Preparation and characterisation of manganese, cobalt and zinc DNA nanoflowers with tuneable morphology, DNA content and size

Recently reported DNA nanoflowers are an interesting class of organic-inorganic hybrid materials which are prepared using DNA polymerases. DNA nanoflowers combine the high surface area and scaffolding of inorganic Mg2P2O7 nanocrystals with the targeting properties of DNA, whilst adding enzymatic stability and enhanced cellular uptake. We have investigated conditions for chemically modifying the inorganic core of these nanoflowers through substitution of Mg2+ with Mn2+, Co2+ or Zn2+ and have characterised the resulting particles. These have a range of novel nanoarchitectures, retain the enzymatic stability of their magnesium counterparts and the Co2+ and Mn2+ DNA nanoflowers have added magnetic properties. We investigate conditions to control different morphologies, DNA content, hybridisation properties, and size. Additionally, we show that DNA nanoflower production is not limited to Ф29 DNA polymerase and that the choice of polymerase can influence the DNA length within the constructs. We anticipate that the added control of structure, size and chemistry will enhance future application

Comparison of 123 I-metaiodobenzylguanidine (MIBG) and 131 I-MIBG semi-quantitative scores in predicting survival in patients with stage 4 neuroblastoma: A report from the Children's Oncology Group

Background 123 I-metaiodobenzylguanidine (MIBG) scans are preferable to 131 I-MIBG for neuroblastoma imaging as they deliver less patient radiation yet have greater sensitivity in disease detection. Both 123 I-MIBG and 131 I-MIBG scans were used for disease assessments of neuroblastoma patients enrolled on Children's Oncology Group (COG) high-risk study A3973. The hypothesis was that 123 I-MIBG and 131 I-MIBG scans were sufficiently similar for clinical purposes in terms of ability to predict survival. Procedure Patients enrolled on COG A3973 with stage 4 disease who completed 123 I-MIBG or 131 I-MIBG scans at diagnosis, post-induction, post-transplant, or post-biotherapy were analyzed. The performance of the Curie score for each MIBG scan type in predicting survival was evaluated. At each time point, survival curves for 123 I-MIBG versus 131 I-MIBG were compared using the log-rank test. Results Of the 413 patients on A3973 with at least one MIBG scan, 350 were stage 4. The 5-year event-free survival (EFS) and overall survival (OS) rates were 33.4 ± 3.6% and 45.6 ± 4.0% (N = 350). At post-induction, EFS ( P  = 0.3501) and OS ( P  = 0.5337) for 123 I-MIBG versus 131 I-MIBG were not significantly different. Similarly, comparisons at the three other time points were non-significant. Conclusions We found no evidence of a statistically significant difference in outcome by type of scan. For future survival analyses of MIBG Curie scores, 123 I-MIBG and 131 I-MIBG results may be combined and analyzed overall, without adjustment for scan type. Pediatr Blood Cancer 2011;56:1041–1045. © 2011 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83739/1/22991_ftp.pd

Towards a Realistic Neutron Star Binary Inspiral: Initial Data and Multiple Orbit Evolution in Full General Relativity

This paper reports on our effort in modeling realistic astrophysical neutron star binaries in general relativity. We analyze under what conditions the conformally flat quasiequilibrium (CFQE) approach can generate ``astrophysically relevant'' initial data, by developing an analysis that determines the violation of the CFQE approximation in the evolution of the binary described by the full Einstein theory. We show that the CFQE assumptions significantly violate the Einstein field equations for corotating neutron stars at orbital separations nearly double that of the innermost stable circular orbit (ISCO) separation, thus calling into question the astrophysical relevance of the ISCO determined in the CFQE approach. With the need to start numerical simulations at large orbital separation in mind, we push for stable and long term integrations of the full Einstein equations for the binary neutron star system. We demonstrate the stability of our numerical treatment and analyze the stringent requirements on resolution and size of the computational domain for an accurate simulation of the system.Comment: 22 pages, 18 figures, accepted to Phys. Rev.

Filamentary condensations in a young cluster

New models are presented for star-forming condensations in clusters. In each model, the condensation mass increases linearly with radius on small scales, and more rapidly on large scales, as in "thermal-nonthermal" models. Spherical condensations with this structure form protostars which match the IMF if their infall is subject to equally likely stopping. However such spherical models do not match the filamentary nature of cluster gas, and they are too extended to form protostars having high mass and short spacing. Two hybrid models are presented, which are spherical on small scales and filamentary on large scales. In and around clusters, cores embedded in linear filaments match the elongation of cluster gas, and the central concentration of low-mass stars. In cluster centers, condensations require a low volume filling factor to produce massive stars with short spacing. These may have stellate shape, where cores are nodes of filamentary networks, as seen in some simulations of colliding flows and of collapsing turbulent clumps. A dense configuration of such stellate condensations may be indistinguishable from a clump forming multiple protostars via filamentary flow paths.Comment: accepted for publication in The Astrophysical Journa

Induction of neural crest stem cells from Bardet–Biedl syndrome patient derived hiPSCs

Neural crest cells arise in the embryo from the neural plate border and migrate throughout the body, giving rise to many different tissue types such as bones and cartilage of the face, smooth muscles, neurons, and melanocytes. While studied extensively in animal models, neural crest development and disease have been poorly described in humans due to the challenges in accessing embryonic tissues. In recent years, patient-derived human induced pluripotent stem cells (hiPSCs) have become easier to generate, and several streamlined protocols have enabled robust differentiation of hiPSCs to the neural crest lineage. Thus, a unique opportunity is offered for modeling neurocristopathies using patient specific stem cell lines. In this work, we make use of hiPSCs derived from patients affected by the Bardet–Biedl Syndrome (BBS) ciliopathy. BBS patients often exhibit subclinical craniofacial dysmorphisms that are likely to be associated with the neural crest-derived facial skeleton. We focus on hiPSCs carrying variants in the BBS10 gene, which encodes a protein forming part of a chaperonin-like complex associated with the cilium. Here, we establish a pipeline for profiling hiPSCs during differentiation toward the neural crest stem cell fate. This can be used to characterize the differentiation properties of the neural crest-like cells. Two different BBS10 mutant lines showed a reduction in expression of the characteristic neural crest gene expression profile. Further analysis of both BBS10 mutant lines highlighted the inability of these mutant lines to differentiate toward a neural crest fate, which was also characterized by a decreased WNT and BMP response. Altogether, our study suggests a requirement for wild-type BBS10 in human neural crest development. In the long term, approaches such as the one we describe will allow direct comparison of disease-specific cell lines. This will provide valuable insights into the relationships between genetic background and heterogeneity in cellular models. The possibility of integrating laboratory data with clinical phenotypes will move us toward precision medicine approaches

Asthma exacerbation and steroid burden in Australian primary care

Peer reviewedPostprin

An Algorithm Informed by the Parathyroid Hormone Level Reduces Hypocalcemic Complications of Thyroidectomy

Ó The Author(s) 2010. This article is published with open access at Springerlink.com Background Measurement of the parathyroid hormone (PTH) level following total thyroidectomy (TTx) may allow prediction of postoperative hypocalcemia. We present an algorithmic method of managing hypocalcemia preemptively, based on the PTH level 1 h after operation. Materials and methods We examined 423 consecutive patients undergoing TTx at a single institution. A subset of patients were managed using an algorithm involving routine postoperative oral calcium administration and the early addition of oral calcitriol in patients with a low 1-h postoperative PTH level. Algorithm patients were compared to a concurrent, conventionally managed group. Outcomes measured included serum calcium levels, symptoms of hypocalcemia, postoperative complications, and receipt of intravenous (IV) calcium. Results The algorithm was applied in 135 patients, and 288 patients were managed conventionally. Critically low calcium levels (total calcium \7.5 mg/dl [1.88 mmol/l] or ionized calcium \0.94 mmol/l) were less common in algorithm patients (10.6 % vs. 25.3%; p \ 0.005). Much of this difference was attributable to the protective impact of the algorithm on patients undergoing TTx for cancer, 30% of whom developed critically low calcium levels when managed conventionally. Among patients requiring IV calcium, algorithm patients received fewer doses (1.29 vs