981 resultados para 10-85
Resumo:
The high morbidity and mortality associated with atherosclerotic coronary vascular disease (CVD) and its complications are being lessened by the increased knowledge of risk factors, effective preventative measures and proven therapeutic interventions. However, significant CVD morbidity remains and sudden cardiac death continues to be a presenting feature for some subsequently diagnosed with CVD. Coronary vascular disease is also the leading cause of anaesthesia related complications. Stress electrocardiography/exercise testing is predictive of 10 year risk of CVD events and the cardiovascular variables used to score this test are monitored peri-operatively. Similar physiological time-series datasets are being subjected to data mining methods for the prediction of medical diagnoses and outcomes. This study aims to find predictors of CVD using anaesthesia time-series data and patient risk factor data. Several pre-processing and predictive data mining methods are applied to this data. Physiological time-series data related to anaesthetic procedures are subjected to pre-processing methods for removal of outliers, calculation of moving averages as well as data summarisation and data abstraction methods. Feature selection methods of both wrapper and filter types are applied to derived physiological time-series variable sets alone and to the same variables combined with risk factor variables. The ability of these methods to identify subsets of highly correlated but non-redundant variables is assessed. The major dataset is derived from the entire anaesthesia population and subsets of this population are considered to be at increased anaesthesia risk based on their need for more intensive monitoring (invasive haemodynamic monitoring and additional ECG leads). Because of the unbalanced class distribution in the data, majority class under-sampling and Kappa statistic together with misclassification rate and area under the ROC curve (AUC) are used for evaluation of models generated using different prediction algorithms. The performance based on models derived from feature reduced datasets reveal the filter method, Cfs subset evaluation, to be most consistently effective although Consistency derived subsets tended to slightly increased accuracy but markedly increased complexity. The use of misclassification rate (MR) for model performance evaluation is influenced by class distribution. This could be eliminated by consideration of the AUC or Kappa statistic as well by evaluation of subsets with under-sampled majority class. The noise and outlier removal pre-processing methods produced models with MR ranging from 10.69 to 12.62 with the lowest value being for data from which both outliers and noise were removed (MR 10.69). For the raw time-series dataset, MR is 12.34. Feature selection results in reduction in MR to 9.8 to 10.16 with time segmented summary data (dataset F) MR being 9.8 and raw time-series summary data (dataset A) being 9.92. However, for all time-series only based datasets, the complexity is high. For most pre-processing methods, Cfs could identify a subset of correlated and non-redundant variables from the time-series alone datasets but models derived from these subsets are of one leaf only. MR values are consistent with class distribution in the subset folds evaluated in the n-cross validation method. For models based on Cfs selected time-series derived and risk factor (RF) variables, the MR ranges from 8.83 to 10.36 with dataset RF_A (raw time-series data and RF) being 8.85 and dataset RF_F (time segmented time-series variables and RF) being 9.09. The models based on counts of outliers and counts of data points outside normal range (Dataset RF_E) and derived variables based on time series transformed using Symbolic Aggregate Approximation (SAX) with associated time-series pattern cluster membership (Dataset RF_ G) perform the least well with MR of 10.25 and 10.36 respectively. For coronary vascular disease prediction, nearest neighbour (NNge) and the support vector machine based method, SMO, have the highest MR of 10.1 and 10.28 while logistic regression (LR) and the decision tree (DT) method, J48, have MR of 8.85 and 9.0 respectively. DT rules are most comprehensible and clinically relevant. The predictive accuracy increase achieved by addition of risk factor variables to time-series variable based models is significant. The addition of time-series derived variables to models based on risk factor variables alone is associated with a trend to improved performance. Data mining of feature reduced, anaesthesia time-series variables together with risk factor variables can produce compact and moderately accurate models able to predict coronary vascular disease. Decision tree analysis of time-series data combined with risk factor variables yields rules which are more accurate than models based on time-series data alone. The limited additional value provided by electrocardiographic variables when compared to use of risk factors alone is similar to recent suggestions that exercise electrocardiography (exECG) under standardised conditions has limited additional diagnostic value over risk factor analysis and symptom pattern. The effect of the pre-processing used in this study had limited effect when time-series variables and risk factor variables are used as model input. In the absence of risk factor input, the use of time-series variables after outlier removal and time series variables based on physiological variable values’ being outside the accepted normal range is associated with some improvement in model performance.
Resumo:
Porphyrins are one of Nature’s essential building blocks that play an important role in several biological systems including oxygen transport, photosynthesis, and enzymes. Their capacity to absorb visible light, facilitate oxidation and reduction, and act as energy- and electron-transfer agents, in particular when several are held closely together, is of interest to chemists who seek to mimic Nature and to make and use these compounds in order to synthesise novel advanced materials. During this project 26 new 5,10-diarylsubstituted porphyrin monomers, 10 dimers, and 1 tetramer were synthesised. The spectroscopic and structural properties of these compounds were investigated using 1D/2D 1H NMR, UV/visible, ATR-IR and Raman spectroscopy, mass spectrometry, X-ray crystallography, electrochemistry and gel permeation chromatography. Nitration, amination, bromination and alkynylation of only one as well as both of the meso positions of the porphyrin monomers have resulted in the expansion of the synthetic possibilities for the 5,10-diarylsubstituted porphyrins. The development of these new porphyrin monomers has led to the successful synthesis of new azo- and butadiyne-linked dimers. The functionalisation of these compounds was investigated, in particular nitration, amination, and bromination. The synthesised dimers containing the azo bridge have absorption spectra that show a large split in the Soret bands and intense Q-bands that have been significantly redshifted. The butadiyne dimers also have intense, red-shifted Q-bands but smaller Soret band splittings. Crystal structures of two new azoporphyrins have been acquired and compared to the azoporphyrin previously synthesised from 5,10,15- triarylsubstituted porphyrin monomers. A completely new cyclic porphyrin oligomer (CPO) was synthesised comprising four porphyrin monomers linked by azo and butadiyne bridges. This is the first cyclic tetramer that has both the azo and butadiyne linking groups. The absorption spectrum of the tetramer exhibits a large Soret split making it more similar to the azo- dimers than the butadiyne-linked dimers. The spectroscopic characteristics of the synthesised tetramer have been compared to the characteristics of other cyclic porphyrin tetramers. The collected data indicate that the new synthesised cyclic tetramer has a more efficient ð-overlap and a better ground state electronic communication between the porphyrin rings.
Coordination of empirical laws and explanatory theory using model-based reasoning in Year 10 science
Resumo:
Prostrate Cancer(PCa)is the most common cause of cancer death amongst Western males. PCa occurs in two distinct stages. In its early stage, growth and development is dependent primarily on male sex hormones (androgens) such as testosterone, although other growth factors have roles maintaining PCa cell survival in this stage. In the later stage of PCa development, growth and.maintenance is independent of androgen stimulation and growth factors including Insulin-like Growth Factor -1 (IGf.:·l) and Epidermal Growth Factor (EGF) are thought to have more crucial roles in cell survival and PCa progression. PCa, in its late stages, is highly aggressive and metastatic, that is, tumorigenic cells migrate from the primary site of the body (prostate) and travel via the systemic and lymphatic circulation, residing and colonising in the bone, lymph node, lung, and in more rare cases, the brain. Metastasis involves both cell migration and tissue degradation activities. The degradation of the extracellular matrix (ECM), the tissue surrounding the organ, is mediated in part by members of a family of 26 proteins called the Matrix Metalloproteases (MMPs), whilst ceil adhesion molecules, of which proteins known as Integrins are included, mediate ce11 migration. A family of proteins known as the ADAMs (A Disintegrin . And Metalloprotease domain) were a recently characterised family at the commencement of this study and now comprise 34 members. Because of their dual nature, possessing an active metaiioprotease domain, homologous to that of the MMPs, and an integrin-binding domain capable of regulating cell-cell and cell-ECM contacts, it was thought likely that members of the ADAMs family may have implications for the progression of aggressive cancers such as those ofthe prostate. This study focussed on two particular ADAMs -9 and -10. ADAM-9 has an active metalloprotease domain, which has been shown to degrade constituents of the ECM, including fibronectin, in vitro. It also has an integrin-binding capacity through association with key integrins involved in PCa progression, such as a6~1. ADAM-10 has no such integrin binding activities, but its bovine orthologue, MADM, is able to degrade coHagen type IV, a major component of basement membranes. It is likely human ADAM-10 has the same activity. It is also known to cleave Ll -a protein involved in cell anchorage activities - and collagen type XVII - which is a principal component of the hemidesmosomes of cellular tight junctions. The cleavage of these proteins enables the cell to be released from the surrounding environment and commence migratory activities, as required in metastasis. Previous studies in this laboratory showed the mRNA expression of the five ADAMs -9,- 10, -11, -15 and -17 in PCa cell lines, characteristic of androgen-dependent and androgen independent disease. These studies were furthered by the characterisation of AD AM-9, -10 and -17 mRNA regulation by Dihydrotestosterone (DHT) in the androgen-responsive cell line (LNCaP). ADAM-9 and -10 mRNA levels were elevated in response to DHT stimulation. Further to these observations, the expression of ADAM-9 and -10 was shown in primary prostate biopsies from patients with PCa. ADAM-1 0 was expressed in the cytoplasm and on the ceH membrane in epithelial and basal cells ofbenign prostate glands, but in high-grade PCa glands, ADAM-I 0 expression was localised to the nucleus and its expression levels appeared to be elevated when compared to low-grade PCa glands. These studies provided a strong background for the hypothesis that ADAM-9 and -10 have key roles in the development ofPCa and provided a basis for further studies.The aims of this study were to: 1) characterise the expression, localisation and levels, of ADAM-9 and -10 mRNA and protein in cell models representing characteristics of normal through androgen-dependent to androgen-independent PCa, as well as to expand the primary PCa biopsy data for ADAM-9 and ADAM-10 to encompass PCa bone metastases 2) establish an in vitro cell system, which could express elevated levels of ADAM-1 0 so that functional cell-based assays such as cell migration, invasion and attachment could be carried out, and 3) to extend the previous hormonal regulation data, to fully characterise the response of ADAM-9 and -10 mRNA and protein levels to DHT, IGF-1, DHT plus IGF-1 and EGF in the hormonal/growth factor responsive cell line LNCaP. For aim 1 (expression of ADAM-9 and -10 mRNA and protein), ADAM-9 and -10 mRNA were characterised by R T -PCR, while their protein products were analysed by Western blot. Both ADAM-9 and -10 mRNA and protein were expressed at readily detectable levels across progressively metastatic PCa cell lines model that represent characteristics of low-grade,. androgen-dependent (LNCaP and C4) to high-grade, androgen-independent (C4-2 and C4-2B) PCa. When the non-tumorigenic prostate cell line RWPE-1 was compared with the metastatic PCa cell line PC-3, differential expression patterns were seen by Western blot analysis. For ADAM-9, the active form was expressed at higher levels in RWPE-1, whilst subcellular fractionation showed that the active form of ADAM-9 was predominantly located in the cell nucleus. For ADAM-I 0, in both of the cell Jines, a nuclear specific isoform of the mature, catalytically active ADAM-I 0 was found. This isoforrn differed by -2 kDa in Mr (smaller) than the cytoplasmic specific isoform. Unprocessed ADAM-I 0 was readily detected in R WPE-1 cell lines but only occasionally detected in PC-3 cell lines. Immunocytochemistry using ADAM-9 and -10 specific antibodies confirmed nuclear, cytoplasmic and membrane expression of both ADAMs in these two cell lines. To examine the possibility of ADAM-9 and -10 being shed into the extracellular environment, membrane vesicles that are constitutively shed from the cell surface and contain membrane-associated proteins were collected from the media of the prostate cell lines RWPE-1, LNCaP and PC-3. ADAM-9 was readily detectable in RWPE- 1 and LNCaP cell membrane vesicles by Western blot analysis, but not in PC-3 cells, whilst the expression of ADAM-I 0 was detected in shed vesicles from each of these prostate cell lines. By Laser Capture Microdissection (LCM), secretory epithelial cells of primary prostate gland biopsies were isolated from benign and malignant glands. These secretory cells, by Western blot analysis, expressed similar Mr bands for ADAM-9 and -10 that were found in PCa cell lines in vitro, indicating that the nuclear specific isoforrn of ADAM-I 0 was present in PCa primary tumours and may represent the predominantly nuclear form of ADAM-I 0 expression, previously shown in high-grade PCa by immunohistochemistry (IHC). ADAM-9 and -10 were also examined by IHC in bone metastases taken from PCa patients at biopsy. Both ADAMs could be detected at levels similar to those shown for Prostate Specific Antigen (PSA) in these biopsies. Furthermore, both ADAM-9 and -10 were predominantly membrane- bound with occasional nuclear expression. For aim 2, to establish a cell system that over-expressed levels of ADAM-10, two fulllength ADAM-I 0 mammalian expression vectors were constructed; ADAM-I 0 was cloned into pcDNA3.1, which contains a CMV promoter, and into pMEP4, containing an inducible metallothionine promoter, whose activity is stimulated by the addition of CdC}z. The efficiency of these two constructs was tested by way of transient transfection in the PCa cell line PC-3, whilst the pcDNA3.1 construct was also tested in the RWPE-1 prostate cell line. Resultant Western blot analysis for all transient transfection assays showed that levels of ADAM-I 0 were not significantly elevated in any case, when compared to levels of the housekeeping gene ~-Tubulin, despite testing various levels of vector DNA, and, for pMEP4, the induction of the transfected cell system with different degrees of stimulation with CdCh to activate the metallothionine promoter post-transfection. Another study in this laboratory found similar results when the same full length ADAM-10 sequence was cloned into a Green Fluorescent Protein (GFP) expressing vector, as no fluorescence was observed by means of transient tran sfection in the same, and other, PCa cell lines. It was hypothesised that the Kozak sequence included in the full-length construct (human ADAMI 0 naturally occurring sequence) is not strong enough to initiate translation in an artificial system, in cells, which, as described in Aim 1, are already expressing readily detectable levels of endogenous ADAM-10. As a result, time constraints prevented any further progress with Aim 2 and functional studies including cell attachment, invasion and migration were unable to be explored. For Aim 3, to characterise the response of ADAM-9 and -10 mRNA and protein levels to DHT, IGF-1, DHT plus IGF-1 and EGF in LNCaP cells, the levels of ADAM-9 and -10 mRNA were not stimulated by DHT or IGF-I alone, despite our previous observations that initially characterised ADAM-9 and -10 mRNA as being responsive to DHT. However, IGF-1 in synergy with DHT did significantly elevate mRNA levels ofboth ADAMs. In the case of ADAM-9 and -10 protein, the same trends of stimulation as found at the rnRNA level were shown by Western blot analysis when ADAM-9 and -10 signal intensity was normalised with the housekeeping protein ~-Tubulin. For EGF treatment, both ADAM-9 and -10 mRNA and protein levels were significantly elevated, and further investigation vm found this to be the case for each of these ADAMs proteins in the nuclear fractions of LNCaP cells. These studies are the first to describe extensively, the expression and hormonal/growth factor regulation of two members of the ADAMs family ( -9 and -1 0) in PCa. These observations imply that the expression of ADAM-9 and -10 have varied roles in PCa whilst it develops from androgen-sensitive (early stage disease), through to an androgeninsensitive (late-stage), metastatic disease. Further studies are now required to investigate the several key areas of focus that this research has revealed, including: • Investigation of the cellular mechanisms that are involved in actively transporting the ADAMs to the cell's nuclear compartment and the ADAMs functional roles in the cell nucleus. • The construction of a full-length human ADAM-10 mammalian expression construct with the introduction of a new Kozak sequence, that elevates ADAM-I 0 expression in an in vitro cell system are required, so that functional assays such as cell invasion, migration and attachment may be carried out to fmd the functional consequences of ADAM expression on cellular behaviour. • The regulation studies also need to be extended by confirming the preliminary observations that the nuclear levels of ADAMs may also be elevated by hormones and growth factors such as DHT, IGF-1 and EGF, as well as the regulation of levels of plasma membrany vesicle associated ADAM expression. Given the data presented in this study, it is likely the ADAMs have differential roles throughout the development of PCa due to their differential cellular localisation and synergistic growth-factor regulation. These observations, along with those further studies outlined above, are necessary in identifying these specific components ofPCa metastasis to which the ADAMs may contribute.
Resumo:
This paper presents a case study of a design for a complete microair vehicle thruster. Fixed-pitch small-scale rotors, brushless motors, lithium-polymer cells, and embedded control are combined to produce a mechanically simple, high-performance thruster with potentially high reliability. The custom rotor design requires a balance between manufacturing simplicity and rigidity of a blade versus its aerodynamic performance. An iterative steady-state aeroelastic simulator is used for holistic blade design. The aerodynamic load disturbances of the rotor-motor system in normal conditions are experimentally characterized. The motors require fast dynamic response for authoritative vehicle flight control. We detail a dynamic compensator that achieves satisfactory closed-loop response time. The experimental rotor-motor plant displayed satisfactory thrust performance and dynamic response.
Resumo:
Internationally, collection of reliable data on new and evolving health-care roles is crucial. We describe a protocol for design and administration of a national census of an emergent health-care role, namely nurse practitioners in Australia using databases held by regulatory authorities. A questionnaire was developed to obtain data on the role and scope of practice of Australian nurse practitioners. Our tool comprised five sections and included a total of 56 questions, using 28 existing items from the National Nursing and Midwifery Labour Force Census and nine items recommended in the Nurse Practitioner Workforce Planning Minimum Data Set. Australian Nurse Registering Authorities (n = 6) distributed the survey on our behalf. This paper outlines our instrument and methods. The survey was administered to 238 authorized Australian nurse practitioners (85% response rate). Rigorous collection of standardized items will ensure health policy is informed by reliable and valid data. We will re-administer the survey 2 years following the first survey to measure change over time.
Resumo:
Objective: To determine whether bifocal and prismatic bifocal spectacles could control myopia in children with high rates of myopic progression. ---------- Methods: This was a randomized controlled clinical trial. One hundred thirty-five (73 girls and 62 boys) myopic Chinese Canadian children (myopia of 1.00 diopters [D]) with myopic progression of at least 0.50 D in the preceding year were randomly assigned to 1 of 3 treatments: (1) single-vision lenses (n = 41), (2) +1.50-D executive bifocals (n = 48), or (3) +1.50-D executive bifocals with a 3–prism diopters base-in prism in the near segment of each lens (n = 46). ---------- Main Outcome Measures: Myopic progression measured by an automated refractor under cycloplegia and increase in axial length (secondary) measured by ultrasonography at 6-month intervals for 24 months. Only the data of the right eye were used. ---------- Results: Of the 135 children (mean age, 10.29 years [SE, 0.15 years]; mean visual acuity, –3.08 D [SE, 0.10 D]), 131 (97%) completed the trial after 24 months. Myopic progression averaged –1.55 D (SE, 0.12 D) for those who wore single-vision lenses, –0.96 D (SE, 0.09 D) for those who wore bifocals, and –0.70 D (SE, 0.10 D) for those who wore prismatic bifocals. Axial length increased an average of 0.62 mm (SE, 0.04 mm), 0.41 mm (SE, 0.04 mm), and 0.41 mm (SE, 0.05 mm), respectively. The treatment effect of bifocals (0.59 D) and prismatic bifocals (0.85 D) was significant (P < .001) and both bifocal groups had less axial elongation (0.21 mm) than the single-vision lens group (P < .001). ---------- Conclusions: Bifocal lenses can moderately slow myopic progression in children with high rates of progression after 24 months.
Resumo:
Background: Early pregnancy loss has been linked to enduring psychological morbidity. Aims: This study aimed to investigate the utility of the Kessler 10 (K10) questionnaire as a brief screening instrument to identify women at risk for the development of psychiatric diagnoses three months post-miscarriage. Method: Participants were 117 consecutive women presenting at a public hospital emergency department and receiving a diagnosis of miscarriage. Main outcome measures: K10 screen for psychological distress and the Structured Clinical Interview for DSM Disorders to determine psychiatric diagnoses. Results: A majority of women (81.2%) experienced elevated levels of distress initially, 24.8% in the very high range. They were not at increased risk of psychiatric diagnoses at three months compared with the general population; however, they were significantly more likely to report subsyndromal symptoms at this time compared with the general population. The baseline K10 score was the only significant predictor of distress at follow-up (r = 0.45, P < 0.001). The receiver operating characteristic curve shows that a cut-off of 14 on the K10 has suitable sensitivity (97%) and specificity (82%) for predicting ongoing psychological distress in women who miscarry. Conclusions: The K10 is effective in identifying women at risk for ensuring psychological symptoms following miscarriage.
Resumo:
A novel Zr-based bulk metallic glass composite was fabricated using stainless steel capillaries as the reinforcement. Large plasticity (14%) was achieved in the composite with a reinforcement volume fraction of 38%. The high plasticity observed can be attributed to the formation of small glass fibers encapsulated by the steel capillaries, which promotes multiple shear bands in both metallic glass matrix and the fibers themselves. A new parameter was also proposed to approximately evaluate the reinforcement efficiency.
Resumo:
The integration of computer technologies into everyday classroom life continues to provide pedagogical challenges for school systems, teachers and administrators. Data from an exploratory case study of one teacher and a multiage class of children in the first years of schooling in Australia show that when young children are using computers for set tasks in small groups, they require ongoing support from teachers, and to engage in peer interactions that are meaningful and productive. Classroom organization and the nature of teacher-child talk are key factors in engaging children in set tasks and producing desirable learning and teaching outcomes.
Resumo:
Identification of hot spots, also known as the sites with promise, black spots, accident-prone locations, or priority investigation locations, is an important and routine activity for improving the overall safety of roadway networks. Extensive literature focuses on methods for hot spot identification (HSID). A subset of this considerable literature is dedicated to conducting performance assessments of various HSID methods. A central issue in comparing HSID methods is the development and selection of quantitative and qualitative performance measures or criteria. The authors contend that currently employed HSID assessment criteria—namely false positives and false negatives—are necessary but not sufficient, and additional criteria are needed to exploit the ordinal nature of site ranking data. With the intent to equip road safety professionals and researchers with more useful tools to compare the performances of various HSID methods and to improve the level of HSID assessments, this paper proposes four quantitative HSID evaluation tests that are, to the authors’ knowledge, new and unique. These tests evaluate different aspects of HSID method performance, including reliability of results, ranking consistency, and false identification consistency and reliability. It is intended that road safety professionals apply these different evaluation tests in addition to existing tests to compare the performances of various HSID methods, and then select the most appropriate HSID method to screen road networks to identify sites that require further analysis. This work demonstrates four new criteria using 3 years of Arizona road section accident data and four commonly applied HSID methods [accident frequency ranking, accident rate ranking, accident reduction potential, and empirical Bayes (EB)]. The EB HSID method reveals itself as the superior method in most of the evaluation tests. In contrast, identifying hot spots using accident rate rankings performs the least well among the tests. The accident frequency and accident reduction potential methods perform similarly, with slight differences explained. The authors believe that the four new evaluation tests offer insight into HSID performance heretofore unavailable to analysts and researchers.
Resumo:
Cutaneous cholecalciferol synthesis has not been considered in making recommendations for vitamin D intake. Our objective was to model the effects of sun exposure, vitamin D intake, and skin reflectance (pigmentation) on serum 25-hydroxyvitamin D (25[OH]D) in young adults with a wide range of skin reflectance and sun exposure. Four cohorts of participants (n = 72 total) were studied for 7-8 wk in the fall, winter, spring, and summer in Davis, CA [38.5° N, 121.7° W, Elev. 49 ft (15 m)]. Skin reflectance was measured using a spectrophotometer, vitamin D intake using food records, and sun exposure using polysulfone dosimeter badges. A multiple regression model (R^sup 2^ = 0.55; P < 0.0001) was developed and used to predict the serum 25(OH)D concentration for participants with low [median for African ancestry (AA)] and high [median for European ancestry (EA)] skin reflectance and with low [20th percentile, ~20 min/d, ~18% body surface area (BSA) exposed] and high (80th percentile, ~90 min/d, ~35% BSA exposed) sun exposure, assuming an intake of 200 IU/d (5 ug/d). Predicted serum 25(OH)D concentrations for AA individuals with low and high sun exposure in the winter were 24 and 42 nmol/L and in the summer were 40 and 60 nmol/L. Corresponding values for EA individuals were 35 and 60 nmol/L in the winter and in the summer were 58 and 85 nmol/L. To achieve 25(OH)D ≥75 nmol/L, we estimate that EA individuals with high sun exposure need 1300 IU/d vitamin D intake in the winter and AA individuals with low sun exposure need 2100-3100 IU/d year-round.