Using averaged models from 4D ultrasound strain imaging allows to significantly differentiate local wall strains in calcified regions of abdominal aortic aneurysms

Abdominal aortic aneurysms are a degenerative disease of the aorta associated with high mortality. To date, in vivo information to characterize the individual elastic properties of the aneurysm wall in terms of rupture risk is lacking. We have used time-resolved 3D ultrasound strain imaging to calculate spatially resolved in-plane strain distributions characterized by mean and local maximum strains, as well as indices of local variations in strains. Likewise, we here present a method to generate averaged models from multiple segmentations. Strains were then calculated for single segmentations and averaged models. After registration with aneurysm geometries based on CT-A imaging, local strains were divided into two groups with and without calcifications and compared. Geometry comparison from both imaging modalities showed good agreement with a root mean squared error of 1.22 ± 0.15 mm and Hausdorff Distance of 5.45 ± 1.56 mm (mean ± sd, respectively). Using averaged models, circumferential strains in areas with calcifications were 23.2 ± 11.7% (mean ± sd) smaller and significantly distinguishable at the 5% level from areas without calcifications. For single segmentations, this was possible only in 50% of cases. The areas without calcifications showed greater heterogeneity, larger maximum strains, and smaller strain ratios when computed by use of the averaged models. Using these averaged models, reliable conclusions can be made about the local elastic properties of individual aneurysm (and long-term observations of their change), rather than just group comparisons. This is an important prerequisite for clinical application and provides qualitatively new information about the change of an abdominal aortic aneurysm in the course of disease progression compared to the diameter criterion.

     

Tandem repeats within the inverted terminal repetition of vaccinia virus DNA

A tandemly repeated sequence within the genome of vaccinia virus is cut to fragments of approximately 70 bp by Hinf I, Taq I or Mbo II. The 70 bp repetition was localized within the much larger (10,300 bp) inverted terminal repetition by restriction analysis of cloned DNA fragments and by hybridization of the purified 70 bp repeat to vaccinia virus DNA restriction fragments. The molar abundance of the 70 bp fragment corresponds to a 30 fold repetition at each end of the genome. The repeating restriction endonuclease sites were mapped by agarose gel electrophoresis of partial Hinf I digests of the terminally labeled cloned DNA fragment. The first of 13 repetitive Hinf I sites occurred approximately 150 bp from the end of the cloned DNA. After an intervening sequence of approximately 435 bp, a second series of 17 repetitive Hinf I sites occurred. The DNA between the two blocks of repetitions has a unique sequence containing single Dde I, Alu I and Sau 3A sites. Tandem repeats within the inverted terminal repetition could serve to accelerate self-annealing of single strands of DNA to form circular structures during replication.     

Factors influencing embryo transfer success in alpacas—A retrospective study

Embryo transfer offers great advantages to South American camelid farmers to reach their breeding goals but the technology still plays a relatively minor role in comparison to other domestic farm animals like cattle. The aim of the present study was to analyse a data set of 5547 single or multiple ovulation embryo transfers performed in commercial alpaca farms in Australia to determine the factors that influence number and quality of embryos produced, embryo transfer success (percentage of crias born) and gestation length following transfer. Logistic binary regression identified the variables day of flushing after mating, embryo diameter, embryo quality, day of transfer after GnRH, and the age of the recipient to have significant impact on the outcome measure embryo transfer success. Transfer of smaller embryos or lower quality embryos resulted in decreased transfer success rates. Optimal days for obtaining embryos from donors were Days 8 and 9 after mating, optimal days for transfer into recipients were Days 7 and 8 after GnRH treatment. Age (>15 years) and body condition of recipients <2 also lowered transfer success rates, while the summer heat had no adverse impact. However, season did influence gestation length, while cria gender did not. In conclusion, results from the analysis of this very large dataset can underpin new recommendations to improve embryo transfer success in alpacas.     

Personal Networks and Mortality Risk in Older Adults: A Twenty-Year Longitudinal Study

Background

Research on aging has consistently demonstrated an increased chance of survival for older adults who are integrated into rich networks of social relationships. Theoretical explanations state that personal networks offer indirect psychosocial and direct physiological pathways. We investigate whether effects on and pathways to mortality risk differ between functional and structural characteristics of the personal network. The objective is to inquire which personal network characteristics are the best predictors of mortality risk after adjustment for mental, cognitive and physical health.

Methods and Findings

Empirical tests were carried out by combining official register information on mortality with data from the Longitudinal Aging Study Amsterdam (LASA). The sample included 2,911 Dutch respondents aged 54 to 85 at baseline in 1992 and six follow-ups covering a time span of twenty years. Four functional characteristics (emotional and social loneliness, emotional and instrumental support) and four structural characteristics (living arrangement, contact frequency, number of contacts, number of social roles) of the personal network as well as mental, cognitive and physical health were assessed at all LASA follow-ups. Statistical analyses comprised of Cox proportional hazard regression models. Findings suggest differential effects of personal network characteristics on survival, with only small gender differences. Mortality risk was initially reduced by functional characteristics, but disappeared after full adjustment for the various health variables. Mortality risk was lowest for older adults embedded in large (HR = 0.986, 95% CI 0.979—0.994) and diverse networks (HR = 0.948, 95% CI 0.917—0.981), and this effect continued to show in the fully adjusted models.

Conclusions

Functional characteristics (i.e. emotional and social loneliness) are indirectly associated with a reduction in mortality risk, while structural characteristics (i.e. number of contacts and number of social roles) have direct protective effects. More research is needed to understand the causal mechanisms underlying these relations.     

Evaluation of accuracy of non-linear finite element computations for surgical simulation: study using brain phantom

In this paper, the accuracy of non-linear finite element computations in application to surgical simulation was evaluated by comparing the experiment and modelling of indentation of the human brain phantom. The evaluation was realised by comparing forces acting on the indenter and the deformation of the brain phantom. The deformation of the brain phantom was measured by tracking 3D motions of X-ray opaque markers, placed within the brain phantom using a custom-built bi-plane X-ray image intensifier system. The model was implemented using the ABAQUS(TM) finite element solver. Realistic geometry obtained from magnetic resonance images and specific constitutive properties determined through compression tests were used in the model. The model accurately predicted the indentation force-displacement relations and marker displacements. Good agreement between modelling and experimental results verifies the reliability of the finite element modelling techniques used in this study and confirms the predictive power of these techniques in surgical simulation.     

Patient-specific non-linear finite element modelling for predicting soft organ deformation in real-time; Application to non-rigid neuroimage registration

Long computation times of non-linear (i.e. accounting for geometric and material non-linearity) biomechanical models have been regarded as one of the key factors preventing application of such models in predicting organ deformation for image-guided surgery. This contribution presents real-time patient-specific computation of the deformation field within the brain for six cases of brain shift induced by craniotomy (i.e. surgical opening of the skull) using specialised non-linear finite element procedures implemented on a graphics processing unit (GPU). In contrast to commercial finite element codes that rely on an updated Lagrangian formulation and implicit integration in time domain for steady state solutions, our procedures utilise the total Lagrangian formulation with explicit time stepping and dynamic relaxation. We used patient-specific finite element meshes consisting of hexahedral and non-locking tetrahedral elements, together with realistic material properties for the brain tissue and appropriate contact conditions at the boundaries. The loading was defined by prescribing deformations on the brain surface under the craniotomy. Application of the computed deformation fields to register (i.e. align) the preoperative and intraoperative images indicated that the models very accurately predict the intraoperative deformations within the brain. For each case, computing the brain deformation field took less than 4 s using an NVIDIA Tesla C870 GPU, which is two orders of magnitude reduction in computation time in comparison to our previous study in which the brain deformation was predicted using a commercial finite element solver executed on a personal computer.     

Homozygous haplotype deficiency reveals deleterious mutations compromising reproductive and rearing success in cattle

Background

Cattle breeding populations are susceptible to the propagation of recessive diseases. Individual sires generate tens of thousands of progeny via artificial insemination. The frequency of deleterious alleles carried by such sires may increase considerably within few generations. Deleterious alleles manifest themselves often by missing homozygosity resulting from embryonic/fetal, perinatal or juvenile lethality of homozygotes.

Results

A scan for homozygous haplotype deficiency in 25,544 Fleckvieh cattle uncovered four haplotypes affecting reproductive and rearing success. Exploiting whole-genome resequencing data from 263 animals facilitated to pinpoint putatively causal mutations in two of these haplotypes. A mutation causing an evolutionarily unlikely substitution in SUGT1 was perfectly associated with a haplotype compromising insemination success. The mutation was not found in homozygous state in 10,363 animals (P = 1.79 × 10⁻⁵) and is thus likely to cause lethality of homozygous embryos. A frameshift mutation in SLC2A2 encoding glucose transporter 2 (GLUT2) compromises calf survival. The mutation leads to premature termination of translation and activates cryptic splice sites resulting in multiple exon variants also with premature translation termination. The affected calves exhibit stunted growth, resembling the phenotypic appearance of Fanconi-Bickel syndrome in humans (OMIM 227810), which is also caused by mutations in SLC2A2.

Conclusions

Exploiting comprehensive genotype and sequence data enabled us to reveal two deleterious alleles in SLC2A2 and SUGT1 that compromise pre- and postnatal survival in homozygous state. Our results provide the basis for genome-assisted approaches to avoiding inadvertent carrier matings and to improving reproductive and rearing success in Fleckvieh cattle.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1483-7) contains supplementary material, which is available to authorized users.     

Subject-specific non-linear biomechanical model of needle insertion into brain

The previous models for predicting the forces acting on a needle during insertion into very soft organs (such as, e.g. brain) relied on oversimplifying assumptions of linear elasticity and specific experimentally derived functions for determining needle-tissue interactions. In this contribution, we propose a more general approach in which the needle forces are determined directly from the equations of continuum mechanics using fully non-linear finite element procedures that account for large deformations (geometric non-linearity) and non-linear stress-strain relationship (material non-linearity) of soft tissues. We applied these procedures to model needle insertion into a swine brain using the constitutive properties determined from the experiments on tissue samples obtained from the same brain (i.e. the subject-specific constitutive properties were used). We focused on the insertion phase preceding puncture of the brain meninges and obtained a very accurate prediction of the needle force. This demonstrates the utility of non-linear finite element procedures in patient-specific modelling of needle insertion into soft organs such as, e.g. brain.     

Hybridization selection and cell-free translation of mRNA''s encoded within the inverted terminal repetition of the vaccinia virus genome

Early polypeptides encoded within the 10,000-base pair terminally repeated region of the vaccinia virus genome were mapped by cell-free translation of mRNA that was selected by hybridization to restriction fragments and to separated strands of a recombinant lambda phage. The results, which were confirmed by hybrid arrest of translation, indicated that polypeptides of 7,500 (7.5K), 19,000 (19K), and 42,000 (42K) daltons mapped at approximately 3.2 to 4.3, 6.5 to 7.2, and 7.2 to 8.3 kilobase pairs from the end of the genome, respectively. mRNA's for the 42K and 7.5K polypeptides were transcribed towards the end of the genome, whereas mRNA for the 19K polypeptide was transcribed in the opposite direction. Including polyadenylic acid tails, the lengths of the mRNA's for the 7.5K, 19K, and 42K polypeptides, determined by gel electrophoresis of denatured RNA, hybridization selection, and cell-free translation, were approximately 1,200, 680, and 1,280 nucleotides, respectively. mRNA's for the 42K and 19K polypeptides were only about 100 nucleotides longer than the minimums required to code for their respective polypeptides, whereas mRNA for the 7.5K polypeptide contained 900 nucleotides of untranslated sequence. This long untranslated portion of the latter mRNA was probably located near the 3' end, because this gene was only inactivated by high doses of UV irradiation. This small target size also excluded certain models for RNA processing involving formation of the mRNA's for the 42K and 7.5K polypeptides from a common promoter. Rabbitpox virus, which has an inverted terminal repetition approximately half that of vaccinia virus, was also shown to encode mRNA's that hybridized to the cloned terminal segment of vaccinia virus DNA.