The OncoSim model: development and use for better decision-making in Canadian cancer control.

The Canadian Partnership Against Cancer was created in 2007 by the federal government to accelerate cancer control across Canada. Its OncoSim microsimulation model platform, which consists of a suite of specific cancer models, was conceived as a tool to augment conventional resources for population-level policy- and decision-making. The Canadian Partnership Against Cancer manages the OncoSim program, with funding from Health Canada and model development by Statistics Canada. Microsimulation modelling allows for the detailed capture of population heterogeneity and health and demographic history over time. Extensive data from multiple Canadian sources were used as inputs or to validate the model. OncoSim has been validated through expert consultation; assessments of face validity, internal validity, and external validity; and model fit against observed data. The platform comprises three in-depth cancer models (lung, colorectal, cervical), with another in-depth model (breast) and a generalized model (25 cancers) being in development. Unique among models of its class, OncoSim is available online for public sector use free of charge. Users can customize input values and output display, and extensive user support is provided. OncoSim has been used to support decision-making at the national and jurisdictional levels. Although simulation studies are generally not included in hierarchies of evidence, they are integral to informing cancer control policy when clinical studies are not feasible. OncoSim can evaluate complex intervention scenarios for multiple cancers. Canadian decision-makers thus have a powerful tool to assess the costs, benefits, cost-effectiveness, and budgetary effects of cancer control interventions when faced with difficult choices for improvements in population health and resource allocation.

Gal4 Driver Transgenic Zebrafish: Powerful Tools to Study Developmental Biology, Organogenesis, and Neuroscience.

Targeted expression by the Gal4-UAS system is a powerful genetic method to analyze the functions of genes and cells in vivo. Although the Gal4-UAS system has been extensively used in genetic studies in Drosophila, it had not been applied to genetic studies in vertebrates until the mid-2000s. This was mainly due to the lack of an efficient transgenesis tool in model vertebrates, such as the P-transposable element of Drosophila, that can create hundreds or thousands of transgene insertions in different loci on the genome and thereby enables the generation of transgenic lines expressing Gal4 in various tissues and cells via enhancer trapping. This situation was revolutionized when a highly efficient transgenesis method using the Tol2 transposable element was developed in the model vertebrate zebrafish. By using the Tol2 transposon system, we and other labs successfully performed gene trap and enhancer trap screens in combination with the Gal4-UAS system. To date, numerous transgenic fish lines that express engineered versions of Gal4 in specific cells, organs, and tissues have been generated and used for various aspects of biological studies. By constructing transgenic fish lines harboring genes of interest downstream of UAS, the Gal4-expressing cells and tissues in those transgenic fish have been visualized and manipulated via the Gal4-UAS system. In this review, we describe how the Gal4-UAS system works in zebrafish and how transgenic zebrafish that express Gal4 in specific cells, tissues, and organs have been used for the study of developmental biology, organogenesis, and neuroscience.

Tol2-mediated transgenesis, gene trapping, enhancer trapping, and Gal4-UAS system.

The Tol2 element is an active transposon that was found from the genome of the Japanese medaka fish. Since the Tol2 transposition system is active in all vertebrate cells tested so far, it has been applied to germ line transgenesis in various model animals including fish, frog, chicken, and mouse, and to gene transfer in culture cells. In zebrafish, the Tol2 system consists of the transposase mRNA and a Tol2 transposon-donor plasmid, and is introduced into fertilized eggs by microinjection. Thus genomic integrations of the Tol2 construct are generated in the germ lineage and transmitted to the offspring very efficiently. By using the Tol2 transposition system, we have developed important genetic methods, such as transgenesis, gene trapping, enhancer trapping, and the Gal4-UAS system in zebrafish and applied to many aspects of biological studies. In this chapter, we describe how these methods are performed.

Using the Cancer Risk Management Model to evaluate the health and economic impacts of cytology compared with human papillomavirus DNA testing for primary cervical cancer screening in Canada.

BACKGROUND: In Canada, discussion about changing from cytology to human papillomavirus (hpv) dna testing for primary screening in cervical cancer is ongoing. However, the Canadian Task Force on Preventive Health Care has not yet made a recommendation, concluding that the evidence is insufficient. METHODS: We used the cervical cancer and hpv transmission models of the Cancer Risk Management Model to study the health and economic outcomes of primary cytology compared with hpv dna testing in 14 screening scenarios with varying screening modalities and intervals. Projected cervical cancer cases, deaths, colposcopies, screens, costs, and incremental cost-effectiveness were evaluated. We performed sensitivity analyses for hpv dna test costs. RESULTS: Compared with triennial cytology from age 25, 5-yearly hpv dna screening alone from age 30 resulted in equivalent incident cases and deaths, but 55% (82,000) fewer colposcopies and 43% (1,195,000) fewer screens. At hpv dna screening intervals of 3 years, whether alone or in an age-based sequence with cytology, screening costs are greater, but at intervals of more than 5 years, they are lower. Scenarios on the cost-effectiveness frontier were hpv dna testing alone every 10, 7.5, 5, or 3 years, and triennial cytology starting at age 21 or 25 when combined with hpv dna testing every 3 years. CONCLUSIONS: Changing from cytology to hpv dna testing as the primary screening test for cervical cancer would be an acceptable strategy in Canada with respect to incidence, mortality, screening and diagnostic test volumes.

Micron scale directional coupler as a transducer for biochemical sensing.

A microfabricated directional coupler (DC) was used for the detection of DNA conjugated with quantum dots. Output optical signals from DCs of a wide range of device lengths correspond well to theoretical and simulation results. Even 20 µm-long DC devices could detect changes in the output optical intensity by monitoring the near-field pattern using a CCD camera. The signal was enhanced 60 × using a 1500 µm-long DC device. For large cladding refractive-index changes between air and water, the normalized signal changed cyclically several times between 0 and 1. The results suggest that the DC can be the basis for miniaturized two-dimensionally integrated biochemical sensors.

The effect of higher-order dispersion on slow light propagation in photonic crystal waveguides.

We have studied the dispersion of ultrafast pulses in a photonic crystal waveguide as a function of optical frequency, in both experiment and theory. With phase-sensitive and time-resolved near-field microscopy, the light was probed inside the waveguide in a non-invasive manner. The effect of dispersion on the shape of the pulses was determined. As the optical frequency decreased, the group velocity decreased. Simultaneously, the measured pulses were broadened during propagation, due to an increase in group velocity dispersion. On top of that, the pulses exhibited a strong asymmetric distortion as the propagation distance increased. The asymmetry increased as the group velocity decreased. The asymmetry of the pulses is caused by a strong increase of higher order dispersion. As the group velocity was reduced to 0.116(9) .c, we found group velocity dispersion of -1.1(3) .10(6) ps(2)/km and third order dispersion of up to 1.1(4) .10(5) ps(3)/km. We have modelled our interferometric measurements and included the full dispersion of the photonic crystal waveguide. Our mathematical model and the experimental findings showed a good correspondence. Our findings show that if the most commonly used slow light regime in photonic crystals is to be exploited, great care has to be taken about higher-order dispersion.

Light-propagation characteristics of Y-branch defect waveguides in AlGaAs-based air-bridge-type two-dimensional photonic crystal slabs.

Y-branch defect waveguides (DWGs) in an AlGaAs-based air-bridge-type two-dimensional (2D) photonic crystal (PC) slab were fabricated, and the resulting optical transmission spectra were measured. Optical beam propagation along the waveguide was successfully observed in vidicon IR images. The measured transmission spectra at the two output ports in the Y-branch DWG were remarkably similar in shape and magnitude. From comparison between the measured and calculated transmission spectra, the observed optical beam was identified as the guided mode based on the Y-branch DWG in the 2D PC slab. The results suggest that the Y-branch DWG used in the experiment has the potential to function as an ultrasmall 3-dB beam splitter with good performance.

Complete nucleotide sequence of a Staphylococcus aureus exfoliative toxin B plasmid and identification of a novel ADP-ribosyltransferase, EDIN-C.

The complete nucleotide sequence of pETB, a 38.2-kb Staphylococcus aureus plasmid encoding the exfoliative toxin B (ETB), was determined. A total of 50 open reading frames were identified on the plasmid genome and, among these, 32 showed sequence similarity to known proteins. pETB contains three copies of IS257, which divide the pETB genome into three regions: (i) a cadmium resistance operon-containing region, (ii) a lantibiotic production gene-containing region, and (iii) the remaining part where genes for plasmid replication and/or maintenance are dispersed. In the third region, genes of various kinds of functions are present among the replication- and maintenance-related genes. They include two virulence-related genes, the etb gene and a gene encoding a novel ADP-ribosyltransferase closely related to EDIN, which belongs to the C3 family of ADP-ribosyltransferases modifying Rho GTPases. They also include genes for a cell wall-anchoring surface protein and a phage resistance protein. Based on the determined sequence of pETB, the genome structures of etb-bearing plasmids (ETB plasmids) from various clinical isolates were analyzed by the PCR scanning method. The data indicate that, although the ETB plasmids are highly heterogeneous in genome size, the fundamental genome organization is well conserved. The size variation of the plasmid is mainly attributed to defined regions which may be hot spots for gene shuffling.

Effects of insulin-like growth factor-1 on Short bowel syndrome without ileocecal valve in rats.

Insulin-like growth factor-1 (IGF-1) can promote enterocyte proliferation which may be beneficial to postoperative conditions after massive small bowel resection (SBR) including the ileocecal valve (ICV). Wistar rats were subjected to SBR including or preserving ICV and continuously received IGF-1 or saline alone. Nutritional status, enterocyte proliferation, liver damage and hepatic IGF-1 mRNA levels were analyzed. Body weights, serum levels of total protein and transferrin, and enterocyte proliferation were significantly lower after SBR including ICV than preserving it. IGF-1 mRNA levels in the liver were decreased after SBR, especially after SBR including ICV. However, IGF-1 therapy significantly attenuated those decreased levels after SBR including ICV. Furthermore, IGF-1 significantly decreased serum liver transaminase levels which were increased after SBR including ICV. Continuous administration of IGF-1 may be available as a supplemented therapy for short bowel syndrome without ICV.

Cultural variations in optimistic and pessimistic bias: do Easterners really expect the worst and Westerners really expect the best when predicting future life events?

The authors compared levels of optimistic and pessimistic bias in the prediction of positive and negative life events between European Americans and Japanese. Study 1 showed that European Americans compared with Japanese were more likely to predict positive events to occur to self than to others. The opposite pattern emerged in the prediction of negative events. Study 2 replicated these cultural differences. Furthermore, positive associations emerged between predictions and occurrence of life events 2 months later for both European Americans and Japanese. Across both studies, results of within-groups analyses indicated that both groups expected negative events to be more likely to occur to others than to self (optimistic bias). In addition, Japanese expected positive events to be more likely to occur to others than to self (pessimistic bias). However, European Americans failed to show the expected optimistic bias for positive events.

[Effects of cernitin pollen-extract (Cernilton) on inflammatory cytokines in sex-hormone-induced nonbacterial prostatitis rats].

Cernitin pollen-extract (Cernilton, CN) is a preparation made from eight kinds of pollen and has been used for various prostatic diseases in Japan and Europe. We reported previously that CN possessed a recovery action on the sex-hormone-induced nonbacterial prostatitis in rats. To clarify the possible mechanism of action of CN, we investigated the effects of CN on inflammatory cytokines (IL-1 beta, IL-6 and TNF-alpha) in the same model. Aged Wistar rats were castrated and injected 17 beta-estradiol (0.25 mg/kg/day, s.c.) for 30 days. CN (630 and 1,260 mg/kg, p.o.) or testosterone (2.5 mg/kg, s.c.) was administered for the last 14 days of the treatment of 17 beta-estradiol. In control rats, prostatic IL-6 and TNF-alpha contents were increased approximately 2-3 fold, and acinar glandular inflammation and stromal proliferation were found histopathologically, as compared with those of intact rats. On the other hand, CN decreased the increased contents of cytokines in a dose-dependent manner. The histopathological changes mentioned above were restored in rats treated with 1,260 mg/kg. Testosterone also ameliorated them significantly. These results indicate that CN has an anti-inflammatory action, and that the inhibitory effect of CN on the prostatic inflammatory cytokine is an important factor in its action.

Confined band gap in an air-bridge type of two-dimensional AlGaAs photonic crystal.

The transmittance spectrum for an air-bridge type of AlGaAs photonic crystal (PC) slabs successfully fabricated was measured. It is found that the observed spectrum is consistent with both the theoretical band structure and the calculated one. Moreover, the transmittance due to the modes below the light line is found to be almost 100%, indicating that the guided modes should exist. The respective stop bands are observed in the gamma-M direction for TM-like and TE-like modes, implying that a photonic band gap should exist for the TE-like guided modes. The present PC is very suited for controlling the radiation field.

WorldSID Prototype Dummy Biomechanical Responses.

The results of biomechanical testing of the WorldSID prototype dummy are presented in this paper. The WorldSID dummy is a new, advanced Worldwide Side Impact Dummy that has the anthropometry of a mid-sized adult male. The first prototype of this dummy has been evaluated by the WorldSID Task Group against previously established corridors for its critical body regions. The response corridors are defined in the International Organization of Standardization (ISO) Technical Report 9790. The prototype is the first version of the WorldSID dummy to be built and tested. This dummy has been subjected to a rigorous program of testing to evaluate, first and foremost its biofidelity, but also its repeatability. Following this initial evaluation, any required modifications will be incorporated into a pre-production version of the WorldSID dummy so that it rates "good" to "excellent" on the ISO dummy biofidelity scale - a rating exceeding that of all current side impact dummies. Also, the overall WorldSID repeatability must not exceed a coefficient of variation of 7% at injury assessment level and this has to be verified for the different body regions. The dummy's head, neck, thorax, abdomen and pelvis were evaluated against the ISO technical report requirements. Testing included drop tests, pendulum impacts, and sled tests. The biofidelity rating of the WorldSID prototype was calculated using the weighted biomechanical test response procedure developed by ISO. The paper presents the results of the testing, which give a very positive indication of the dummy's potential. Based on this evaluation of the dummy biofidelity, the WorldSID prototype dummy exhibits a biofidelity rating of 6.15 that corresponds to an ISO biofidelity classification of "fair". In addition, the dummy shows good repeatability with a global coefficient of variation of 3.30% for the pendulum and rigid sled tests.

Comparison of urine cytology between the ileal conduit and Indiana pouch.

OBJECTIVE: To compare the cytomorphologic features of urine obtained from two different kinds of urinary diversions constructed after total bladder resection. STUDY DESIGN: The smears of urine from 11 ileal conduits and 6 Indiana pouches were evaluated. All patients underwent total bladder resection due to transitional cell carcinoma (TCC) or other kinds of cancer before urine diversion. RESULTS: The cytologic features of Indiana pouch urine include degenerated, small, round cells without columnar cells derived from intestinal epithelium. In ileal conduit urine, well-preserved columnar cells and degenerated, small, round cells were frequently observed. The columnar cells in ileal conduit urine exhibited cytologic features that should be distinguished from TCC cells. CONCLUSION: The method of reconstructing the urinary tract is important in urine cytology from urine diversions because the cytomorphologic features of urine are different between the two kinds of urinary diversions. Since columnar cells in ileal conduit urine might lead to misdiagnosis as TCC, special consideration is required to examine ileal conduit urine.

[The mental health of school children after the Great Hanshin-Awaji Earthquake: II. Longitudinal analysis].

UNLABELLED: We conducted surveys to investigate the nature of the recovery processes and psychological reactions of children and adolescents affected by the Great Hanshin Awaji Earthquake. The investigations were carried out 4 times at 4 months, 6 months, one year and two years after the disaster. SUBJECTS: About 9000 school children in the 3rd grade, the 5th grade, the 8th grade living in the disaster area. METHOD: The questionnaire consisted of 9-12 items regarding situation and behavior when the earthquake occurred, and 22 items regarding mental health condition, and was filled out in the classroom under supervision by the teacher in charge. The responses were rated from 1 to 4 depending on the frequency of the symptoms, and statistically analyzed. RESULTS: By factor analysis, three factors were elicited. Factor 1 was interpreted as being related to fear and anxiety, factor 2 as related to depression and physical symptoms, and factor 3 as related to pro-social tendencies. These 3 factors were distinct and stable throughout all 4 surveys and each of them showed unique recovery processes. The mean score of factor 1 was highest at 4 months after the earthquake, and decreased as time passed. This factor shows that fear and anxiety seem to be directly related to the experience of the earthquake. According to the severity of the disaster, more severe damage brought about a higher mean score of factor 1. Furthermore, younger children and girls were more strongly affected. Each of the differences in the severity of disaster, in age, and in gender decreased as time passed. The mean score of factor 2 peaked at 6 months, and it slightly recovered after one year. However, the score at the 1st year was still higher than that of the 4th month. At two years the score returned to almost the same level as that of the 4th month. We think that factor 2, involving depressive mood and psychophysical symptoms, may be a secondary phenomenon to fear and anxiety. Other possibilities are that they may be caused by environmental changes after the disaster, inconveniences of daily life, loss of jobs of parents, or masked by hypomanic mood which covered over the disaster area soon after the earthquake (so-called heroic phase). Older children have a greater tolerance for depressive mood and psychophysical symptoms, but those symptoms occurring in older children have a tendency to continue for a longer time. Girls are more heavily affected and need more time to recover from trauma than boys. The mean score of factor 3 showed a gradual decrease as time passed. There was no difference in the way of decrease according to the severity of disaster, age and gender. It may be natural that, since the interest in the earthquake decreased as time passed, consideration for the victims decreased. CONCLUSIONS: The problems of mental health of children and adolescents after the disaster may consist of at least 2 different components; "fear and anxiety," which appeared just after the disaster and decreased earlier; "depressive and psychophysical symptoms" appeared later and stayed longer.

Asymmetric aldol reaction of enol trichloroacetate catalyzed by (S, S)-(EBTHI)TiCl(OMe).

(S,S)-Ethylenebis(tetrahydroindenyl)titanium chloride methoxide, (S, S)-(EBTHI)TiCl(OMe) (3) was synthesized from the corresponding titanium dichloride. The asymmetric aldol reaction of enol trichloroacetate of cyclohexanone 1 with aromatic aldehydes was studied in the presence of a catalytic amount of the chiral titanium complex 3, with the result that the optically active syn aldol adduct 2 was preferentially obtained with up to 91% ee.