Medizinische und gesundheitsökonomische Bewertung der Radiochirurgie zur Behandlung von Hirnmetastasen

Hintergrund: Für die Therapie maligner Neubildungen stellt die Strahlentherapie wichtige Behandlungsmöglichkeiten dar, die sich in den vergangenen Jahrzehnten deutlich weiterentwickelt haben. Hierzu gehört unter anderem die stereotaktische Radiochirurgie (SRS), die durch eine einmalige Applikation fokussierter hoher Strahlendosen in einem klar definierten Zeitraum gekennzeichnet ist. Von besonderer Bedeutung ist die SRS für die Behandlung von Hirnmetastasen. Fragestellung: Ziel dieses HTA-Berichts ist die Erstellung einer umfassenden Übersicht der aktuellen Literatur der Behandlung von Hirnmetastasen, um die Radiochirurgie als alleinige Therapie oder in Kombination mit Therapiealternativen bezüglich der medizinischen Wirksamkeit, Sicherheit und Wirtschaftlichkeit sowie ethischer, sozialer und juristischer Aspekte zu vergleichen. Methodik: Relevante Publikationen deutscher und englischer Sprache werden über eine strukturierte Datenbank- sowie mittels Handrecherche zwischen Januar 2002 und August 2007 identifiziert. Die Zielpopulation bilden Patienten mit einer oder mehreren Hirnmetastasen. Eine Beurteilung der methodischen Qualität wird unter Beachtung von Kriterien der evidenzbasierten Medizin (EbM) durchgeführt. Ergebnisse: Von insgesamt 1.495 Treffern erfüllen 15 Studien die medizinischen Einschlusskriterien. Insgesamt ist die Studienqualität stark eingeschränkt und mit Ausnahme von zwei randomisierte kontrollierte Studien (RCT) und zwei Metaanalysen werden ausschließlich historische Kohortenstudien identifiziert. Die Untersuchung relevanter Endpunkte ist uneinheitlich. Qualitativ hochwertige Studien zeigen, dass die Ergänzung der Ganzhirnbestrahlung (WBRT) zur SRS sowie der SRS zur WBRT mit einer verbesserten lokalen Tumorkontrolle und Funktionsfähigkeit einhergeht. Nur im Vergleich zur alleinigen WBRT resultiert die Kombination von SRS und WBRT jedoch bei Patienten mit singulären Hirnmetastasen, RPA-Klasse 1 (RPA = Rekursive Partitionierungsanalyse) und bestimmten Primärtumoren in verbesserter Überlebenszeit. Die Therapiesicherheit zeigt in beiden Fällen keine deutlichen Unterschiede zwischen den Interventionsgruppen. Methodisch weniger hochwertige Studien finden keine eindeutigen Unterschiede zwischen SRS und WBRT, SRS und Neurochirurgie (NC) sowie SRS und hypofraktionierter Strahlentherapie (HCSRT). Die Lebensqualität wird in keiner Studie untersucht. Durch die Datenbankrecherche werden 320 Publikationen für den ökonomischen Bereich identifiziert. Insgesamt werden fünf davon für den vorliegenden Health Technology Assessment (HTA)-Bericht verwendet. Die Qualität der Publikationen ist dabei unterschiedlich. Bezüglich der Wirtschaftlichkeit verschiedener Gerätealternativen ergibt sich, unter der Annahme gleicher Wirksamkeit, eine starke Abhängigkeit von der Anzahl der behandelten Patienten. Im Fall, dass die beiden Gerätealternativen nur für die SRS verwandt werden, liegen Hinweise vor, dass das Gamma Knife kostengünstiger sein kann. Andernfalls ist es sehr wahrscheinlich, dass der flexiblere modifizierte Linearbeschleuniger kostengünstiger ist. Nach einem HTA sind die Gesamtkosten für ein Gamma Knife und einen dedizierten Linearbeschleuniger ungefähr gleich, während ein modifizierter Linearbeschleuniger günstiger ist. Für ethische, juristische und soziale Fragestellungen werden keine relevanten Publikationen identifiziert. Diskussion: Insgesamt sind sowohl die Qualität als auch die Quantität identifizierter Studien stark reduziert. Es zeigt sich jedoch, dass die Prognose von Patienten mit Hirnmetastasen auch unter modernsten therapeutischen Möglichkeiten schlecht ist. Ausreichend starke Evidenz gibt es lediglich für die Untersuchung ergänzender WBRT zur SRS und der ergänzenden SRS zur WBRT. Ein direkter Vergleich von SRS und WBRT, SRS und NC sowie SRS und HCSRT ist hingegen nicht möglich. Die Wirtschaftlichkeit verschiedener Gerätealternativen hängt von der Patientenzahl und den behandelten Indikationen ab. Für ausgelastete dedizierte Systeme, liegen Hinweise vor, dass sie kostengünstiger sein können. Bei flexibler Nutzung scheinen modifizierte Systeme wirtschaftlich vorteilhafter. Diese Aussagen erfolgen unter der nicht gesicherten Annahme gleicher Wirksamkeit der Alternativen. Die Behandlungspräzision der Geräte kann Einfluss auf die Gerätewahl haben. Zu neueren Gerätealternativen wie z. B. dem CyberKnife liegen bisher keine Untersuchungen vor. Aus der wirtschaftlich vorteilhaften hohen Auslastung folgt aber eine begrenzte Geräteanzahl in einem vorgegebenen Gebiet, was evtl. einen gleichberechtigten, wohnortnahen Zugang zu dieser Technik erschwert. Schlussfolgerungen: Die Kombination SRS und WBRT geht mit einer verbesserten lokalen Tumorkontrolle und Funktionsfähigkeit gegenüber der jeweils alleinigen Therapie einher. Nur für Patienten mit singulärer Metastase resultiert dies in Vorteilen der Überlebenszeit. Qualitativ hochwertige Studien sind notwendig um die SRS direkt mit WBRT und NC zu vergleichen. Weiterhin sollte besonders die Lebensqualität in zukünftigen Studien mitberücksichtigt werden. Bei der Art des verwendeten Gerätes zeichnet sich eine deutliche Abhängigkeit der Wirtschaftlichkeit der Geräte von der erreichbaren Auslastung ab. Hohe Patientenzahlen bieten Vorteile für spezialisierte Systeme und bei geringeren Patientenzahlen ist die Flexibilität modifizierter System vorteilhaft. Weitere Studien z. B. zum CyberKnife sind wünschenswert. Insgesamt ist die Studienlage insbesondere für das deutsche Gesundheitssystem sehr mangelhaft.

Decision support system architecture for consultant selection

Decision Support System (DSS) has played a significant role in construction project management. This has been proven that a lot of DSS systems have been implemented throughout the whole construction project life cycle. However, most research only concentrated in model development and left few fundamental aspects in Information System development. As a result, the output of researches are complicated to be adopted by lay person particularly those whom come from a non-technical background. Hence, a DSS should hide the abstraction and complexity of DSS models by providing a more useful system which incorporated user oriented system. To demonstrate a desirable architecture of DSS particularly in public sector planning, we aim to propose a generic DSS framework for consultant selection. It will focus on the engagement of engineering consultant for irrigation and drainage infrastructure. The DSS framework comprise from operational decision to strategic decision level. The expected result of the research will provide a robust framework of DSS for consultant selection. In addition, the paper also discussed other issues that related to the existing DSS framework by integrating enabling technologies from computing. This paper is based on the preliminary case study conducted via literature review and archival documents at Department of Irrigation and Drainage (DID) Malaysia. The paper will directly affect to the enhancement of consultant pre-qualification assessment and selection tools. By the introduction of DSS in this area, the selection process will be more efficient in time, intuitively aided qualitative judgment, and transparent decision through aggregation of decision among stakeholders.

Using Media Technologies in English

English has long been the subject where print text has reigned supreme. Increasingly in our networked and electronically connected world, however, we can be using digital technologies to create and respond to texts studied in English classrooms. The current approach to English includes the concept of ‘multiliteracies,’ which suggests that print texts alone are necessary but not sufficient’ (E.Q, 2000) and that literacy includes the flexible and sustainable mastery of a repertoire of practices. This also includes the decoding and deployment of media technologies (E.Q, 2000). This has become more possible in Australia as secondary students have increasing access to computers and online platforms at home and at school. With the advent of web 2.0., with its interactive platforms and free media making software, teachers and students can use this software to access information and emerging online literature in English covering a range of text types and new forms for authentic audiences and contexts. This chapter is concerned with responding to literary and mediated texts through the use of technologies. If we remain open to trying out new textual forms and see our digital ‘native students’ (Prensky, 2007) as our best resource, we can move beyond technophobia, become digital travellers’ ourselves and embrace new digital forms in our classrooms.

The speed paradox : the misalignment between driver attitudes and speeding behaviour

This paper reports on a study investigating preferred driving speeds and frequency of speeding of 320 Queensland drivers. Despite growing community concern about speeding and extensive research linking it to road trauma, speeding remains a pervasive, and arguably, socially acceptable behaviour. This presents an apparent paradox regarding the mismatch between beliefs and behaviours, and highlights the necessity to better understand the factors contributing to speeding. Utilising self-reported behaviour and attitudinal measures, results of this study support the notion of a speed paradox. Two thirds of participants agreed that exceeding the limit is not worth the risks nor is it okay to exceed the posted limit. Despite this, more than half (58.4%) of the participants reported a preference to exceed the 100km/hour speed limit, with one third preferring to do so by 10 to 20 km/hour. Further, mean preferred driving speeds on both urban and open roads suggest a perceived enforcement tolerance of 10%, suggesting that posted limits have limited direct influence on speed choice. Factors that significantly predicted the frequency of speeding included: exposure to role models who speed; favourable attitudes to speeding; experiences of punishment avoidance; and the perceived certainty of punishment for speeding. These findings have important policy implications, particularly relating to the use of enforcement tolerances.

Validation of the WHOQOL-BREF among women following childbirth

Background: There is an increasing interest in measuring quality of life (QOL) in clinical settings and in clinical trials. None of the commonly used QOL instrument have been validated for use postnatally. Aim: To assess the psychometric properties of the 26-item WHOQOL-BREF among women following childbirth. Methods: Using a prospective cohort design we recruited 320 women within the first few days of childbirth. At six weeks postpartum, participants were asked to complete the WHOQOL-BREF, the Edinburgh Postnatal Depression Index and the Australian Unity Wellbeing Index. Validation of the WHOQOL-BREF included an analysis of internal consistency, discriminate validity, convergent validity and an examination of the domain structure. Results: 221 (69.1%) women returned their six-week questionnaire. All domains of the WHOQOL-BREF met reliability standards (alpha coefficient exceeding 0.70). The questionnaire discriminated well between known groups (depressed and non-depressed women. P = <0.000) and demonstrated satisfactory correlations with the Australian Unity Wellbeing index (r = >0.45). The domain structure of the WHOQOL-BREF was also valid in this population of new mothers, with moderate to high correlation between individual items and the domain structure to which the items were originally assigned. Conclusion: The WHOQOL-BRF is well-accepted and valid instrument in this population and may be used in postnatal clinical settings or for assessing intervention effects in research studies.

Androgen-regulated genes differentially modulated by the androgen receptor coactivator L-dopa decarboxylase in human prostate cancer cells

Background The androgen receptor is a ligand-induced transcriptional factor, which plays an important role in normal development of the prostate as well as in the progression of prostate cancer to a hormone refractory state. We previously reported the identification of a novel AR coactivator protein, L-dopa decarboxylase (DDC), which can act at the cytoplasmic level to enhance AR activity. We have also shown that DDC is a neuroendocrine (NE) marker of prostate cancer and that its expression is increased after hormone-ablation therapy and progression to androgen independence. In the present study, we generated tetracycline-inducible LNCaP-DDC prostate cancer stable cells to identify DDC downstream target genes by oligonucleotide microarray analysis. Results Comparison of induced DDC overexpressing cells versus non-induced control cell lines revealed a number of changes in the expression of androgen-regulated transcripts encoding proteins with a variety of molecular functions, including signal transduction, binding and catalytic activities. There were a total of 35 differentially expressed genes, 25 up-regulated and 10 down-regulated, in the DDC overexpressing cell line. In particular, we found a well-known androgen induced gene, TMEPAI, which wasup-regulated in DDC overexpressing cells, supporting its known co-activation function. In addition, DDC also further augmented the transcriptional repression function of AR for a subset of androgen-repressed genes. Changes in cellular gene transcription detected by microarray analysis were confirmed for selected genes by quantitative real-time RT-PCR. Conclusion Taken together, our results provide evidence for linking DDC action with AR signaling, which may be important for orchestrating molecular changes responsible for prostate cancer progression.

Implications of patterns of carbon pools and fluxes across a semiarid environmental gradient

Landscape scale environmental gradients present variable spatial patterns and ecological processes caused by climate, topography and soil characteristics and, as such, offer candidate sites to study environmental change. Data are presented on the spatial pattern of dominant species, biomass, and carbon pools and the temporal pattern of fluxes across a transitional zone shifting from Great Basin Desert scrub, up through pinyon-juniper woodlands and into ponderosa pine forest and the ecotones between each vegetation type. The mean annual temperature (MAT) difference across the gradient is approximately 3 degrees C from bottom to top (MAT 8.5-5.5) and annual precipitation averages from 320 to 530 mm/yr, respectively. The stems of the dominant woody vegetation approach a random spatial pattern across the entire gradient, while the canopy cover shows a clustered pattern. The size of the clusters increases with elevation according to available soil moisture which in turn affects available nutrient resources. The total density of woody species declines with increasing soil moisture along the gl-adient, but total biomass increases. Belowground carbon and nutrient pools change from a heterogenous to a homogenous distribution on either side of the woodlands. Although temperature controls the: seasonal patterns of carbon efflux from the soils, soil moisture appears to be the primary driving variable, but response differs underneath the different dominant species, Similarly, decomposition of dominant litter occurs faster-at the cooler and more moist sites, but differs within sites due to litter quality of the different species. The spatial pattern of these communities provides information on the direction of future changes, The ecological processes that we documented are not statistically different in the ecotones as compared to the: adjoining communities, but are different at sites above the woodland than those below the woodland. We speculate that an increase in MAT will have a major impact on C pools and C sequestering and release processes in these semiarid landscapes. However, the impact will be primarily related to moisture availability rather than direct effects of an increase in temperature. (C) 1998 Elsevier Science B.V.

Improving road safety through deterrence-based initiatives : a review of research

The efficacy of road safety countermeasures to deter motorists from engaging in illegal behaviours is extremely important when considering the personal and economic impact of road accidents on the community. Within many countries, deterrence theory has remained a cornerstone to criminology and criminal justice policy, particularly within the field of road safety, as policy makers and enforcement agencies attempt to increase perceptions regarding the certainty, severity and swiftness of sanctions for those who engage in illegal motoring behaviours. Using the Australian experience (particularly the tremendous amount of research into drink driving), the current paper reviews the principles underpinning deterrence theory, the utilisation of the approach within some contemporary road safety initiatives (e.g., Random Breath Testing) as well as highlights some methods to enhance a deterrent effect. The paper also provides direction for future deterrence-based research, in particular, considering the powerful impact of non-legal sanctions, punishment avoidance as well as creating culturally embedded behavioural change.

Alkaline hydrothermal treatment of titanate nanostructures

Since its initial proposal in 1998, alkaline hydrothermal processing has rapidly become an established technology for the production of titanate nanostructures. This simple, highly reproducible process has gained a strong research following since its conception. However, complete understanding and elucidation of nanostructure phase and formation have not yet been achieved. Without fully understanding phase, formation, and other important competing effects of the synthesis parameters on the final structure, the maximum potential of these nanostructures cannot be obtained. Therefore this study examined the influence of synthesis parameters on the formation of titanate nanostructures produced by alkaline hydrothermal treatment. The parameters included alkaline concentration, hydrothermal temperature, the precursor material‘s crystallite size and also the phase of the titanium dioxide precursor (TiO2, or titania). The nanostructure‘s phase and morphology was analysed using X-ray diffraction (XRD), Raman spectroscopy and transmission electron microscopy. X-ray photoelectron spectroscopy (XPS), dynamic light scattering (non-invasive backscattering), nitrogen sorption, and Rietveld analysis were used to determine phase, for particle sizing, surface area determinations, and establishing phase concentrations, respectively. This project rigorously examined the effect of alkaline concentration and hydrothermal temperature on three commercially sourced and two self-prepared TiO2 powders. These precursors consisted of both pure- or mixed-phase anatase and rutile polymorphs, and were selected to cover a range of phase concentrations and crystallite sizes. Typically, these precursors were treated with 5–10 M sodium hydroxide (NaOH) solutions at temperatures between 100–220 °C. Both nanotube and nanoribbon morphologies could be produced depending on the combination of these hydrothermal conditions. Both titania and titanate phases are comprised of TiO6 units which are assembled in different combinations. The arrangement of these atoms affects the binding energy between the Ti–O bonds. Raman spectroscopy and XPS were therefore employed in a preliminary study of phase determination for these materials. The change in binding energy from a titania to a titanate binding energy was investigated in this study, and the transformation of titania precursor into nanotubes and titanate nanoribbons was directly observed by these methods. Evaluation of the Raman and XPS results indicated a strengthening in the binding energies of both the Ti (2p3/2) and O (1s) bands which correlated to an increase in strength and decrease in resolution of the characteristic nanotube doublet observed between 320 and 220 cm.1 in the Raman spectra of these products. The effect of phase and crystallite size on nanotube formation was examined over a series of temperatures (100.200 �‹C in 20 �‹C increments) at a set alkaline concentration (7.5 M NaOH). These parameters were investigated by employing both pure- and mixed- phase precursors of anatase and rutile. This study indicated that both the crystallite size and phase affect nanotube formation, with rutile requiring a greater driving force (essentially �\harsher. hydrothermal conditions) than anatase to form nanotubes, where larger crystallites forms of the precursor also appeared to impede nanotube formation slightly. These parameters were further examined in later studies. The influence of alkaline concentration and hydrothermal temperature were systematically examined for the transformation of Degussa P25 into nanotubes and nanoribbons, and exact conditions for nanostructure synthesis were determined. Correlation of these data sets resulted in the construction of a morphological phase diagram, which is an effective reference for nanostructure formation. This morphological phase diagram effectively provides a .recipe book�e for the formation of titanate nanostructures. Morphological phase diagrams were also constructed for larger, near phase-pure anatase and rutile precursors, to further investigate the influence of hydrothermal reaction parameters on the formation of titanate nanotubes and nanoribbons. The effects of alkaline concentration, hydrothermal temperature, crystallite phase and size are observed when the three morphological phase diagrams are compared. Through the analysis of these results it was determined that alkaline concentration and hydrothermal temperature affect nanotube and nanoribbon formation independently through a complex relationship, where nanotubes are primarily affected by temperature, whilst nanoribbons are strongly influenced by alkaline concentration. Crystallite size and phase also affected the nanostructure formation. Smaller precursor crystallites formed nanostructures at reduced hydrothermal temperature, and rutile displayed a slower rate of precursor consumption compared to anatase, with incomplete conversion observed for most hydrothermal conditions. The incomplete conversion of rutile into nanotubes was examined in detail in the final study. This study selectively examined the kinetics of precursor dissolution in order to understand why rutile incompletely converted. This was achieved by selecting a single hydrothermal condition (9 M NaOH, 160 °C) where nanotubes are known to form from both anatase and rutile, where the synthesis was quenched after 2, 4, 8, 16 and 32 hours. The influence of precursor phase on nanostructure formation was explicitly determined to be due to different dissolution kinetics; where anatase exhibited zero-order dissolution and rutile second-order. This difference in kinetic order cannot be simply explained by the variation in crystallite size, as the inherent surface areas of the two precursors were determined to have first-order relationships with time. Therefore, the crystallite size (and inherent surface area) does not affect the overall kinetic order of dissolution; rather, it determines the rate of reaction. Finally, nanostructure formation was found to be controlled by the availability of dissolved titanium (Ti4+) species in solution, which is mediated by the dissolution kinetics of the precursor.

Improving matching process in social network using implicit and explicit user information

Personalised social matching systems can be seen as recommender systems that recommend people to others in the social networks. However, with the rapid growth of users in social networks and the information that a social matching system requires about the users, recommender system techniques have become insufficiently adept at matching users in social networks. This paper presents a hybrid social matching system that takes advantage of both collaborative and content-based concepts of recommendation. The clustering technique is used to reduce the number of users that the matching system needs to consider and to overcome other problems from which social matching systems suffer, such as cold start problem due to the absence of implicit information about a new user. The proposed system has been evaluated on a dataset obtained from an online dating website. Empirical analysis shows that accuracy of the matching process is increased, using both user information (explicit data) and user behavior (implicit data).

'Attaching' warning statements by facsimile consumer protection prevails!

Section 366 of the Property Agents and Motor Dealers Act 2000 (Qld) (‘PAMDA’) mandates that all contracts for the sale of residential property in Queensland (other than contracts formed on a sale by auction) have a warning statement ‘attached’ as the first or top sheet. Alternative judicial views have emerged concerning the possibility of attaching a warning statement to a contract sent by facsimile. In recognition of the consumer protection nature of the legislation, in MP Management (Aust) Pty Ltd v Churven [2002] QSC 320 Muir J favoured a restrictive view of the word ‘attached’ requiring physical joinder of the warning statement to the relevant contract. In contrast, in MNM Developments Pty Ltd v Gerrard [2005] QDC 10 Newton DCJ opined that the requirements of the PAMDA could be met where the warning statement preceded the contract of sale in a facsimile transmission sent in one continuous stream. Newton DCJ considered that this broader approach promoted commercial convenience. In an appeal from the decision of Newton DCJ, in MNM Developments Pty Ltd v Gerrard [2005] QCA 230 a majority of the Queensland Court of Appeal has held that the restrictive view propounded by Muir J is correct. Notwithstanding possible commercial inconvenience, it is not possible for a warning statement to be attached to a contract sent by facsimile.