DFTB+, a software package for efficient approximate density functional theory based atomistic simulations.

DFTB+ is a versatile community developed open source software package offering fast and efficient methods for carrying out atomistic quantum mechanical simulations. By implementing various methods approximating density functional theory (DFT), such as the density functional based tight binding (DFTB) and the extended tight binding method, it enables simulations of large systems and long timescales with reasonable accuracy while being considerably faster for typical simulations than the respective ab initio methods. Based on the DFTB framework, it additionally offers approximated versions of various DFT extensions including hybrid functionals, time dependent formalism for treating excited systems, electron transport using non-equilibrium Green's functions, and many more. DFTB+ can be used as a user-friendly standalone application in addition to being embedded into other software packages as a library or acting as a calculation-server accessed by socket communication. We give an overview of the recently developed capabilities of the DFTB+ code, demonstrating with a few use case examples, discuss the strengths and weaknesses of the various features, and also discuss on-going developments and possible future perspectives.

Reactions to Gudair® vaccination identified in sheep used for biomedical research.

CASE REPORT: We report Gudair® vaccination (against ovine Johne's disease, Mycobacterium avium subsp. paratuberculosis) site reactions in sheep used as a surgical model in biomedical research and discuss the actual and potential impact these lesions may have on surgical procedures, particularly in otology. Nine female Merino-cross sheep (Ovis aries) were enrolled in a project designed to investigate the healing capabilities of the malleus bone in the middle ear. The sheep were 12-18 months of age. Eight sheep had lesions near the base of the right ear that were discovered when surgery was performed. The size of the lesions varied and all lesions had a thick capsule containing various amount of caseous material. Two lesions had a draining tract where purulent material was apparent at the lowest point. The prescapular lymph nodes were not palpable in any of the sheep. Aerobic growth of various organisms was reported from four sheep lesions when the purulent material was transferred to a broth media. Histopathological examination revealed intralesional Mycobacteria and focal caseous necrosis or granulomatous dermatitis and cellulitis in seven of the eight lesions. Mild necrotising to granulomatous dermatitis and cellulitis was described in the lesion where organisms were not found. CONCLUSIONS: The lesions were confirmed at the end of the study to be associated with the vaccination and did not cause any known adverse effects on the research. However, it is important to acknowledge the risk of contamination these lesions could have on a sterile surgical site.

Extended Lagrangian Excited State Molecular Dynamics.

An extended Lagrangian framework for excited state molecular dynamics (XL-ESMD) using time-dependent self-consistent field theory is proposed. The formulation is a generalization of the extended Lagrangian formulations for ground state Born-Oppenheimer molecular dynamics [Phys. Rev. Lett. 2008 100, 123004]. The theory is implemented, demonstrated, and evaluated using a time-dependent semiempirical model, though it should be generally applicable to ab initio theory. The simulations show enhanced energy stability and a significantly reduced computational cost associated with the iterative solutions of both the ground state and the electronically excited states. Relaxed convergence criteria can therefore be used both for the self-consistent ground state optimization and for the iterative subspace diagonalization of the random phase approximation matrix used to calculate the excited state transitions. The XL-ESMD approach is expected to enable numerically efficient excited state molecular dynamics for such methods as time-dependent Hartree-Fock (TD-HF), Configuration Interactions Singles (CIS), and time-dependent density functional theory (TD-DFT).

Numerical Optimization of Density Functional Tight Binding Models: Application to Molecules Containing Carbon, Hydrogen, Nitrogen, and Oxygen.

New parametrizations for semiempirical density functional tight binding (DFTB) theory have been developed by the numerical optimization of adjustable parameters to minimize errors in the atomization energy and interatomic forces with respect to ab initio calculated data. Initial guesses for the radial dependences of the Slater-Koster bond integrals and overlap integrals were obtained from minimum basis density functional theory calculations. The radial dependences of the pair potentials and the bond and overlap integrals were represented by simple analytic functions. The adjustable parameters in these functions were optimized by simulated annealing and steepest descent algorithms to minimize the value of an objective function that quantifies the error between the DFTB model and ab initio calculated data. The accuracy and transferability of the resulting DFTB models for the C, H, N, and O system were assessed by comparing the predicted atomization energies and equilibrium molecular geometries of small molecules that were not included in the training data from DFTB to ab initio data. The DFTB models provide accurate predictions of the properties of hydrocarbons and more complex molecules containing C, H, N, and O.

Extended Lagrangian formulation of charge-constrained tight-binding molecular dynamics.

The extended Lagrangian Born-Oppenheimer molecular dynamics formalism [Niklasson, Phys. Rev. Lett., 2008, 100, 123004] has been applied to a tight-binding model under the constraint of local charge neutrality to yield microcanonical trajectories with both precise, long-term energy conservation and a reduced number of self-consistent field optimizations at each time step. The extended Lagrangian molecular dynamics formalism restores time reversal symmetry in the propagation of the electronic degrees of freedom, and it enables the efficient and accurate self-consistent optimization of the chemical potential and atomwise potential energy shifts in the on-site elements of the tight-binding Hamiltonian that are required when enforcing local charge neutrality. These capabilities are illustrated with microcanonical molecular dynamics simulations of a small metallic cluster using an sd-valent tight-binding model for titanium. The effects of weak dissipation on the propagation of the auxiliary degrees of freedom for the chemical potential and on-site Hamiltonian matrix elements that is used to counteract the accumulation of numerical noise during trajectories was also investigated.

Efficient parallel linear scaling construction of the density matrix for Born-Oppenheimer molecular dynamics.

We present an algorithm for the calculation of the density matrix that for insulators scales linearly with system size and parallelizes efficiently on multicore, shared memory platforms with small and controllable numerical errors. The algorithm is based on an implementation of the second-order spectral projection (SP2) algorithm [ Niklasson, A. M. N. Phys. Rev. B 2002 , 66 , 155115 ] in sparse matrix algebra with the ELLPACK-R data format. We illustrate the performance of the algorithm within self-consistent tight binding theory by total energy calculations of gas phase poly(ethylene) molecules and periodic liquid water systems containing up to 15,000 atoms on up to 16 CPU cores. We consider algorithm-specific performance aspects, such as local vs nonlocal memory access and the degree of matrix sparsity. Comparisons to sparse matrix algebra implementations using off-the-shelf libraries on multicore CPUs, graphics processing units (GPUs), and the Intel many integrated core (MIC) architecture are also presented. The accuracy and stability of the algorithm are illustrated with long duration Born-Oppenheimer molecular dynamics simulations of 1000 water molecules and a 303 atom Trp cage protein solvated by 2682 water molecules.

Gender differences in symptoms in partial responders to proton pump inhibitors for gastro-oesophageal reflux disease.

BACKGROUND: Gender differences may exist in the symptom experience of patients with gastro-oesophageal reflux disease (GERD) who have a partial response to proton pump inhibitors (PPIs). OBJECTIVE: The purpose of this study was to analyse gender differences in partial responders to PPIs. METHODS: Patients with GERD who responded partially to PPIs (n = 580; NCT00703534) completed the Reflux Symptom Questionnaire 7-day recall (RESQ-7) and the Gastrointestinal Symptom Rating Scale (GSRS). Anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale. RESULTS: Women had significantly higher RESQ-7 domain scores than men for Heartburn (frequency: 4.3 vs 3.9; intensity: 3.1 vs 2.8), Burping (frequency: 4.9 vs 4.4; intensity: 3.1 vs 2.8) and Hoarseness, cough and difficulty swallowing (frequency: 2.6 vs 2.2; intensity: 1.8 vs 1.5), and had higher GSRS domain discomfort scores than men for Abdominal pain (3.51 vs 3.23), Indigestion (3.80 vs 3.45) and Constipation (2.69 vs 2.17) (all p < 0.05). Anxiety and depression were significantly more prevalent in women than in men. CONCLUSION: In this population of partial responders, women had more frequent/intense heartburn and extra-oesophageal symptoms and more discomfort from abdominal pain, indigestion and constipation than men. Comorbid anxiety and depression may contribute to the increased symptom burden in women.

Secular trends in weight, height and BMI in young Swedes: the 'Grow up Gothenburg' studies.

AIM: This study aims to document secular differences in anthropometry (level and variability of weight, height, BMI) in two cohorts born around 1990 and 1974 and examined as young adults. METHODS: Descriptive results are presented for the complete cohorts. The final analysis age-matched the cohorts (mean, 18.8 years) and employed CDC z-scores to compare means and distributions of weight, height and BMI. RESULTS: Z-scores for weight, height and BMI were higher in later-born (1990) boys, while in girls weight and height increased over this period without resulting in increased BMI. At the same time, in boys the BMI variances increased, confirming a simultaneous emergence of more overweight and more underweight. In girls, the BMI variance did not increase significantly. Sensitivity analyses, excluding subjects not born in Sweden, confirmed increasing BMI trends in boys. CONCLUSION: This study documents that gender differences in the recent childhood obesity epidemic can also be observed in young Swedes as they enter adulthood. Comparing two cohorts of high school students born around 1974 or 1990, less favourable trends in weight status were seen in boys than in girls. Finally, secular increases in height, already observed earlier in the 20th century, continued in these more contemporary cohorts.

Preschool children born moderately preterm have increased waist circumference at two years of age despite low body mass index.

AIM: To investigate the development of waist circumference (WC) in preschool children born preterm compared with a population-based reference. BACKGROUND: Children born preterm are reported to be insulin resistant, despite being lean during early childhood. We hypothesize that the mechanism is through increased visceral adiposity. METHODS: Data from 4446 preschool children (2169 girls/2277 boys) born in 2001-2006 from a population-based study were compared with longitudinal measurements of body mass index (BMI) and WC from a cohort of 152 children (64 girls/88 boys) born moderately preterm in 2002-2004 (gestational age, 32-37 weeks). RESULTS: In the preterm children, the mean WC was 2.8 cm larger compared with the reference group (p < 0.001) at 2 years of age but not at 5 years of age. There was no significant difference in the mean BMI at 2 years of age. The preterm group was significantly leaner at 5 years of age, with a mean BMI of 15.13 compared with 15.98 in the reference group (p < 0.001). CONCLUSION: Children born moderately preterm present as lean during early childhood but have an increased waist circumference in infancy, pointing towards a change in fat distribution with more abdominal fat. This may have implications for their metabolic status.

Early postnatal growth variables are related to morphologic and functional ophthalmologic outcome in children born preterm.

AIM: To evaluate the association between gestational age (GA), early and late postnatal growth variables and ophthalmologic outcome in ex-preterm children. methods: Children (GA < 32 weeks, n = 66), previously examined regarding insulin-like growth factor 1 (IGF-1) serum concentrations in relation to ROP, underwent ophthalmologic examination at median 5.6 years. Weight, height, and head circumference (HC) were measured and expressed as SDS. Growth variables were analysed in relation to ophthalmologic outcome. RESULTS: At follow-up 74% had some ophthalmologic abnormality and 17% had visual impairment. Poor visual acuity was correlated with low GA (r(s) = 0.29, p = 0.019), low weight at 32 weeks (r(s) = 0.30, p = 0.013), and low weight (r(s) = 0.37, p = 0.0025), height (r(s) = 0.41, p = 0.0007) and HC (r(s) = 0.55, p < 0.0001) at follow-up. Hyperopic children (25%) had low neonatal IGF-1 (p = 0.0096) and HC at follow-up (p = 0.022). Poor visual perception was correlated with low early weight (r(s) = 0.38, p = 0.0036) and HC at follow-up (r(s) = 0.39, p = 0.0024). Head circumference at follow-up was correlated with GA (r(s) = 0.40, p = 0.0012), neonatal IGF-1 (r(s) = 0.37, p = 0.0031), and early weight (r(s) = 0.27, p = 0.035). CONCLUSIONS: In very preterm children, early and later postnatal growth is closely related to visual acuity and perception at follow-up. In addition, IGF-1 concentrations and early growth are correlated with head circumference and refraction at follow-up.

New insights into the development of retinopathy of prematurity--importance of early weight gain.

UNLABELLED: Evidence is accumulating that one of the strongest predictors of retinopathy of prematurity (ROP), in addition to low gestational age, is poor weight gain during the first weeks of life. In infants born preterm, the retina is not fully vascularised. The more premature the child, the larger is the avascular area. In response to hypoxia, vascular endothelial growth factor (VEGF) is secreted. For appropriate VEGF-induced vessel growth, sufficient levels of insulin-like growth factor I (IGF-I) in serum are necessary. IGF-I is a peptide, related to nutrition supply, which is essential for both pre- and post-natal general growth as well as for growth of the retinal vasculature. In prematurely born infants, serum levels are closely related to gestational age and are lower in more prematurely born infants. At preterm birth the placental supply of nutrients is lost, growth factors are suddenly reduced and general as well as vascular growth slows down or ceases. In addition, the relative hyperoxia of the extra-uterine milieu, together with supplemental oxygen, causes a regression of already developed retinal vessels. Postnatal growth retardation is a major problem in very preterm infants. Both poor early weight gain and low serum levels of IGF-I during the first weeks/months of life have been found to be correlated with severity of ROP. CONCLUSION: This review will focus on the mechanisms leading to ROP by exploring factors responsible for poor early weight gain and abnormal vascularisation of the eye of the preterm infant.

Paternal sperm concentration and growth and cognitive development in children born with a gestational age more than 32 weeks after assisted reproductive therapy.

BACKGROUND: A possible impact of paternal sperm quality on the outcome in children born after assisted reproductive technologies, especially ICSI, has been discussed. The objective of this study was to assess whether sperm concentration has any influence on growth and cognitive development in children born with a gestational age more than 32 weeks after ICSI or IVF. METHODS: Singleton children born after ICSI (n = 492) or IVF (n = 265) from five European countries were examined at age 5 years. The ICSI group was divided into five subgroups according to paternal sperm origin and sperm concentration: (1) epididymal and testicular sperm group, (2) ejaculated sperm < 1 x 10(6)/ml, (3) ejaculated sperm 1-4.99 x 10(6)/ml, (4) ejaculated sperm 5-19.99 x 10(6)/ml and (5) ejaculated sperm > or = 20 x 10(6)/ml. The IVF group was divided into two subgroups: (1) < 20 x 10(6)/ml and (2) > or = 20 x 10(6)/ml. Growth parameters at birth and age 5 were evaluated. Cognitive development was assessed with the Wechsler Preschool and Primary Scale of Intelligence-Revised. RESULTS: No significant difference was found for gestational age, birth weight and birth weight standard deviation scores (SDS) between the ICSI and IVF sperm groups. No significant difference in height and weight at age 5 or SDS weight or height or BMIs at age 5 was found. There was no significant difference in total intelligence quotient (IQ)--performance or verbal IQ--between the groups. CONCLUSION: We found no indication that growth and cognitive development in ICSI and IVF children differed depending on paternal sperm concentration.

Sample preserving deep interface characterization technique.

We propose a nondestructive technique based on atomic core-level shifts to characterize the interface quality of thin film nanomaterials. Our method uses the inherent sensitivity of the atomic core-level binding energies to their local surroundings in order to probe the layer-resolved binary alloy composition profiles at deeply embedded interfaces. From an analysis based upon high energy x-ray photoemission spectroscopy and density functional theory of a Ni/Cu fcc (100) model system, we demonstrate that this technique is a sensitive tool to characterize the sharpness of a buried interface. We performed controlled interface tuning by gradually approaching the diffusion temperature of the multilayer, which lead to intermixing. We show that core-level spectroscopy directly reflects the changes in the electronic structure of the buried interfaces, which ultimately determines the functionality of the nanosized material.

Overuse of acid suppressive therapy in hospitalised patients with pulmonary diseases.

OBJECTIVES: Overuse of acid suppressive therapy (AST) has been reported in hospitalised patients, but the use in specific patient categories is unexplored. We assessed the use of and indication for AST and upper endoscopic investigations in hospitalised patients on a pulmonary ward compared with patients on other wards. METHODS: 301 patients were enrolled in the study. 162 were hospitalised on a pulmonary ward with a control group consisting of 139 from both a surgical and general internal medicine ward. Adequate indications for AST were those strongly supported by medical literature. RESULTS: Among the 301 patients enrolled, 132 (44%) used AST. 78 (59%) had no adequate indication for AST. On the pulmonary ward 79 (49%) patients used AST, compared to only 10 (20%) on the internal medicine ward (P < 0.05). On the pulmonary ward 68% of the patients had no adequate indication for AST, which was more common than inappropriate use of ASTon the control wards (P < 0.05). The most common inadequate indication for AST was peptic ulcer prophylaxis during corticoidsteroid therapy. CONCLUSION: In hospitalised patients a significant overuse of AST was observed, particularly among pulmonary patients. More adequate use of AST can contribute to substantial savings for the health-care system.

Knee-heel length measurements in preterm infants: evaluation of a simple electronically equipped instrument.

AIM: To compare and evaluate a mini-knemometer with a simple and inexpensive electronic caliper with regard to precision, handling error (technical error) and estimation of growth velocity. METHODS: Thirty-five prematurely born infants, with a median gestational age of 29 (range 24-33) wk and a median birthweight of 960 (range 480-2,480) g, were measured on 409 different occasions with both instruments. On each occasion, five independent readings were made. RESULTS: There was no significant difference in precision between the two instruments, when measuring growth velocity over a 4 wk period (median 0.41, range 0.10-0.59 mm d(-1)). The handling error in this study, calculated as the mean standard deviation, was 0.36 (SD 0.18, coefficient of variation 0.38%) mm for the simple electronic caliper and 0.59 mm for the mini-knemometer. Short-term growth was detectable within 2 d when growth velocity was normal. CONCLUSION: Longitudinal measurement of lower leg length is a gentle and useful complementary method for assessing growth in preterm infants. An inexpensive electronic caliper is well suited for routine use in clinical practice, with measurements taken once or twice a week.

Elastic guided waves in a layered plate with rectangular cross section.

Guided waves in a layered elastic plate of rectangular cross section (finite width and thickness) has been studied in this paper. A semianalytical finite element method in which the deformation of the cross section is modeled by two-dimensional finite elements and analytical representation of propagating waves along the length of the plate has been used. The method is applicable to arbitrary number of layers and general anisotropic material properties of each layer, and is similar to the stiffness method used earlier to study guided waves in a laminated composite plate of infinite width. Numerical results showing the effect of varying the width of the plate on the dispersion of guided waves are presented and are compared with those for an infinite plate. In addition, effect of thin anisotropic coating or interface layers on the guided waves is investigated.

Cerebral palsy in preterm infants: a population-based case-control study of antenatal and intrapartal risk factors.

UNLABELLED: Previous studies have indicated that foetomaternal infection increases the risk of spastic cerebral palsy (CP) in term infants, whereas this association appears to be less evident in preterm infants. The aim of this study was to analyse infection-related risk factors for spastic CP in preterm infants. A population-based series of preterm infants with spastic CP, 91 very preterm (<32 wk) and 57 moderately preterm (32-36 wk), born in 1983-90, were included and matched with a control group (n = 296). In total, 154 maternal, antenatal and intrapartal variables were retrieved from obstetric records. In the entire group, histological chorioamnionitis/pyelonephritis, long interval between rupture of membranes and birth, admission-delivery interval <4 h and Apgar scores of <7 at 1 min just significantly increased the risk of CP, and Apgar scores of <7 at 5 and 10 min were strongly associated with an increased risk. Abruptio placentae, Apgar scores <7 at 1 min and pathological non-stress test (reason for delivery) were significant risk factors of CP only in the moderately preterm and hemiplegic groups, whereas fever before delivery was a significant risk factor in the very preterm and spastic diplegic groups. Antibiotics during pregnancy was associated with CP only in the spastic diplegic CP group. CONCLUSION: Antenatal infections marginally increased the risk of CP. Low Apgar score and abruptio placentae were associated with CP, especially in moderately preterm infants with hemiplegic CP.

Swedish population-based longitudinal reference values from birth to 18 years of age for height, weight and head circumference.

UNLABELLED: This study aimed to update growth reference values for height, weight and head circumference in order to reflect the changes in body size in the Swedish population during the past two decades. The data came from a large longitudinal growth study on 3650 full-term healthy Swedish children who were born between 1973 and 1975. All of these 1801 girls and 1849 boys had longitudinal data for height and weight from birth to final height. Comparison with previous Swedish growth reference values based on children born between 1955 and 1958 revealed that there have been secular changes in body size. For instance, at 18 y of age, the updated height and weight reference values are 180.4 cm for males and 167.7 cm for females, i.e. 1.9 cm taller and 5.7 kg heavier for males and 2.3 cm taller and 3.4 kg heavier for females compared with the previous reference values. CONCLUSION: These new growth reference values provide current national standards for growth monitoring and evaluation since the year 2000.

Variation in size at birth in infants born small for gestational age in Lithuania.

UNLABELLED: The aim of this study was to describe the heterogeneity in body proportions of infants born small for gestational age (SGA), defined by birthweight, and to study the relationship of placental size with neonatal anthropometric measurements. Anthropometry was evaluated in 107 symmetrically and asymmetrically growth-retarded infants born SGA (birthweight <-2 SD) and compared with 181 appropriate-for-gestational age infants (AGA; birthweight and length +/- 2 SD). Study children were born at Kaunas University Hospital during the period from 1 January 1998 to 25 August 2000. Two-thirds of SGA children were light (SGA(W)) and one-third was both light and short (SGA(WL)) for gestational age. Infants in both SGA groups were significantly leaner than AGA children. SGA(WL) infants had significantly larger heads in relation to their length compared with SGA(W) and even AGA children, probably indicating a brain-sparing effect. SGA(WL) children had the lowest mean placental weight, but the highest placental weight to birthweight (PW/BW) ratio. The PW/BW ratio was inversely correlated with most infant measurements; the strongest negative relationship was observed with birthlength and lower leg length. CONCLUSION: There is heterogeneity in children born SGA, defined by birthweight. It is suggested that the two SGA groups represent the continuum of intrauterine growth retardation, with an initial reduction in trophic growth and a subsequent retardation of linear growth. The PW/BW ratio is a strong indicator for impaired prenatal linear growth.