A Consistent BGK Model with Velocity-Dependent Collision Frequency for Gas Mixtures.

We derive a multi-species BGK model with velocity-dependent collision frequency for a non-reactive, multi-component gas mixture. The model is derived by minimizing a weighted entropy under the constraint that the number of particles of each species, total momentum, and total energy are conserved. We prove that this minimization problem admits a unique solution for very general collision frequencies. Moreover, we prove that the model satisfies an H-Theorem and characterize the form of equilibrium.

Staphylococcus aureus enterotoxin sensitization is associated with allergic poly-sensitization and allergic multimorbidity in adolescents.

BACKGROUND: Staphylococcus aureus (S. aureus) carriage and sensitization to S. aureus enterotoxins (SEs) have been associated with allergic diseases. From the Tromsø Study Fit Futures 2, we have previously shown an association between S. aureus carriage and severe allergic disease and allergic multimorbidity. However, the role of S. aureus carriage and SE sensitization on allergic multimorbidity and allergic sensitization is unclear. OBJECTIVE: To study associations of both nasal S. aureus carriage and SE sensitization to allergic disease and allergic sensitization. METHODS: A cross-sectional study of a school-based cohort in late adolescence (aged 18-19 years: The Tromsø Study Fit Futures 2). Self-reported allergic diseases were assessed using the Mechanisms of the Development of ALLergy questionnaire (MeDALL). Participants were tested for nasal S. aureus carriage, serum total IgE and specific IgE to SEs, and food and inhalant allergens. RESULTS: A total of 868 participants were studied. Sensitization to at least one food or inhalant allergen was found in 319 of 765 (41.7%), and to at least one SE in 173 of 656 (26.2%) participants. SE sensitization, but not S. aureus carriage, was associated with poly-sensitization to food and inhalant allergens. SE-sensitized participants had higher median specific IgE to inhalant allergens (41.4 kUA /L, IQR 10.1-118.4) compared to non-SE-sensitized participants (18.0 kUA /L, IQR 5.5-48.6, P=.004), but not to food allergens. SE sensitization was associated with allergic multimorbidity. CONCLUSION: Sensitization to SEs may play a role in the development of allergen poly-sensitization and allergic multimorbidity.

Colonisation and interaction between S. epidermidis and S. aureus in the nose and throat of healthy adolescents.

Nasal colonisation with Staphylococcus aureus is a risk factor for developing nosocomial infections. It has been reported that S. epidermidis may produce a serine protease (Esp) inhibiting S. aureus biofilm formation and nasal colonisation. We aimed to analyse the correlation between S. aureus nasal and/or throat carriage and co-colonisation with S. epidermidis strains carrying esp, and the inhibitory effects of S. epidermidis culture supernatants on S. aureus biofilm formation and growth. We obtained 114 S. epidermidis isolates from the nose and 74 S. aureus from the nose and/or throat of healthy adolescents. S. aureus biofilm formation was analysed in a microtitre plate assay and the prevalence of ica, encoding biofilm formation, and esp was analysed with polymerase chain reaction (PCR). Inhibitory effects of S. epidermidis culture supernatants on S. aureus biofilm formation and growth was analysed in vitro. esp prevalence and expression was correlated with inhibitory effects. We detected biofilm formation in 45/74 (61%) S. aureus strains. The ica operon was more prevalent in isolates colonising the nose (12/15; 80%) versus isolates colonising the throat only (8/46; 17%). Almost two-thirds of S. epidermidis culture supernatants displayed high (≥ 50%) S. aureus biofilm inhibitory activity, without affecting growth. We found no correlation between the level of inhibitory activity and S. aureus colonisation. esp was ubiquitous in S. epidermidis, but esp expression did not correlate with biofilm inhibitory activity. S. epidermidis culture supernatants inhibit S. aureus biofilm formation, but do not affect bacterial growth. esp expression was not correlated with the inhibitory effects observed.

The potential influence of morphology on the evolutionary divergence of an acoustic signal.

The evolution of acoustic behaviour and that of the morphological traits mediating its production are often coupled. Lack of variation in the underlying morphology of signalling traits has the potential to constrain signal evolution. This relationship is particularly likely in field crickets, where males produce acoustic advertisement signals to attract females by stridulating with specialized structures on their forewings. In this study, we characterize the size and geometric shape of the forewings of males from six allopatric populations of the black field cricket (Teleogryllus commodus) known to have divergent advertisement calls. We sample from each of these populations using both wild-caught and common-garden-reared cohorts, allowing us to test for multivariate relationships between wing morphology and call structure. We show that the allometry of shape has diverged across populations. However, there was a surprisingly small amount of covariation between wing shape and call structure within populations. Given the importance of male size for sexual selection in crickets, the divergence we observe among populations has the potential to influence the evolution of advertisement calls in this species.

Developmental plasticity, morphological variation and evolvability: a multilevel analysis of morphometric integration in the shape of compound leaves.

The structure of compound leaves provides flexibility for morphological change by variation in the shapes, sizes and arrangement of leaflets. Here, we conduct a multilevel analysis of shape variation in compound leaves to explore the developmental plasticity and evolutionary potential that are the basis of diversification in leaf shape. We use the methods of geometric morphometrics to study the shapes of individual leaflets and whole leaves in 20 taxa of Potentilla (sensu lato). A newly developed test based on the bootstrap approach suggests that uncertainty in the molecular phylogeny precludes firm conclusions whether there is a phylogenetic signal in the data on leaf shape. For variation among taxa, variation within taxa, as well as fluctuating asymmetry, there is evidence of strong morphological integration. The patterns of variation are similar across all three levels, suggesting that integration within taxa may act as a constraint on evolutionary change.

A practical guide to neonatal volume guarantee ventilation.

A recent systematic review and meta-analysis shows that volume-targeted ventilation (VTV) compared with pressure-limited ventilation (PLV) reduce death and bronchopulmonary dysplasia, pneumothorax, hypocarbia and severe cranial ultrasound abnormalities. In this paper, we present published research and our experience with volume guarantee (VG) ventilation, a VTV mode available on the Dräger Babylog 8000plus and VN500 ventilators. The VG algorithm measures the expired tidal volume (V(T)) for each inflation and adjusts the peak inflating pressure for the next inflation to deliver a V(T) set by the clinician. The advantage of controlling expired V(T) is that this is less influenced by endotracheal tube leak than inspired V(T). VG ventilation can be used with an endotracheal tube leak up to ∼50%. Initial set V(T) for infants with respiratory distress syndrome should be 4.0 to 5.0 ml kg(-1). The set V(T) should be adjusted to maintain normocapnoea. Setting the peak inflating pressure limit well above the working pressure is important to enable the ventilator to deliver the set V(T), and to avoid frequent alarms. This paper provides a practical guide on how to use VG ventilation.

Prenatal alcohol exposure alters the patterns of facial asymmetry.

Directional asymmetry, the systematic differences between the left and right body sides, is widespread in human populations. Changes in directional asymmetry are associated with various disorders that affect craniofacial development. Because facial dysmorphology is a key criterion for diagnosing fetal alcohol syndrome (FAS), the question arises whether in utero alcohol exposure alters directional asymmetry in the face. Data on the relative position of 17 morphologic landmarks were obtained from facial scans of children who were classified as either FAS or control. Shape data obtained from the landmarks were analyzed with the methods of geometric morphometrics. Our analyses showed significant directional asymmetry of facial shape, consisting primarily of a shift of midline landmarks to the right and a displacement of the landmarks around the eyes to the left. The asymmetry of FAS and control groups differed significantly and average directional asymmetry was increased in those individuals exposed to alcohol in utero. These results suggest that the developmental consequences of fetal alcohol exposure affect a wide range of craniofacial features in addition to those generally recognized and used for diagnosis of FAS.

A search for quantitative trait loci exhibiting imprinting effects on mouse mandible size and shape.

Genomic imprinting refers to the pattern of monoallelic parent-of-origin-dependent gene expression where one of the two alleles at a locus is expressed and the other silenced. Although some genes in mice are known to be imprinted, the true scope of imprinting and its impact on the genetic architecture of a wide range of morphometric traits is mostly unknown. We therefore searched for quantitative trait loci (QTL) exhibiting imprinting effects on mandible size and shape traits in a large F(3) population of mice originating from an intercross of the LG/J (Large) and SM/J (Small) inbred strains. We discovered a total of 51 QTL affecting mandible size and shape, 6 of which exhibited differences between reciprocal heterozygotes, the usual signature of imprinting effects. However, our analysis showed that only one of these QTL (affecting mandible size) exhibited a pattern consistent with true imprinting effects, whereas reciprocal heterozygote differences in the other five all were due to maternal genetic effects. We concluded that genomic imprinting has a negligible effect on these specific morphometric traits, and that maternal genetic effects may account for many of the previously reported instances of apparent genomic imprinting.

Persistent strains of coagulase-negative staphylococci in a neonatal intensive care unit: virulence factors and invasiveness.

Coagulase-negative staphylococci (CoNS) are the major cause of nosocomial bacteraemia in neonates. The aim of this study was to investigate whether persistent strains of CoNS possess specific bacterial characteristics as compared with sporadic non-cluster isolates. In total, 180 blood culture isolates (95 contaminants and 85 invasive isolates) obtained from a single neonatal unit over a 12-year period were studied. Pulsed-field gel electrophoresis (PFGE) identified 87 persistent CoNS strains (endemic clones). The two largest PFGE clusters belonged to a single clonal complex according to multilocus sequence typing. Patients colonised or infected with endemic clones were of lower gestational age than those infected with non-cluster strains. One Staphylococcus haemolyticus cluster appeared to selectively colonise and infect the most extreme pre-term infants. Endemic clones were characterised by high levels of antibiotic resistance and biofilm formation. All 51 isolates belonging to the two largest PFGE clusters were ica operon-positive. Genes encoding Staphylococcus epidermidis surface protein B and the production of phenol-soluble modulins (PSMs) were also more prevalent among endemic clones than among non-cluster strains. However, endemic clones were not more prevalent among invasive isolates than among contaminants. These findings indicate that multiple selective factors, including antibiotic resistance, biofilm formation, surface proteins with adhesive properties, and PSMs regulated by agr, increase the ability of CoNS to persist in a hospital environment. It may be more prudent, when searching for new therapeutic targets, to focus on ubiquitous components of CoNS instead of putative virulence factors that do not clearly contribute to increased invasive capacity.

Neonatal morbidity and mortality in a Tanzanian tertiary care referral hospital.

In developing countries, neonatal mortality accounts for 50-70% of infant mortality. The purpose of this study was to describe morbidity and mortality patterns, with a focus on neonatal infections, in a Tanzanian special care baby unit (SCBU). During a 3-month period, 246 consecutive admissions to the SCBU at Kilimanjaro Christian Medical Centre were audited. Prematurity, low birthweight and suspected infection accounted for 61% of all admissions. The overall mortality rate was 19%, but varied considerably according to gestational age, birthweight and diagnosis. Thirty-one neonates (two-thirds of all deaths) died during the 1st 24 hours of life. Of 27 infants admitted on grounds of perinatal asphyxia, 11 (41%) died, and, of 19 infants with a gestational age <31 weeks, 13 (68%) died. More than two-thirds of all infants were treated with antibiotics. Septicaemia confirmed by blood culture was found in 16 cases. The susceptibility pattern of bacterial isolates did not indicate high rates of resistance to commonly used antibacterial agents. A reduction in the number of preterm deliveries and improved perinatal care to avoid and treat perinatal asphyxia would be the two most important measures in reducing neonatal mortality in this setting.

Rapid PCR detection of the methicillin resistance gene, mecA, on the hands of medical and non-medical personnel and healthy children and on surfaces in a neonatal intensive care unit.

The hands of medical personnel are the chief vectors for transmission of antibiotic-resistant bacteria and probably serve as an important reservoir for antibiotic resistance genes in hospitals. In this survey we examined different reservoirs of the methicillin resistance gene, mecA, using a simplified PCR method. Samples (n = 151) were taken from the hands of medical and non-medical personnel and healthy children and from surfaces in a neonatal intensive care unit (NICU). We also performed sampling from 4 different body sites in 5 of the medical personnel. Fifteen out of 16 nurses (94%) from the ICU carried the mecA gene on their hands, whereas only 35% of the paediatric nurses were mecA-positive. Of all medical personnel, 44% carried the mecA gene on their hands. There was a significant difference (p < 0.015) between medical and non-medical personnel in terms of the carriage rate of mecA. Four samples from surfaces in a NICU--2 ventilators, 1 bench and 1 telephone--were positive for mecA. Our results are comparable with those from previous studies on reservoirs of methicillin-resistant coagulase-negative staphylococci using conventional culture techniques.

Rapid detection of the methicillin-resistance gene, mecA, in coagulase-negative Staphylococci.

Phenotypical methods are routinely used to detect methicillin resistance in Staphylococci. These methods are time-consuming and there are difficulties in detecting all resistant strains carrying the mecA gene. We detected methicillin-resistant Staphylococci in biological samples by PCR amplification of mecA, without the time-consuming step of identifying a bacterial isolate. Methicillin-resistant Staphylococci isolates were also detected by screening on agar supplemented with oxacillin. The biological samples were collected from the hands of 17 healthcare workers at the Department of Paediatrics at the University Hospital of Tromsø. mecA was amplified in 12 of the 17 samples. The gene was verified by DNA sequencing of the PCR amplicon. Using the phenotypical method, methicillin-resistant Staphylococci were isolated from 6 of the samples. In all 6 of these samples, mecA was amplified by PCR. We conclude that PCR is a sensitive and specific method for detecting methicillin resistance in Staphylococci. The PCR detection of mecA is rapid, fairly simple and can easily be assimilated into the routines of a clinical microbiological laboratory.

Genetic architecture of mandible shape in mice: effects of quantitative trait loci analyzed by geometric morphometrics.

This study introduces a new multivariate approach for analyzing the effects of quantitative trait loci (QTL) on shape and demonstrates this method for the mouse mandible. We quantified size and shape with the methods of geometric morphometrics, based on Procrustes superimposition of five morphological landmarks recorded on each mandible. Interval mapping for F(2) mice originating from an intercross of the LG/J and SM/J inbred strains revealed 12 QTL for size, 25 QTL for shape, and 5 QTL for left-right asymmetry. Multivariate ordination of QTL effects by principal component analysis identified two recurrent features of shape variation, which involved the positions of the coronoid and angular processes relative to each other and to the rest of the mandible. These patterns are reminiscent of the knockout phenotypes of a number of genes involved in mandible development, although only a few of these are possible candidates for QTL in our study. The variation of shape effects among the QTL showed no evidence of clustering into distinct groups, as would be expected from theories of morphological integration. Further, for most QTL, additive and dominance effects on shape were markedly different, implying overdominance for specific features of shape. We conclude that geometric morphometrics offers a promising new approach to address problems at the interface of evolutionary and developmental genetics.

[Stickler's syndrome--an underdiagnosed condition?]. / Sticklers syndrom--en underdiagnostisert tilstand?

BACKGROUND: Stickler's syndrome is an autosomal dominantly inherited connective tissue disorder characterised by ocular, orofacial, skeletal and auditory features. The estimated prevalence is 1:10,000. MATERIAL AND METHODS: We present a girl with the salient features of Stickler syndrome. Based on a literature search on Medline, we present an overview of this disorder. RESULTS: The patient presented at birth with Pierre Robin sequence and bilateral exophtalmus. Serial ophthalmological investigations have revealed a non-progressive myopia of high degree and abnormalities of the vitreous gel architecture. From the age of three, she had joint hypermobility and joint pain. Her intelligence is normal, but she requires speech therapy because of problems with articulation. INTERPRETATION: Recent research has provided a better understanding of the molecular genetic background of this condition. According to mutations in three genes encoding type II- and/or type XI-collagen, Stickler's syndrome can be subclassified into type 1, 2 and 3, but there is a considerable clinical overlap in symptoms. Patients with mild symptoms may be undiagnosed. Once the diagnosis is established, a coordinated multidisciplinary follow-up approach is recommended.

Quantitative genetics of geometric shape in the mouse mandible.

We combine the methods of geometric morphometrics and multivariate quantitative genetics to study the patterns of phenotypic and genetic variation of mandible shape in random-bred mice. The data are the positions of 11 landmarks on the mandibles of 1,241 mice from a parent-offspring breeding design. We use Procrustes superimposition to extract shape variation and restricted maximum likelihood to estimate the additive genetic and environmental components of variance and covariance. Matrix permutation tests showed that the genetic and phenotypic as well as the genetic and environmental covariance matrices were similar, but not identical. Likewise, principal component analyses revealed correspondence in the patterns of phenotypic and genetic variation. Patterns revealed in these analyses also showed similarities to features previously found in the effects of quantitative trait loci and in the phenotypes generated in gene knockout experiments. We used the multivariate version of the breeders' equation to explore the potential for short-term response to selection on shape. In general, the correlated response is substantial and regularly exceeds the direct response: Selection applied locally to one landmark usually produces a response in other parts of the mandible as well. Moreover, even selection for shifts of the same landmark in different directions can yield dramatically different responses. These results demonstrate the role of the geometry and anatomical structure of the mandible, which are key determinants of the patterns of the genetic and phenotypic covariance matrices, in molding the potential for adaptive evolution.

Inferring developmental modularity from morphological integration: analysis of individual variation and asymmetry in bumblebee wings.

Organisms are built from distinct modules, which are internally coherent but flexible in their relationships among one another. We examined morphological variation within and between two candidate modules: the fore- and hindwings of bumblebees (Hymenoptera: Apidae: Bombus empatiens). We used the techniques of geometric morphometrics (Procrustes superimposition) to analyze the variation of landmark configurations in fore- and hindwings. Regression was used to correct for size-related shape variation (allometry). Principal component analysis revealed patterns of variation that were remarkably similar for individual variation and fluctuating asymmetry (FA). Because covariation of FA among parts must be due to direct transmission of the developmental perturbations causing FA, this agreement of patterns suggests that much of individual variation is also due to direct developmental interactions within each developing wing. Moreover, partial least squares analysis indicated that the patterns of shape covariation between fore- and hindwings were nearly the same as the patterns of within-wing variation. Shape covariation of FA was only found in bees that had been reared under elevated CO(2) concentration but not in bees from the control treatment, suggesting that the mechanisms of developmental interactions between fore- and hindwings are related to gas exchange. We conclude that the fore- and hindwings are developmental modules that maintain internal coherence through direct developmental interactions and are connected to each other only by relatively few links that use the system of interactions within modules.

Morphological intergration between development compartments in the Drosophila wing.

Developmental integration is the covariation among morphological structures due to connections between the developmental processes that built them. Here we use the methods of geometric morphometrics to study integration in the wing of Drosophila melanogaster. In particular, we focus on the hypothesis that the anterior and posterior wing compartments are separate developmental units that vary independently. We measured both variation among genetically diverse individuals and random differences between body sides of single individuals (fluctuating asymmetry, FA). For both of these sources of variation, the patterns of variation identified by principal component analyses all involved landmarks in both the anterior and posterior compartments simultaneously. Analyses focusing exclusively on the covariation between the anterior and posterior compartments, by the partial least-squares method, revealed pervasive integration of the two compartments, for both individual variation and FA. These analyses clearly indicate that the anterior and posterior compartments are not separate units of variation, but that the covariation between compartments is sufficient to account for nearly all the variation throughout the entire wing. We conclude that variation among individuals as well as the developmental perturbations responsible for FA generate shape variation primarily through developmental processes that are integrated across both compartments. In contrast, much less of the shape variation in our sample can be attributed to the localized processes that establish the identity of particular wing veins.

Left-right asymmetry of fly wings and the evolution of body axes.

The body plan of Drosophila, and presumably that of other insects, develops under the control of anterio-posterior and dorsal ventral axes, but no evidence for a left-right axis has yet been found. We used geometric morphometrics to study the wings in three species of flies: Drosophila melanogaster, Musca domestica and Glossina palpalis gambiensis. In all three species, we found that both size and shape showed subtle, but statistically significant directional asymmetry. For size, these asymmetries were somewhat inconsistent within and between species, but for shape, highly significant directional asymmetry was found in all samples examined. These systematic left-right differences imply the existence of a left-right axis that conveys distinct positional identities to the wing imaginal discs on either body side. Hence, the wing discs of Drosophila may be a new model to study the developmental genetics of left-right asymmetry. The asymmetries of shape were similar among species, suggesting that directional asymmetry has been evolutionarily conserved since the three lineages diverged. We discuss the implications of this evolutionary conservatism in conjunction with results from earlier studies that showed a lack of genetic variation for directional asymmetry in Drosophila.

Heterochrony and allometry: the analysis of evolutionary change in ontogeny.

The connection between development and evolution has become the focus of an increasing amount of research in recent years, and heterochrony has long been a key concept in this relation. Heterochrony is defined as evolutionary change in rates and timing of developmental processes; the dimension of time is therefore an essential part in studies of heterochrony. Over the past two decades, evolutionary biologists have used several methodological frameworks to analyse heterochrony, which differ substantially in the way they characterize evolutionary changes in ontogenies and in the resulting classification, although they mostly use the same terms. This review examines how these methods compare ancestral and descendant ontogenies, emphasizing their differences and the potential for contradictory results from analyses using different frameworks. One of the two principal methods uses a clock as a graphical display for comparisons of size, shape and age at a particular ontogenic stage, whereas the other characterizes a developmental process by its time of onset, rate, and time of cessation. The literature on human heterochrony provides particularly clear examples of how these differences produce apparent contradictions when applied to the same problem. Developmental biologists recently have extended the concept of heterochrony to the earliest stages of development and have applied it at the cellular and molecular scale. This extension brought considerations of developmental mechanisms and genetics into the study of heterochrony, which previously was based primarily on phenomenological characterizations of morphological change in ontogeny. Allometry is the pattern of covariation among several morphological traits or between measures of size and shape; unlike heterochrony, allometry does not deal with time explicitly. Two main approaches to the study of allometry are distinguished, which differ in the way they characterize organismal form. One approach defines shape as proportions among measurements, based on considerations of geometric similarity, whereas the other focuses on the covariation among measurements in ontogeny and evolution. Both are related conceptually and through the use of similar algebra. In addition, there are close connections between heterochrony and changes in allometric growth trajectories, although there is no one-to-one correspondence. These relationships and outline links between different analytical frameworks are discussed.