Femoral lengthening in young patients : an evidence-based comparison between motorized lengthening nails and external fixation

BACKGROUND Femoral lengthening is a procedure of great importance in the treatment of congenital and acquired limb deficiencies. Technological advances have led to the latest designs of fully implantable motorized intramedullary lengthening nails. The use of these nails has increased over the last few years. AIM To review and critically appraise the literature comparing the outcome of femoral lengthening in children using intramedullary motorized lengthening nails to external fixation. METHODS Electronic databases (MEDLINE, CINAHL, EMBASE, Cochrane) were systematically searched in November 2019 for studies comparing the outcome of femoral lengthening in children using magnetic lengthening nails and external fixation. The outcomes included amount of gained length, healing index, complications and patient reported outcomes. RESULTS Of the 452 identified studies, only two (retrospective and non-randomized) met the inclusion criteria. A total of 91 femora were included. In both studies, the age of patients treated with nails ranged from 15 to 21 years compared to 9 to 15 years for patients in the external fixation group. Both devices achieved the target length. Prevalence of adverse events was less in the nail (60%-73%) than in the external fixation (81%-100%) group. None of the studies presented patient reported outcomes. CONCLUSION The clinical effectiveness of motorized nails is equivalent or superior to external fixation for femoral lengthening in young patients. The available literature is limited and does not provide evidence on patient quality of life or cost effectiveness of the interventions

Time--Distance Helioseismology Data Analysis Pipeline for Helioseismic and Magnetic Imager onboard Solar Dynamics Observatory (SDO/HMI) and Its Initial Results

The Helioseismic and Magnetic Imager onboard the Solar Dynamics Observatory (SDO/HMI) provides continuous full-disk observations of solar oscillations. We develop a data-analysis pipeline based on the time-distance helioseismology method to measure acoustic travel times using HMI Doppler-shift observations, and infer solar interior properties by inverting these measurements. The pipeline is used for routine production of near-real-time full-disk maps of subsurface wave-speed perturbations and horizontal flow velocities for depths ranging from 0 to 20 Mm, every eight hours. In addition, Carrington synoptic maps for the subsurface properties are made from these full-disk maps. The pipeline can also be used for selected target areas and time periods. We explain details of the pipeline organization and procedures, including processing of the HMI Doppler observations, measurements of the travel times, inversions, and constructions of the full-disk and synoptic maps. Some initial results from the pipeline, including full-disk flow maps, sunspot subsurface flow fields, and the interior rotation and meridional flow speeds, are presented.Comment: Accepted by Solar Physics topical issue 'Solar Dynamics Observatory

High bone mass phenotype in a cohort of patients with Osteogenesis Imperfecta caused due to BMP1 and C-propeptide cleavage variants in COL1A1

Objectives Osteogenesis Imperfecta (OI) is a heterogeneous condition mainly characterised by bone fragility; extra-skeletal features in OI include blue sclerae, dentinogenesis imperfecta, skin laxity and joint hyper-extensibility. Most patients with OI are thought to have a low bone mass but contrary to expectations there are certain forms of OI with high bone mass which this study explores in further detail. Method A cohort of n = 6 individuals with pathogenic variants in BMP1 and the C-propeptide cleavage variants in COL1A1 were included in this study. Detailed clinical and radiological phenotyping was done and correlated with genotype to identify patterns of clinical presentation and fracture history in this cohort of patients. This data was compared to previously reported literature in this group. Results 2 patients with BMP1 and 4 patients with pathogenic variants in C-propeptide region in COL1A1 were deep-phenotyped as part of this study and 1 patient with C-propeptide variant in COL1A1, showed low bone mineral density. In those with an elevated bone mineral density, this became even more apparent on bisphosphonate therapy. Patients in this cohort had variable clinical presentation ranging from antenatal presentation to more of an insidious course resulting in later confirmation of genetic diagnosis up to 19 years of age. Conclusions Patients with pathogenic variants in the C-propeptide region of COL1A1/A2 and BMP1 appear to have a high bone mass phenotype with increased sensitivity to bisphosphonate therapy. It is important to closely monitor patients with these genotypes to assess their response to therapy and tailor their treatment regime accordingly

Materializing digital collecting: an extended view of digital materiality

If digital objects are abundant and ubiquitous, why should consumers pay for, much less collect them? The qualities of digital code present numerous challenges for collecting, yet digital collecting can and does occur. We explore the role of companies in constructing digital consumption objects that encourage and support collecting behaviours, identifying material configuration techniques that materialise these objects as elusive and authentic. Such techniques, we argue, may facilitate those pleasures of collecting otherwise absent in the digital realm. We extend theories of collecting by highlighting the role of objects and the companies that construct them in materialising digital collecting. More broadly, we extend theories of digital materiality by highlighting processes of digital material configuration that occur in the pre-objectification phase of materialisation, acknowledging the role of marketing and design in shaping the qualities exhibited by digital consumption objects and consequently related consumption behaviours and experiences

The BRCA2 c.68-7T > A variant is not pathogenic : A model for clinical calibration of spliceogenicity

Although the spliceogenic nature of the BRCA2 c.68-7T > A variant has been demonstrated, its association with cancer risk remains controversial. In this study, we accurately quantified by real-time PCR and digital PCR (dPCR), the BRCA2 isoforms retaining or missing exon 3. In addition, the combined odds ratio for causality of the variant was estimated using genetic and clinical data, and its associated cancer risk was estimated by case-control analysis in 83,636 individuals. Co-occurrence in trans with pathogenic BRCA2 variants was assessed in 5,382 families. Exon 3 exclusion rate was 4.5-fold higher in variant carriers (13%) than controls (3%), indicating an exclusion rate for the c.68-7T > A allele of approximately 20%. The posterior probability of pathogenicity was 7.44x10(-115). There was neither evidence for increased risk of breast cancer (OR 1.03; 95% CI 0.86-1.24) nor for a deleterious effect of the variant when co-occurring with pathogenic variants. Our data provide for the first time robust evidence of the nonpathogenicity of the BRCA2 c.68-7T > A. Genetic and quantitative transcript analyses together inform the threshold for the ratio between functional and altered BRCA2 isoforms compatible with normal cell function. These findings might be exploited to assess the relevance for cancer risk of other BRCA2 spliceogenic variants.Peer reviewe

Energetic particle influence on the Earth's atmosphere

This manuscript gives an up-to-date and comprehensive overview of the effects of energetic particle precipitation (EPP) onto the whole atmosphere, from the lower thermosphere/mesosphere through the stratosphere and troposphere, to the surface. The paper summarizes the different sources and energies of particles, principally galactic cosmic rays (GCRs), solar energetic particles (SEPs) and energetic electron precipitation (EEP). All the proposed mechanisms by which EPP can affect the atmosphere are discussed, including chemical changes in the upper atmosphere and lower thermosphere, chemistry-dynamics feedbacks, the global electric circuit and cloud formation. The role of energetic particles in Earth’s atmosphere is a multi-disciplinary problem that requires expertise from a range of scientific backgrounds. To assist with this synergy, summary tables are provided, which are intended to evaluate the level of current knowledge of the effects of energetic particles on processes in the entire atmosphere

Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus.

BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. CONCLUSION: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.UK funding includes Cancer Research UK and NIH.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13058-016-0718-

Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study

A41 Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study In: Addiction Science & Clinical Practice 2017, 12(Suppl 1): A4