 1983(1358 mIU/ml vs. 731 mIU/ml [p<0.001]). The comparison of the 4 cohorts showed a significant decrease (p<0.001) in GMTs of Mab in the female population with increasing age (670, 771, 1173, and 1821 mUI/ml, respectively, in the 12-18, 19-22, 23-30, and 31-40 years age groups). For the 1st time in France, we show in women of childbearing age that in 2005-2006 neutralizing Mab GMTs were far above protective threshold for all age groups. Women in younger age groups (with high MVC) have significantly lower Mab titers. A lower passive transfer of Mab to their offsprings could result in a shorter period of measles protection and question the measles vaccine 1st dose at 1 year.

Immunohistochemical analysis of dystrophin-associated proteins in Becker/Duchenne muscular dystrophy with huge in-frame deletions in the NH2-terminal and rod domains of dystrophin.

The absence of dystrophin causes the drastic reduction of the dystrophin-associated proteins (DAPs) in the sarcolemma and the loss of the linkage between the subsarcolemmal cytoskeleton and the extracellular matrix in Duchenne muscular dystrophy (DMD) skeletal muscle. Here, we report a mild reduction of the DAPs in the unique Becker muscular dystrophy patients with huge deletions in the rod domain of dystrophin and a moderate reduction of the DAPs in patients with huge deletions that involve both the NH2-terminal and rod domains of dystrophin. The phenotype of the latter patients was more severe than that of the former. In both cases, however, the reduction in the DAPs was milder than in typical DMD patients or DMD patients lacking the COOH-terminal domains of dystrophin. Our results suggest that (a) the NH2-terminal and rod domains of dystrophin may not be essential for the interaction with the sarcolemmal glycoprotein complex; and (b) defects in the actin binding activity of dystrophin may cause disruption of the anchorage of the dystrophin-glycoprotein complex to the subsarcolemmal cytoskeleton, which may render muscle fibers susceptible to degeneration.

[Tonsillectomy in 2005]. / L'amygdalectomie en 2005.

During the past years, the number of tonsillectomies (only palatine tonsils are taken off) has decreased, indications for surgery have changed. A multi-disciplinal group of paediatricians tried to elaborate the state of the art in the field. Tonsils are the first line defense of high respiratory tract. The immune functions of their lymphoid tissue are multiple: mucosal antigens capture, presentation to lymphocytes, antigens specific proliferation of lymphocytes T and B, differentiation of lymphocytes in effectors lymphocytes and immune lymphocytes. Epithelial cells on the tonsils' surface express non-specific defense. These facts explain partly tonsils' hypertrophy. Tonsillectomy has no general immune consequences. In 2002, in France, 75,000 tonsillectomies were realized, of which 90% were in children. Tonsil's hypertrophy is the major indication, mandatory when sleep apnoeas exist. The main historical tonsillectomy indication for recurrent tonsillitis should decrease due to a more precise diagnostic (rapid test at bed site), an efficient antibiotics therapy and better care for pain. Other indications are scarce. Surgery, feasible from 9 months of age, requires a brief general anaesthesia and has very few contra-indications. The technique, operator dependent, relies on his experience. The only potentially severe complication is an haemorrhage due to scab fall between the eighth and twelfth days. It requires explanation and a written note given to parents. The possibility of lack of feeding and voice modification, usually transitory, should be known. Multiple consequences of tonsillectomy especially allergy have been alleged. Since the years 1980, it is well established that pre-existing allergy or asthma are not a contraindication. More, its deleterious impact on allergic children has not been demonstrated. Last, a gain of weight post-tonsillectomy is possible and could become a risk if excessive.

[A twelve-year-old teenager with bone pain and white papules]. / Douleurs osseuses et papules blanchâtres chez un adolescent de 12 ans.

Here we present a case report in which a teenager, with papules on the arm and back since the infancy, complained of back and right knee pain at the age of 12 years. The radiological examination led to the diagnosis of osteopoikilosis and melorheostosis. The Buschke-Ollendorff syndrome (BOS) associates osteopoikilosis (asymptomatic bone dysplasia) and disseminated dermatofibrosis. The BOS is rare, and its association with melorheostosis (another bone dysplasia in which pain and deformity may occur) makes the prognosis uncertain. This case report highlights the diagnosis problems related with bone pain in paediatrics. The purpose of this manuscript is to present the characteristics of two bone dysplasias: osteopoikilosis and melorheostosis, and to discuss the involvement of each one in the clinical picture of our patient.

Successful engraftment after autologous transplantation of 10-day cultured bone marrow activated by interleukin 2 in patients with acute lymphoblastic leukemia.

Disease recurrence remains the major problem in autologous bone marrow transplantation (BMT) for hematologic malignancies. To improve the therapeutic efficiency of autologous BMT, we investigated the use of autologous marrow activated in vitro with interleukin 2 (IL-2) to generate killer cells for in vivo purging. A feasibility trial was initiated in 5 patients with poor prognosis acute lymphoblastic leukemia, who were transplanted, after marrow ablative therapy, with autologous marrow cultured for 10 days with 10(3) units of IL-2/ml. A highly significant increase in NK activity and an induction of LAK activity were observed after incubation. Patients received 0.64 to 1.56 X 10(8) cultured BM cells/kg and 1.87 to 44.8 x 10(4) CFU-GM/kg. Four patients engrafted and achieved granulocyte counts > 0.5 x 10(9)/l on days 35, 24, 36 and 22 after transplant. Three of these patients showed platelet recovery to > 50 x10(9)/l on days 25, 42 and 40 after transplant. One patient remained thrombocytopenic until relapse. One patient died on day 12 after transplant. This study demonstrates that cultured BM activated with IL-2 can be used successfully for hematological rescue in the clinical setting.

Characterization of inflammatory reaction in upper airways of cystic fibrosis patients.

Inflammatory cell populations have not been yet precisely evaluated in cystic fibrosis (CF) airways. We intended to characterize morphological modifications, inflammatory cell infiltration and cell proliferation in nasal tissues obtained from 15 CF patients and from 6 non-CF patients with nasal polyposis. Morphological analysis showed an intense inflammatory infiltration in CF and non-CF tissues with only few modifications in the epithelium from CF tissues. Inflammatory cell populations characterized by specific immunolabeling were quantified, showing a predominance of macrophages and T- and B-lymphocytes and only moderate numbers of neutrophils in CF tissues; in non-CF polyps, lymphocytes and eosinophils were abundant. Proliferating cell percentages quantified after proliferating cell nuclear antigen immunolabeling were 5.3+/-4.1% (mean +/- SD) in CF polyps and 3.1+/-1.2% in non-CF polyps in epithelium but were very low in lamina propria. Intense inflammation in nasal tissues from CF patients is therefore dominated by macrophages and lymphocytes rather than by neutrophils. While morphology is preserved, proliferation is high in epithelium from CF polyps. These findings should be regarded in the future for a better understanding of inflammation in CF airway disease.

Clinical value of the determination of an interferon-induced enzyme activity: studies of the 2'5' oligoadenylate synthetase activity in peripheral blood lymphocytes of patients.

The 2'5' oligoadenylate synthetase (2'5' A synthetase) is one of the interferon-induced enzymes. The measurement of its activity may thus reveal the presence of interferon, which is one of the body's non-specific antiviral, antitumor, and immunoregulatory agents. We found a constant level of this enzyme activity (mean value: 0.31 units +/- 0.13 S. D.) when measured in the white blood cells of healthy subjects (104). The majority of the patients with viral (27/30), bacterial (13/16) and autoimmune (15/16) diseases showed a 2'5' A synthetase activity greater than 0.57 units (mean value of the control + S. D.). Conversely the 2'5' A synthetase activity level was normal or low in malignancies and in diseases depending on other aetiologies than those described above. Therefore this simple an rapid biochemical assay seems to be useful for clinical study of infectious and inflammatory diseases.

Multicenter prospective study of children with sickle cell disease: radiographic and psychometric correlation.

After obtaining familial informed consent, between January 1996 and July 1997, 173 children (5 to 15 years old) with sickle cell disease were enrolled in a prospective multicenter study using blood screening, transcranial Doppler ultrasonography (n = 143), cerebral magnetic resonance imaging (n = 144), and neuropsychologic performance evaluation (n = 156) (Wechsler Intelligence tests WISC-III, WIPPSI-R), which were also performed in 76 sibling controls (5 to 15 years old). Among the 173 patients with sickle cell disease (155 homozygous for hemoglobin SS, 8 sickle cell beta0 thalassemia, 3 sickle cell beta+ thalassemia, 7 sickle cell hemoglobin C disease SC), 12 (6.9%) had a history of overt stroke, and the incidence of abnormal transcranial Doppler ultrasonography (defined as mean middle cerebral artery velocity > 200 cm/sec or absent) was 8.4% in the overall study population and 9.6% in patients with homozygous sickle cell anemia The silent stroke rate was 15%. Significantly impaired cognitive functioning was observed in sickle cell disease patients with a history of stroke (Performance IQ and Full Scale IQ), but also in patients with silent strokes (Similarities, Vocabulary, and Verbal Comprehension). However, infarcts on magnetic resonance imaging were not the only factors of cognitive deficit: Verbal IQ, Performance IQ, and Full Scale IQ were strongly impaired in patients with severe chronic anemia (hematocrit < or = 20%) and in those with thrombocytosis (platelets > 500 x 10(9)/L). Multivariate logistic regression analysis showed that abnormal magnetic resonance imaging (odds ratio [OR] = 2.76) (P = .047), hematocrit < or =20% (OR = 5.85) (P = .005), and platelets > 500 x 10(9)/L (OR = 3.99) (P = .004) were independent factors of cognitive deficiency (Full Scale IQ < 75) in sickle cell disease patients. The unfavorable effect of low hematocrit has already been suggested, but this is the first report concerning an effect of thrombocytosis and showing that silent stroke alone is not a factor of cognitive deficit when not associated with low hematocrit or thrombocytosis. The effect of hydroxyurea, which is known to increase hematocrit and decrease platelet count, on cognitive functioning of sickle cell patients should be evaluated prospectively.

Incidence of primary ciliary dyskinesia in children with recurrent respiratory diseases.

The goal of the study was to evaluate the incidence of primary ciliary dyskinesia (PCD) in children suffering from recurrent respiratory tract infections (RRIs) by means of noninvasive method. Respiratory ciliated cells were collected by nasal brushing in 118 children (4.6 +/- 2.5 years) with RRIs. The ciliary beat frequency (CBF) was measured with a stroboscopic method, and when the CBF was abnormal, the ciliary ultrastructure was analyzed by a quantitative method. The CBF could be measured in 106 patients (90%) and was abnormal in 15 patients. The ciliary ultrastructure was found to be abnormal in 11 of 15 patients: PCD was diagnosed in 6 cases, and acquired ciliary defects were observed in the remaining 5 patients. Our conclusion, that PCD is rare but net exceptional (5.6%) in children with RRIs, justifies the systematic investigation of ciliated cells in such patients. For this purpose, nasal brushing can be used to sample ciliated cells even in young children.

Eczema herpeticum of the child. An unusual manifestation of herpes simplex virus infection.

Two children aged 7 months with eczema herpeticum received treatment consisting of intravenous acyclovir and human plasma with a high titer of herpes simplex virus antibodies. One recovered following two recurrences, but the other died rapidly, suffering both septicemia due to Pseudomonas aeruginosa and herpetic encephalitis. In both cases, the virus involved was a herpes simplex virus type 1 (HSV 1). The various isolates obtained before, during and after treatment remained equally sensitive to acyclovir. These observations highlight three points: the unpredictable and sometimes dramatic development of eczema herpeticum in the young child; the urgency of early diagnosis and treatment; the role of environment in viral contamination.

Epidemiology of pneumococcal infections in French children.

UNLABELLED: Since 1977, resistance to beta-lactams and other families of antibiotics among isolates of Streptococcus pneumoniae has increased alarmingly worldwide. France is particularly affected by this phenomenon; in 1997 the French National Reference Centre for Pneumococci reported that 44% of S. pneumoniae strains were penicillin non-susceptible (PNSS). Furthermore, resistance to macrolides (53%) and sulphonamides (37%) was comparable; in addition, >50% of PNSS had a high level of resistance to penicillin and were multiresistant. The highest frequency of resistance is observed in children, particularly those with acute otitis media (AOM). CONCLUSION: The clinical consequences of increasing antibiotic resistance are evident for meningitis and AOM, prompting clinicians to consider alternative agents such as high-dose cefotaxime (300 mg/ kg/d) or ceftriaxone (100mg/kg/d) plus vancomycin (60 mg/kg/d) for meningitis, and high-dose amoxicillin (> 80 mg/kg/d) or ceftriaxone (50 mg/kg/d) for AOM.

[Idiopathic nephrotic syndrome and the HLA allele. Prevalence of age-related DR7]. / Syndrome néphrotique idiopathique et allèle HLA. Prévalence de DR7 liée à l'âge.

High prevalence of HLA DR7 was well documented in idiopathic nephrotic syndrome (INS) of childhood. Our data in 43 INS, child and adult patients, did not show any significant difference from control group, specially for HLA DR7. Moreover a significant difference occurred when the data was compared in child and adult INS patients. HLA DR7 was more frequent when the nephrotic syndrome appeared before 15 years old. There was no correlation between the presence of HLA DR7 and those of allergy history or increased serum IgE level, on the opposite with previous data. The presence of DR7 would favor its onset at an earlier age. Alternatively, the difference in DR7 prevalence could be an additional argument for considering that the corticosensitivity and negative histological criteria might collect, under the same name, different glomerulopathies.

[Epidemiology of purpura fulminans and early therapeutic recommendations]. / Epidémiologie du purpura fulminans et recommandations thérapeutiques actuelles.

Despite major advances in pediatrics intensive care, meningococcemia remains an important cause of mortality en France (10 to 30%). Parenteral antibiotic given immediately is associated with a substantial reduction in mortality. So the Conseil supérieur d'hygiène publique de France recommend that general practitioners should administer promptly, preferably intravenously, whenever purpura fulminans is suspected, ceftriaxone (i.m., i.v.), cefotaxime (i.v.) or Amoxicillin (i.m., i.v.).

[TNF receptor-associated periodic syndrome (TRAPS): clinical aspects and physiopathology of a rare familial disease]. / Le TNF-receptor associated periodic syndrome (TRAPS): aspects cliniques et physiopathologiques d'une maladie familiale rare.

Hereditary periodic fever syndromes are defined as recurrent attacks of generalized inflammation for which no infectious or auto-immune cause can be identified. Minimal clinical variations, a unique biochemical-specific abnormality and the mode of genetic inheritance distinguish the four main diseases: familial Mediterranean fever, hyper-immunoglobulinemia D, TNF-receptor-associated periodic syndrome (TRAPS) and Muckle Wells syndrome. It presents with prolonged attacks of fever and severe localized inflammation. TRAPS is caused by dominantly inherited mutations in the gene encoding the first TNF receptor, which result in decreased serum levels of soluble TNF-receptor leading to inflammation due to unopposed TNF-alpha action. Corticosteroid treatment is not completely effective in most TRAPS patients. Preliminary experiences with recombinant TNF-receptor analogues in the treatment appear be promising.

[Bidirectional cell traffic between mother and fetus: new insights in pediatric and adult disorders]. / Trafic bidirectionnel de cellules entre mère et foetus: un éclairage nouveau dans les pathologies de l'adulte et de l'enfant.

There is a heavy traffic of cells and DNA through the placenta during pregnancy. The rate of fetal cells in the maternal blood is correlated with abnormalities, such as aneuploidy and pre-eclampsia. Studying and quantifying these cells could improve antenatal diagnosis techniques, especially for Down syndrome. Maternal-fetal microchimerism is frequently observed in several auto-immune diseases in adulthood, such as systemic scleroderma. Studies suggest a rather allo-immune pathophysiology, involving maternal-fetal HLA compatibility. Microchimerism is also found in auto-immune diseases in children. Thus, the cells traffic offers new insights for antenatal diagnosis techniques and pathophysiology of auto-immune diseases.