Predicting growth and curve progression in the individual patient with adolescent idiopathic scoliosis: design of a prospective longitudinal cohort study

<p>Abstract</p> <p>Background</p> <p>Scoliosis is present in 3-5% of the children in the adolescent age group, with a higher incidence in females. Treatment of adolescent idiopathic scoliosis is mainly dependent on the progression of the scoliotic curve. There is a close relationship between curve progression and rapid (spinal) growth of the patient during puberty. However, until present time no conclusive method was found for predicting the timing and magnitude of the pubertal growth spurt in total body height, or the curve progression of the idiopathic scoliosis.</p> <p>The goal of this study is to determine the predictive value of several maturity indicators that reflect growth or remaining growth potential, in order to predict timing of the peak growth velocity of total body height in the individual patient with adolescent idiopathic scoliosis. Furthermore, different parameters are evaluated for their correlation with curve progression in the individual scoliosis patient.</p> <p>Methods/design</p> <p>This prospective, longitudinal cohort study will be incorporated in the usual care of patients with adolescent idiopathic scoliosis. All new patients between 8 and 17 years with adolescent idiopathic scoliosis (Cobb angle >10 degrees) visiting the outpatient clinic of the University Medical Center Groningen are included in this study. Follow up will take place every 6 months. The present study will use a new ultra-low dose X-ray system which can make total body X-rays. Several maturity indicators are evaluated like different body length dimensions, secondary sexual characteristics, skeletal age in hand and wrist, skeletal age in the elbow, the Risser sign, the status of the triradiate cartilage, and EMG ratios of the paraspinal muscle activity.</p> <p>Correlations of all dimensions will be calculated in relationship to the timing of the pubertal growth spurt, and to the progression of the scoliotic curve. An algorithm will be made for the optimal treatment strategy in the individual patient with adolescent idiopathic scoliosis.</p> <p>Discussion</p> <p>This study will determine the value of many maturity indicators and will be useful as well for other clinicians treating children with disorders of growth. Since not all clinicians have access to the presented new 3D X-ray system or have the time to make EMG's, for example, all indicators will be correlated to the timing of the peak growth velocity of total body height and curve progression in idiopathic scoliosis. Therefore each clinician can chose which indicators can be used best in their practice.</p> <p>Trial registration number</p> <p>NTR2048</p

Profiling allele-specific gene expression in brains from individuals with autism spectrum disorder reveals preferential minor allele usage.

One fundamental but understudied mechanism of gene regulation in disease is allele-specific expression (ASE), the preferential expression of one allele. We leveraged RNA-sequencing data from human brain to assess ASE in autism spectrum disorder (ASD). When ASE is observed in ASD, the allele with lower population frequency (minor allele) is preferentially more highly expressed than the major allele, opposite to the canonical pattern. Importantly, genes showing ASE in ASD are enriched in those downregulated in ASD postmortem brains and in genes harboring de novo mutations in ASD. Two regions, 14q32 and 15q11, containing all known orphan C/D box small nucleolar RNAs (snoRNAs), are particularly enriched in shifts to higher minor allele expression. We demonstrate that this allele shifting enhances snoRNA-targeted splicing changes in ASD-related target genes in idiopathic ASD and 15q11-q13 duplication syndrome. Together, these results implicate allelic imbalance and dysregulation of orphan C/D box snoRNAs in ASD pathogenesis

Chaste: an open source C++ library for computational physiology and biology

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials

Dermatofibrosarcoma protuberans treated by micrographic surgery

Dermatofibrosarcoma protuberans is an uncommon cutaneous tumour which rarely metastasises. However, local recurrence following apparently adequate surgical excision is well recognised, presumably as a result of sub-clinical contiguous growth, for which micrographically controlled excision would be a logical treatment. A retrospective study of all patients treated by micrographic surgery, from April 1995–March 2000, at a tertiary skin oncology centre. Twenty-one patients (11 males), age 14 to 71 years with dermatofibrosarcoma protuberans on the trunk (10 patients), groin (four), head and neck (four), and limbs (three) were treated. In 15 patients one micrographic layer cleared the tumour, and four were cleared with two layers. For one patient the second stage was completed by conventional excision guided by positive margins. Another patient with a multiply recurrent perineal dermatofibrosarcoma protuberans, not cleared in one area after two layers, died from a pulmonary embolus before total clearance could be achieved. There was no correlation between tumour size and lateral excision margin. No recurrence was observed during the follow-up, from 21 to 80 months, median 47 months. The study provides further support for micrographic surgery as the treatment of choice for dermatofibrosarcoma protuberans

Designing nanomaterials with desired mechanical properties by constraining the evolution of their grain shapes

Grain shapes are acknowledged to impact nanomaterials' overall properties. Research works on this issue include grain-elongation and grain-strain measurements and their impacts on nanomaterials' mechanical properties. This paper proposes a stochastic model for grain strain undergoing severe plastic deformation. Most models deal with equivalent radii assuming that nanomaterials' grains are spherical. These models neglect true grain shapes. This paper also proposes a theoretical approach of extending existing models by considering grain shape distribution during stochastic design and modelling of nanomaterials' constituent structures and mechanical properties. This is achieved by introducing grain 'form'. Example 'forms' for 2-D and 3-D grains are proposed. From the definitions of form, strain and Hall-Petch-Relationship to Reversed-Hall-Petch-Relationship, data obtained for nanomaterials' grain size and conventional materials' properties are sufficient for analysis. Proposed extended models are solved simultaneously and tested with grain growth data. It is shown that the nature of form evolution depends on form choice and dimensional space. Long-run results reveal that grain boundary migration process causes grains to become spherical, grain rotation coalescence makes them deviate away from becoming spherical and they initially deviate away from becoming spherical before converging into spherical ones due to the TOTAL process. Percentage deviations from spherical grains depend on dimensional space and form: 0% minimum and 100% maximum deviations were observed. It is shown that the plots for grain shape functions lie above the spherical (control) value of 1 in 2-D grains for all considered grain growth mechanisms. Some plots lie above the spherical value, and others approach the spherical value before deviating below it when dealing with 3-D grains. The physical interpretations of these variations are explained from elementary principles about the different grain growth mechanisms. It is observed that materials whose grains deviate further away from the spherical ones have more enhanced properties, while materials with spherical grains have lesser properties. It is observed that there exist critical states beyond which Hall-Petch Relationship changes to Reversed Hall-Petch Relationship. It can be concluded that if grain shapes in nanomaterials are constrained in the way they evolve, then nanomaterials with desired properties can be designed

Autotrophic and heterotrophic acquisition of carbon and nitrogen by a mixotrophic chrysophyte established through stable isotope analysis

Collectively, phagotrophic algae (mixotrophs) form a functional continuum of nutritional modes between autotrophy and heterotrophy, but the specific physiological benefits of mixotrophic nutrition differ among taxa. Ochromonas spp. are ubiquitous chrysophytes that exhibit high nutritional flexibility, although most species generally fall towards the heterotrophic end of the mixotrophy spectrum. We assessed the sources of carbon and nitrogen in Ochromonas sp. strain BG-1 growing mixotrophically via short-term stable isotope probing. An axenic culture was grown in the presence of either heat-killed bacteria enriched with ^(15)N and ^(13)C, or unlabeled heat-killed bacteria and labeled inorganic substrates (^(13)C-bicarbonate and ^(15)N-ammonium). The alga exhibited high growth rates (up to 2 divisions per day) only until heat-killed bacteria were depleted. NanoSIMS and bulk IRMS isotope analyses revealed that Ochromonas obtained 84–99% of its carbon and 88–95% of its nitrogen from consumed bacteria. The chrysophyte assimilated inorganic ^(13)C-carbon and ^(15)N-nitrogen when bacterial abundances were very low, but autotrophic (photosynthetic) activity was insufficient to support net population growth of the alga. Our use of nanoSIMS represents its first application towards the study of a mixotrophic alga, enabling a better understanding and quantitative assessment of carbon and nutrient acquisition by this species

Restoration of diaphragmatic function after diaphragm reinnervation by inferior laryngeal nerve; experimental study in rabbits

OBJECTIVES: To assess the possibilities of reinnervation in a paralyzed hemidiaphragm via an anastomosis between phrenic nerve and inferior laryngeal nerve in rabbits. Reinnervation of a paralyzed diaphragm could be an alternative to treat patients with ventilatory insufficiency due to upper cervical spine injuries. MATERIAL AND METHOD: Rabbits were divided into five groups of seven rabbits each. Groups I and II were respectively the healthy and the denervated control groups. The 3 other groups were all reinnervated using three different surgical procedures. In groups III and IV, phrenic nerve was respectively anastomosed with the abductor branch of the inferior laryngeal nerve and with the trunk of the inferior laryngeal nerve. In group V, the fifth and fourth cervical roots were respectively anastomosed with the abductor branch of the inferior laryngeal nerve and with the nerve of the sternothyroid muscle (originating from the hypoglossal nerve). Animals were evaluated 4 months later using electromyography, transdiaphragmatic pressure measurements, sonomicrometry and histological examination. RESULTS: A poor inspiratory activity was found in quiet breathing in the reinnervated groups, with an increasing pattern of activity during effort. In the reinnervated groups, transdiaphragmatic pressure measurements and sonomicrometry were higher in group III with no significant differencewith groups IV and V. CONCLUSION: Inspiratory contractility of an hemidiaphragm could be restored with immediate anastomosis after phrenic nerve section between phrenic nerve and inferior laryngeal nerve