Effective field theory for lattice nuclei.

We show how nuclear effective field theory (EFT) and ab initio nuclear-structure methods can turn input from lattice quantum chromodynamics (LQCD) into predictions for the properties of nuclei. We argue that pionless EFT is the appropriate theory to describe the light nuclei obtained in LQCD simulations carried out at pion masses heavier than the physical pion mass. We solve the EFT using the effective-interaction hyperspherical harmonics and auxiliary-field diffusion Monte Carlo methods. Fitting the three leading-order EFT parameters to the deuteron, dineutron, and triton LQCD energies at m_{π}≈800 MeV, we reproduce the corresponding alpha-particle binding and predict the binding energies of mass-5 and mass-6 ground states.

Puckering free energy of pyranoses: A NMR and metadynamics-umbrella sampling investigation.

We present the results of a combined metadynamics-umbrella sampling investigation of the puckered conformers of pyranoses described using the GROMOS 45a4 force field. The free energy landscape of Cremer-Pople puckering coordinates has been calculated for the whole series of α and ß aldohexoses, showing that the current force field parameters fail in reproducing proper puckering free energy differences between chair conformers. We suggest a modification to the GROMOS 45a4 parameter set which improves considerably the agreement of simulation results with theoretical and experimental estimates of puckering free energies. We also report on the experimental measurement of altrose conformer populations by means of NMR spectroscopy, which show good agreement with the predictions of current theoretical models.

Communications: Ab initio dynamics of rare thermally activated reactions.

We introduce a framework to investigate ab initio the dynamics of rare thermally activated reactions, which cannot be studied using the existing techniques. The electronic degrees of freedom are described at the quantum-mechanical level in the Born-Oppenheimer approximation, while the nuclear degrees of freedom are coupled to a thermal bath, through a classical Langevin equation. This method is based on the path integral representation for the stochastic dynamics and yields the time evolution of both nuclear and electronic degrees of freedom, along the most probable reaction pathways, without spending computational time to explore metastable states. As a first illustrative application, we characterize the dominant pathway in the cyclobutene-->butadiene reaction, using the semiempirical Parametrized Model 3 (PM3) approach.

[Bladder malformations in a model of myelomeningocele. Preliminary report]. / Influencia del tipo de cobertura prenatal sobre el desarrollo vesical en un modelo de mielomeningocele.

PURPOSE: To describe the presence of bladder malformations in a surgically induced model of myelomeningocele (MMC). METHODS: A MMC like defect was created in the mid gestation using the previously described model in sheep. Bladders were examined macroscopically and histopathological changes were assessed using H-E. RESULTS: Non prenatally corrected animals presented dilated bladders and separation between muscle bundles. Those malformations were not found in corrected animals or controls. CONCLUSIONS: Some bladder changes can be described in a surgically-induced model of MMC. These changes could be prevented using open fetal surgery.

[Prenatal techniques to prevent central nervous system malformations in the surgically induced model of myelomeningocele]. / El modelo de mielomeningocele en oveja presenta alteraciones cerebrales semejantes a las del humano y estas pueden ser prevenidas mediante cirugía fetal abierta.

AIM: To describe central nervous system malformations in the surgically induced model of Myelomeningocele (MMC) and their prevention using different prenatal treatments. METHODS: MMC was surgically created in 33 fetal lambs. Fifteen did not undergo fetal repair (group A). Of the lambs that did undergo repair, 10 were repaired with open two layer surgical closure (group B), 5 with fetoscopic coverage using bioglue (group C) and 3 fetoscopically using a patch (group D). All procedures were recorded and lamb brains and spinal cords were examined grossly and microscopically in coronal sections for structural organization anomalies. Histopathological changes were assessed using HE and S-100 neural marker. RESULTS: Hydrocephalus, Arnold-Chiari type II (AC-II) malformation and some neuronal migration disorders were observed in group A. Brains from group B and D were not hydrocephalic and had neither cell migration disorders nor hindbrain herniation. Group C presents mild degrees of hydrocephalus and AC-II. In group C lumbar lesion was covered by fibrous tissue. CONCLUSIONS: Some of the central nervous system abnormalities observed in human disease are present in the surgically induced model of MMC. In this model avoidance of fluid drainage using open fetal surgery limits malformation severity.

On the calculation of puckering free energy surfaces.

Cremer-Pople puckering coordinates appear to be the natural candidate variables to explore the conformational space of cyclic compounds and in literature different parametrizations have been used to this end. However, while every parametrization is equivalent in identifying conformations, it is not obvious that they can also act as proper collective variables for the exploration of the puckered conformations free energy surface. It is shown that only the polar parametrization is fit to produce an unbiased estimate of the free energy landscape. As an example, the case of a six-membered ring, glucuronic acid, is presented, showing the artifacts that are generated when a wrong parametrization is used.

Dominant reaction pathways in high-dimensional systems.

This paper is devoted to the development of a theoretical and computational framework denominated dominant reaction pathways (DRPs) to efficiently sample the statistically significant thermally activated reaction pathways, in multidimensional systems. The DRP approach is consistently derived from the Langevin equation through a systematic expansion in the thermal energy, k(B)T. Its main advantage with respect to existing simulation techniques is that it provides a natural and rigorous framework to perform the path sampling using constant displacement steps, rather than constant time steps. In our previous work, we have shown how to obtain the set of most probable reaction pathways, i.e., the lowest order in the k(B)T expansion. In this work, we show how to compute the corrections to the leading order due to stochastic fluctuations around the most probable trajectories. We also discuss how to obtain predictions for the evolution of arbitrary observables and how to generate conformations, which are representative of the transition state ensemble. We illustrate how our method works in practice by studying the diffusion of a point particle in a two-dimensional funneled external potential.

Bilateral adrenal neuroblastoma is different.

BACKGROUND/AIMS: Bilateral adrenal neuroblastoma is rare and can be due to multifocal primary or contralateral metastasis. Staging is confusing in these patients and treatment guidelines are difficult to set. The present study examines the clinical, biological and therapeutic features of bilateral adrenal neuroblastoma. METHODS: We identified 4 cases primarily located in both adrenals out of 148 neuroblastomas treated between 1992 and 2006. We studied the clinicopathological findings and biological features, including MYCN amplification, and analyzed the treatment strategies and results. RESULTS: All patients were younger than 6 months of age and all had multiple liver metastases. Three had subcutaneous nodules and massive liver enlargement. All underwent chemotherapy prior to operation. Two babies had large bilateral tumors without preservable glands and underwent bilateral adrenalectomy. Both had MYCN gene amplification and died of widespread (brain and bone) metastases some weeks later. In the remaining two patients adrenalectomy was performed on the side of the larger tumor with tumor enucleation on the other side to preserve hormonal function followed by 2 courses of mild chemotherapy in one patient. These tumors were not amplified. Both of these children are doing well. CONCLUSIONS: Bilateral adrenal neuroblastomas fit neither into stage 4 s nor into stage 4. Their clinical behavior is exceptional with a number of multicystic forms, variable MYCN amplification, widespread metastases and a high mortality. Bilateral adrenalectomy is sometimes unavoidable, but unilateral removal with contralateral enucleation, partial resection or observation are valid alternatives. Mortality is higher than in regular stage 4 s cases. This particular group of neuroblastomas required individually tailored therapeutic strategies based on the size, extent and prognostic markers.

[Congenital cystic adenomatoid malformation: prenatal diagnosis, surgical treatment results and long-term follow-up]. / Malformación adenomatoidea quística: diagnóstico prenatal, resultados de la cirugía y seguimiento a largo plazo.

PURPOSE: (PD), possibility of regresion and hidden mortality are open questions in congenital cystic adenomatoid malformation (CCAM) treatment. METHODS: Children with CCAM were reviewed focused on: PD, postnatal diagnosis, clinic, radiology, histology and evolution. RESULTS: Seventeen fetus had PD of CCAM. Five gestations were electively finished (41%) with PD of CCAM previous to 20th week, 3/5 (60%) were type III and 2/5 (40%) type I; 4/5 (80%) presented mediastinal shift and 1/5 (20%) hidrops. Two fetuses (11%) suffered fetal demise in 20th and 32th week; 1 type 1 and 1 type III; 1/2 (50%) presented hidrops and 2/2 (100%) mediastinal shift. Two (12%) died before 24 hours after birth without intervention possibility due to respiratory instability, 1 type II and 1 type III, both with mediastinal shift (100%). In one fetus with a type III malformation the image disappeared completely in 32th week and no intervention was done. Fourteen patients were operated (8 girls and 6 boys); 7/14 (50%) had PD, average diagnosis week was 21.9 (range 19.1-35.5), 5/7 (71%) was type I, 1/7 (14%) type II and 1/7 (14%) type III. None had mediastinal shift or hidrops. Average postnatal diagnosis week was 7 months (range 0.1-29). In 10/14 (71.4%) there were not respiratory difficulty during neonatal period and 3/10 (30%) suffered respiratory infections afterwards. Average week of operation was 8 months (range 0.1-30). PD was according with histology in 6/7 (86%) patients. After an average follow-up period of 4.3 years (range 1-9.5) the only complication is a pectus excavatum. CONCLUSIONS: More than half of patients with PD of CCAM died without intervention. Half of cases of CCAM are diagnosed prenatally. Type of CCAM in PD is according to histology in 86% of the cases. Fetuses with hidrops present a worse prognosis. Surgical timing do not seem to influence on outcome.

[The etiology of congenital diaphragmatic hernia and esophageal atresia: the Hox genes]. / Los genes Hox en la etiología de la hernia diafragmática congénita y la atresia de esófago.

BACKGROUND: Prenatal administration of adriamycin or nitrofen to pregnant mice produce in the embryos, respectively, esophageal atresia/VACTERL association (EA) or congenital diaphragmatic hernia (CDH). Various genes and signalling pathways like sonic hedgehog, Gli family, retinoic acid and homeotic genes have been pointed out in the origin of these malformations. Hox genes are master regulatory genes involved in embryo segmentation and other main development processes. Hoxa3, Hoxb3, Hoxc3, Hoxc4 and Hoxa5 knock-out mice show cardiac, tracheal, lung and diaphragmatic malformations, EA and phenotypes that resemble that of VACTERL syndrome. We present herein some of our findings in the expression of these genes in both experimental models. MATERIAL AND METHODS: Pregnant mice were exposed either to 4 mg/kg of adriamycin or vehicle on embryonic days 7,5 and 8,5; embryos were recovered at four endpoints (E13 to 16). On the other hand, nitrofen was given to pregnant mice on embryonic day 8th and embryos were recovered at E14, E16 and E19. The embryos or, separately, their lungs and hearts, were randomly processed for immunohistochemical or molecular biology studies (RT-PCR). We used antibodies for Hoxa3, Hoxb3 and Hoxd3 proteins and specific primers for Hoxa3, Hoxa5, Hoxb3, Hoxb5, Hoxc4 and Hoxd3 genes. RESULTS: EA: Upon immunohistochemistry, adriamycin-exposed embryos showed a severe decrease in expression of Hoxa3, Hoxb3 and Hoxb3 proteins in heart, skin, foregut but not in the heart. RT-PCR studies showed a statistically significant decrease of the four genes studied in the lungs of OA mice when compared to controls. CDH: Upon RT-PCR assessment the expression of Hoxa5 and Hoxb3 were higher in nitrofen-exposed mice than in controls on E14 and E19 and weaker on E16. As regards immunohistochemical localization, expression of the three genes was similar in nitrofen and control animals. CONCLUSIONS: Both experimental models exhibit an alteration in the expression of several proximal Hox genes, specially in lung and car- diac tissues. The malformations in these organs associated with CDH and EA could be in part caused by these alterations. Due to their specific participation in lung and foregut morphogenesis, their study could let us to better understand the mechanisms of CDH and EA.

Exact monte carlo method for continuum fermion systems

We offer a new proposal for the Monte Carlo treatment of many-fermion systems in continuous space. It is based upon diffusion Monte Carlo with significant modifications: correlated pairs of random walkers that carry opposite signs, different functions "guide" walkers of different signs, the Gaussians used for members of a pair are correlated, and walkers can cancel so as to conserve their expected future contributions. We report results for free-fermion systems and a fermion fluid with 14 3He atoms, where it proves stable and correct. Its computational complexity grows with particle number, but slowly enough to make interesting physics within the reach of contemporary computers.

Equation of state of solid 3He

We present results of diffusion Monte Carlo calculations for the bcc and hcp phases of solid 3He, using a recent ab initio interatomic potential, including two- and three-body terms. This potential is found to yield an equation of state for condensed 4He in excellent agreement with experiment, in a wide density range. For 3He, we find a systematic discrepancy, worth 0.7 K, between our computed equation of state and a commonly accepted experimental one. We attribute such a discrepancy to an improper choice of reference energy in the determination of the experimental equation of state.

Amniotic fluid stem cells rescue both in vitro and in vivo growth, innervation, and motility in nitrofen-exposed hypoplastic rat lungs through paracrine effects.

Lung hypoplasia can be prevented in vitro by retinoic acid (RA). Recent evidence suggests that amniotic fluid stem (AFS) cells may integrate injured lungs and influence their recovery. We tested the hypothesis that AFS cells might improve lung growth and motility by paracrine mechanisms. Pregnant rats received either nitrofen or vehicle on E9.5. In vitro E13 embryonic lungs were cultured in the presence of culture medium alone or with RA, basophils, or AFS cells. In vivo green fluorescent protein-expressing (GFP(+)) rat AFS cells were transplanted in nitrofen-exposed rats on E10.5. E13 lung explants were cultured before analysis. The surface, the number of terminal buds, and the frequency of bronchial contractions were assessed. Protein gene product 9.5 (PGP 9.5) and α-actin protein levels were measured. The lung explants transplanted with AFS cells were stained for α-actin, PGP 9.5, and TTF-1. The levels of FGF-10, VEGFα, and TGF-ß1 secreted by the AFS cells in the culture medium were measured. Comparison between groups was made by ANOVA. In vitro, the surface, the number of terminal buds, and the bronchial peristalsis were increased in nitrofen+AFS cell explants in comparison with nitrofen-exposed lungs. While nitrofen+RA lungs were similar to nitrofen+AFS ones, basophils did not normalize these measurements. PGP 9.5 protein was decreased in nitrofen lungs, but after adding AFS cells, the value was similar to controls. No differences were found in the expression of α-actin. In vivo, the surface, number of terminal buds, and peristalsis were similar to control after injection of AFS cells in nitrofen-exposed rats. Colocalization with TTF-1-positive cells was found. The levels of FGF-10 and VEGFα were increased in nitrofen+AFS cell explants, while the levels of TGF-ß1 were similar to controls. Lung growth, bronchial motility, and innervation were decreased in nitrofen explants and rescued by AFS cells both in vitro and in vivo, similarly to that observed before with RA. The AFS cell beneficial effect was probably related to paracrine action of growth factor secretion.

Transumbilical laparo-assisted appendectomy: a safe operation for the whole spectrum of appendicitis in children-a single-centre experience.

The paper reports the results of a retrospective review of the medical charts of 203 patients admitted to a pediatric surgical unit with a diagnosis of acute appendicitis between January 2006 and December 2010 when a transumbilical laparoscopic-assisted appendectomy (TULAA) was introduced as a new surgical technique. Among 203 admitted patients, 7 (3.5%) had a localized appendiceal abscess and were treated with antibiotics. All of them responded to antibiotics and underwent TULAA interval appendectomy 8 weeks later. 196 patients (96.5%) underwent immediate surgery. In 12/181 (6.6%) urgent cases, conversion to laparotomy was necessary, in 3 patients because of bowel distension and in 9 for retrocecal position of appendix. In all 181 TULAA completed procedures, one trocar was used in 151 cases (89.4%), two trocars in 16 (9.4%), and three trocars in 2 (1.2%). The mean operative time for single port TULAA was 52' Complications included 5 wound infections and 5 intra-abdominal abscesses, all managed conservatively. In conclusion, TULAA is a safe, minimally invasive approach with acute appendicitis, regardless of the perforation status, and can be recommended in the pediatric urgical settings.

Microscopically computing free-energy profiles and transition path time of rare macromolecular transitions.

We introduce a rigorous method to microscopically compute the observables which characterize the thermodynamics and kinetics of rare macromolecular transitions for which it is possible to identify a priori a slow reaction coordinate. In order to sample the ensemble of statistically significant reaction pathways, we define a biased molecular dynamics (MD) in which barrier-crossing transitions are accelerated without introducing any unphysical external force. In contrast to other biased MD methods, in the present approach the systematic errors which are generated in order to accelerate the transition can be analytically calculated and therefore can be corrected for. This allows for a computationally efficient reconstruction of the free-energy profile as a function of the reaction coordinate and for the calculation of the corresponding diffusion coefficient. The transition path time can then be readily evaluated within the dominant reaction pathways approach. We illustrate and test this method by characterizing a thermally activated transition on a two-dimensional energy surface and the folding of a small protein fragment within a coarse-grained model.

Parafollicular C-cells of the thyroid are decreased in patients with congenital diaphragmatic hernia.

BACKGROUND: Parathyroid and thymic anomalies related to embryonic neural crest dysfunction have been demonstrated in rats with congenital diaphragmatic hernia (CDH). These rats, like infants with CDH, have conotruncal, facial, and other neurocristal defects. The present study examines whether parafollicular C-cells (CC) of the thyroid, whose embryogenesis is related to that of the parathyroids and thymus, might also be abnormal in babies with CDH. MATERIAL AND METHODS: Autopsy sections of the thyroids of 12 babies dead from CDH and of 11 controls were stained with anti-calcitonin antibodies. Calcitonin-stained areas and the histological distribution of CC within the thyroid gland were assessed. Mann-Whitney tests were used for comparison, with p<0.05 considered significant. RESULTS: The proportion of stained surface to total thyroid surface was significantly smaller in CDH babies than in controls (0.035±0.030% vs. 0.072±0.052%, p<0.05). A normal central CC location was demonstrated in both groups. CONCLUSIONS: Parafollicular thyroid C-cells are deficient in patients with CDH. These findings further support the involvement of neural crest dysregulation in the pathogenesis of CDH and the pertinence of using this experimental model to investigate the human condition. The clinical effects of this anomaly are unknown and probably irrelevant, but they are currently under scrutiny.