Multicentric carpotarsal osteolysis is caused by mutations clustering in the amino-terminal transcriptional activation domain of MAFB

Multicentric carpotarsal osteolysis (MCTO) is a rare skeletal dysplasia characterized by aggressive osteolysis, particularly affecting the carpal and tarsal bones, and is frequently associated with progressive renal failure. Using exome capture and next-generation sequencing in five unrelated simplex cases of MCTO, we identified previously unreported missense mutations clustering within a 51 base pair region of the single exon of MAFB, validated by Sanger sequencing. A further six unrelated simplex cases with MCTO were also heterozygous for previously unreported mutations within this same region, as were affected members of two families with autosomal-dominant MCTO. MAFB encodes a transcription factor that negatively regulates RANKL-induced osteoclastogenesis and is essential for normal renal development. Identification of this gene paves the way for development of novel therapeutic approaches for this crippling disease and provides insight into normal bone and kidney development.

Novel risk loci for rheumatoid arthritis in Han Chinese and congruence with risk variants in Europeans

Objective To investigate differences in genetic risk factors for rheumatoid arthritis (RA) in Han Chinese as compared with Europeans. Methods A genome-wide association study was conducted in China with 952 patients and 943 controls, and 32 variants were followed up in 2,132 patients and 2,553 controls. A transpopulation meta-analysis with results from a large European RA study was also performed to compare the genetic architecture across the 2 ethnic remote populations. Results Three non-major histocompatibility complex (non-MHC) loci were identified at the genome-wide significance level, the effect sizes of which were larger in anti-citrullinated protein antibody (ACPA)-positive patients than in ACPA-negative patients. These included 2 novel variants, rs12617656, located in an intron of DPP4 (odds ratio [OR] 1.56, P = 1.6 × 10 -21), and rs12379034, located in the coding region of CDK5RAP2 (OR 1.49, P = 1.1 × 10-16), as well as a variant at the known CCR6 locus, rs1854853 (OR 0.71, P = 6.5 × 10-15). The analysis of ACPA-positive patients versus ACPA-negative patients revealed that rs12617656 at the DPP4 locus showed a strong interaction effect with ACPAs (P = 5.3 × 10-18), and such an interaction was also observed for rs7748270 at the MHC locus (P = 5.9 × 10-8). The transpopulation meta-analysis showed genome-wide overlap and enrichment in association signals across the 2 populations, as confirmed by prediction analysis. Conclusion This study has expanded the list of alleles that confer risk of RA, provided new insight into the pathogenesis of RA, and added empirical evidence to the emerging polygenic nature of complex trait variation driven by common genetic variants. Copyright © 2014 by the American College of Rheumatology.

Arson-associated homicide in Australia: A five year follow-up

Arson homicides are rare, representing only two percent of all homicides in Australia each year. In this study, data was collected from the AIC’s National Homicide Monitoring Program (NHMP) to build on previous research undertaken into arson-associated homicides (Davies & Mouzos 2007) and to provide more detailed analysis of cases and offenders. Over the period 1989 to 2010, there were 123 incidents of arson-associated homicide, involving 170 unique victims and 131 offenders. The majority of incidents (63%) occurred in the victim’s home and more than half (57%) of all victims were male. It was found that there has been a 44 percent increase in the number of incidents in the past decade. It is evident that a considerable proportion of the identified arson homicides involved a high degree of premeditation and planning. These homicides were commonly committed by an offender who was well known to the victim, with over half of the victims (56%) specifically targeted by the offender. This paper therefore provides a valuable insight into the nature of arson homicides and signposts areas for further investigation.

Introduction to "Learning Chinese as a Heritage Language : An Australia Perspective"

The book grapples with the complex entanglement of identity construction, language choice, cultural heritage, and social orders. Specifically, the book investigates how Chinese Australians negotiate their Chineseness and capitalise on resources through learning Chinese as a heritage language in Australia and beyond. Though the book is concerned with Chinese Australians, knowledge built and lessons learned can provide insight into other multicultural settings where people of Chinese descent are becoming increasingly prominent in representing the cultural and linguistic diversity of the society, and more recently, in contributing to the economic dynamics of the society. In addition, the focus on the potholes and distractions as well as the benefits and gains of heritage language learning is not restricted to Chinese diaspora, but relevant to ethnic minority individuals and communities elsewhere.

On the mathematical modeling of wound healing angiogenesis in skin as a reaction-transport process

Over the last 30 years, numerous research groups have attempted to provide mathematical descriptions of the skin wound healing process. The development of theoretical models of the interlinked processes that underlie the healing mechanism has yielded considerable insight into aspects of this critical phenomenon that remain difficult to investigate empirically. In particular, the mathematical modeling of angiogenesis, i.e., capillary sprout growth, has offered new paradigms for the understanding of this highly complex and crucial step in the healing pathway. With the recent advances in imaging and cell tracking, the time is now ripe for an appraisal of the utility and importance of mathematical modeling in wound healing angiogenesis research. The purpose of this review is to pedagogically elucidate the conceptual principles that have underpinned the development of mathematical descriptions of wound healing angiogenesis, specifically those that have utilized a continuum reaction-transport framework, and highlight the contribution that such models have made toward the advancement of research in this field. We aim to draw attention to the common assumptions made when developing models of this nature, thereby bringing into focus the advantages and limitations of this approach. A deeper integration of mathematical modeling techniques into the practice of wound healing angiogenesis research promises new perspectives for advancing our knowledge in this area. To this end we detail several open problems related to the understanding of wound healing angiogenesis, and outline how these issues could be addressed through closer cross-disciplinary collaboration.

Advances in solid-catalytic and non-catalytic technologies for biodiesel production

The insecure supply of fossil fuel coerces the scientific society to keep a vision to boost investments in the renewable energy sector. Among the many renewable fuels currently available around the world, biodiesel offers an immediate impact in our energy. In fact, a huge interest in related research indicates a promising future for the biodiesel technology. Heterogeneous catalyzed production of biodiesel has emerged as a preferred route as it is environmentally benign needs no water washing and product separation is much easier. The number of well-defined catalyst complexes that are able to catalyze transesterification reactions efficiently has been significantly expanded in recent years. The activity of catalysts, specifically in application to solid acid/base catalyst in transesterification reaction depends on their structure, strength of basicity/acidity, surface area as well as the stability of catalyst. There are various process intensification technologies based on the use of alternate energy sources such as ultrasound and microwave. The latest advances in research and development related to biodiesel production is represented by non-catalytic supercritical method and focussed exclusively on these processes as forthcoming transesterification processes. The latest developments in this field featuring highly active catalyst complexes are outlined in this review. The knowledge of more extensive research on advances in biofuels will allow a deeper insight into the mechanism of these technologies toward meeting the critical energy challenges in future.

In vitro modeling of the prostate cancer microenvironment

Prostate cancer is the most commonly diagnosed malignancy in men and advanced disease is incurable. Model systems are a fundamental tool for research and many in vitro models of prostate cancer use cancer cell lines in monoculture. Although these have yielded significant insight they are inherently limited by virtue of their two-dimensional (2D) growth and inability to include the influence of tumour microenvironment. These major limitations can be overcome with the development of newer systems that more faithfully recreate and mimic the complex in vivo multi-cellular, three-dimensional (3D) microenvironment. This article presents the current state of in vitro models for prostate cancer, with particular emphasis on 3D systems and the challenges that remain before their potential to advance our understanding of prostate disease and aid in the development and testing of new therapeutic agents can be realised.

A process mining-based investigation of adverse events in care processes

This paper proposes the Clinical Pathway Analysis Method (CPAM) approach that enables the extraction of valuable organisational and medical information on past clinical pathway executions from the event logs of healthcare information systems. The method deals with the complexity of real-world clinical pathways by introducing a perspective-based segmentation of the date-stamped event log. CPAM enables the clinical pathway analyst to effectively and efficiently acquire a profound insight into the clinical pathways. By comparing the specific medical conditions of patients with the factors used for characterising the different clinical pathway variants, the medical expert can identify the best therapeutic option. Process mining-based analytics enables the acquisition of valuable insights into clinical pathways, based on the complete audit traces of previous clinical pathway instances. Additionally, the methodology is suited to assess guideline compliance and analyse adverse events. Finally, the methodology provides support for eliciting tacit knowledge and providing treatment selection assistance.

Single molecule microscopy in 3D cell cultures and tissues

From the onset of the first microscopic visualization of single fluorescent molecules in living cells at the beginning of this century, to the present, almost routine application of single molecule microscopy, the method has well-proven its ability to contribute unmatched detailed insight into the heterogeneous and dynamic molecular world life is composed of. Except for investigations on bacteria and yeast, almost the entire story of success is based on studies on adherent mammalian 2D cell cultures. However, despite this continuous progress, the technique was not able to keep pace with the move of the cell biology community to adapt 3D cell culture models for basic research, regenerative medicine, or drug development and screening. In this review, we will summarize the progress, which only recently allowed for the application of single molecule microscopy to 3D cell systems and give an overview of the technical advances that led to it. While initially posing a challenge, we finally conclude that relevant 3D cell models will become an integral part of the on-going success of single molecule microscopy.

Visible light enhanced oxidant free dehydrogenation of aromatic alcohols using Au-Pd alloy nanoparticle catalysts

We find that visible light irradiation of gold–palladium alloy nanoparticles supported on photocatalytically inert ZrO2 significantly enhances their catalytic activity for oxidant-free dehydrogenation of aromatic alcohols to the corresponding aldehydes at ambient temperatures. Dehydrogenation is also the dominant process in the selective oxidation of the alcohols to the corresponding aldehydes with molecular oxygen. The alloy nanoparticles strongly absorb light and exhibit superior catalytic and photocatalytic activity when compared to either pure palladium or gold nanoparticles. Analysis with a free electron gas model for the bulk alloy structure reveals that the alloying increases the surface charge heterogeneity on the alloy particle surface, which enhances the interaction between the alcohol molecules and the metal NPs. The increased surface charge heterogeneity of the alloy particles is confirmed with density function theory applied to small alloy clusters. Optimal catalytic activity was observed with a Au : Pd molar ratio of 1 : 186, which is in good agreement with the theoretical analysis. The rate-determining step of the dehydrogenation is hydrogen abstraction. The conduction electrons of the nanoparticles are photo-excited by the incident light giving them the necessary energy to be injected into the adsorbed alcohol molecules, promoting the hydrogen abstraction. The strong chemical adsorption of alcohol molecules facilitates this electron transfer. The results show that the alloy nanoparticles efficiently couple thermal and photonic energy sources to drive the dehydrogenation. These findings provide useful insight into the design of catalysts that utilize light for various organic syntheses at ambient temperatures.

Tracking the patient journey by combining multiple hospital database systems

With new national targets for patient flow in public hospitals designed to increase efficiencies in patient care and resource use, better knowledge of events affecting length of stay will support improved bed management and scheduling of procedures. This paper presents a case study involving the integration of material from each of three databases in operation at one tertiary hospital and demonstrates it is possible to follow patient journeys from admission to discharge. What is known about this topic? At present, patient data at one Queensland tertiary hospital are assembled in three information systems: (1) the Hospital Based Corporate Information System (HBCIS), which tracks patients from in-patient admission to discharge; (2) the Emergency Department Information System (EDIS) containing patient data from presentation to departure from the emergency department; and (3) Operation Room Management Information System (ORMIS), which records surgical operations. What does this paper add? This paper describes how a new enquiry tool may be used to link the three hospital information systems for studying the hospital journey through different wards and/or operating theatres for both individual and groups of patients. What are the implications for practitioners? An understanding of the patients’ journeys provides better insight into patient flow and provides the tool for research relating to access block, as well as optimising the use of physical and human resources.

Temporal and environmental influences on the vocal behaviour of a nocturnal bird

Temporal and environmental variation in vocal activity can provide information on avian behaviour and call function not available to short-term experimental studies. Intersexual differences in this variation can provide insight into selection effects. Yet factors influencing vocal behaviour have not been assessed in many birds, even those monitored by acoustic methods. This applies to the New Zealand kiwi (Apterygidae), for which call censuses are used extensively in conservation monitoring, yet which have poorly understood acoustic ecology. We investigated little spotted kiwi Apteryx owenii vocal behaviour over 3 yr, measuring influences on vocal activity in both sexes from time of night, season, weather conditions and lunar cycle. We tested hypotheses that call rate variation reflects call function, foraging efficiency, historic predation risk and variability in sound transmission, and that there are inter-sexual differences in call function. Significant seasonal variation showed that vocalisations were important in kiwi reproduction, and inter-sexual synchronisation of call rates indicated that contact, pair-bonding or resource defence were key functions. All weather variables significantly affected call rates, with elevated calling during increased humidity and ground moisture indicating a relation between vocal activity and foraging conditions. A significant decrease in calling activity on cloudy nights, combined with no moonlight effect, suggests an impact of light pollution in this species. These influences on vocal activity provide insight into kiwi call function, have direct consequences for conservation monitoring of kiwi, and have wider implications in understanding vocal behaviour in a range of nocturnal birds

Monitoring care processes in the gynecologic oncology department

The care processes of healthcare providers are typically considered as human-centric, flexible, evolving, complex and multi-disciplinary. Consequently, acquiring an insight in the dynamics of these care processes can be an arduous task. A novel event log based approach for extracting valuable medical and organizational information on past executions of the care processes is presented in this study. Care processes are analyzed with the help of a preferential set of process mining techniques in order to discover recurring patterns, analyze and characterize process variants and identify adverse medical events.

Evolution of a ~2.7 Ga large igneous province: A volcanological, geochemical and geochronological study of the Agnew Greenstone Belt, and new regional correlations for the Kalgoorlie Terrane (Yilgarn Craton, Western Australia)

The thick package of ~2.7 Ga mafic and ultramafic lavas and intrusions preserved among the Neoarchean of the Kalgoorlie Terrene in Western Australia provides valuable insight into geological processes controlling the most prodigious episode of growth and preservation of juvenile continental crust in Earth’s history. Limited exposure of these rocks results in uncertainty about their age, physical and chemical characteristics, and stratigraphic relationships. This in turn prevents confident correlation of regional occurrences of mafic and ultramafic successions (both intrusive and extrusive) and hinders the interpretation of tectonic setting and magmatic evolution. A recent stratigraphic drilling program of the Neoarchean stratigraphy of the Agnew Greenstone Belt in Western Australia has provided continuous exposures through a c. 7 km thick sequence of mafic and ultramafic units. In this study, we present a volcanological, lithogeochemical and chronological study of the Agnew Greenstone Belt, and provide the first pre-2690 Ma regional correlation across the Kalgoorlie Terrane. The Agnew Greenstone Belt records ~30 m.y. of episodic ultramafic-mafic magmatism that includes two cycles, each defined by a komatiite that is overlain by units that become more evolved and contaminated with time. The sequence is divided into nine conformable packages, each consisting of stacked subaqueous lava flows and comagmatic intrusions, as well as two sills without associated extrusions. Lavas, with the exception of intercalations between two units, form a layer-cake stratigraphy and were likely erupted from a system of fissures tapping the same magma source. The komatiites are not contaminated by continental crust ([La/Sm]PM ~0.7) and are of the Al-undepleted Munro-type. Crustal contamination is evident in many units (Songvang Basalt, Never Can Tell Basalt, Redeemer Basalt, and Turrett Dolerite), as judged by [La/Sm]>1, negative Nb and Ti anomalies, and geochemical mixing trends towards felsic contaminants. Crystal fractionation was also significant, with early olivine and chromite (Mg#>65) followed by plagioclase and clinopyroxene removal (Mg<65), and in the most evolved case, titanomagnetite accumulation. Three new TIMS dates on granophyric zones of mafic sills and one ICP-MS date from an interflow felsic tuff are presented and used for regional stratigraphic correlation. Cycle I magmatism began at ~2720 Ma and ended ~2705 Ma, whereas cycle II began ~2705 Ma and ended at 2690.7±1.2 Ma. Regional correlations indicate the western Kalgoorlie Terrane consists of a remarkably similar stratigraphy that can be recognised at Agnew, Ora Banda and Coolgardie, whereas the eastern part of the terrane (e.g., Kambalda Domain) does not include cycle I, but correlates well with cycle II. This research supports an autochthonous model of greenstone formation, in which one large igneous province, represented by two complete cycles, is constructed on sialic crust. New stratigraphic correlations for the Kalgoorlie Terrane indicate that many units can be traced over distances >100 km, which has implications for exploration targeting for stratigraphically hosted ultramafic Ni and VMS deposits.

Fear memory reactivation after extinction activates plasticity in the lateral amygdala

Little is known about the neuronal changes that occur within the lateral amygdala (LA) following fear extinction. In fear extinction, the repeated presentation of a conditioned stimulus (CS), in the absence of a previously paired aversive unconditioned stimulus (US), reduces fear elicited by the CS. Fear extinction is an active learning process that leads to the formation of a consolidated extinction memory, however it is fragile and prone to spontaneous recovery and renewal under environmental changes such as context. Understanding the neural mechanisms underlying fear extinction is of great clinical relevance, as psychological treatments of several anxiety disorders rely largely on extinction-based procedures and relapse is major clinical problem. This study investigated plasticity in the LA following fear memory reactivation in rats with and without extinction training. Phosphorylated MAPK (p44/42 ERK/MAPK), a protein kinase required in the amygdala for fear learning and its extinction, was used as a marker for neuronal plasticity. Rats (N = 11) underwent a Pavlovian auditory fear conditioning and extinction paradigm, and later received a single conditioned stimulus presentation to reactivate the fear memory. Results showed more pMAPK+ expressing neurons in the LA following extinction-reactivation compared to control rats, with the largest number of pMAPK+ neurons counted in the ventral LA, especially including the ventro-lateral subdivision (LAvl). These findings indicate that LA subdivision specific plasticity occurs to the conditioned fear memory in the LAvl following extinction-reactivation. These findings provide important insight into the organisation of fear memories in the LA, and pave the way for future research in the memory mechanisms of fear extinction and its pathophysiology.