155 resultados para Point mutations


Relevância:

20.00% 20.00%

Publicador:

Resumo:

The April 2015 edition of Curriculum Perspectives has a special focus and casts light on the continuing development of the Australian Curriculum. This paper provides an introduction to a series of papers in the Point and Counterpoint section of this edition on the Review of the Australian Curriculum with reference to History. It makes clear that History is one of the most contested areas of the curriculum and that whilst politicians and policy makers are concerned with the importance of history in relation to national identity and nation building, history serves other purposes. The paper reiterates the need to pay attention to the particularities of discipline–based knowledge for the study of history in schools and the central role of inquiry for student learning in history. In doing so, it establishes the context for the five papers which follow.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

As cities are rapidly developing new interventions against climate change, embedding renewable energy in public spaces is an important strategy. However, most interventions primarily include environmental sustainability while neglecting the social and economic interrelationships of electricity production. Although there is a growing interest in sustainability within environmental design and landscape architecture, public spaces are still awaiting viable energy-conscious design and assessment interventions. The purpose of this paper is to investigate this issue in a renowned public space—Ballast Point Park in Sydney—using a triple bottom line (TBL) case study approach. The emerging factors and relationships of each component of TBL, within the context of public open space, are identified and discussed. With specific focus on renewable energy distribution in and around Ballast Point Park, the paper concludes with a general design framework, which conceptualizes an optimal distribution of onsite electricity produced from renewable sources embedded in public open spaces.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Background: It is important for nutrition intervention in malnourished patients to be guided by accurate evaluation and detection of small changes in the patient’s nutrition status over time. However, the current Subjective Global Assessment (SGA) is not able to detect changes in a short period of time. The aim of the study was to determine whether 7-point SGA is more time sensitive to nutrition changes than the conventional SGA. Methods: In this prospective study, 67 adult inpatients assessed as malnourished using both the 7-point SGA and conventional SGA were recruited. Each patient received nutrition intervention and was followed up post-discharge. Patients were reassessed using both tools at 1, 3 and 5 months from baseline assessment. Results: It took significantly shorter time to see a one-point change using 7-point SGA compared to conventional SGA (median: 1 month vs. 3 months, p = 0.002). The likelihood of at least a one-point change is 6.74 times greater in 7-point SGA compared to conventional SGA after controlling for age, gender and medical specialties (odds ratio = 6.74, 95% CI 2.88-15.80, p<0.001). Fifty-six percent of patients who had no change in SGA score had changes detected using 7-point SGA. The level of agreement was 100% (k = 1, p < 0.001) between 7-point SGA and 3-point SGA and 83% (k=0.726, p<0.001) between two blinded assessors for 7-point SGA. Conclusion: The 7-point SGA is more time sensitive in its response to nutrition changes than conventional SGA. It can be used to guide nutrition intervention for patients.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

An increasingly regulated higher education sector is renewing its attention to those activities referred to as ‘moderation’ in its efforts to ensure that judgements of student achievement are based on appropriate standards. Moderation practices conducted throughout the assessment process can result in purposes identified as equity, justification, accountability and community building. This paper draws on the limited studies of moderation and wider relevant research on judgement, standards and professional learning to test commonly used moderation practices against these identified purposes. The paper concludes with recommendations for maximising the potential of moderation practices to establish and maintain achievement standards.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

This paper explores how threshold uncertainty affects cooperative behaviors in the provision of public goods and the prevention of public bads. The following facts motivate our study. First, environmental (resource) problems are either framed as public bads prevention or public goods provision. Second, the occurrence of these problems is characterized by thresholds that are interchangeably represented as "nonconvexity," "bifurcation," "bi-stability," or "catastrophes." Third, the threshold location is mostly unknown. We employ a provision point mechanism with threshold uncertainty and analyze the responses of cooperative behaviors to uncertainty and to the framing for each type of social preferences categorized by a value orientation test. We find that aggregate framing effects are negligible, although the response to the frame is the opposite depending on the type of social preferences. "Cooperative" subjects become more cooperative in negative frames than in positive frames, whereas "individualistic" subjects are less cooperative in negative frames than in positive ones. This finding implies that the insignificance of aggregate framing effects arises from behavioral asymmetry. We also find that the percentage of cooperative choices non-monotonically varies with the degree of threshold uncertainty, irrespective of framing and value orientation. Specifically, the degree of cooperation is highest at intermediate levels of threshold uncertainty and decreases as the uncertainty becomes sufficiently large.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Background In the emergency department, portable point-of-care testing (POCT) coagulation devices may facilitate stroke patient care by providing rapid International Normalized Ratio (INR) measurement. The objective of this study was to evaluate the reliability, validity, and impact on clinical decision-making of a POCT device for INR testing in the setting of acute ischemic stroke (AIS). Methods A total of 150 patients (50 healthy volunteers, 51 anticoagulated patients, 49 AIS patients) were assessed in a tertiary care facility. The INR's were measured using the Roche Coaguchek S and the standard laboratory technique. Results The interclass correlation coefficient and 95% confidence interval between overall POCT device and standard laboratory value INRs was high (0.932 (0.69 - 0.78). In the AIS group alone, the correlation coefficient and 95% CI was also high 0.937 (0.59 - 0.74) and diagnostic accuracy of the POCT device was 94%. Conclusions When used by a trained health professional in the emergency department to assess INR in acute ischemic stroke patients, the CoaguChek S is reliable and provides rapid results. However, as concordance with laboratory INR values decreases with higher INR values, it is recommended that with CoaguChek S INRs in the > 1.5 range, a standard laboratory measurement be used to confirm the results.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The 12.7-10.5 Ma Cougar Point Tuff in southern Idaho, USA, consists of 10 large-volume (>10²-10³ km³ each), high-temperature (800-1000 °C), rhyolitic ash-flow tuffs erupted from the Bruneau-Jarbidge volcanic center of the Yellowstone hotspot. These tuffs provide evidence for compositional and thermal zonation in pre-eruptive rhyolite magma, and suggest the presence of a long-lived reservoir that was tapped by numerous large explosive eruptions. Pyroxene compositions exhibit discrete compositional modes with respect to Fe and Mg that define a linear spectrum punctuated by conspicuous gaps. Airfall glass compositions also cluster into modes, and the presence of multiple modes indicates tapping of different magma volumes during early phases of eruption. Equilibrium assemblages of pigeonite and augite are used to reconstruct compositional and thermal gradients in the pre-eruptive reservoir. The recurrence of identical compositional modes and of mineral pairs equilibrated at high temperatures in successive eruptive units is consistent with the persistence of their respective liquids in the magma reservoir. Recurrence intervals of identical modes range from 0.3 to 0.9 Myr and suggest possible magma residence times of similar duration. Eruption ages, magma temperatures, Nd isotopes, and pyroxene and glass compositions are consistent with a long-lived, dynamically evolving magma reservoir that was chemically and thermally zoned and composed of multiple discrete magma volumes.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

This study investigated a potential source of inaccuracy for diode measurements in modulated beams; the effect of diode housing asymmetry on measurement results. The possible effects of diode housing asymmetry on the measurement of steep dose gradients were evaluated by measuring 5x5 cm2 beam profiles, with three cylindrical diodes and two commonly used ionization chambers, with each dosimeter positioned in a 3D scanning water tank with its stem perpendicular to the beam axis (horizontal) and parallel to the direction of scanning. The resulting profiles were used to compare the penumbrae measured with the diode stem pointing into (equivalent to a “stem-first” setup) and out of the field (equivalent to a “stem-last” setup) in order to evaluate the effects of dosimeter alignment and thereby identify the effects of dosimeter asymmetry. The stem-first and stem-last orientations resulted in differences of up to 0.2 mm in the measured 20-80% penumbra widths and differences of up to 0.4 mm in the off axis position of the 90% isodose. These differences, which are smaller than previously reported for older model dosimeters, were apparent in the profile results for both diodes and small volume ionization chambers. As an extension to this study, the practical use of all five dosimeters was exemplified by measuring point doses in IMRT test beams. These measurements showed good agreement (within 2%) between the diodes and the small volume ionization chamber, with all of these dosimeters being able to identify a region 3% under-dosage which was not identified by a larger volume (6 mm diameter) ionization chamber. The results of this work should help to remove some of the barriers to the use of diodes for modulated radiotherapy dosimetry in the future.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

From an economic perspective, the sustainability crisis is ultimately characterized by a worsening relationship between the resources required to support the global population and the ability of the earth to supply them. Despite the ever-increasing threat of a calamity, modern society appears unable to alter its course. The very systems which underpin global human endeavor seem to actively prevent meaningful change and the one irrepressible goal to which all societies seem to strive is the very thing that makes such endeavor ultimately life threatening: that of global growth. Using the Australian experience as an exemplar, this paper explores how the concept of growth infiltrates societal reactions to the crisis at various scales – global, national and regional. Analysis includes historic studies, a critique of current misconceptions around population demographics, comparative evaluation of various interventions in the Australian context and considerations around potential ways to address the crisis.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Ectopic calcification (EC), which is the pathological deposition of calcium and phosphate in extra-skeletal tissues, may be associated with hypercalcaemic and hyperphosphataemic disorders, or it may occur in the absence of metabolic abnormalities. In addition, EC may be inherited as part of several monogenic disorders and studies of these have provided valuable insights into the metabolic pathways regulating mineral metabolism. For example, studies of tumoural calcinosis, a disorder characterised by hyperphosphataemia and progressive EC, have revealed mutations of fibroblast growth factor 23 (FGF23), polypeptide N-acetyl galactosaminyltransferase 3 (GALNT3) and klotho (KL), which are all part of a phosphate-regulating pathway. However, such studies in humans are limited by the lack of available large families with EC, and to facilitate such studies we assessed the progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) for EC. This identified two mutants with autosomal recessive forms of EC, and reduced lifespan, designated Ecalc1 and Ecalc2. Genetic mapping localized the Ecalc1 and Ecalc2 loci to a 11.0 Mb region on chromosome 5 that contained the klotho gene (Kl), and DNA sequence analysis identified nonsense (Gln203Stop) and missense (Ile604Asn) Kl mutations in Ecalc1 and Ecalc2 mice, respectively. The Gln203Stop mutation, located in KL1 domain, was severely hypomorphic and led to a 17-fold reduction of renal Kl expression. The Ile604Asn mutation, located in KL2 domain, was predicted to impair klotho protein stability and in vitro expression studies in COS-7 cells revealed endoplasmic reticulum retention of the Ile604Asn mutant. Further phenotype studies undertaken in Ecalc1 (kl203X/203X) mice demonstrated elevations in plasma concentrations of phosphate, FGF23 and 1,25-dihydroxyvitamin D. Thus, two allelic variants of Kl that develop EC and represent mouse models for tumoural calcinosis have been established. © 2015 Esapa et al.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Background The genetic mutation resulting in osteogenesis imperfecta (OI) type V was recently characterised as a single point mutation (c.-14C > T) in the 5' untranslated region (UTR) of IFITM5, a gene encoding a transmembrane protein with expression restricted to skeletal tissue. This mutation creates an alternative start codon and has been shown in a eukaryotic cell line to result in a longer variant of IFITM5, but its expression has not previously been demonstrated in bone from a patient with OI type V. Methods Sanger sequencing of the IFITM5 5' UTR was performed in our cohort of subjects with a clinical diagnosis of OI type V. Clinical data was collated from referring clinicians. RNA was extracted from a bone sample from one patient and Sanger sequenced to determine expression of wild-type and mutant IFITM5. Results: All nine subjects with OI type V were heterozygous for the c.-14C > T IFITM5 mutation. Clinically, there was heterogeneity in phenotype, particularly in the manifestation of bone fragility amongst subjects. Both wild-type and mutant IFITM5 mRNA transcripts were present in bone. Conclusions The c.-14C > T IFITM5 mutation does not result in an RNA-null allele but is expressed in bone. Individuals with identical mutations in IFITM5 have highly variable phenotypic expression, even within the same family.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Short-rib polydactyly syndromes (SRPS I-V) are a group of lethal congenital disorders characterized by shortening of the ribs and long bones, polydactyly, and a range of extraskeletal phenotypes. A number of other disorders in this grouping, including Jeune and Ellis-van Creveld syndromes, have an overlapping but generally milder phenotype. Collectively, these short-rib dysplasias (with or without polydactyly) share a common underlying defect in primary cilium function and form a subset of the ciliopathy disease spectrum. By using whole-exome capture and massive parallel sequencing of DNA from an affected Australian individual with SRPS type III, we detected two novel heterozygous mutations in WDR60, a relatively uncharacterized gene. These mutations segregated appropriately in the unaffected parents and another affected family member, confirming compound heterozygosity, and both were predicted to have a damaging effect on the protein. Analysis of an additional 54 skeletal ciliopathy exomes identified compound heterozygous mutations in WDR60 in a Spanish individual with Jeune syndrome of relatively mild presentation. Of note, these two families share one novel WDR60 missense mutation, although haplotype analysis suggested no shared ancestry. We further show that WDR60 localizes at the base of the primary cilium in wild-type human chondrocytes, and analysis of fibroblasts from affected individuals revealed a defect in ciliogenesis and aberrant accumulation of the GLI2 transcription factor at the centrosome or basal body in the absence of an obvious axoneme. These findings show that WDR60 mutations can cause skeletal ciliopathies and suggest a role for WDR60 in ciliogenesis.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Bidirectional (anterograde and retrograde) motor-based intraflagellar transport (IFT) governs cargo transport and delivery processes that are essential for primary cilia growth and maintenance and for hedgehog signaling functions. The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies. Here, by using exome sequencing and a targeted next-generation sequencing panel, we identified a total of 11 mutations in WDR34 in 9 families with the clinical diagnosis of Jeune syndrome (asphyxiating thoracic dystrophy). WDR34 encodes a WD40 repeat-containing protein orthologous to Chlamydomonas FAP133, a dynein intermediate chain associated with the retrograde intraflagellar transport motor. Three-dimensional protein modeling suggests that the identified mutations all affect residues critical for WDR34 protein-protein interactions. We find that WDR34 concentrates around the centrioles and basal bodies in mammalian cells, also showing axonemal staining. WDR34 coimmunoprecipitates with the dynein-1 light chain DYNLL1 in vitro, and mining of proteomics data suggests that WDR34 could represent a previously unrecognized link between the cytoplasmic dynein-1 and IFT dynein-2 motors. Together, these data show that WDR34 is critical for ciliary functions essential to normal development and survival, most probably as a previously unrecognized component of the mammalian dynein-IFT machinery.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

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.