Long-term stability of adipose tissue generated from a vascularized pedicled fat flap inside a chamber

Background Numerous studies demonstrate the generation and short-term survival of adipose tissue; however, long-term persistence remains elusive. This study evaluates long-term survival and transferability of de novo adipose constructs based on a ligated vascular pedicle and tissue engineering chamber combination. Methods Defined adipose tissue flaps were implanted into rats in either intact or perforated domed chambers. In half of the groups, the chambers were removed after 10 weeks and the constructs transferred on their vascular pedicle to a new site, where they were observed for a further 10 weeks. In the remaining groups, the tissue construct was observed for 20 weeks inside the chamber. Tissue volume was assessed using magnetic resonance imaging and histologic measures, and constructs were assessed for stability and necrosis. Sections were assessed histologically and for proliferation using Ki-67. Results At 20 weeks, volume analysis revealed an increase in adipose volume from 0.04 ± 0.001 ml at the time of insertion into the chambers to 0.27 ± 0.004 ml in the closed and 0.44 ± 0.014 ml in the perforated chambers. There was an additional increase of approximately 10 to 15 percent in tissue volume in flaps that remained in chambers for 20 weeks, whereas the volume of the transferred tissue not in chambers remained unaltered. Histomorphometric assessment of the tissues documented no signs of hypertrophy, fat necrosis, or atypical changes of the newly generated tissue. Conclusion This study presents a promising new method of generating significant amounts of mature, vascularized, stable, and transferable adipose tissue for permanent autologous soft-tissue replacement.

Priority Threat Management for Pilbara Species of Conservation Significance

This project provides a costed and appraised set of management strategies for mitigating threats to species of conservation significance in the Pilbara IBRA bioregion of Western Australia (hereafter 'the Pilbara'). Conservation significant species are either listed under federal and state legislation, international agreements or considered likely to be threatened in the next 20 years. Here we report on the 17 technically and socially feasible management strategies, which were drawn from the collective experience and knowledge of 49 experts and stakeholders in the ecology and management of the Pilbara region. We determine the relative ecological cost-effectiveness of each strategy, calculated as the expected benefit of management to the persistence of 53 key threatened native fauna and flora species, divided by the expected cost of management. Finally we provide decision support to assist prioritisation of the strategies on the basis of ecological cost-effectiveness.

Dynamic modelling of long-term care decisions

This paper describes and analyzes research on the dynamics of long-term care and the policy relevance of identifying the sources of persistence in caregiving arrangements (including the effect of dynamics on parameter estimates, implications for family welfare, parent welfare, child welfare, and cost of government programs). We discuss sources and causes of observed persistence in caregiving arrangements including inertia/state dependence (confounded by unobserved heterogeneity) and costs of changing caregivers. We comment on causes of dynamics including learning/human capital accumulation; burnout; and game-playing. We suggest how to deal with endogenous geography; dynamics in discrete and continuous choices; and equilibrium issues (multiple equilibria, dynamic equilibria). We also present an overview of commonly used longitudinal data sets and evaluate their relative advantages/disadvantages. We also discuss other data issues related to noisy measures of wealth and family structure. Finally, we suggest some methods to handle econometric problems such as endogeneous geography. © 2014 Springer Science+Business Media New York.

Mastery motivation in children with intellectual disability : Is there evidence for a Down syndrome behavioural phenotype?

The main purpose of the current study was to provide empirical evidence to support or refute assumptions of phenotypic deficits in motivation for children with Down syndrome. Children with moderate intellectual disability associated with etiologies other than Down syndrome were recruited in an extension of a previous study that involved children with Down syndrome and typically developing children. The participants were 29 children with moderate intellectual disability and 33 children with Down syndrome who were matched on mental age to 33 typically developing children, aged 3 to 8 years. Mastery motivation was assessed on task measures of curiosity, preference for challenge, and persistence, as well as parental reports. There were no significant group differences on the mastery motivation tasks. Parental ratings of mastery motivation differed, with typically developing children generally being rated more highly than each of the disability groups. The view that motivational deficits are part of the Down syndrome behavioural phenotype was not supported.

Motivation in children with intellectual disabilities

This article addresses the questions of whether there are motivational deficits in children with intellectual disabilities, whether those with Down syndrome are more likely to display motivational deficits, and how motivation might be supported. The available literature that has examined motivation in children with intellectual disabilities was considered and integrated to address the questions outlined above. There is little published research on this vital topic. Reports on motivational problems differ depending upon the method of data collection. Observational studies using structured tasks generally reveal no differences between children with intellectual disabilities and typically developing children matched for mental age. When reports of parents or teachers are used, children with intellectual disabilities appear to have deficits in motivation. No evidence was found for a particular deficit in children with Down syndrome. The results of this review challenge the perception that children with intellectual disabilities will generally have motivational problems, although it is clear that motivation is a complex construct, not easily examined in those with intellectual disabilities. Strategies for addressing problems and for maintaining motivation, based on theory and evidence, are provided. These strategies are applicable across a range of settings including the home, school, and more adult-oriented services.

Senataxin plays an essential role with DNA damage response proteins in meiotic recombination and gene silencing

Senataxin, mutated in the human genetic disorder ataxia with oculomotor apraxia type 2 (AOA2), plays an important role in maintaining genome integrity by coordination of transcription, DNA replication, and the DNA damage response. We demonstrate that senataxin is essential for spermatogenesis and that it functions at two stages in meiosis during crossing-over in homologous recombination and in meiotic sex chromosome inactivation (MSCI). Disruption of the Setx gene caused persistence of DNA double-strand breaks, a defect in disassembly of Rad51 filaments, accumulation of DNA:RNA hybrids (R-loops), and ultimately a failure of crossing-over. Senataxin localised to the XY body in a Brca1-dependent manner, and in its absence there was incomplete localisation of DNA damage response proteins to the XY chromosomes and ATR was retained on the axial elements of these chromosomes, failing to diffuse out into chromatin. Furthermore persistence of RNA polymerase II activity, altered ubH2A distribution, and abnormal XY-linked gene expression in Setx⁻/⁻ revealed an essential role for senataxin in MSCI. These data support key roles for senataxin in coordinating meiotic crossing-over with transcription and in gene silencing to protect the integrity of the genome.

Long-term experiments with an adaptive spherical view representation for navigation in changing environments

Real-world environments such as houses and offices change over time, meaning that a mobile robot’s map will become out of date. In this work, we introduce a method to update the reference views in a hybrid metrictopological map so that a mobile robot can continue to localize itself in a changing environment. The updating mechanism, based on the multi-store model of human memory, incorporates a spherical metric representation of the observed visual features for each node in the map, which enables the robot to estimate its heading and navigate using multi-view geometry, as well as representing the local 3D geometry of the environment. A series of experiments demonstrate the persistence performance of the proposed system in real changing environments, including analysis of the long-term stability.

Modelling the dynamics of Plasmodium falciparum histidine-rich protein 2 in human malaria to better understand malaria rapid diagnostic test performance

BACKGROUND: Effective diagnosis of malaria is a major component of case management. Rapid diagnostic tests (RDTs) based on Plasmodium falciparumhistidine-rich protein 2 (PfHRP2) are popular for diagnosis of this most virulent malaria infection. However, concerns have been raised about the longevity of the PfHRP2 antigenaemia following curative treatment in endemic regions. METHODS: A model of PfHRP2 production and decay was developed to mimic the kinetics of PfHRP2 antigenaemia during infections. Data from two human infection studies was used to fit the model, and to investigate PfHRP2 kinetics. Four malaria RDTs were assessed in the laboratory to determine the minimum detectable concentration of PfHRP2. RESULTS: Fitting of the PfHRP2 dynamics model indicated that in malaria naive hosts, P. falciparum parasites of the 3D7 strain produce 1.4 x 10(-)(1)(3) g of PfHRP2 per parasite per replication cycle. The four RDTs had minimum detection thresholds between 6.9 and 27.8 ng/mL. Combining these detection thresholds with the kinetics of PfHRP2, it is predicted that as few as 8 parasites/muL may be required to maintain a positive RDT in a chronic infection. CONCLUSIONS: The results of the model indicate that good quality PfHRP2-based RDTs should be able to detect parasites on the first day of symptoms, and that the persistence of the antigen will cause the tests to remain positive for at least seven days after treatment. The duration of a positive test result following curative treatment is dependent on the duration and density of parasitaemia prior to treatment and the presence and affinity of anti-PfHRP2 antibodies.

Do children and adolescents with Down syndrome have deficits in motivation?

There appears to be a general acceptance that individuals with intellectual disability (ID) have deficits in motivation. Yet research with infants and young children has usually identified few differences in motivation for children with ID compared with those of the same mental age who are developing typically. Studies of motivation in children with ID in the middle years of childhood or adolescence are almost non-existent. However, research conducted more than 30 years ago (Harter & Zigler, 1974) continues to be cited as evidence of motivational deficits in those with ID even though the life experiences of people with ID have changed dramatically since that time.

Temporal Characterization of Ossification of the Crania in Australian Subadults: New standards for Age Estimation using Computed Tomography

After attending this presentation, attendees will gain awareness of the ontogeny of cranial maturation, specifically: (1) the fusion timings of primary ossification centers in the basicranium; and (2) the temporal pattern of closure of the anterior fontanelle, to develop new population-specific age standards for medicolegal death investigation of Australian subadults. This presentation will impact the forensic science community by demonstrating the potential of a contemporary forensic subadult Computed Tomography (CT) database of cranial scans and population data, to recalibrate existing standards for age estimation and quantify growth and development of Australian children. This research welcomes a study design applicable to all countries faced with paucity in skeletal repositories. Accurate assessment of age-at-death of skeletal remains represents a key element in forensic anthropology methodology. In Australian casework, age standards derived from American reference samples are applied in light of scarcity in documented Australian skeletal collections. Currently practitioners rely on antiquated standards, such as the Scheuer and Black1 compilation for age estimation, despite implications of secular trends and population variation. Skeletal maturation standards are population specific and should not be extrapolated from one population to another, while secular changes in skeletal dimensions and accelerated maturation underscore the importance of establishing modern standards to estimate age in modern subadults. Despite CT imaging becoming the gold standard for skeletal analysis in Australia, practitioners caution the application of forensic age standards derived from macroscopic inspection to a CT medium, suggesting a need for revised methodologies. Multi-slice CT scans of subadult crania and cervical vertebrae 1 and 2 were acquired from 350 Australian individuals (males: n=193, females: n=157) aged birth to 12 years. The CT database, projected at 920 individuals upon completion (January 2014), comprises thin-slice DICOM data (resolution: 0.5/0.3mm) of patients scanned since 2010 at major Brisbane Childrens Hospitals. DICOM datasets were subject to manual segmentation, followed by the construction of multi-planar and volume rendering cranial models, for subsequent scoring. The union of primary ossification centers of the occipital bone were scored as open, partially closed or completely closed; while the fontanelles, and vertebrae were scored in accordance with two stages. Transition analysis was applied to elucidate age at transition between union states for each center, and robust age parameters established using Bayesian statistics. In comparison to reported literature, closure of the fontanelles and contiguous sutures in Australian infants occur earlier than reported, with the anterior fontanelle transitioning from open to closed at 16.7±1.1 months. The metopic suture is closed prior to 10 weeks post-partum and completely obliterated by 6 months of age, independent of sex. Utilizing reverse engineering capabilities, an alternate method for infant age estimation based on quantification of fontanelle area and non-linear regression with variance component modeling will be presented. Closure models indicate that the greatest rate of change in anterior fontanelle area occurs prior to 5 months of age. This study complements the work of Scheuer and Black1, providing more specific age intervals for union and temporal maturity of each primary ossification center of the occipital bone. For example, dominant fusion of the sutura intra-occipitalis posterior occurs before 9 months of age, followed by persistence of a hyaline cartilage tongue posterior to the foramen magnum until 2.5 years; with obliteration at 2.9±0.1 years. Recalibrated age parameters for the atlas and axis are presented, with the anterior arch of the atlas appearing at 2.9 months in females and 6.3 months in males; while dentoneural, dentocentral and neurocentral junctions of the axis transitioned from non-union to union at 2.1±0.1 years in females and 3.7±0.1 years in males. These results are an exemplar of significant sexual dimorphism in maturation (p<0.05), with girls exhibiting union earlier than boys, justifying the need for segregated sex standards for age estimation. Studies such as this are imperative for providing updated standards for Australian forensic and pediatric practice and provide an insight into skeletal development of this population. During this presentation, the utility of novel regression models for age estimation of infants will be discussed, with emphasis on three-dimensional modeling capabilities of complex structures such as fontanelles, for the development of new age estimation methods.

Evolution to a chronic disease niche correlates with increased sensitivity to tryptophan availability for the obligate intracellular bacterium Chlamydia pneumoniae

The chlamydiae are obligate intracellular parasites that have evolved specific interactions with their various hosts and host cell types to ensure their successful survival and consequential pathogenesis. The species Chlamydia pneumoniae is ubiquitous, with serological studies showing that most humans are infected at some stage in their lifetime. While most human infections are asymptomatic, C. pneumoniae can cause more-severe respiratory disease and pneumonia and has been linked to chronic diseases such as asthma, atherosclerosis, and even Alzheimer's disease. The widely dispersed animal-adapted C. pneumoniae strains cause an equally wide range of diseases in their hosts. It is emerging that the ability of C. pneumoniae to survive inside its target cells, including evasion of the host's immune attack mechanisms, is linked to the acquisition of key metabolites. Tryptophan and arginine are key checkpoint compounds in this host-parasite battle. Interestingly, the animal strains of C. pneumoniae have a slightly larger genome, enabling them to cope better with metabolite restrictions. It therefore appears that as the evolutionarily more ancient animal strains have evolved to infect humans, they have selectively become more "susceptible" to the levels of key metabolites, such as tryptophan. While this might initially appear to be a weakness, it allows these human C. pneumoniae strains to exquisitely sense host immune attack and respond by rapidly reverting to a persistent phase. During persistence, they reduce their metabolic levels, halting progression of their developmental cycle, waiting until the hostile external conditions have passed before they reemerge.

The association between the measurement of adherence to anti-diabetes medicine and the HbA1c

BACKGROUND: Adherence to medicines is important in subjects with diabetes, as nonadherence is associated with an increased risk of morbidity and mortality. However, it is not clear whether there is an association between adherence to medicines and glycaemic control, as not all studies have shown this. One of the reasons for this discrepancy may be that, although there is a standard measure of glycaemic control i.e. HbA1c, there is no standard measure of adherence to medicines. Adherence to medicines can be measured either qualitatively by Morisky or non-Morisky methods or quantitatively using the medicines possession ratio (MPR). AIMS OF THE REVIEW: The aims of this literature review are (1) to determine whether there is an association between adherence to anti-diabetes medicines and glycaemic control, and (2) whether any such association is dependent on how adherence is measured. Methods A literature search of Medline, CINAHL and the Internet (Google) was undertaken with search terms; 'diabetes' with 'adherence' (or compliance, concordance, persistence, continuation) with 'HbA1c' (or glycaemic control). RESULTS: Twenty-three studies were included; 10 qualitative and 12 quantitative studies, and one study using both methods. For the qualitative methods measurements of adherence to anti-diabetes medicines (non-Morisky and Morisky), eight out of ten studies show an association with HbA1c. Nine of ten studies using the quantitative MPR, and two studies using MPR for insulin only, have also shown an association between adherence to anti-diabetes medicines and HbA1c. However, the one study that used both Morisky and MPR did not show an association. Three of the four studies that did not show a relationship, did not use a range of HbA1c values in their regression analysis. The other study that did not show a relationship was specifically in a low income population. CONCLUSIONS: Most studies show an association between adherence to anti-diabetes medicines and HbA1c levels, and this seems to be independent of method used to measure adherence. However, to show an association it is necessary to have a range of HbA1c values. Also, the association is not always apparent in low income populations.

Benefits of integrating complementarity into priority threat management

Conservation decision tools based on cost-effectiveness analysis are used to assess threat management strategies for improving species persistence. These approaches rank alternative strategies by their benefit to cost ratio but may fail to identify the optimal sets of strategies to implement under limited budgets because they do not account for redundancies. We devised a multi objective optimization approach in which the complementarity principle is applied to identify the sets of threat management strategies that protect the most species for any budget. We used our approach to prioritize threat management strategies for 53 species of conservation concern in the Pilbara, Australia. We followed a structured elicitation approach to collect information on the benefits and costs of implementing 17 different conservation strategies during a 3-day workshop with 49 stakeholders and experts in the biodiversity, conservation, and management of the Pilbara. We compared the performance of our complementarity priority threat management approach with a current cost-effectiveness ranking approach. A complementary set of 3 strategies: domestic herbivore management, fire management and research, and sanctuaries provided all species with >50% chance of persistence for $4.7 million/year over 20 years. Achieving the same result cost almost twice as much ($9.71 million/year) when strategies were selected by their cost-effectiveness ranks alone. Our results show that complementarity of management benefits has the potential to double the impact of priority threat management approaches.

Sex-specific roost selection by bats in clearfell harvested plantation forest : improved knowledge advises management

To maximize energetic savings, female bats often roost communally whilst pregnant or with non-volant dependents, whereas male bats more often roost alone; however, differences in selection of roosts by sex have not often been investigated. Better understanding of female colony locations could focus management to protect the majority of bats. New Zealand's long-tailed bat (Chalinolobus tuberculatus) roost in exotic plantation forest, where sex-specific roost selection has not been investigated, and therefore such management is not possible. We investigated sex-specific roost selection by long-tailed bats for the first time. Roosts and paired nonroosts were characterized testing predictions that males and females select roosts that differ from non-roosts, and males and females select different roosts. Females and males chose Pinus radiata roosts that differed from non-roost trees. Results suggest each sex chose roosts that maximized energetic savings. Female bats used roosts closer to water sources, that warmed earlier in the day, which allowed maintenance of high temperatures. Males appeared to choose roosts that allowed torpor use for long periods of the day. Males may be less selective with their roost locations than females, as they roosted further from water sources. This could allow persistence of male bats in marginal habitat. As all female long-tailed bats chose roosts within 150 m of waterways, management to protect bats could be focused here. To protect bats least able to escape when roosts are harvested, harvest of forest stands selected by female bats as roost sites should be planned when bats are not heavily pregnant nor have non-volant dependents.

The performance of diversified emerging market equity funds

We investigate the performance of globally diversified emerging market equity funds during the first decade of the twenty-first century. A vast majority of these funds do not outperform the market benchmark even before transaction costs. The systematic risk of most of the funds is similar to that of the market benchmark portfolio, which may suggest that they aim to offer diversification benefits rather than seeking superior risk-adjusted returns through active management. We do not find any evidence of market timing ability amongst these funds. Finally, whilst we detect persistence in performance, this result is driven mainly by the poorly performing funds.