Monte Carlo dosimetry for stereotactic radiosurgery

Stereotactic radiosurgery (SRS) treatments for brain cancers require small and precisely shaped photon beams. These beams can be generated by fitting a linear accelerator with a micro-multileaf collimator (mMLC) such as the BrainLAB m3, which offers greater flexibility for field shaping than standard SRS cone collimators

Effect of Oil Price on Emissions Trading Market: VAR Analysis

In this study, we investigated the relationship of European Union carbon dioxide CO2 allowances EUAs prices and oil prices by employing a VAR analysis, Granger causality test and impulse response function. If oil price continues increasing, companies will decrease dependency on fossil fuels because of an increase in energy costs. Therefore, the price of EUAs may be affected by variations in oil prices if the greenhouse gases discharged by the consumption of alternative energy are less than that of fossil fuels. There are no previous studies that investigated these relationships. In this study, we analyzed eight types of EUAs EUA05 to EUA12 with a time series daily data set during 2005-2007 collected from a European Climate Exchange time series data set. Differentiations in these eight types were redemption period. We used the New York Mercantile Exchange light sweet crude price as an oil price. From our examination, we found that only the EUA06 and EUA07 types of EUAs Granger-cause oil prices and vice versa and other six types of EUAs do not Granger-cause oil price. These results imply that the earlier redemption period types of EUAs are more sensitive to oil price. In employing the impulse response function, the results showed that a shock to oil price has a slightly positive effect on all types of EUAs for a very short period. On the other hand, we found that a shock to price of EUA has a slightly negative effect on oil price following a positive effect in only EUA06 and EUA07 types. Therefore, these results imply that fluctuations in EUAs prices and oil prices have little effect on each other. Lastly, we did not consider the substitute energy prices in this study, so we plan to include the prices of coal and natural gas in future analyses.

Dosimetry of cone-defined stereotactic radiosurgery fields with a commercial synthetic diamond detector

Purpose Small field x-ray beam dosimetry is difficult due to a lack of lateral electronic equilibrium, source occlusion, high dose gradients and detector volume averaging. Currently there is no single definitive detector recommended for small field dosimetry. The objective of this work was to evaluate the performance of a new commercial synthetic diamond detector, namely the PTW 60019 microDiamond, for the dosimetry of small x-ray fields as used in stereotactic radiosurgery (SRS). Methods Small field sizes were defined by BrainLAB circular cones (4 – 30 mm diameter) on a Novalis Trilogy linear accelerator and using the 6 MV SRS x-ray beam mode for all measurements. Percentage depth doses were measured and compared to an IBA SFD and a PTW 60012 E diode. Cross profiles were measured and compared to an IBA SFD diode. Field factors, Ω_(Q_clin,Q_msr)^(f_clin,f_msr ), were calculated by Monte Carlo methods using BEAMnrc and correction factors, k_(Q_clin,Q_msr)^(f_clin,f_msr ), were derived for the PTW 60019 microDiamond detector. Results For the small fields of 4 to 30 mm diameter, there were dose differences in the PDDs of up to 1.5% when compared to an IBA SFD and PTW 60012 E diode detector. For the cross profile measurements the penumbra values varied, depending upon the orientation of the detector. The field factors, Ω_(Q_clin,Q_msr)^(f_clin,f_msr ), were calculated for these field diameters at a depth of 1.4 cm in water and they were within 2.7% of published values for a similar linear accelerator. The corrections factors, k_(Q_clin,Q_msr)^(f_clin,f_msr ), were derived for the PTW 60019 microDiamond detector. Conclusions We conclude that the new PTW 60019 microDiamond detector is generally suitable for relative dosimetry in small 6 MV SRS beams for a Novalis Trilogy linear equipped with circular cones.

Informing methods for preparing public health overviews of reviews: a comparison of public health overviews with Cochrane Overviews published between 1999 and 2014

Background: Overviews of systematic reviews (SRs) are useful for public health policy; however there is an absence of Cochrane Overviews covering public health (PH) topics. Objectives: We sought to analyze the methodological approaches used in existing Cochrane Overviews and Protocols for overviews (primarily clinical in nature), and compare these to the methods and approaches used in PH overviews (non-Cochrane). The intent was to identify issues that would be relevant for undertaking Cochrane overviews. Methods: We conducted a descriptive analysis of overviews published between 1999 and 2014. We searched the Cochrane Database of Systematic Reviews for Cochrane Protocols for overviews and Cochrane Overviews, and the HealthEvidence.org for PH overviews. The primary characteristics of the overviews and elements of the methodology were extracted and compared. Results: A total of 61 overviews of SRs were included in our analysis; specifically, this included 21 Cochrane Protocols for overviews, 15 Cochrane Overviews, and 27 non-Cochrane PH overviews. Amongst the overviews, the most significant differences are that PH overviews (non-Cochrane) tend to: include earlier and more reviews, greater number of participants, allow lower levels of evidence, use assessment tools other than AMSTAR (A Measurement Tool to Assess Systematic Reviews, i.e. a tool for assessing quality of SRs), not assess quality of evidence in reviews, search more databases overall, specify search limits including English-only reviews, and not consider recent primary studies for inclusion. Some of these differences clearly related to quality, however many relate to the nuances of PH interventions. Conclusions: The methodology in Cochrane overviews and PH overviews varies widely. Future PH overviews may benefit from the Cochrane methodology but the Cochrane approach requires modification to accommodate PH research methodology. Additionally, the use of databases that pre-screen and quality assess relevant PH systematic reviews may help expedite the search process.

The O-specific polysaccharide structure and biosynthetic gene cluster of Yersinia pseudotuberculosis serotype O:11

In the Yersinia pseudotuberculosis serotyping scheme, 21 serotypes are present originating from about 30 different O-factors distributed within the species. With regard to the chemical structures of lipopolysaccharides (LPSs) and the genetic basis of their biosynthesis, a number, but not all, of Y. pseudotuberculosis strains representing different serotypes have been investigated. In order to present an overall picture of the relationship between genetics and structures, we have been working on the genetics and structures of various Y. pseudotuberculosis O-specific polysaccharides (OPSs). Here, we present a structural and genetic analysis of the Y. pseudotuberculosis serotype O:11 OPS. Our results showed that this OPS structure has the same backbone as that of Y. pseudotuberculosis O:1b, but with a 6d-l-Altf side-branch instead of Parf. The 3′ end of the gene cluster is the same as that for O:1b and has the genes for synthesis of the backbone and for processing the completed repeat unit. The 5′ end has genes for synthesis of 6d-l-Altf and its transfer to the repeating unit backbone. The pathway for the synthesis of the 6d-l-Altf appears to be different from that for 6d-l-Altp in Y. enterocolitica O:3. The chemical structure of the O:11 repeating unit is [Figure]

Genetic characterisation and structural analysis of the O-specific polysaccharide of Yersinia pseudotuberculosis serotype O:1c

Many, but not all, of the current 21 serotypes of Yersinia pseudotuberculosis have been investigated with regard to the chemical structures of their O-specific polysaccharide (OPS) and the genetic basis of their biosynthesis. Completion of the genetics and structures of the remaining serotypes will enhance our understanding of the emerging relationship between genetics and structures within this species. Here, we present a structural and genetic analysis of the Y. pseudotuberculosis serotype O:1c OPS. Our results showed that this OPS has the same backbone as Y. pseudotuberculosis O:2b, but with a 3,6-dideoxy-D-ribo-hexofuranose (paratofuranose, Parf) side-branch instead of a 3,6-dideoxy-D-xylo-hexopyranose (abequopyranose, Abep). The 3'-end of the gene cluster is the same as for O:2b and has the genes for synthesis of the backbone and for processing the completed repeat unit. The 5'-end of the cluster consists of the same genes as O:1b for synthesis of Parf and a related gene for its transfer to the repeating unit backbone.

Soluble mediators in platelet concentrates modulate dendritic cell inflammatory responses in an experimental model of transfusion

The transfusion of platelet concentrates (PCs) is widely used to treat thrombocytopenia and severe trauma. Ex vivo storage of PCs is associated with a storage lesion characterized by partial platelet activation and the release of soluble mediators, such as soluble CD40 ligand (sCD40L), RANTES, and interleukin (IL)-8. An in vitro whole blood culture transfusion model was employed to assess whether mediators present in PC supernatants (PC-SNs) modulated dendritic cell (DC)-specific inflammatory responses (intracellular staining) and the overall inflammatory response (cytometric bead array). Lipopolysaccharide (LPS) was included in parallel cultures to model the impact of PC-SNs on cell responses following toll-like receptor-mediated pathogen recognition. The impact of both the PC dose (10%, 25%) and ex vivo storage period was investigated [day 2 (D2), day 5 (D5), day 7 (D7)]. PC-SNs alone had minimal impact on DC-specific inflammatory responses and the overall inflammatory response. However, in the presence of LPS, exposure to PC-SNs resulted in a significant dose associated suppression of the production of DC IL-12, IL-6, IL-1a, tumor necrosis factor-a (TNF-a), and macrophage inflammatory protein (MIP)-1b and storage-associated suppression of the production of DC IL-10, TNF-a, and IL-8. For the overall inflammatory response, IL-6, TNF-a, MIP-1a, MIP-1b, and inflammatory protein (IP)-10 were significantly suppressed and IL-8, IL-10, and IL-1b significantly increased following exposure to PC-SNs in the presence of LPS. These data suggest that soluble mediators present in PCs significantly suppress DC function and modulate the overall inflammatory response, particularly in the presence of an infectious stimulus. Given the central role of DCs in the initiation and regulation of the immune response, these results suggest that modulation of the DC inflammatory profile is a probable mechanism contributing to transfusion-related complications.

Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects

Introduction: A number of genetic-association studies have identified genes contributing to ankylosing spondylitis (AS) susceptibility but such approaches provide little information as to the gene activity changes occurring during the disease process. Transcriptional profiling generates a 'snapshot' of the sampled cells' activity and thus can provide insights into the molecular processes driving the disease process. We undertook a whole-genome microarray approach to identify candidate genes associated with AS and validated these gene-expression changes in a larger sample cohort. Methods: A total of 18 active AS patients, classified according to the New York criteria, and 18 gender- and age-matched controls were profiled using Illumina HT-12 whole-genome expression BeadChips which carry cDNAs for 48,000 genes and transcripts. Class comparison analysis identified a number of differentially expressed candidate genes. These candidate genes were then validated in a larger cohort using qPCR-based TaqMan low density arrays (TLDAs). Results: A total of 239 probes corresponding to 221 genes were identified as being significantly different between patients and controls with a P-value <0.0005 (80% confidence level of false discovery rate). Forty-seven genes were then selected for validation studies, using the TLDAs. Thirteen of these genes were validated in the second patient cohort with 12 downregulated 1.3- to 2-fold and only 1 upregulated (1.6-fold). Among a number of identified genes with well-documented inflammatory roles we also validated genes that might be of great interest to the understanding of AS progression such as SPOCK2 (osteonectin) and EP300, which modulate cartilage and bone metabolism. Conclusions: We have validated a gene expression signature for AS from whole blood and identified strong candidate genes that may play roles in both the inflammatory and joint destruction aspects of the disease.

Synthesis and luminescent properties of star-burst D-Pi-A compounds based on 1,3,5-triazine core and carbazole end-capped phenylene ethynylene arms

Two new star-burst compounds based on 1,3,5-triazine core and carbazole end-capped phenylene ethynylene arms (1a and 1b) were synthesized and characterized. Their photophysical properties were investigated systematically via spectroscopic and theoretical methods. Both compounds exhibit strong 1π–π⁎ transitions in the UV region and intense 1π–π⁎/intramolecular charge transfer (1ICT) absorption bands in the UV–vis region. Introducing the carbazole end-capped phenylene ethynylene arm on the 1,3,5-triazine core causes a slight bathochromic shift and enhanced molar extinction coefficient of the 1π–π⁎/1ICT transition band. Both compounds are emissive in solution at room temperature and 77 K, which exhibit pronounced positive solvatochromic effect. The emitting state could be ascribed to 1ICT state in more polar solvent, and 1π–π⁎ state in low-polarity solvent. The high emission quantum yields (Φem=0.90~1.0) of 1a and 1b (in hexane and toluene) make them potential candidates as efficient light-emitting materials. The spectroscopic studies and theoretical calculations indicate that the photophysical properties of these compounds can be tuned by the carbazole end-capped phenylene ethynylene arm, which would also be useful for rational design of photofunctional materials.

Evidence-based recommendations for the diagnosis of ankylosing spondylitis: Results from the Australian 3E initiative in rheumatology

• As part of the 3E program, we conducted a systematic literature review and gathered consensus from 23 practising Australian rheumatologists to develop guidelines for early identification of ankylosing spondylitis and specialist referral. • In three rounds of break-out sessions followed by discussion and voting, the specialist panel addressed three questions related to diagnosis of ankylosing spondylitis: In individuals with back pain, what are the early clinical features that suggest ankylosing spondylitis? How useful is imaging in identifying early ankylosing spondylitis? Based on which clinical features should a general practitioner refer a patient to a rheumatologist for further evaluation? • The panel agreed on six recommendations related to the three questions: 1a. Early clinical features to suggest ankylosing spondylitis include inflammatory back pain and age at symptom onset < 45 years. 1b. The absence of symptomatic response to an appropriate course of non-steroidal anti-inflammatory drugs makes the diagnosis of ankylosing spondylitis less likely. 1c. Raised inflammatory markers are supportive, but their absence does not rule out the diagnosis of ankylosing spondylitis. 2a. Despite low sensitivity to detect changes of early ankylosing spondylitis, plain radiographs of the pelvis and spine are appropriate initial imaging techniques. 2b. Magnetic resonance imaging is a useful imaging modality for detecting early changes of ankylosing spondylitis. 3. Individuals with inflammatory back pain should be referred to a rheumatologist for further evaluation. • Effective dissemination and implementation of these recommendations are important to standardise the approach to early diagnosis of ankylosing spondylitis.

Efficient designs for sampling and subsampling in fisheries research based on ranked sets

Sampling strategies are developed based on the idea of ranked set sampling (RSS) to increase efficiency and therefore to reduce the cost of sampling in fishery research. The RSS incorporates information on concomitant variables that are correlated with the variable of interest in the selection of samples. For example, estimating a monitoring survey abundance index would be more efficient if the sampling sites were selected based on the information from previous surveys or catch rates of the fishery. We use two practical fishery examples to demonstrate the approach: site selection for a fishery-independent monitoring survey in the Australian northern prawn fishery (NPF) and fish age prediction by simple linear regression modelling a short-lived tropical clupeoid. The relative efficiencies of the new designs were derived analytically and compared with the traditional simple random sampling (SRS). Optimal sampling schemes were measured by different optimality criteria. For the NPF monitoring survey, the efficiency in terms of variance or mean squared errors of the estimated mean abundance index ranged from 114 to 199% compared with the SRS. In the case of a fish ageing study for Tenualosa ilisha in Bangladesh, the efficiency of age prediction from fish body weight reached 140%.

Efficient regression analysis with ranked-set sampling

This article is motivated by a lung cancer study where a regression model is involved and the response variable is too expensive to measure but the predictor variable can be measured easily with relatively negligible cost. This situation occurs quite often in medical studies, quantitative genetics, and ecological and environmental studies. In this article, by using the idea of ranked-set sampling (RSS), we develop sampling strategies that can reduce cost and increase efficiency of the regression analysis for the above-mentioned situation. The developed method is applied retrospectively to a lung cancer study. In the lung cancer study, the interest is to investigate the association between smoking status and three biomarkers: polyphenol DNA adducts, micronuclei, and sister chromatic exchanges. Optimal sampling schemes with different optimality criteria such as A-, D-, and integrated mean square error (IMSE)-optimality are considered in the application. With set size 10 in RSS, the improvement of the optimal schemes over simple random sampling (SRS) is great. For instance, by using the optimal scheme with IMSE-optimality, the IMSEs of the estimated regression functions for the three biomarkers are reduced to about half of those incurred by using SRS.

Partial intervertebral fusion secures successful outcomes after thoracoscopic anterior scoliosis correction: A low-dose computed tomography study

Study Design Retrospective review of prospectively collected data. Objectives To analyze intervertebral (IV) fusion after thoracoscopic anterior spinal fusion (TASF) and explore the relationship between fusion scores and key clinical variables. Summary of Background Information TASF provides comparable correction with some advantages over posterior approaches but reported mechanical complications, and their relationship to non-union and graft material is unclear. Similarly, the optimal combination of graft type and implant stiffness for effecting successful radiologic union remains undetermined. Methods A subset of patients from a large single-center series who had TASF for progressive scoliosis underwent low-dose computed tomographic scans 2 years after surgery. The IV fusion mass in the disc space was assessed using the 4-point Sucato scale, where 1 indicates <50% and 4 indicates 100% bony fusion of the disc space. The effects of rod diameter, rod material, graft type, fusion level, and mechanical complications on fusion scores were assessed. Results Forty-three patients with right thoracic major curves (mean age 14.9 years) participated in the study. Mean fusion scores for patient subgroups ranged from 1.0 (IV levels with rod fractures) to 2.2 (4.5-mm rod with allograft), with scores tending to decrease with increasing rod size and stiffness. Graft type (autograft vs. allograft) did not affect fusion scores. Fusion scores were highest in the middle levels of the rod construct (mean 2.52), dropping off by 20% to 30% toward the upper and lower extremities of the rod. IV levels where a rod fractured had lower overall mean fusion scores compared to levels without a fracture. Mean total Scoliosis Research Society (SRS) questionnaire scores were 98.9 from a possible total of 120, indicating a good level of patient satisfaction. Conclusions Results suggest that 100% radiologic fusion of the entire disc space is not necessary for successful clinical outcomes following thoracoscopic anterior selective thoracic fusion.

Amber teething necklaces: Is there any basis to their use in teething infants?

Introduction. Baltic amber-bead necklaces or bracelets are commonly used for managing teething symptoms in infants. The effectiveness of these beads is claimed to be from succinic acid release (a compound said to have analgesic and anti-inflammatory properties), which is then absorbed through the skin. Aims. To investigate whether succinic acid is contained in Baltic amber teething necklaces purchased in Australia, whether it can be released from the beads, and whether it has anti-inflammatory activity. Methods. Infrared spectroscopy was used to confirm that the teething necklaces were made of Baltic amber. The amount of succinic acid contained within the beads was quantified, and succinic acid release from intact beads was measured in phosphate buffered saline (PBS) pH 5.5 or octanol. Anti-inflammatory activity of succinic acid was compared with ibuprofen, paracetamol and hydrocortisone in vitro using THP-1 human macrophages stimulated with LPS. Secretion of the cytokines IL-1a, IL-1b, IL-8 and TNF-α were determined by ELISA. Results. Each necklace (33 beads in length) contained 19.17 ± 4.89 mg of succinic acid (mean ± se). Over a 6-month period, no succinic acid was detected in PBS. While 0.13 ± 0.09 mg of succinic acid per necklace was released in octanol, this was due to only one replicate of amber beads which had fragmented into shards free-floating in the solvent. Succinic acid had no effect on cytokine secretion unless extremely high concentrations were used and changes were likely to be associated with cell apoptosis and death. Discussion. No evidence for anti-inflammatory activity was found in the cytokines studied. It is possible that succinic acid could exert an effect via some other mechanism, but while the teething necklaces do contain small quantities of succinic acid, it is highly unlikely to be released from intact beads.

The antihypertensive drug pindolol attenuates long-term but not short-term binge-like ethanol consumption in mice

Alcohol dependence is a debilitating disorder with current therapies displaying limited efficacy and/or compliance. Consequently, there is a critical need for improved pharmacotherapeutic strategies to manage alcohol use disorders (AUDs). Previous studies have shown that the development of alcohol dependence involves repeated cycles of binge-like ethanol intake and abstinence. Therefore, we used a model of binge-ethanol consumption (drinking-in-the-dark) in mice to test the effects of compounds known to modify the activity of neurotransmitters implicated in alcohol addiction. From this, we have identified the FDA-approved antihypertensive drug pindolol, as a potential candidate for the management of AUDs. We show that the efficacy of pindolol to reduce ethanol consumption is enhanced following long-term (12-weeks) binge-ethanol intake, compared to short-term (4-weeks) intake. Furthermore, pindolol had no effect on locomotor activity or consumption of the natural reward sucrose. Because pindolol acts as a dual beta-adrenergic antagonist and 5-HT1A/1B partial agonist, we examined its effect on spontaneous synaptic activity in the basolateral amygdala (BLA), a brain region densely innervated by serotonin- and norepinephrine-containing fibres. Pindolol increased spontaneous excitatory post-synaptic current frequency in BLA principal neurons from long-term ethanol consuming mice but not naïve mice. Additionally, this effect was blocked by the 5-HT1A/1B receptor antagonist methiothepin, suggesting that altered serotonergic activity in the BLA may contribute to the efficacy of pindolol to reduce ethanol intake following long-term exposure. Although further mechanistic investigations are required, this study demonstrates the potential of pindolol as a new treatment option for AUDs that can be fast-tracked into human clinical studies.