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.

[Vitamin D status in 6- to 10-year-old children: a French multicenter study in 326 children]. / Statut en vitamine D des enfants de 6 à 10ans : étude nationale multicentrique chez 326 enfants.

OBJECTIVE: To assess the vitamin D status of children aged 6-10years in the French general population for whom no guidelines have yet been defined due to insufficient data. METHOD: The study was conducted during two winters with very different sunshine levels: 5 March to 17 April 2012 and 8 January to 16 April 2013 in 20 then 22 centers. Three hundred children (60 children for each year of age) attending an ambulatory care unit or outpatient department for a reason unrelated to vitamin D status were included at the end of winter in 20 hospital centers (ten centers in the northern half of France above latitude 46-47°N/Lille: 50°N and ten centers in the southern half of France below latitude 46-47°N/Marseille: 43°N). Centralized 25 hydroxyvitamin D (25(OH)D), alkaline phosphatase (ALP), and parathormone (PTH) assays were performed on leftover blood samples. The currently accepted normal range for 25(OH)D was used to define the following categories: ≤25nmol/L: severe vitamin D deficiency, 25nmol/L100nmol/L: high vitamin D status. A standardized questionnaire was used to collect the child's characteristics, use of a vitamin D supplement, and milk and dairy product intake. The cumulative number of hours of sunshine over the 90days prior to inclusion in each center was obtained from the Météo-France weather bureau. RESULTS: 25(OH)D assays were performed in 326 children; more than 95% of children received milk and dairy products and 38% had received a vitamin D supplement since starting the school year: 3.1% of children in the overall population presented severe vitamin D deficiency, 34.4% presented vitamin D deficiency, 53.1% had a sufficient vitamin D status, and 9.5% had a 25(OH)D concentration >100nmol/L with no impact on serum calcium and urinary calcium. Children living in the north of France generally had lower 25(OH)D levels than children living in the south of France. In the non-supplemented population (n=188), 5.3% of children presented severe vitamin D deficiency, 45.2% presented vitamin D deficiency and 48.4% had sufficient 25(OH)D levels. The percentage of children with severe vitamin D deficiency or vitamin D deficiency was twofold higher during the winter with poor sunshine compared to the sunnier winter with a less marked north/south difference. No case of severe vitamin D deficiency was observed in the supplemented population (n=119); 10-15% of children presented vitamin D deficiency and 22.7% had a 25(OH)D concentration >100nmol/L, while remaining within the acceptable range. Two cases of hypervitaminosis without hypercalcemia were identified: one after an unknown loading dose with a calcium/creatinine ratio in the normal range (0.8); for the second one, no additional information could be obtained. Vitamin D supplementation considerably reduced the north/south difference and the Winter1/Winter2 difference. A child not receiving a vitamin D supplement had a ninefold higher risk of vitamin D deficiency at the end of winter than a child receiving a vitamin D supplement (OR=8.8; 95%CI, 4.6-16.8). CONCLUSION: At least one-third of children aged 6-10years presented deficient 25(OH)D levels. None of the children receiving a vitamin D supplement presented severe vitamin D deficiency, only a small number of children presented vitamin D deficiency (n=16 (13.4%)), and no signs of overload were observed, while one half of non-supplemented children (n=95 (50.5%)) presented at least vitamin D deficiency at the end of winter. These results support the need for vitamin D supplementation during winter in children aged 6-10years.

[Catch-up vaccination of worldwide newcoming (adopted, refugee or migrant) children in France]. / Mise à jour des vaccinations de l'enfant arrivant de l'étranger (adopté, réfugié ou migrant) en France.

In France, international adoption includes around to 90,000 children since 1980 and near 300,000 immigrant children were counted in 2008. This population is heterogeneous, according to age and country of origin, and its large number. It is not easy to completely and surely assess the vaccine status of the child. Due to a great variability of individual situations, it is not possible to have systematic and unchangeable rules. This article aims to give an update of catch-up vaccination of internationally adopted or refugee or migrant children in France. The vaccination status of a child who recently arrived in France is complex and has to be adapted to his country of origin. Some of them were never vaccinated whereas the vaccine status of others is uncertain or unknown. Three parameters have to be considered: the age of the child, the country of origin, and sometimes serology in the case of doubts of his vaccine status. Catch-up vaccination of foreign children has to be adapted to French vaccine recommendations, as a reference, and to vaccines already administered to the child.

[Prophylactic prescription of vitamin D in France: national multicenter epidemiological study of 3240 children under 6 years of age]. / Prescription prophylactique de la vitamine D en France : enquête épidémiologique multicentrique nationale chez 3240 enfants de moins de 6 ans.

AIMS: The aim of the study was to assess compliance with the current recommendations of prophylactic prescription of vitamin D via a multicentric cross-sectional epidemiological survey of 3240 children under 6 years of age. METHOD: Parent questionnaires and data from the health records of children presenting to the emergency departments of 25 teaching hospitals and hospital centers provided information on the children's characteristics, their prescriptions, and other vitamin D intake. Based on the currently applicable recommendations, intakes of 600-1,200 IU/day - 900-1500 IU/day for children with pigmented skin and/or premature and/or hypotrophic children - are considered adequate. RESULTS: In 1606 infants, 9.8% of the prescriptions were below and 23.7% were above the recommendations; in 1256 children between 18 months and 5 years of age, 53.4% of the prescriptions were below and 5.1% were above the recommendations. Children at risk, those from the southern half of France, and those between 18 months and 5 years of age were more likely to receive a prescription below the recommendations; their risk of receiving a prescription above the recommended guidelines was smaller. Of the children aged between 61 and 71 months, 85% had not received any prescription at all during the previous 12 months. These results were compared with the laboratory data collected from a subsample of children. There was a significant correlation between the adequacy of the prescription and the biological vitamin D status both for 25-hydroxyvitamin D (25-OH-D) serological concentrations and for calciuria. CONCLUSIONS: Only 66.6% of the prescriptions in children between 0 and 18 months of age and 41.5% in children between 19 months and 5 years of age comply with the recommendations; 53.4% of the prescriptions in the latter age group are below the current recommendations.

[Current events in vaccination]. / Actualités en matière de vaccination.

The annual meeting of the Infectious Disease Society of America (IDSA) ; which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010 ; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve - but for how long ? - the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55 %, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine calendars that cover a whole lifetime should be promoted, since the vaccination of adults and seniors is a determining factor of good health at all ages.

[Current events in vaccination]. / Actualités en matière de vaccination.

The annual meeting of the Infectious Disease Society of America (IDSA); which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve--but for how long?--the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55%, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine calendars that cover a whole lifetime should be promoted, since the vaccination of adults and seniors is a determining factor of good health at all ages.

[Serotype 19F pneumococcal meningitis in an imunocompetent infant immunized with heptavalent pneumococcal conjugated vaccine Prevenar]. / Méningite à pneumocoque de sérotype 19F chez un enfant immunocompétent ayant reçu 3 injections du vaccin pneumococcique conjugué heptavalent Prevenar((R)).

INTRODUCTION: Seven cases of pneumococcal meningitis caused by serotypes covered by the available vaccine occurred in France in vaccinated children, 4 of which were caused by serotype 19F. CASE REPORT: A 3-year-old child, who had received 3 doses of the 7-valent pneumococcal conjugate vaccine Prevenar but not the 4th injection, presented with bacterial meningitis after acute media otitis. The identified bacterium was a 19F serotype of Streptococcus pneumoniae. COMMENTS: This vaccine failure was characterized by an immune memory installation defect and underscores the necessity of the booster dose of vaccine during the 2nd year of life to acquire rates of protective and lasting antibodies. Serotype 19F of S. pneumoniae is particular since, despite good immunogenecity, it induces antibodies with weak avidity. We describe a case of pneumococcal meningitis caused by 19F serotype S. pneumoniae, which is included in the vaccine, in an immunocompetent child. Such events should be inventoried. They can reveal rates of antibodies that are very weak defenders, in spite of the vaccination, reflecting the absence of implementation of immunizing memory. Furthermore, an underlying immune deficit must be ruled out.

[Inaugural trunk dystonia revealing Langerhans cell histiocytosis]. / Manifestations pseudoneurologiques révélatrices d'une histiocytose langerhansienne.

Langerhans cell histiocytosis (LCH) is a multisystemic disease, which may present with neurological involvement. We report the case of a 20-month-old girl with initial liver and skin involvement. Initial symptoms were recurrent episodes of trunk dystonia, lasting approximately 2 months prior to the diagnosis of LCH. No brain MRI abnormality was demonstrated at initial work-up and over 7 years of follow-up, except for a postpituitary involvement noted after 3 years of follow-up. These episodes of dystonia subsided during the first week of specific LCH chemotherapy (vinblastine and steroid), suggesting that they may have resulted from hepatalgia related to the histiocytic infiltration of the liver.

[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.

[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.

[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.

Safety and immunogenicity of a combined DTPa-IPV vaccine administered as a booster from 4 years of age: a review.

A combined DTPa-IPV booster vaccine was administered as a 4th or 5th dose after DTPa or DTPw priming. Over 99% vaccines developed antibody levels considered to be protective to diphtheria, tetanus and poliovirus, and >95% mounted a response to acellular pertussis antigens. Rectal temperature >39.5 degrees C was observed in at most 3.2% of vaccinees. Swelling >50 mm occurred in 24% of DTPa-primed compared to 5.5% of DTPw-primed children. Large swelling involving the entire upper arm (extending to involve the elbow joint) was reported for up to 1.2% of DTPa-primed subjects, which is consistent with literature reports for other DTPa vaccines.