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.

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.

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.

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.

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.

Arabidopsis AUX1 gene: a permease-like regulator of root gravitropism.

The plant hormone auxin regulates various developmental processes including root formation, vascular development, and gravitropism. Mutations within the AUX1 gene confer an auxin-resistant root growth phenotype and abolish root gravitropic curvature. Polypeptide sequence similarity to amino acid permeases suggests that AUX1 mediates the transport of an amino acid-like signaling molecule. Indole-3-acetic acid, the major form of auxin in higher plants, is structurally similar to tryptophan and is a likely substrate for the AUX1 gene product. The cloned AUX1 gene can restore the auxin-responsiveness of transgenic aux1 roots. Spatially, AUX1 is expressed in root apical tissues that regulate root gravitropic curvature.

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.

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.

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.

Diet and urinary steroids in black and white North American men and black South African men.

Urinary steroid hormone content was determined in Black and White North American men and in rural Black South African men between 40 and 55 years of age and in Black South African men over 60 years of age when maintained on their customary diets or when transferred to a vegetarian or Western diet, respectively. When eating their customary diets, Black South African men had lower levels of urinary estrogens and androgens than did Black and White North American men. The total androgen content decreased significantly in Black North American men on the vegetarian diet and increased in Black South African men fed a Western diet. Urinary excretion of estrogens was higher in older than in younger rural Black South African men. Data indicated that a vegetarian diet modified androgen and estrogen metabolism in North American men and that a Western diet was associated with higher levels of urinary steroid hormones in young Black South African men. Diet-related changes in steroid metabolism in rural Black South African men were age dependent. The relationship of the increased urinary excretion of steroid hormones in Black South African men, a low-risk group fed a Western diet, and the decreased excretion in Black and White North American men, high-risk groups fed a vegetarian diet, to the development of prostatic cancer remains to be clarified.

Response to luteinizing releasing hormone, thyrotrophic releasing hormone, and human chorionic gonadotropin administration in healthy men at different risks for prostatic cancer and in prostatic cancer patients.

A comparative study of the pituitary and testicular response to luteinizing releasing hormone (LHRH), thyrotrophic releasing hormone (TRH), and human chorionic gonadotrophin (HCG) administration was carried out in (a) low-risk young South African black men and high-risk North American black men for prostatic cancer and (b) healthy elderly South African men and South African black men with prostatic cancer. A comparable HCG response occurred in young South African and North American black men, while a greater release of prolactin, but a lesser release of luteinizing hormone in response to LHRH:TRH occurred in South African black men. The response to HCG was comparable in elderly and young South African black men, although the prolactin release in response to TRH was greater in elderly men. A more prolonged release of luteinizing hormone was evident in men with prostatic cancer. Higher estradiol and estrone but lower androstenedione levels occurred in men with prostatic cancer. Data suggest that, in the elderly South African black men with prostatic cancer, estrogen metabolism is modified and that either the estrogen level or the higher estrogen:androgen levels modify the pituitary response to LHRH:TRH. A Western diet enhanced the changes in hormone profiles evident in black South African men with prostatic cancer.

Effect of diet on plasma and urinary hormones in South African black men with prostatic cancer.

Epidemiological evidence suggests that the incidence and death rate from prostatic cancer, an endocrine-associated disease, are related to environmental factors including diet. In this study, a comparison of serum and urinary levels of steroid hormones was carried out in healthy elderly rural vegetarian South African black men, a low-risk population, and a comparable group of men with prostatic cancer. In these prostatic cancer patients, plasma androgen levels decreased, while estrogen levels increased. Concomitantly, the androsterone:etiocholanolone ratio increased, and a greater proportion of estrogens was excreted as estriol. When transferred to a Western diet, plasma androgens showed a further decrease and a greater increase in estrone in prostatic cancer patients. In prostatic cancer patients, the total urinary androgen and estrogen levels were unaltered. However, in elderly healthy men, the Western diet decreased the excretion of estrogens and androgens. Thus, a Western diet supplemented the decrease in plasma androgens initially present in these patients. Evidence suggests that the decrease in plasma androgens increases the estrogen: androgen ratio, which may lead to hyperplasia of the prostatic ductal epithelia, a change enhanced by a Western diet. Changes in urinary steroid hormone levels in South African black patients comparable to those reported in white prostatic cancer patients indicate that hormonal changes must be related to several environmental factors, apart from diet. A simultaneous study of the steroid hormone composition of blood and prostatic fluid in this low-risk population is suggested.

Environmental factors and breast and prostatic cancer.

Despite epidemiological evidence supporting a causal relationship between environmental factors and the development of breast and prostatic cancers, direct confirmation is unproven. Differences in hormone profiles in cancer patients and in patients with an increasing number of potential risk factors together with differences n life style and diet, suggest a relationship between diet, hormonal metabolism, and these endocrine-associated cancers. Modification of hormonal status by diet in men and women at different risk suggests that specific dietary components play a major role in these diseases.

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.

Allele-specific interactions between ttg and gl1 during trichome development in Arabidopsis thaliana.

Trichome development in Arabidopsis thaliana is a well-characterized model for the study of plant cell differentiation. Two genes that play an essential role in the initiation of trichome development are GL1 and TTG. Mutations in either gene prevent the initiation of most trichomes. The GL1 gene encodes a myb-related transcription factor. Mutations in TTG are pleiotropic, affecting anthocyanins, root hairs, and seed coat mucilage in addition to trichomes. Six ttg alleles were examined and shown to form a hypomorphic series. The severity of all aspects of the ttg phenotype varied in parallel in this allelic series. The weakest allele, ttg-10, causes frequent clusters of adjacent trichomes, suggesting a role for TTG in inhibiting neighboring cells from choosing the trichome fate. This allele results from a mutation in the 5'-untranslated region of ttg and creates an out-of-frame upstream AUG codon. The ttg-10 allele shows several unusual genetic interactions with the weak hypomorphic gl1-2 allele, including intergenic noncomplementation and a synthetic glabrous phenotype. These interactions are specific for the gl1-2 allele. The implication of these results for current models of trichome development is discussed.

Lung cancer in Africans in a South African city population in transition.

In South Africa, a study has been carried out on a series of African patients with lung cancer, who were admitted in 1994-1999 to King Edward VIII Hospital (2000 beds), and who lived in Durban (population includes approximately 650 000 resident Africans). In the urban context, Africans have recently experienced numerous changes in environmental, socio-economic and dietary factors and in other respects, thereby undergoing considerable westernization of lifestyle, compared with the past and the situation still prevailing among Africans in rural areas. In the period indicated, the mean annual number of patients admitted with lung cancer included 56 men and 9 women, thereby yielding standardized incidence rates of 15.5 and 3.5, respectively, per 100 000. While such data have their limitations, it is noteworthy that in the South African Cancer Registry for 1993-1995 the corresponding rates (pathology based) for African men and women for the whole country, rural and urban, were 11.7 and 2.6, respectively, per 100 000. In comparison, in the Registry the corresponding rates reported for white South African men and women were 22.3 and 12.3 per 100 000. With the ongoing transitional changes prevailing, most particularly concerning rises in smoking among adolescents, there is little chance of controlling further rises in the occurrence of the disease. It is significant that in the US, African Americans have been reported to have the highest rate for lung cancer in the world.

Outcomes of febrile children presumed to be immunocompetent who present with leukopenia or neutropenia to an ambulatory setting.

UNLABELLED: To determine significant medical outcomes in febrile children presenting to an ambulatory setting with neutropenia and/or leukopenia. METHODS: Retrospective medical record review conducted on febrile patients who had a blood culture drawn, with white blood cell counts less than 5,000/mm3 and/or an absolute neutrophil count less than 1000/mm3. Ninety-one patients were identified; 5 with positive blood culture results, 13 with significant non-oncologic disease, and 3 patients with leukemia who had involvement of 2 or more cell lines. CONCLUSIONS: In the majority of patients, clinical judgment, physical findings, and review of all cell lines of the complete blood cell count identified those with significant disease.