Single-agent versus combination chemotherapy in patients with advanced non-small cell lung cancer and a performance status of 2 : prognostic factors and treatment selection based on two large randomized clinical trials

Purpose: Data from two randomized phase III trials were analyzed to evaluate prognostic factors and treatment selection in the first-line management of advanced non-small cell lung cancer patients with performance status (PS) 2. Patients and Methods: Patients randomized to combination chemotherapy (carboplatin and paclitaxel) in one trial and single-agent therapy (gemcitabine or vinorelbine) in the second were included in these analyses. Both studies had identical eligibility criteria and were conducted simultaneously. Comparison of efficacy and safety was performed between the two cohorts. A regression analysis identified prognostic factors and subgroups of patients that may benefit from combination or single-agent therapy. Results: Two hundred one patients were treated with combination and 190 with single-agent therapy. Objective responses were 37 and 15%, respectively. Median time to progression was 4.6 months in the combination arm and 3.5 months in the single-agent arm (p < 0.001). Median survival imes were 8.0 and 6.6 months, and 1-year survival rates were 31 and 26%, respectively. Albumin <3.5 g, extrathoracic metastases, lactate dehydrogenase ≥200 IU, and 2 comorbid conditions predicted outcome. Patients with 0-2 risk factors had similar outcomes independent of treatment, whereas patients with 3-4 factors had a nonsignificant improvement in median survival with combination chemotherapy. Conclusion: Our results show that PS2 non-small cell lung cancer patients are a heterogeneous group who have significantly different outcomes. Patients treated with first-line combination chemotherapy had a higher response and longer time to progression, whereas overall survival did not appear significantly different. A prognostic model may be helpful in selecting PS 2 patients for either treatment strategy. © 2009 by the International Association for the Study of Lung Cancer.

Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: Results from two phase I studies

Purpose: PTK787/ZK 222584 (PTK/ZK), an orally active inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, inhibits VEGF-mediated angiogenesis. The pharmacodynamic effects of PTK/ZK were evaluated by assessing changes in contrast-enhancement parameters of metastatic liver lesions using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with advanced colorectal cancer treated in two ongoing, dose-escalating phase I studies. Patients and Methods: Twenty-six patients had DCE-MRI performed at baseline, day 2, and at the end of each 28-day cycle. Doses of oral PTK/ZK ranged from 50 to 2000 mg once daily. Tumor permeability and vascularity were assessed by calculating the bidirectional transfer constant (Ki). The percentage of baseline Ki (% of baseline Ki) at each time point was compared with pharmacokinetic and clinical end points. Results: A significant negative correlation exists between the % of baseline Ki and increase in PTK/ZK oral dose and plasma levels (P = .01 for oral dose; P = .0001 for area under the plasma concentration curve at day 2). Patients with a best response of stable disease had a significantly greater reduction in Ki at both day 2 and at the end of cycle 1 compared with progressors (mean difference in % of baseline Ki, 47%, P = .004%; and 51%, P = .006; respectively). The difference in % of baseline Ki remained statistically significant after adjusting for baseline WHO performance status. Conclusion: These findings should help to define a biologically active dose of PTK/ZK. These results suggest that DCE-MRI may be a useful biomarker for defining the pharmacological response and dose of angiogenesis inhibitiors, such as PTK/ZK, for further clinical development. © 2003 by American Society of Clinical Oncology.

Drying kinetics, quality changes and shrinkage of two grape varieties of Italy

Two varieties of grapes, white grape and red grape grown in the Campania region of Italy were selected for the study of drying characteristics, moisture diffusion, quality changes (colour) and shrinkage behaviour. Comparisons were made with treated and untreated grapes under constant drying condition of 50o C in a conventional drying system. This temperature was selected to represent farm drying conditions. Grapes were purchased from a local market from the same supplier to maintain the same size of grapes and same properties. An abrasive physical treatment was used as pretreatment. The drying curves were constructed and drying kinetics was calculated using several commonly available models. It was found that treated samples shows better drying characteristics than untreated samples. The objective of this study is to obtain drying kinetics which can be used to optimize the drying operations in grape drying.

Within-subject intra- and inter-method consistency of two experimental risk attitude elicitation methods

We compare the consistency of choices in two methods used to elicit risk preferences on an aggregate as well as on an individual level. We ask subjects to choose twice from a list of nine decisions between two lotteries, as introduced by Holt and Laury (2002, 2005) alternating with nine decisions using the budget approach introduced by Andreoni and Harbaugh (2009). We find that, while on an aggregate (subject pool) level the results are consistent, on an individual (within-subject) level, behaviour is far from consistent. Within each method as well as across methods we observe low (simple and rank) correlations.

Primary stability of two uncemented acetabular components of different geometry : hemispherical or peripherally enhanced?

Objective This study compared the primary stability of two commercially available acetabular components from the same manufacturer, which differ only in geometry; a hemispherical and a peripherally enhanced design (peripheral self-locking (PSL)). The objective was to determine whether altered geometry resulted in better primary stability. Methods Acetabular components were seated with 0.8 mm to 2 mm interference fits in reamed polyethylene bone substrate of two different densities (0.22 g/cm3 and 0.45 g/cm3). The primary stability of each component design was investigated by measuring the peak failure load during uniaxial pull-out and tangential lever-out tests. Results There was no statistically significant difference in seating force (p = 0.104) or primary stability (pull-out p = 0.171, lever-out p = 0.087) of the two components in the low-density substrate. Similarly, in the high-density substrate, there was no statistically significant difference in the peak pull-out force (p = 0.154) or lever-out moment (p = 0.574) between the designs. However, the PSL component required a significantly higher seating force thanthe hemispherical cup in the high-density bone analogue (p = 0.006). Conclusions Higher seating forces associated with the PSL design may result in inadequate seating and increased risk of component malpositioning or acetabular fracture in the intra-operative setting in high-density bone stock. Our results, if translated clinically, suggest that a purely hemispherical geometry may have an advantage over a peripherally enhanced geometry in high density bone stock.

Repeatability and comparison of peripheral eye lengths with two instruments

Purpose: To assess intrasessional and intersessional repeatability of two commercial partial coherence interferometry instruments for measuring peripheral eye lengths and to investigate the agreement between the two instruments. Methods: Central and peripheral eye lengths were determined with the IOLMaster (Carl-Zeiss Meditec AG, Jena, Germany) and the Lenstar (Haag Streit, Bern, Switzerland) in seven adults. Measurements were performed out to 35° and 30° from fixation for horizontal and vertical visual fields, respectively, in 5° intervals. An external fixation target at optical infinity was used. At least four measurements were taken at each location for each instrument, and measurements were taken at two sessions. Results: The mean intrasessional SDs for the IOLMaster along both the horizontal and vertical visual fields were 0.04 ± 0.04 mm; corresponding results for the Lenstar were 0.02 ± 0.02 mm along both fields. The intersessional SDs for the IOLMaster for the horizontal and vertical visual fields were ±0.11 and ±0.08 mm, respectively; corresponding limits for the Lenstar were ±0.05 and ±0.04 mm. The intrasessional and intersessional variability increased away from fixation. The mean differences between the two instruments were 0.01 ± 0.07 mm and 0.02 ± 0.07 mm in the horizontal and vertical visual fields, but the lengths with the Lenstar became greater than those with the IOLMaster as axial length increased (rate of approximately 0.016 mm/mm). Conclusions: Both the IOLMaster and the Lenstar demonstrated good intrasessional and intersessional repeatability for peripheral eye length measurements, with the Lenstar showing better repeatability. The Lenstar would be expected to give a slightly greater range of eye lengths than the IOLMaster across the visual field.

Nucleotide sequences of an Australian and a Canadian isolate of potato leafroll luteovirus and their relationships with two European isolates

The genomes of an Australian and a Canadian isolate of potato leafroll virus have been cloned and sequenced. The sequences of both isolates are similar (about 93%), but the Canadian isolate (PLRV-C) is more closely related (about 98% identity) to a Scottish (PLRV-S) and a Dutch isolate (PLRV-N) than to the Australian isolate (PLRV-A). The 5'-terminal 18 nucleotide residues of PLRV-C, PLRV-A, PLRV-N and beet western yellows virus have 17 residues in common. In contrast, PLRV-S shows no obvious similarity in this region. PLRV-A and PLRV-C genomic sequences have localized regions of marked diversity, in particular a 600 nucleotide residue sequence in the polymerase gene. These data provide a world-wide perspective on the molecular biology of PLRV strains and their comparison with other luteoviruses and related RNA plant viruses suggests that there are two major subgroups in the plant luteoviruses.

Two cycles of voluminous pyroclastic volcanism and sedimentation related to episodic granite emplacement during the late Archean : Eastern Yilgarn Craton, Western Australia

The thick piles of late-Archean volcaniclastic sedimentary successions that overlie the voluminous greenstone units of the eastern Yilgarn Craton, Western Australia, record the important transition from the cessation in mafic-ultramafic volcanism to cratonisation between about 2690 and 2655 Ma. Unfortunately, an inability to clearly subdivide the superficially similar sedimentary successions and correlate them between the various geological terranes and domains of the eastern Yilgarn Craton has led to uncertainty about the timing and nature of the region's palaeogeographic and palaeotectonic evolution. Here, we present the results of some 2025 U–Pb laser-ablation-ICP-MS analyses and 323 Sensitive High-Resolution Ion Microprobe (SHRIMP) analyses of detrital zircons from 14 late-Archean felsic clastic successions of the eastern Yilgarn Craton, which have enabled correlation of clastic successions. The results of our data, together with those compiled from previous studies, show that the post-greenstone sedimentary successions include two major cycles that both commenced with voluminous pyroclastic volcanism and ended with widespread exhumation and erosion associated with granite emplacement. Cycle One commences with an influx of rapidly reworked feldspar-rich pyroclastic debris. These units, here-named the Early Black Flag Group, are dominated by a single population of detrital zircons with an average age of 2690–2680 Ma. Thick (up to 2 km) dolerite bodies, such as the Golden Mile Dolerite, intrude the upper parts of the Early Black Flag Group at about 2680 Ma. Incipient development of large granite domes during Cycle One created extensional basins predominantly near their southeastern and northwestern margins (e.g., St Ives, Wallaby, Kanowna Belle and Agnew), into which the Early Black Flag Group and overlying coarse mafic conglomerate facies of the Late Black Flag Group were deposited. The clast compositions and detrital-zircon ages of the late Black Flag Group detritus match closely the nearby and/or stratigraphically underlying successions, thus suggesting relatively local provenance. Cycle Two involved a similar progression to that observed in Cycle One, but the age and composition of the detritus were notably different. Deposition of rapidly reworked quartz-rich pyroclastic deposits dominated by a single detrital-zircon age population of 2670–2660 Ma heralded the beginning of Cycle Two. These coarse-grained quartz-rich units, are name here the Early Merougil Group. The mean ages of the detrital zircons from the Early Merougil Group match closely the age of the peak in high-Ca (quartz-rich) granite magmatism in the Yilgarn Craton and thus probably represent the surface expression of the same event. Successions of the Late Merougil Group are dominated by coarse felsic conglomerate with abundant volcanic quartz. Although the detrital zircons in these successions have a broad spread of age, the principal sub-populations have ages of about 2665 Ma and thus match closely those of the Early Merougil Group. These successions occur most commonly at the northwestern and southeastern margins of the granite batholiths and thus are interpreted to represent resedimented units dominted by the stratigraphically underlying packages of the Early Merougil Group. The Kurrawang Group is the youngest sedimentary units identified in this study and is dominated by polymictic conglomerate with clasts of banded iron formation (BIF), granite and quartzite near the base and quartz-rich sandstone units containing detrital zircons aged up to 3500 Ma near the top. These units record provenance from deeper and/or more-distal sources. We suggest here that the principal driver for the major episodes of volcanism, sedimentation and deformation associated with basin development was the progressive emplacement of large granite batholiths. This interpretation has important implication for palaeogeographic and palaeotectonic evolution of all late-Archean terranes around the world.

Is the two hour recommended maximum driving time appropriate for both healthy older and treated obstructive sleep apnoea drivers?

Objectives The UK Department for Transport recommends taking a break from driving every 2 h. This study investigated: (i) if a 2 h drive time on a monotonous road is appropriate for OSA patients treated with CPAP, compared with healthy age matched controls, (ii) the impact of a night’s sleep restriction (with CPAP) and (iii) what happens if these patients miss one nights’ CPAP treatment. Methods About 19 healthy men aged 52–74 y (m = 66.2 y) and 19 OSA participants aged 50–75 y (m = 64.4 y) drove an interactive car simulator under monotonous motorway conditions for 2 h on two afternoons, in a counterbalanced design; (1) following a normal night’s sleep (8 h). (2) following a restricted night’s sleep (5 h), with normal CPAP use (3) following a night without CPAP treatment. (n = 11) Lane drifting incidents, indicative of falling asleep, were recorded for up to 2 h depending on competence to continue driving. Results Normal sleep: Controls drove for an average of 95.9 min (s.d. 37 min) and treated OSA drivers for 89.6 min (s.d. 29 min) without incident. 63.2% of controls and 42.1% of OSA drivers successfully completed the drive without an incident. Sleep restriction: 47.4% of controls and 26.3% OSA drivers finished without incident. Overall: controls drove for an average of 89.5 min (s.d. 39 min) and treated OSA drivers 65 min (s.d. 42 min) without incident. The effect of condition was significant [F(1.36) = 9.237, P < 0.05, eta2 = 0.204]. Stopping CPAP: 18.2% of drivers successfully completed the drive. Overall, participants drove for an average of 50.1 min (s.d. 38 min) without incident. The effect of condition was significant [F(2) = 8.8, P < 0.05, eta2 = 0.468]. Conclusion 52.6% of all drivers were able to complete a 2 hour drive under monotonous conditions after a full night’s sleep. Sleep restriction significantly affected both control and OSA drivers. We find evidence that treated OSA drivers are more impaired by sleep restriction than healthy control, as they were less able to sustain safely the 2 h drive without incidents. OSA drivers should be aware that non-compliance with CPAP can significantly impair driving performance. It may be appropriate to recommend older drivers take a break from driving every 90 min especially when undertaking a monotonous drive, as was the case here.

Stored blood products augment inflammation in a two-event model of Transfusion Related Acute Lung Injury (TRALI)

Aim/Background TRALI is hypothesised to develop via a two-event mechanism involving both the patieint's underlying morbidity and blood product factors. The storage of cellular products has been implicated in cases of non-antibody mediated TRALI, however the pathophysiological mechanisms are undefined. We investigated blood product storage-related modulation of inflmmatory cells and medicators involved in TRALI. Methods In an in vitro mode, fresh human whole blood was mixed with culture media (control) or LPS as a 1st event and "transfused" with 10% (v/v) pooled supernatant (SN) from Day 1 (d1, n=75) or Day 42 (D42, n=113) packed red blood cells (PRBCs) as a 2nd event. Following 6hrs, culture SN was used to assess the overall inflammatory response (cytometric bead array) and a duplicate assay containing protein transport inhibitor was used to assess neutrophil- and monocyte-specific inflmamatory responses using multi-colour flow cytometry. Panels: IL-6, IL-8, IL-10, IL-12, IL-1, TNF, MCP-1, IP-10, MIP-1. One-way ANOVA 95% CI. Results In the absence of LPS, exposure to D1 or D42 PRBC-SN reduced monocyte expression of IL-6, IL-8 and Il-10. D42 PRBC-SN also reduced monocyte IP-10, and the overall IL-8 production was increased. In the presence of LPS, D1-PRBC SN only modified overall IP-10 levels which were reduced. However, cf LPS alone, the combination of LPS and D42 PRBC-SN resulted in increased neutrophil and monocyte productionof IL-1 and IL-8 as well as reduced monocyte TNF production. Additionally, LPS and D42 PRBC-SN resulted in overall inflmmatory changes: elevated IL-8,

Evaluation of two-view geometry methods with automatic ground-truth generation

A large number of methods have been published that aim to evaluate various components of multi-view geometry systems. Most of these have focused on the feature extraction, description and matching stages (the visual front end), since geometry computation can be evaluated through simulation. Many data sets are constrained to small scale scenes or planar scenes that are not challenging to new algorithms, or require special equipment. This paper presents a method for automatically generating geometry ground truth and challenging test cases from high spatio-temporal resolution video. The objective of the system is to enable data collection at any physical scale, in any location and in various parts of the electromagnetic spectrum. The data generation process consists of collecting high resolution video, computing accurate sparse 3D reconstruction, video frame culling and down sampling, and test case selection. The evaluation process consists of applying a test 2-view geometry method to every test case and comparing the results to the ground truth. This system facilitates the evaluation of the whole geometry computation process or any part thereof against data compatible with a realistic application. A collection of example data sets and evaluations is included to demonstrate the range of applications of the proposed system.

Flexible design of decoupling and matching networks for two strongly coupled antennas

The flexible design of decoupling and matching networks for coupled antennas is introduced. The network includes three parts: circuits for impedance transformation, an element for odd-mode decoupling and conventional matching networks. It is found that all three parts are determined by one parameter of the ABCD matrix of the impedance transformation circuit. Thus a large variety of circuits with different element values can be used for decoupling which relaxes the practical design constraints.

Calligraphy and causation : two obstetric management cases

Child born with gross hydrocephalus - cerebral palsy - questions surrounding obstetrician's notes - ultrasound not ordered - illegible handwriting - importance of legible, accurate and detailed medical records - causation - child born with congenital varicella syndrome (CVS) - chicken pox - forseeability of risk.

Scepticism and trust: two counterpoint essentials in science education for complex socio-scientific issues

In this response to Tom G. K. Bryce and Stephen P. Day’s (Cult Stud Sci Educ. doi:10.1007/s11422-013-9500-0, 2013) original article, I share with them their interest in the teaching of climate change in school science, but I widen it to include other contemporary complex socio-scientific issues that also need to be discussed. I use an alternative view of the relationship between science, technology and society, supported by evidence from both science and society, to suggest science-informed citizens as a more realistic outcome image of school science than the authors’ one of mini-scientists. The intellectual independence of students Bryce and Day assume, and intend for school science, is countered with an active intellectual dependence. It is only in relation to emerging and uncertain scientific contexts that students should be taught about scepticism, but they also need to learn when, and why to trust science as an antidote to the expressions of doubting it. Some suggestions for pedagogies that could lead to these new learnings are made. The very recent fifth report of the IPCC answers many of their concerns about climate change.