Reviewing causes of death of individuals with intellectual disability in New South Wales, Australia: a record-linkage study.

BACKGROUND: People with intellectual disability (ID) have a much higher mortality rate than the general population. To reduce the rate of mortality of people with ID, it is critical that causes of death are properly understood, recorded and reported. Formal reviews of causes of death are used in some countries to ensure that causes of death are accurate. To date, the impact of these formal reviews on understanding causes of death of people with ID has not been quantified. METHODS: The study aimed to quantify the impact of formal reviews of deaths on the understanding of causes of death of people with ID who died while living in residential care. Individuals (851) with ID who died in residential care in New South Wales (NSW), Australia, between 1 December 2002 and 31 December 2013, who had a cause of death recorded in both the NSW Cause of Death Unit Record File (COD-URF; cause of death recorded at time of death) and NSW Ombudsman dataset (cause of death recorded after in-depth review) were included in the study. We assessed agreement in coding for cause of death by comparing the International Classification of Diseases 10th Revision (ICD-10) codings at three levels of diagnostic specificity, for both underlying and additional causes of death. We conducted our analysis through both descriptive comparison and through two boosted regression trees. RESULTS: Approximately half of the underlying causes of death were different after review by the NSW Ombudsman compared with the COD-URF. Certain causes of death (determined by ICD-10 chapter) were less likely to predict matches between the dataset than others, with individuals with mental, behavioural and neurodevelopmental disorders recorded in the COD-URF least likely to have a matching cause of death in NSW Ombudsman dataset. For deaths where there was no agreement at any level between the datasets, a high level of unknown causes of death was recorded. CONCLUSIONS: Formal review of deaths of people with ID in residential care is important to determining true causes of death and therefore developing appropriate health policy for people with ID.

Design and engineering colloidal magnetic particles for nanoscale thermometry.

Thermometry based on magnetic nanoparticles (MNPs) is an emerging technology that allows for remote temperature measurements throughout a volume that are impossible to achieve using conventional probe-based or optical methods. This metrology is based on the temperature-dependent nature of these particles' magnetization; however, commercially available MNPs generally display insufficient magneto-thermosensitivity for practical use in applications near room temperature. Here we present engineered MNPs based on cobalt-doped ferrites developed for 200 K - 400 K thermometry applications. The synthesis relies on easily scalable solution chemistry routes, and is tunable to afford MNPs of controlled size and composition. These improved nanothermometers form the basis of our effort to develop a practical means for spatially resolved, 3D, high-sensitivity measurements of temperature based on AC magnetometry.

Novel Probiotic Mechanisms of the Oral Bacterium Streptococcus sp. A12 as Explored with Functional Genomics.

Health-associated biofilms in the oral cavity are composed of a diverse group of microbial species that can foster an environment that is less favorable for the outgrowth of dental caries pathogens, like Streptococcus mutans A novel oral bacterium, designated Streptococcus A12, was previously isolated from supragingival dental plaque of a caries-free individual and was shown to interfere potently with the growth and virulence properties of S. mutans In this study, we applied functional genomics to begin to identify molecular mechanisms used by A12 to antagonize, and to resist the antagonistic factors of, S. mutans Using bioinformatics, genes that could encode factors that enhance the ability of A12 to compete with S. mutans were identified. Selected genes, designated potential competitive factors (pcf), were deleted. Certain mutant derivatives showed a reduced capacity to compete with S. mutans compared to that of the parental strain. The A12 pcfO mutant lost the ability to inhibit comX -inducing peptide (XIP) signaling by S. mutans, while mutants with changes in the pcfFEG locus were impaired in sensing of, and were more sensitive to, the lantibiotic nisin. Loss of PcfV, annotated as a colicin V biosynthetic protein, resulted in diminished antagonism of S. mutans Collectively, the data provide new insights into the complexities and variety of factors that affect biofilm ecology and virulence. Continued exploration of the genomic and physiological factors that distinguish commensals from truly beneficial members of the oral microbiota will lead to a better understanding of the microbiome and new approaches to promote oral health.IMPORTANCE Advances in defining the composition of health-associated biofilms have highlighted the important role of beneficial species in maintaining health. Comparatively little, however, has been done to address the genomic and physiological bases underlying the probiotic mechanisms of beneficial commensals. In this study, we explored the ability of a novel oral bacterial isolate, Streptococcus A12, to compete with the dental pathogen Streptococcus mutans using various gene products with diverse functions. A12 displayed enhanced competitiveness by (i) disrupting intercellular communication pathways of S. mutans, (ii) sensing and resisting antimicrobial peptides, and (iii) producing factors involved in the production of a putative antimicrobial compound. Research on the probiotic mechanisms employed by Streptococcus A12 is providing essential insights into how beneficial bacteria may help maintain oral health, which will aid in the development of biomarkers and therapeutics that can improve the practice of clinical dentistry.

Separation of double-wall carbon nanotubes by electronic type and diameter.

We introduce a new procedure for the efficient isolation and subsequent separation of double-wall carbon nanotubes (DWCNTs). A simplified, rate zonal ultracentrifugation (RZU) process is first applied to obtain samples of highly-enriched DWCNTs from a raw carbon nanotube material that has both single- and double-wall carbon nanotubes. Using this purified DWCNT suspension, we demonstrate for the first time that DWCNTs can be further processed using aqueous two-phase extraction (ATPE) for sequential separation by electronic structure and diameter. Additionally, we introduce analytical ultracentrifugation (AUC) as a new method for DWCNT characterization to assess DWCNT purity in separated samples. Results from AUC analysis are utilized to compare two DWCNT separation schemes. We find that RZU processing followed by sequential bandgap and diameter sorting via ATPE provides samples of highest DWCNT enrichment, whereas single-step redox sorting of the same raw material through ATPE yields SWCNT/DWCNT mixtures of similar diameter and electronic character. The presented methods offer significant advancement in DWCNT processing and separation while also providing a promising alternative for DWCNT sample analysis.

Enhancing single-wall carbon nanotube properties through controlled endohedral filling.

Chemical control of the endohedral volume of single-wall carbon nanotubes (SWCNTs) via liquid-phase filling is established to be a facile strategy to controllably modify properties of SWCNTs in manners significant for processing and proposed applications. Encapsulation of over 20 different compounds with distinct chemical structures, functionalities, and effects is demonstrated in SWCNTs of multiple diameter ranges, with the ability to fill the endohedral volume based on the availability of the core volume and compatibility of the molecule's size with the cross-section of the nanotube's cavity. Through exclusion of ingested water and selection of the endohedral chemical environment, significant improvements to the optical properties of dispersed SWCNTs such as narrowed optical transition linewidths and enhanced fluorescence intensities are observed. Examples of tailoring modified properties towards applications or improved processing by endohedral passivation are discussed.

Glucose oxidase-catalyzed growth of gold nanoparticles enables quantitative detection of attomolar cancer biomarkers.

Ultrasensitive and quantitative detection of cancer biomarkers is an unmet challenge because of their ultralow concentrations in clinical samples. Although gold nanoparticle (AuNP)-based immunoassays offer high sensitivity, they were unable to quantitatively detect targets of interest most likely due to their very narrow linear ranges. This article describes a quantitative colorimetric immunoassay based on glucose oxidase (GOx)-catalyzed growth of 5 nm AuNPs that can detect cancer biomarkers from attomolar to picomolar levels. In addition, the limit of detection (LOD) of prostate-specific antigen (PSA) of this approach (93 aM) exceeds that of commercial enzyme-linked immunosorbent assay (ELISA) (6.3 pM) by more than 4 orders of magnitude. The emergence of red or purple color based on enzyme-catalyzed growth of 5 nm AuNPs in the presence of target antigen is particularly suitable for point-of-care (POC) diagnostics in both resource-rich and resource-limited settings.

Ticks and associated diseases: a retrospective review.

This is a retrospective review of contributions to the understanding of ticks and associated diseases published in Medical and Veterinary Entomology since its first issue. It highlights the large and significant changes in the style and conduct of this field over the last 25 years. The selected papers refer to disease-related categories of host immunity to ticks, population dynamics, pathogen transmission and tick control.

Increased anti-leukemic activity of decitabine via AR-42-induced upregulation of miR-29b: a novel epigenetic-targeting approach in acute myeloid leukemia.

Histone deacetylase (HDAC) inhibitors either alone or in combination with hypomethylating agents have limited clinical effect in acute myeloid leukemia (AML). Previously, we demonstrated that AML patients with higher miR (microRNA)-29b expression had better response to the hypomethylating agent decitabine. Therefore, an increase in miR-29b expression preceding decitabine treatment may provide a therapeutic advantage. We previously showed that miR-29b expression is suppressed by a repressor complex that includes HDACs. Thus, HDAC inhibition may increase miR-29b expression. We hypothesized that priming AML cells with the novel HDAC inhibitor (HDACI) AR-42 would result in increased response to decitabine treatment via upregulation of miR-29b. Here, we show that AR-42 is a potent HDACI in AML, increasing miR-29b levels and leading to downregulation of known miR-29b targets (that is, SP1, DNMT1, DNMT3A and DNMT3B). We then demonstrated that the sequential administration of AR-42 followed by decitabine resulted in a stronger anti-leukemic activity in vitro and in vivo than decitabine followed by AR-42 or either drug alone. These preclinical results with AR-42 priming before decitabine administration represent a promising, novel treatment approach and a paradigm shift with regard to the combination of epigenetic-targeting compounds in AML, where decitabine has been traditionally given before HDACIs.

Transmission electron microscopy characterization of colloidal copper nanoparticles and their chemical reactivity.

A colloidal synthesis method was developed to produce face centered cubic (fcc) Cu nanoparticles in the presence of surfactants in an organic solvent under an Ar environment. Various synthetic conditions were explored to control the size of the as-prepared nanoparticles by changing the precursor, varying the amount of surfactants, and tuning the reaction temperature. Transmission electron microscopy (TEM), selected-area electron diffraction, and high-resolution TEM were used as the main characterization tools. Upon exposure to air, these nanoparticles are oxidized at different levels depending on their sizes: (1) an inhomogeneous layer of fcc Cu(2)O forms at the surface of Cu nanoparticles (about 30 nm); (2) Cu nanoparticles (about 5 nm) are immediately oxidized into fcc Cu(2)O nanoparticles (about 6 nm). The occurrence of these different levels of oxidization demonstrates the reactive nature of Cu nanoparticles and the effect of size on their reactivity. Furthermore, utilization of their chemical reactivity and conversion of spherical Cu nanoparticles into CuS nanoplates through the nanoscale Kirkendall effect were demonstrated. The oxidization and sulfidation of Cu nanoparticles were compared. Different diffusion and growth behaviors were involved in these two chemical transformations, resulting in the formation of isotropic Cu(2)O nanoparticles during oxidization and anisotropic CuS nanoplates during sulfidation.

Genotypic diversity, a survival strategy for the apicomplexan parasite Theileria parva.

The tick-borne protozoan parasite Theileria parva causes East Coast fever (ECF), a severe lymphoproliferative disease of cattle that is a major constraint to the improvement of livestock in eastern, central and southern Africa. Studies in cattle experimentally infected with T. parva have shown that the protective cytotoxic T lymphocyte (CTL) response is tightly focused, with individual animals recognizing only one or two dominant antigens, the identity of which varies with MHC class I phenotype. It is well known that cross-protection between T. parva stocks is limited, but precise evaluation of genetic diversity in field populations of the parasite has been hampered by a lack of molecular markers spanning the genome. A recently described panel of satellite markers has provided evidence for substantial genotypic diversity and recombination but does not provide cover for large segments of the genome. To address this deficiency, we undertook to identify additional polymorphic markers covering these regions and we report herein 42 newly identified PCR-RFLP markers distributed across the 4 T. parva chromosomes, as well as 19 new satellite markers for chromosomes 1 and 2. This brings the total number of available polymorphic markers to 141 for the 8.5 Mb genome. We have used these markers to characterise existing parasite stabilates and have also shown that passage of the parasite through naïve cattle and ticks can lead to substantial changes of parasite populations in resulting stabilates. These markers have also been used to show that passage of mixed parasites through an immunised calf results in the removal of the immunising genotype from the parasite population produced by ticks fed on this animal.

Endophytic actinobacteria induce defense pathways in Arabidopsis thaliana.

Endophytic actinobacteria, isolated from healthy wheat tissue, which are capable of suppressing a number wheat fungal pathogens both in vitro and in planta, were investigated for the ability to activate key genes in the systemic acquired resistance (SAR) or the jasmonate/ethylene (JA/ET) pathways in Arabidopsis thaliana. Inoculation of A. thaliana (Col-0) with selected endophytic strains induced a low level of SAR and JA/ET gene expression, measured using quantitative polymerase chain reaction. Upon pathogen challenge, endophyte-treated plants demonstrated a higher abundance of defense gene expression compared with the non-endophyte-treated controls. Resistance to the bacterial pathogen Erwinia carotovora subsp. carotovora required the JA/ET pathway. On the other hand, resistance to the fungal pathogen Fusarium oxysporum involved primarily the SAR pathway. The endophytic actinobacteria appear to be able to "prime" both the SAR and JA/ET pathways, upregulating genes in either pathway depending on the infecting pathogen. Culture filtrates of the endophytic actinobacteria were investigated for the ability to also activate defense pathways. The culture filtrate of Micromonospora sp. strain EN43 grown in a minimal medium resulted in the induction of the SAR pathway; however, when grown in a complex medium, the JA/ET pathway was activated. Further analysis using Streptomyces sp. strain EN27 and defense-compromised mutants of A. thaliana indicated that resistance to E. carotovora subsp. carotovora occurred via an NPR1-independent pathway and required salicylic acid whereas the JA/ET signaling molecules were not essential. In contrast, resistance to F. oxysporum mediated by Streptomyces sp. strain EN27 occurred via an NPR1-dependent pathway but also required salicylic acid and was JA/ET independent.

Influence of the colloidal environment on the magnetic behavior of cobalt nanoparticles.

The magnetic properties of 10 nm diameter surfactant-coated cobalt (Co) nanoparticles in 1,2-dichlorobenzene (DCB) are investigated by a series of sequential magnetic moment (m) vs temperature (T) measurements. A rapid rise in magnetic moment around 250 K during warming and an abrupt drop at 234 K during cooling are observed when a nonsaturating external magnetic field is applied. Differential scanning calorimetry (DSC) measurements demonstrate that the rapid rise and abrupt drop in magnetization are associated with the melting and freezing of the solvent. Magnetic measurements of these Co nanoparticles in DCB are also used to probe their aging over a period of 70 days. The saturation magnetic moment of Co nanoparticles in DCB stored in air at room temperature decreases by nearly 40% over 70 days. Transmission electron microscopy (TEM) characterizations are reported to show the time evolution in the size, shape, and crystalline structures of DCB-immersed nanoparticles.

Dielectric response of aligned semiconducting single-wall nanotubes.

We report measurements of the full intrinsic optical anisotropy of isolated single-wall carbon nanotubes (SWNTs). By combining absorption spectroscopy with transmission ellipsometry and polarization-dependent resonant Raman scattering, we obtain the real and imaginary parts of the SWNT permittivity from aligned semiconducting SWNTs dispersed in stretched polymer films. Our results are in agreement with theoretical predictions, highlighting the limited polarizability of excitons in a quasi-1D system.

Comparative measures of single-wall carbon nanotube dispersion.

Model composites of DNA-wrapped single-wall carbon nanotubes in poly(acrylic acid) are used to evaluate metrics of nanotube dispersion. By varying the pH of the precursor solutions, we introduce a controlled deviation from ideal behavior. On the basis of small-angle neutron scattering, changes in near-infrared fluorescence intensity are strongly correlated with dispersion, while optical absorption spectroscopy and resonant Raman scattering are less definitive. Our results represent the first systematic comparison of currently accepted measures of nanotube dispersion.

Cloned Theileria parva produces lesser infections in ticks compared to uncloned T. parva despite similar infections in cattle.

Experimental transmissions of cloned Theileria parva in cattle with Rhipicephalus appendiculatus ticks were compared to transmissions with uncloned T. parva during studies on the potential for genetic recombination during syngamy of Theileria to produce antigenic diversity for evasion of bovine immunity. Prevalence and abundance of T. parva infection in adult ticks, which resulted from the feeding of nymphs on the calves, were significantly higher in the uncloned compared to the cloned T. parva. Development of sporoblasts of T. parva in the ticks to produce infective sporozoites was similar. There was no statistically significant difference in the clinical course of infection in cattle between cloned and uncloned T. parva. It was concluded that cloned T. parva has characteristics that reduce its viability during the tick stages of its life cycle.

The known distribution and ecological preferences of the tick subgenus Boophilus (Acari: Ixodidae) in Africa and Latin America.

A compilation of the known distribution of Boophilus ticks in Africa and Latin America is presented, together with details on climate preferences. B. annulatus is recorded mainly in the western part of a strip from the equator to parallel 20 degrees N. It associates with woodlands and forests (lowland rain forest and secondary grassland). This species is also present in the Mediterranean region, associated to woodland and open areas. B. decoloratus extends southern to parallel 20 degrees N, in woodland with montane vegetation and Zambezian miombo; some records have been collected in the highveld grassland. B. geigyi is mainly collected in the western range of a stripe extending between parallels 5 degrees N and 18 degrees N, associated with Sudanian woodland, lowland rain forest with secondary grassland and woodland. Confirmed records of microplus in Africa are restricted to Malagasy region and south and eastern Africa, being predominant in the Zambezian miombo, deciduous forest with secondary grassland, and woodland. In Latin America, microplus is abundant in the Mesoamerican corridor to Venezuela and Colombia, and southern in Brazil and Argentina. The tick is mainly associated to the biomes of Chaco and Pampas in Argentina, the North-central moist Andes, the Atlantic forest (southern range) and the moist Meso-American vegetation (northern range). Most collections of B. annulatus and B. geigyi came from areas where winter minimum temperature is above 15 degrees C, maximum temperatures remain between 33 and 36 degrees C and maximum rainfall is recorded between June and September. B. decoloratus and African B. microplus are recorded in sites with low temperatures in May-September. Minimum temperature requirements are similar for both B. decoloratus and African B. microplus, and both are around 4 degrees C less than the value recorded for collections of Latin-American B. microplus. The rainfall pattern observed for decoloratus shows a minimum in May and June. The requirements of total rainfall are highest for B. microplus in Latin America, while records of African B. microplus are concentrated in areas of low rainfall between May and October, and high rainfall between November and March (low rainfall in the same period for B. decoloratus). Statistical analysis revealed the existence of populations (demes) with ecologically different requirements within each tick species. Both B. annulatus and B. decoloratus showed many different demes clearly associated to defined areas. The collections of Latin American B. microplus are very homogeneous according climate preferences and well separated from the African counterpart.

Validation of the proposed International Society for Heart and Lung Transplantation grading system for primary graft dysfunction after lung transplantation.

BACKGROUND: A scoring system was recently proposed to grade the severity of primary graft dysfunction (PGD), a frequent early complication of lung transplantation. The purposes of this study are to: (1) validate the PGD grading system with respect to patient outcomes; and (2) compare the performance of criteria employing the arterial oxygenation to fraction of inspired oxygen (P/F) ratio to an alternative grading system employing the oxygenation index (OI). METHODS: We retrospectively reviewed the medical records of 402 patients having undergone lung transplantation at our institution from 1992 through 2004. The ISHLT PGD grading system was modified and grades were assigned up to 48 hours post-transplantation as follows: Grade 1 PGD, P/F > 300; Grade 2, P/F 200 to 300; and Grade 3, P/F < 200. A worst score T(0-48) was also assigned, which reflects the highest grade recorded between T0 and T48. RESULTS: The prevalence of severe PGD (P/F Grade 3) declined after transplant, from 25% at T0 to 15% at T48. Grouping patients by P/F grade at T48 demonstrated the clearest differentiation of 90-day death rates (Grade 1, 7%; Grade 2, 12%; Grade 3, 33%) (p = 0.0001). T48 OI grade also differentiates 90-day death rates. There was no difference in longer-term survival between patients with PGD Grades 1 and 2. OI grade at T0 qualitatively improved differential mortality between Grades 1 and 2; however, the differences did not reach statistical significance. Patients with a worst score T(0-48) of Grade 3 PGD did have significantly decreased long-term survival, as well as longer ICU and hospital stay, when compared with Grades 1 and 2 PGD. Significant risk factors for short- and long-term mortality in our multivariate model were P/F Grade 3 [worst score T(0-48) as well as T0 grade], single-lung transplant, use of cardiopulmonary bypass and high pre-operative mean pulmonary artery pressure. CONCLUSIONS: There is an increased risk of short- and long-term mortality and length of hospital stay associated with severe (Grade 3) PGD. The proposed ISHLT grading system can rapidly identify patients with poor outcomes who may benefit from early, aggressive treatment. Refinement of the scoring system may further improve patient risk stratification.