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

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

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

A multi-disciplinary commentary on preclinical research to investigate vascular contributions to dementia

Although dementia research has been dominated by Alzheimer's disease (AD), most dementia in older people is now recognised to be due to mixed pathologies, usually combining vascular and AD brain pathology. Vascular cognitive impairment (VCI), which encompasses vascular dementia (VaD) is the second most common type of dementia. Models of VCI have been delayed by limited understanding of the underlying aetiology and pathogenesis. This review by a multidisciplinary, diverse (in terms of sex, geography and career stage), cross-institute team provides a perspective on limitations to current VCI models and recommendations for improving translation and reproducibility. We discuss reproducibility, clinical features of VCI and corresponding assessments in models, human pathology, bioinformatics approaches, and data sharing. We offer recommendations for future research, particularly focusing on small vessel disease as a main underpinning disorder

Chronic kidney disease and valvular heart disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies conference

Chronic kidney disease (CKD) is a major risk factor for valvular heart disease (VHD). Mitral annular and aortic valve calcifications are highly prevalent in CKD patients and commonly lead to valvular stenosis and regurgitation, as well as complications including conduction system abnormalities and endocarditis. VHD, especially mitral regurgitation and aortic stenosis, is associated with significantly reduced survival among CKD patients. Knowledge related to VHD in the general population is not always applicable to CKD patients because the pathophysiology may be different, and CKD patients have a high prevalence of comorbid conditions and elevated risk for periprocedural complications and mortality. This Kidney Disease: Improving Global Outcomes (KDIGO) review of CKD and VHD seeks to improve understanding of the epidemiology, pathophysiology, diagnosis, and treatment of VHD in CKD by summarizing knowledge gaps, areas of controversy, and priorities for research